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Material Information
- Title:
- Arousal and memory performance in Parkinsonism
- Creator:
- Hanger, Philip Andrew, 1961-
- Publisher:
- University of Florida
- Publication Date:
- 1989
- Language:
- English
- Physical Description:
- viii, 126 leaves : ill. ; 29 cm.
Subjects
- Subjects / Keywords:
- Analysis of variance ( jstor )
Basal ganglia ( jstor ) Dementia ( jstor ) Diseases ( jstor ) Frontal lobe ( jstor ) Memory ( jstor ) Neurology ( jstor ) Parkinson disease ( jstor ) Rhyme ( jstor ) Warnings ( jstor ) Arousal ( mesh ) Department of Clinical and Health Psychology thesis, Ph.D. ( mesh ) Dissertations, Academic -- College of Health Related Professions -- Department of Clinical and Health Psychology -- UF ( mesh ) Memory ( mesh ) Parkinson Disease -- physiopathology ( mesh ) Research ( mesh )
Notes
- Thesis:
- Thesis (Ph.D.)--University of Florida, 1989.
- Bibliography:
- Bibliography: leaves 115-125.
- General Note:
- Typescript.
- General Note:
- Vita.
- Statement of Responsibility:
- by Philip Andrew Hanger.
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AROUSAL AND MEMORY PERFORMANCE
IN PARKINSONISM
By
PHILIP ANDREW HANGER
A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 1989
ACKNOWLEDGMENTS
I would like to thank the members of my dissertation committee for their help and guidance, especially Dr. Russell Bauer who has provided invaluable support and direction not only on this investigation, but throughout my graduate training. I wish to dedicate this project to Emily and Victoria, who came to mind whenever I questioned the necessity of my efforts.
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TABLE OF CONTENTS
Page
ACKNOWLEDGMENTS. . . . . . . . . .ii
LIST OF TABLES . . . . . . . . . v
ABSTRACT vi
INTRODUCTION . . . . . . . . . 1
Parkinson's Disease . . . . . . 1
Pathophysiology of Parkinson's Disease. . 3
Cortical/Subcortical Distinctions . . . 6 Treatment of Parkinson's Disease . . . 8
Neuropsychology of the Basal Ganglia. . . 10 Neuropsychology of the Frontal System . . 13 Neuropsychology of Parkinson's Disease. . 16
SExecutive Functions . . . . . 17 SPsychomotor Function . . . . . 20
J Memory Functions . . . . . . 21
SVisuospatial and Visuoperceptual
Functions . . . . . . . 25
Language Related Functions . . . 26
Depression in Parkinson's Disease . . . 28
Arousal . 32
Arousal and Parkinson's Disease . . . 37
Arousal and Memory in Parkinson's Disease . 39
Hypotheses . . . . . . . . 42
METHOD 48
Subjects 48
Materials 49
Standardized Measures . . . . 50 Experimental Measures . . . . 50
Verbal memory . . . . . 50
Reaction Time Task . . . . 56
Equipment. . . . . . . . 58
Physiological Measures . . . . 58
Procedure . 59
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RESULTS 61
Standardized Measures . . . . . . 61
Experimental Memory Tests . . . . . 63 Self-Rated Arousal Test . . . . . 67
Levels of Processing Test . . . . . 70
Electrodermal Response (EDR) . . . 71
SCORE. . 73
-Reaction Time Task. . . . . . . 78
Summary of Results. . . . . . . 82
DISCUSSION 84
J Memory Performance in Parkinson's Disease . 84
Arousal and Memory Performance. . . . 90
Limitations . . . . . . . . 100
Conclusions . . . . . . . . 102
APPENDICES 105
A. LOP301 ACQUISITION . . . . . . 106
B. MLOP301 ANSWER SHEET . . . . . 107
C. LOP302 ACQUISITION . . . . . . 108
D. MLOP302 ANSWER SHEET . . . . . 109
E. AR RATING LIST . . . . . . . 110
F. AR SUBJECT INSTRUCTIONS . . . . 111 G. SAM AROUSAL RATING GUIDE . . . . 112
H. AR RECOGNITION LIST . . . . . 114
REFERENCES 115
BIOGRAPHICAL SKETCH . . . . . . . 126
iv
LIST OF TABLES
Table Title Pae
1. Standardized Measures
Means (Standard Deviations). . . . 62
2. Experimental Memory Tests
Means (Standard Deviations). . . . 63
3. Analysis of Variance
Experimental Memory Tests. . . . 66
4. Analysis of Variance
Self-Rated Arousal Memory Test . . 70
5. Analysis of Variance
Levels of Processing Test. . . . 71
6. Levels of Processing
Mean EDR (Standard Deviation). . . 72
7. Analysis of Variance
EDR AGE 72
8. Analysis of Variance
LOP SCORE . . . . . . 75
9. Analysis of Variance
Reaction Time Task . . . . . 81
v
Abstract of Dissertation Presented to the Graduate School of the University of Florida in Partial Fulfillment of
the Requirements for the Degree of Doctor of Philosophy
AROUSAL AND MEMORY PERFORMANCE IN PARKINSONISM
By
Philip Andrew Hanger
August, 1989
Chairman: Russell M. Bauer, Ph.D. Major Department: Clinical and Health Psychology
Research has suggested that cognitive deficits are associated with Parkinson's Disease (PD), including impaired verbal memory. PD patients have also shown decreased cognitive and motor initiation relative to normal controls suggesting that resting or tonic arousal may be reduced in PD. Pharmacological evidence has shown that treatment of PD using L-dopa reportedly increases the patient's subjective and behavioral arousal. The present study examined the degree to which arousal, both tonic and phasic, affects memory performance. Recognition of information acquired under tonic arousal was assessed using the Wechsler Memory Scale and the Verbal Recognition Test.
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Recognition of information acquired during
self-initiated increased arousal (auto-evoked) was assessed using the Levels of Processing Test. Recording of electrodermal responsivity (EDR) was obtained during the acquisition phase of this task to validate the expected change in arousal associated with different cognitive processes involved. Recognition of information acquired during externally elicited increased arousal (exo-evoked) was assessed using the Self-Rated Arousal Test. In addition, the Reaction Time Task was used to assess auto-evoked arousal and resulting motor responding.
The results demonstrated that PD subjects display an
overall impairment in their delayed verbal recognition. PD subjects' recognition performance acquired during auto-evoked arousal was equivalent to normal controls. Similarly, PD subjects showed a comparable improvement to normal control subjects in reaction times following a warning stimulus. EDR did not differentiate across the different levels of cognitive processing required at acquisition, although examination of this data suggests that these readings may not have been accurate. PD subjects displayed improved recognition of words acquired under increased exo-evoked arousal, similar to normal control subjects. The pattern of recognition performances
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suggested that PD patients have relatively intact arousal function, but that their tonic arousal level may be impaired.
The results of this study are discussed in terms of
their implications for educating PD patients to compensate for their verbal memory deficit with the aid of different learning strategies.
viii
INTRODUCTION
Parkinson's Disease
James Parkinson first described a "shaking palsy"
(p. 845), which would later bear his name, as a movement disorder with intact "senses" (p. 845) and intellect (Parkinson, 1817; cited in Taylor, Saint-Cyr, & Lang, 1986a). However, since this early description, there has been disagreement regarding the presence of dementia in Parkinson's disease (PD). Authors as early as Charcot (cited in Mortimer, Christensen, & Webster, 1975) and as recently as Brown and Marsden (1988) have argued that a dementia of some form is common in the disease, while others have denied the presence of dementia in PD (c.f., Schwab, Fabing, & Prichard, 1951; Marsden, 1982).
Parkinson's disease is a relatively common disorder, with average age of onset over 50 years, affecting approximately 25 of every 10,000 persons within this age range (Mayeux, 1984). A triad of motor dysfunction is commonly seen in the disease: tremor, bradykinesia, and
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rigidity. However, many patients also exhibit cognitive and emotional changes as well (Taylor et al., 1986a).
The cognitive changes that have been reported range from a small cluster of deficits to a more global dementia. Mortimer and associates (Mortimer, Christensen, & Webster, 1985) stated that from 20 to 40% of PD patients have moderate to severe dementia. They report that this dementia is more likely to occur in older patients although motor dysfunction (bradykinesia) is still the predominant symptom. Hietanen and Teravainen (1988) proposed that the probability of dementia associated with PD increases with age. They stated that the age of first onset of the disease does not correlate significantly with the occurrence of dementia, but that duration of the illness is a more crucial factor, and that patients with early onset (prior to age 60) are as likely to develop a dementia as patients with late onset (after age 60).
Etiologically, PD exists in postencephalitic,
artheriosclerotic, and idiopathic forms, but until recently these have all come under the common diagnostic label, "Parkinson's disease" (Marsden, 1982). However, PD is not a homogeneous disorder, and even within subtypes there is heterogeneity (Taylor et al., 1986a). These authors report
3
that while there is generally an agreement on the classic triad of motor symptoms associated with PD, progression of these motor symptoms varies considerably among individual patients. Most recent studies generally use subjects classified with the more common, idiopathic diagnosis of PD.
Pathophysiology of Parkinson's Disease
The pathophysiology of PD has been attributed to a dopaminergic syndrome. Loss of pigmented cells in the substantia nigra, pars compacta (SNpc) responsible for the production of dopamine, was observed in PD patients (Marsden, 1982). The result of this cell loss is a depletion in dopamine transmission along the pathway from the SNpc to the striatum (caudate and putamen) with eventual connections to the globus pallidus, thalamus, and frontal cortex, particularly the supplemental motor area (SMA) and mesial frontal region. While the frontal lobe is not directly involved in this nigrostriatal dopamine system, input to the frontal region via subcortical, dopamine dependent structures is affected since the striatum receives its dopaminergic input almost exclusively from the SN (Moore, Bhatnagar, & Heller, 1971), resulting in disruption of frontal lobe function.
4
Another group of dopamine producing cells in the
ventral tegmental area (VTA) has also been shown to be disrupted in PD (Javoy-Agid & Agid, 1980). This region, along with the medial part of the SN, is linked to the brain's two other major dopamine systems, the mesolimbic and mesocortical systems. Dopamine innervation of such limbic structures as the hypothalamus and the nucleus accumbens originates from both the SN and VTA. In addition, regions of the amygdala, hippocampus, and prefrontal cortex receive fibers from the mesocortical dopamine system that originate predominately in the VTA (Thierry, Tassin, Blanc, & Glowinski, 1978).
Mayeux and associates (Mayeux, Stern, Sano, Cote, & Williams, 1987) suggested that an additional alteration in the norepinephrine metabolism within PD is also responsible for cognitive changes associated with the disease. Dubois and his group (Dubois, Danze, Pillon, Cusimano, Lhermitte, & Agid, 1987) suggested that an alteration in the central cholinergic system exists within PD. They detected this transmitter disruption in PD patients who do not display cognitive impairment as of yet.
5
A greater amount of plaques and neurofibrillary
tangles, granulovacuolar degeneration, and cortical cell loss were observed by Hakim and Mathieson (1979) in a number of PD patients compared with sex- and age-matched controls who died of infarct or trauma. The occurrence of these pathological changes typical of dementia, Alzheimer's type (DAT), confounds the estimate of the existence of a dementing process due to PD alone. Boller and his associates (Boller, Mizutani, Roessmann, & Gambetti, 1980) observed that within a group of 29 PD patients, 9 diagnosed with severe dementia also showed a significant degree of plaques and neurofibrillary tangles.
Other studies, however, have failed to confirm the percentage of Alzheimer's-like lesions found in PD patients. For example, Jellinger and Grisold (1982) found that out of a series of 100 consecutive PD patients brought to autopsy, only 4 showed lesions characteristic of DAT as well. These same investigators found that lesions characteristic of PD were also found in 7 of 146 cases diagnosed as DAT. These latter findings suggest that, while an overlap between these two disease processes is indeed present, it appears to be somewhat limited. The most common belief is that a small percentage of those
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patients with PD also have DAT, although there is evidence to suggest that the type of cognitive deficits seen in these diseases is unique to itself (Taylor et al., 1986a).
Cortical/Subcortical Distinctions
Although PD primarily involves subcortical disruption, the cortical/subcortical distinction becomes blurred since the pathophysiological changes involve cortical structures as well. For example, Boller et al. (1980) reported similar patterns of cortical degeneration for these diseases. However, another study (Mortimer, Christensen, & Webster, 1985) concluded that, while the frequency of abnormal cortical findings is higher in PD patients than in the general population, there was no convincing direct association between these abnormal cortical findings and the presence of dementia.
The term, subcortical dementia, was used to describe a syndrome characterized by inertia, apathy, forgetfulness, defective ability to manipulate knowledge, and slowness in the rate of information processing (Albert, Feldman, & Willis, 1974; Albert, 1978). These symptoms were ascribed to a number of diseases with predominant subcortical pathology, such as PD, Huntington's disease, and progressive supranuclear palsy. The absence of apraxia,
7
agnosia, and aphasia was typically used to distinguish the subcortical picture from a cortical dementia, such as DAT. Several authors have reported that there are a number of clinical distinctions between these two groups as well (c.f. Benson, 1983, for summary).
Huber and associates (Huber, Shuttleworth, Paulson,
Bellchambers, & Clapp, 1986) demonstrated the distinction between the cortical (DAT) and subcortical (PD) types of dementia. They concluded that PD was characterized by a mild impairment of memory and visuospatial functions, yet no impairment of language or praxis. They noted that depression was also a frequent symptom. Patients with DAT, on the other hand, performed markedly different, with overall mental function, memory performance and visuospatial functioning more severely impaired. In addition, there was a significant disturbance of language-related functions and praxis. Depression was also present in several patients. Their results suggest that there was a qualitative as well as quantitative difference in the dementias associated with PD and DAT.
8
Treatment of Parkinson's Disease
The demonstration that there exists a depletion of
dopamine in the SNpc and striatum of PD patients led to the therapeutic use of L-3, 4-dihydroxyphenylalanine (also known as levodopa or L-dopa), the immediate precursor of dopamine. This precursor is capable of passing the blood-brain barrier, whereas dopamine itself is not. While there is no direct evidence that the functional integrity of the dopaminergic pathway is restored by the administration of L-dopa, studies of cerebrospinal homovanillic acid (HVA), a dopamine metabolite, suggest that an increased synthesis of dopamine in the central nervous system does result from L-dopa administration (Yahr, Duvoisin, Schear, Barrett, & Hoehn, 1969). Johansson and Roos (1965) had earlier reported a marked decrease in the dopamine by-product, HVA, found in the cerebrospinal fluid of untreated PD patients. The assumption made by Yahr and his group was that in PD, the diseased dopaminergic neuron is readily able to synthesize dopamine if presented with the immediate precursor, but that it has difficulty synthesizing dopamine at the natural first stage, using tyrosine, from which L-dopa is derived.
9
Double-blind studies using L-dopa have demonstrated a marked improvement in the motor symptoms associated with PD, including decreased rigidity, akinesia, and tremor. In addition, mental changes following administration include improvement in memory, stabilization of sleeping pattern, decreased nervousness, and increased arousal (Yahr et al., 1969).
One side-effect associated with prolonged use of L-dopa is described as an "on-off phenomenon" (p. 292). This includes rapid, unpredictable fluctuations between akinesia and dyskinesia, usually independent of the frequency of L-dopa doses or L-dopa level within the bloodstream (Marsden & Parkes, 1976). A comparison between the cognitive status during the on and off states revealed a general disinhibition of language, worsened memory, perseverative responding, and a worsening of mood associated with the off state (Delis, Direnfeld, Alexander, & Kaplan, 1982; Girotti, Carella, Grassi, Soliveri, Marano, & Caraceni, 1986).
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Neuropsychology of the Basal Ganglia
Since PD involves subcortical pathology, it is useful to understand the behavioral manifestation associated with disruption to these structures in the absence of PD. One of the primary structures within the subcortex is the basal ganglia and a set of circumscribed neuropsychological deficits has been attributed to damage in this region.
The striatum is situated so as to process sensory-cortical input as well as to influence motor-cortical output. However, most behavioral studies of basal ganglia function have focused on the motor components associated with this region of the brain (c.f. West, Michael, Knowles, Chapin, & Woodward, 1987). Schneider (1987) emphasized that while many studies examining the role of the basal ganglia in motor function regard the system as having a direct influence on spinal motor function, it in fact is several synapses away from these final spinal pathways and must therefore influence movement indirectly. In addition, while the striatum receives input from motor and somatosensory cortex, output from the basal ganglia does not reach the primary motor cortex directly but is instead directed to the SMA and premotor areas (Nauta & Domesick, 1984). The SMA in turn can alter the responsiveness of the precentral motor neurons to sensory
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inputs, resulting in modulation of discrete movements of individual body parts (Tanji & Kurata, 1985). The SMA therefore serves as the link between intention formation and the programming and execution of specific actions. Studies of basal ganglia lesions in rats revealed that they had difficulty when required to use somatosensory feedback in the performance of a proprioceptively guided forelimb reaching task. These motoric abnormalities were not evident during spontaneous locomotion, but became apparent when limb movements had to be generated on the basis of somatosensory feedback (Schneider & Olazabal, 1984). The SMA therefore receives sensory information from the body schema for initiating and modifying motor programs. The observation was also made that damage to the SMA results in impairment of intentional action arising out of internal sensory information as opposed to an environmentally contingent, response action. It can therefore be said that the SMA provides the internal drive for intentional movement.
The observation has been made that disruption of the dopaminergic system involving the basal ganglia does more than disrupt movement. Patients often respond as if they are not functioning under normal control of internal cues.
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Clinical examples are seen in PD patients who demonstrate improved gait when required to step over lines on the floor, without which they would merely take a few steps and then become unable to initiate any further movement. These patients are unable to utilize proper sensorimotor coordination and require additional visual stimulation (e.g. lines on the floor). Lit (1968) suggested that PD patients, under highly emotional stimulation are able to perform movements which they would have great difficulty accomplishing under normal levels of arousal. He describes the PD patient crossing the street with a typical slow, shuffled gait being able to dash to the curb at the sound of an oncoming automobile as an example of "paradoxical kinesia" (p. 865).
Memory disturbance typically associated with damage to the basal ganglia, specifically the caudate nucleus, has been described by Butters and his colleagues (Butters, Wolfe, Martone, Granholm, & Cermak, 1985). They differentiate the memory disorder seen in Huntington's Disease (HD), which involves progressive atrophy of the basal ganglia, from cortical amnesia according to recognition memory performance and procedural memory (skill learning). These authors state that while both patient
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groups display impaired free recall of verbal information relative to normal control subjects, the HD patients memory performance improves significantly, in fact comparably to normal controls on recognition memory testing, whereas the cortical amnesics do not show this benefit. However, they found that the cortical amnesics were able to demonstrate normal acquisition of a cognitive procedural task, but that the HD patients had marked difficulty doing so. They concluded that the learning and retention of skills and general procedures may be dependent on the normal functioning of the basal ganglia.
Neuropsychology of the Frontal System
While the frontal system is not directly implicated in PD, many of the subcortical structures that are damaged in the disease have direct connection to the frontal cortex (Stuss & Benson, 1984). It is therefore useful to understand the behavioral manifestations which result from damage (and/or disruption of input) to this region.
Tilney (1928) proposed that the frontal lobes played a large evolutionary role in separating the human race from that of primates. Halstead (1947) suggested that the frontal association cortex was responsible for the highest
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intellectual and moral functions found in man. However, our knowledge of frontal lobe function has remained relatively limited and controversial, and Teuber's (1964) description of frontal lobe function as "a riddle" is still somewhat true today. Part of the reason for this description is the fact that the functions of the frontal lobe are complex and interrelated. In addition, our knowledge of frontal function has been hindered by inadequate test procedures and lack of control over the size and location of cortical lesions in that region (Stuss & Benson, 1984).
Several broad (and vague) descriptive statements
provided below have been extracted from a summary by Stuss and Benson (p.22, 1984), and are generally accepted as examples of impaired function associated with frontal dysfunction:
1. "Prefrontal damage can separate action
(response) from knowledge." This deficit is
illustrated by patients who demonstrate
understanding (via verbal report) of the expected behavior but are unable to produce said behavior.
2. "Prefrontal damage can impair the ability to
handle sequential behaviors." Patients exhibit an
inability to put items in an organized sequence,
have difficulty making recency judgements on
memory tasks, and display impaired performance on sequential motor tasks, resulting in perseverative
responding.
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3. "Prefrontal damage can impair the ability to
establish or change a set." This deficit is
apparent on tests requiring sustaining attention or on sorting tasks, with the resultant behavior
appearing random and perseverative.
4. "Prefrontal damage can impair the ability to
maintain a set in the face of interference." This becomes especially apparent on memory tests which
employ an interference paradigm, such as the
Brown-Petersen Consonant Trigram Memory Test.
5. "Prefrontal damage impairs the ability to monitor personal behavior." Patients display
uncorrected, erroneous actions and do not appear
to benefit from feedback regarding their behavior.
6. "Prefrontal damage can produce attitudes of
unconcern, unawareness, and apathy." Often times
frontal patients will ignore or actively deny many
of their deficits.
Schacter (1987) provided a further elaboration on the memory deficit associated with frontal lobe pathology. From both a review of the literature as well as his own findings, he concluded that the memory deficits associated with frontal dysfunction were qualitatively different from those in patients who do not exhibit frontal pathology. He described the frontal memory impairment as involving a deficit in remembering certain types of contextual or spatiotemporal information. He concluded that the frontal lobe's influence on amnesia was not solely via deficits in motivational or strategic processes but could also be associated with a failure in a a highly specific memory
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function. This deficit is referred to as a "source amnesia" by Squire (p. 568, 1982).
Stuss and Benson (1984) caution that rarely are the
frontal lobes individually disturbed; instead the deficits seen are often combined with impaired function secondary to damage in other regions of the brain. In addition, many functions localized to the frontal lobes may also involve input from other regions of the cortex and it is therefore not valid to refer to such an impairment as being related to frontal dysfunction alone.
Neuropsychology of Parkinson's Disease
The issue of whether the cognitive changes observed in PD are related to a cortical versus a subcortical dementing process is complicated by the fact that within the disease there are symptoms consistent with frontal pathology as well as basal ganglia dysfunction. The possibility of an interactive deficit is a reasonable assumption given the work of Lee (1984), who was unable to produce a primate model of PD following lesions to the SNpc. This finding suggests that the subcortical pathology of PD extends beyond the SNpc, possibly including other neuropathological changes or a reorganization of neural circuits. Taylor and her associates (Taylor et al., 1986a) propose that in
17
nondemented PD patients, the cognitive deficits reflect a prefrontal component resulting from a combination of disturbed caudate outflow and reduced availability of input to the lateral convexity of the prefrontal region.
Below are some of the findings within the literature on neuropsychological function typically associated with PD. These findings are grouped according to major theoretical functions and do not necessarily represent anatomical delineations.
Executive Functions.
Evidence of impaired frontal function in PD patients was reported by Taylor et al. (1986a). Using the Wisconsin Card Sorting Test, they found that PD patients generated significantly fewer categories and required more trials to attain the first category when compared with age-matched control subjects. Patients did not exhibit a perseverative response style on this test. Performance on the Halstead-Reitan Trail Making Test was not significantly different from controls when the groups were equated for motor slowing. PD patients produced significantly fewer responses on a design fluency task, and while they were relatively more prolific on a verbal fluency task (FAS), their overall performance was still below that of normal
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control subjects. They also displayed errors of serial position on visual and verbal span tasks. These authors stated that PD patients exhibited an inability to initiate concepts as well as a tendency to verbalize, but not execute correct responses.
On a simple reaction time task, PD patients were significantly slower to respond than control subjects (Bloxham, Dick, & Moore, 1987). However, when they were given a warning signal in the same reaction paradigm they were able to allocate attentional resources and respond as quickly as the control group. In a second experiment, subjects were required to simultaneously perform a
continuous task with the right hand while making their responses to the reaction time task with the left. In this situation, patients were still slower to respond, but the overall effect of interference from the second task was the same for both patients and controls. An interesting finding in this study was that for the PD patients, the advantage of the warning signal was lost after long intervals (> 200 milliseconds) regardless of whether the second tasks were being performed. These authors suggest that this finding reflects that PD patients were behaving as if they were constantly performing a motor task even when they were apparently at rest.
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Taylor et al. (1986a) also reported that PD patients had difficulty with the execution of simultaneous and competing motor tasks. In this study, subjects were required to continuously maintain a finger tapper with one hand while sorting beads by their shape with the other. These authors reported that the tapping component of the task, on which PD patients were impaired, was not under visual guidance as subjects were attending visually to the sorting task. Therefore the tapping required some form of automatic, internal program which was deficient in this group. They cite Goldberg (1986), who proposed that the SMA of the frontal lobe was responsible for the planning of actions which are guided by such internal cues, in concluding that this structure was impaired in PD.
Flowers and Robertson (1985) demonstrated that PD
patients have difficulty in alternating between conceptual sets on an Odd-Man-Out choice discrimination task. In this task, subjects are required to indicate which of a set of letters or numbers is different from the others on two series of cards, using two rules of classification alternately on successive trials. The number of correct choices on each trial and the kind of errors made indicate the ability of subjects to apply a concept consistently and
20
to alternate between one response set and another. The difficulty was believed to result from an instability of the cognitive set as opposed to a loss of the patients' reasoning ability, increased perseveration, or distractibility. A similar finding was reported by Iversen and Mishkin (1970) using monkeys with frontal lesions. This study found that subjects had difficulty alternating between two rules when the stimuli remained the same but the rules guiding the correct choice alternated. These authors believed that the deficient performance was due to an inability by the subjects to apply the rule.
Psychomotor Function.
Researchers generally agree that the movement disorder associated with PD includes akinesia, bradykinesia, and tremor. These deficits show progressive deterioration with the course of the disease (Lieberman, 1974). While primary motor skills reportedly remain intact in PD (Marsden, 1982), an impairment is seen in their ability to execute learned motor programs automatically. This is demonstrated in patients who are only able to execute separate components of complex movements, resulting in slow, inefficient progress. Flowers (1978) reported that when visual cues are provided, their movements approach normal.
21
Memory Functions.
Taylor and her associates (1986a) found that PD
patients showed poorer immediate recall of prose material on the Logical Memory subtest of the Wechsler Memory Scale. Interestingly, this deficit was not observed for delayed recall of this material, and since the PD patients were able to retrieve as many elements from long-term storage as normal control subjects did, they concluded that encoding/retrieval processes were adequate in PD. An explanation for the differential performance at immediate recall was that, while the presentation of the information was consistent for all subjects, the rate of presentation may have been too rapid, and therefore the deficit in recall reflected a slowness to encode material. At immediate recall the information is not yet fully processed, but by delayed recall, after a period of consolidation, the information is available.
Recall of supraspan verbal lists was impaired for PD patients relative to controls when overall production was the dependent variable (Taylor et al., 1986a). However, when the data were further analyzed, they discovered that the PD group demonstrated comparable recall to controls for
22
items at the beginning and end of the list (i.e. primacy and recency effects). Recognition memory was not significantly different between the two groups. The authors admit the evidence for frontal lobe involvement in the memory disturbance seen in PD is "meagre" (p. 850). They point out that patients with damage to the hippocampus display poor recall of words from the beginning of a list (primacy deficit), a deficit not observed in their PD patients. In addition, temporal lobe patients display impaired recognition memory, whereas the PD subjects in their study did not. These authors conclude that the areas most likely responsible for the memory deficits observed in their study were the frontal lobes. They base this position on the previous findings as well as the evidence for deficits on other nonmemory tasks sensitive to frontal dysfunction and the spared abilities sensitive to posterior cortical association areas,
Tweedy, Langer, and McDowell (1982) found that PD patients showed a delayed release from proactive interference on a word-list learning task as well as an impaired ability to benefit from semantic cueing on this task. Pirozollo et al. (1982) reported impaired visual memory in PD. They found that PD patients had poorer
23
recall than NC subjects of visually presented geometric figures following a delay. Yet Flowers and associates (Flowers, Pearce, & Pearce, 1984) demonstrated that PD patients were within normal limits on tests of visual recognition, both at immediate and delayed recall. They concluded that PD does not affect learning of this material, but rather its retrieval.
Frith, Bloxham, and Carpenter (1986) had PD patients
learn two novel skills in which they were required to track a moving target using a joystick. In the first condition, they only had to anticipate the movements of a "semi-predictable" (p. 664) target. While in the second, the movements of the joystick were mirror-reversed in relation to the target. This study showed that PD patients' performance was poorer that control subjects on both tasks. However, PD patients did show evidence of learning, as demonstrated by performance savings, even after a ten minute delay. The major difference between the control and patients groups appeared to be within the first minute of each practice phase, during which the control group tended to show marked improvement while subjects in the PD group showed relatively little increase in accuracy. The authors concluded that this rapid, although
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temporary improvement in performance represented the acquisition of a motor set, and that the impaired initial learning seen in PD subjects was due to a difficulty in acquiring such a set.
Helkala and colleagues (Helkala, Laulumaa, Soininen, & Riekkinen, (1988) compared PD and DAT patients on recall of Buschke's list learning task and on a test of story recall. They found differences in performance to exist on delayed recall of the Buscke paradigm in that the performance of PD subjects was superior to that seen in DAT subjects, although no difference was found on immediate recall. There was no nonpatient control group for comparison purposes; therefore, the relative ability of PD subjects could not be assessed. However, it appeared from the group means that the DAT subjects displayed a significantly greater decline in performance relative to the mild decline shown by PD subjects. A similar pattern was observed on recall of the prose material, with PD subjects significantly better on delayed recall, but with no difference on immediate recall. The authors concluded that this difference was evidence for better functioning within PD relative to DAT of the entorhinal cortex and hippocampus, which was proposed to be responsible for
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long-term storage of information. Interestingly, this study did not provide a non-patient control group, and so the conclusion of intact functioning of these cortical areas could not be made from these data.
Visuospatial and Visuoperceptual Functions.
There have been several reports suggesting that PD patients have a deficit in spatial orientation. Proctor and associates (Proctor, Riklan, Cooper, & Teuber, 1964) demonstrated that PD patients were impaired in their ability to judge visual-vertical, both when their body was tilted and when in an upright position. PD patients have also been shown to have impaired performance on subtests from the Wechsler Adult Intelligence Scale (WAIS) which require significant visuospatial ability; these include Picture Arrangement, Block Design, Object Assembly, and Digit Symbol (Pirozollo et al., 1982). Albert (1978) reported that on the Hooper Test of Visual Organization, PD patients displayed significant difficulty compared with age-matched controls in combining the abstracted visual material into a meaningful whole.
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In contrast to the visuospatial deficits reported
above, there have been fewer studies that report impaired visuoconstructional abilities in PD (c.f., Bowen, 1976, for review). Matthews and Haaland (1979) argue that many construction tasks require a great deal of manual dexterity in the manipulation of objects and that the motor impairments associated with PD obviously confound the findings making it appear that visuoconstruction functioning was poorer than it actually was. However, Pirozollo et al. (1982) found that when PD patients were given untimed visuospatial tasks that also did not require a great deal of fine motor coordination, their scores were still below those obtained by normal control subjects.
Language Related Functions.
It is typically assumed that language abilities are grossly intact in PD (Boller, 1980). Levita and Rikland (1973) reported that they found PD and control subjects did not differ in verbal abilities, including verbal fluency. However, there have been scattered reports of language impairments associated with PD within the literature. Matison and associates (Matison, Mayeux, Rosen, & Fahn, 1982) reported naming and verbal fluency deficits in a
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group of PD patients who were not otherwise cognitively impaired. In addition, this group reported that PD patients frequently experienced "tip-of-the-tongue" (p. 567) phenomenon, a type of word finding deficit.
Pirozollo et al. (1982) demonstrated that PD patients' performance on the Vocabulary subtest of the WAIS was comparable to control subjects, but their performance on the Information subtest was relatively poorer. The Vocabulary subtest is often used as a general indicator of language ability, strongly dependent on education level, and they suggest that the Information subtest requires greater memory involvement for successful performance. Matthew and Haaland (1979) found that PD subjects obtained Verbal IQ Scores on the WAIS which were lower than that of age-matched controls, although this difference did not reach statistical significance.
Mortimer and colleagues (Mortimer, Christensen, &
Webster, 1985) suggested that the variability of findings regarding language deficits in PD was due partly to a bias in subject selection factors. They proposed that studies generally chose patients on the basis of presence or absence of dementia, which includes screening for language deficits. Since PD subjects in most studies have already
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been prescreened to eliminate language deficits, it comes as no surprise that language impairments fail to arise in most of these studies.
Depression in Parkinson's Disease
Symptoms of depression are commonly associated with PD, with a reported incidence between 40 to 50% of the patient population (Mayeux, 1982; Taylor, Saint-Cyr, & Lang, 1987). One assumption is that the depression is an adjustment reaction to having a chronic illness such as PD. However, a number of findings suggest that this may not completely account for the nature of the mood changes associated with PD. Robins (1976) reported that PD patients have a higher frequency of depressive symptoms than do patients with other chronic disorders having similar physical disabilities. Celesia and Wanamaker (1972) found that severity of the depression bears little relationship to the severity of the motor impairment observed in PD patients. Mayeux et al. (1981) reported that in many PD patients the depressed mood predated the onset of the motor symptoms entirely.
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Brown and Wilson (1972) suggested that the etiology of the depression in PD may be related to neurotransmitter systems involving serotonin, dopamine, and norepinephrine, which are reportedly reduced in PD. Mayeux, Williams, Stern, and Cote (1984) studied 50 consecutive idiopathic PD patients and found that 36% of them were depressed according to DSM-III criteria (APA, 1980). In this study, cerebrospinal fluid was obtained from lumbar puncture in 45 of the original patients as well as 15 age-matched, non-depressed neurologic controls. Metabolites of dopamine, serotonin, and noradrenaline were assayed and the results showed that only the metabolite for serotonin was significantly lower in depressed PD patients than in both the control and non-depressed PD groups.
Weingarter and his colleagues (Weingarter, Cohen,
Murphy, Martello, & Gerdt, 1981) reported changes in the information processing ability of endogenously depressed patients. Using a Levels of Processing technique (Craik & Lockhart, 1972), they identified a weakness in the ability of depressed patients to encode information to be remembered. They concluded that this represented incomplete or insufficient use of strategies in organizing and transferring information to long term memory when the
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information was of the episodic type and required conscious effort.
In an attempt to replicate the findings of Weingarter et al. (1981) in depressed PD patients, Taylor, Saint-Cyr, and Lang (1986b) used the Beck Depression Inventory (BDI) as a quantitative measure of depression. They found that regardless of whether PD patients reported moderate or severe levels of depression, short term memory performance was not impaired. In contrast, endogenously depressed patients with moderate to severe depression were impaired on several short term memory tasks. The demonstration that PD patients were able to perform within normal limits on these memory tasks regardless of their self-reported level of depression led the authors to conclude that, unlike the endogenous depressed patients, PD patients maintain adequate ability to use encoding strategies.
An additional finding from this study (Taylor et al.,
1986b) was that few of the depressed PD patients reported self-destructive thoughts, guilt, or experiencing a sense of failure; all of which are characteristic of a negative mood state associated with endogenous depression according to the DSM-III criteria (APA, 1980). However, the majority of PD patients exhibited signs associated with depressed
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mood (i.e. tearfulness and agitation) during the study across all level of BDI ratings. The authors noted that this depressive affect was readily elicited in PD patients when stress was introduced during testing sessions. In addition, unlike endogenously depressed individuals who tended to become untestable when affectively aroused, they found they were able to test through the depressed moods displayed by the PD patients.
The results of the study by Taylor et al. (1986b)
suggest that the depression seen in PD may represent an entity different from that seen in endogenous depression. The authors proposed the possibility that depression in PD represents a similar, transmitter-related deficit which they propose affects the prefrontal region by nature of the deficient nigrostriatal and mesocortical dopaminergic pathways reported in PD. In addition, they note that the regulation of mood has been linked to structures in the prefrontal cortex which rely in part on basal ganglia output (Nauta, 1971). They cite Fibiger (1984) who proposed that the dopamine depletion in the prefrontal cortex of PD patients may predispose them to experience depression, which can be more easily exacerbated by frustration or stress.
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Arousal
One of the symptoms of subcortical brain damage
reported in the literature is impairment of arousal and/or attention (Oscar-Berman, Gade, Feldman, & Saavedra, 1979). Arousal is often used interchangeably with terms such as activation, awareness, emotion, and others (Klove, 1987). Pribram and McGuinness (1975) distinguished between three related neural systems responsible for arousal. They proposed that the first system was responsible for phasic arousal, a change in the level of arousal in response to input stimulation. They suggested that the amygdala was largely responsible for mediating phasic changes in arousal. The second system was responsible for controlling activation or the tonic physiological readiness of the organism to respond. Control of this resting arousal level was believed to involve the basal ganglia. The third system, involving the hippocampus, was responsible for coordinating arousal and activation, and required effort.
Increased arousal is detected neurologically as a change in activity in the Reticular Activating System (RAS). When the cortex receives sufficient afferent impulses it is considered to be aroused; in other words,
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the critical number of cortical neurons have been brought into activation, resulting in a state of alertness. This arousal is a generalized activation of not only the cortex, but of the autonomic system as well, specifically the sympathetic nervous system. Afferent pathways lead into the RAS and if sufficient impulses are received, the RAS discharges into the cortex to produce the aroused state (Netter, 1975).
According to Klove (1987), input from the sensory systems is sent to the cortex but is also sent along collateral fibers to the RAS. These connections to the RAS then result in connections to the thalamus and to wide areas of the cortex thus allowing for the generalized cortical activation.
Arousal influences consciousness as well as an
individual's emotional state. Kissin (1986) proposed that the electrical activity of the brain associated with consciousness reflected activation, while the energy level of the organism associated with the intensity of the emotional state reflected arousal. The level of arousal is considered to be associated with the ratio of sympathetic to parasympathetic activities. High levels of sympathetic activity produce increased arousal, and high levels of parasympathetic activity result in lowered arousal.
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Control of activation on the other hand is accomplished through the influence of the hypothalamus, thalamus, limbic, and nigrostriatal systems upon the RAS. Inhibitory input to the RAS results in a reduction in the level of consciousness, while an increased excitation of the RAS increases the level of activation of the brain, resulting in behavioral excitation (Kissin, 1986). He warns that there is an optimal range for the level of arousal such that activation outside this range may result in impairment. Too high a level of arousal may result in disorganized behavior or distractibility, while an individual with too low a level of arousal may appear drowsy and have difficulty attending.
Joseph and associates (Joseph, Forrest, Fiducia, Como, & Siegel, 1981) reported a significant correspondence between electrophysiological measurement of cortical activation and behavioral arousal. These authors discovered that high- and low-active rats (identical strains) displayed significantly different visual evoked potential amplitudes. In addition, behavioral responsiveness to complex (open- versus close-field), novel, and intense forms of stimuli were correlated with cortical activation, as indicated by amplitude of visual evoked potential.
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The orienting response (OR) has typically been thought of as an involuntary attentional mechanism which alerts the organism when an unexpected stimulus occurs and is considered an example of an externally elicited, "exo-evoked", change in arousal (p. 128; Sokolov, 1966). Lynn (1966) proposed three types of stimuli which spontaneously evoke the OR; these are novel stimuli, conflicting stimuli, and stimuli with which we have attributed some prior significance.
Ohman (1979) proposed that the OR indicated a call for information processing resources required for a deeper analysis of the eliciting stimuli. Support for this view was provided by the research of Simons, Ohman, and Lang (1979) who showed that electrodermal response (EDR) magnitude to a warning stimulus was larger when a high interest, imperative stimulus was expected than when a low interest stimulus was expected. These authors conclude that the change in electrodermal activity reflected a general mobilization of energy for efficient performance of the task, a reaction time measure, which was sensitive to the arousing quality of the imperative stimulus.
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Spinks and associates (Spinks, Blowers, & Shek, 1985) suggested that the anticipatory process of the OR was consistent with the functions of the autonomic nervous system: protection, activation, and integration. They found that skin conductance responses to orienting activity was predictive of the anticipated task demands. The OR was stronger the more information was anticipated at a given moment. They proposed that the autonomic nervous system coordinates preparedness in order to optimally deal with future situations. Preparedness at the cognitive level, is considered by Luria (1973) to be representative of adaptive change in cortical "tone" (p. 214), and equivalent with the concept of arousal.
Holloway and Parsons (1971) described habituation is a highly labile, reversible process which occurs even when the stimuli are neither meaningful, intense, or when they are expected, and often not at all under conditions of increased alertness. They demonstrated that a group of heterogeneous "brain damaged" (p. 625) patients failed to show normal habituation to the OR using an auditory stimulus. Failure of habituation was thought to reflect disruption in the cortical modulation of lower brain centers which govern autonomic activity.
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Arousal and Parkinson's Disease
An effective pharmacological treatment for the motor disability seen in PD involves administration of the dopamine precursor, L-dopa. Several studies have reported additional arousing and antidepressant effects associated with this treatment, and the conclusion was made that a deficit in arousal exists in PD and that this decreased arousal likely contributes to neuropsychological deficits observed in PD (Elithorn, Lunzer, & Weinman, 1975; Godwin-Austen, Tomlinson, Frears, & Kok, 1969).
The administration of L-dopa is thought to increase the turnover of catecholamines and increase dopamine stores (Hornykiewicz, 1966). The proposed site of action of this increase in dopamine activity is the basal ganglia, and it is through the mesolimbic dopamine system's projections to the midbrain (i.e. RAS) that increased arousal is effected by administration of L-dopa (Horvath & Meares, 1974). These authors observed that PD patients treated with L-dopa demonstrated increased psychophysiological arousal, in terms of a decreased habituation rate, increased OR, and increased levels of electrodermal responsivity (EDR), and behaviorally, in the form of faster reaction times. They
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reported that such a delay in habituation of the OR was also representative of a behavioral index of increased arousal.
Brown and Marsden (1988) suggested that PD patients have an impairment in their ability to maintain internal attentional control. They propose that the PD patients have reduced resources available in their "Supervisory Attentional System" (p. 332; SAS), a hypothetical construct responsible for determining which of several conflicting, simultaneous tasks take precedence for their attention. These authors stated that our subconscious allows for automatic processing and performance of several different tasks (schemata) simultaneously. But there are times when these schemata conflict, at which point a "scheduler" (p. 338), the SAS, determines which schemata to give precedence to, dependent on the environmental demands. They propose that PD patients are still capable of scheduling their attention, but that when the attentional demands become too great and exceed the limited resources of their SAS, they are not able to function efficiently. These authors propose that the decreased arousal in PD is a reflection of the decreased resources available to the SAS.
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Arousal and Memory in Parkinson's Disease
Tasks which require the subject to impose organization and an encoding scheme demand considerable cognitive effort requiring an internally elicited increase in arousal, known as auto-evoked arousal (Hernandez-Peon, 1968). On verbal memory tasks that did not require considerable organization and therefore less effort, PD patients' recall was not significantly different from normal controls (Weingartner, Burns, Diebel, & Lewitt, 1984). In this study, PD patients did not appear to be impaired on tasks which require access to acquired knowledge, i.e. semantic memory. In contrast, DAT patients displayed a disruption in their ability to access these semantic stores. These authors believed that the impairment observed in PD patients more closely resembled the pattern of deficits associated with depression; involving impairment of information processing for tasks requiring considerable cognitive capacity and effort/arousal. This suggests that a deficit in auto-evoked arousal may be involved in PD. DAT patients demonstrated impaired recall regardless of the degree of effort required. The conclusion made from these findings was that different mechanisms mediate automatic processing versus demanding, capacity-limited, effortful processing
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(auto-evoked arousal), and that automatic processing (exo-evoked arousal) is spared in PD.
Brown and his colleagues (Brown, Marsden, Quinn, & Wyke, 1984) found that Parkinson's disease patients who display the on-off phenomenon demonstrate a decrease in arousal and cognitive function in the off phase of this condition. Arousal in this study was assessed by subjects' self-ratings on a scale containing bipolar adjective pairs such as alert-drowsy. Cognitive function was assessed using a test of general reasoning ability for verbal, numerical and spatial material adapted from Heim (1974). The off phase was believed to be associated with decreased dopamine in the striatum, suggesting that a deficit in this neurochemical process may be responsible in part for the reduced arousal seen with PD.
Huber and his associates (Huber, Shulman, Paulson, & Shuttleworth, 1987) supported the findings of Brown et al. (1984) by their observation that a fluctuation in memory performance in PD was correlated with fluctuations in plasma dopamine levels associated, not only with patients demonstrating the on-off phenomenon, but in typical PD patients as well. But, Huber's group proposed that the memory impairment reflected a state-dependent effect
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related to the dopamine blood levels. They found that when dopamine levels changed in either direction between the time of initial learning and later recall testing, recall performance was impaired relative to conditions when the dopamine level remained constant across these two time periods. These results suggest memory performance in PD is more dependent on the variability in dopamine level than on the absolute level of dopamine. However, one additional finding was that during the acquisition phase, even the PD groups who were at optimal levels of dopamine required more trials to learn the same amount of information compared to normal controls. The authors concluded that while rate of acquisition of new verbal material was impaired in PD, the retention of this material was grossly intact, provided the level of dopamine at recall was similar to what it was at acquisition.
As the previous review demonstrates, the term arousal has been used throughout the literature to refer to a variety of different constructs. For purposes of clarity, the present study will refer to arousal as the readiness of the organism to act, its responsiveness. Tasks which elicit more effort (behavioral or cognitive) are therefore associated with greater arousal. An increase in this level
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of arousal may be reflected in a facilitation of the organisms ability to respond behaviorally, such as on a reaction time task (c.f., Bloxham et al., 1987) and physiologically, for example as a change in electrodermal responsivity (c.f., Cohen & Waters, 1985). Hernandez-Peon (1968) suggested that a change in the level of arousal (phasic) could be brought about from stimulation outside the organism as well as from internal sources (i.e. will). Auto-evoked changes in arousal are those behavioral or physiological responses which are elicited from within the organism. Conversely, an exo-evoked change in arousal is a change in responsivity which is elicited from an external source such as a warning signal or pain.
Hypotheses
The preceding discussion has presented evidence in support of the involvement of decreased dopaminergic functioning in the cognitive deficits associated with PD. Several studies suggest that the deficits involve learning and memory (c.f., Mortimer, Pirozollo, Hansch, & Webster, 1982), and it has also been suggested that cognitive abilities improve with L-dopa treatment (c.f., Elithorn, Lunzer, & Weinman, 1975). It is difficult to determine
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whether these cognitive changes are the result of either a generalized or specific effect (Brown, Marsden, Quinn, & Wyke, 1984).
Mohr and associates (Mohr, Fabbrini, Ruggieri, Fedio, & Chase, 1987) reported that PD patients treated with L-dopa manifested relatively selective cognitive changes, disconfirming a generalized alerting effect of L-dopa. In their study, increased performance was only observed on two tests of delayed verbal memory; the Logical Memory and Paired Associates subtests from the Wechsler Memory Scale. Both of these measures assess episodic memory, a function which is impaired in PD (Squire & Cohen, 1984). Weingartner et al. (1984) also reported deficits of episodic memory in PD, especially on tasks requiring effortful processing, which elicit auto-evoked arousal.
Cohen and Waters (1985) suggest there is a relationship between the level of arousal related to the cognitive effort associated with processing information and the recall of that information. They stated that previous investigations have examined whether psychophysiological responsivity was related to attentional demands which influence memory performance. The previous review provided evidence supporting impaired memory function and
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arousal mechanisms in PD. This line of evidence naturally leads to the question of the interaction of arousal and memory in PD.
The current study explored the extent to which arousal elicited from exo-evoked and auto-evoked sources affected memory performance in PD. The previous literature review suggests several hypotheses regarding the interactive relationship of arousal and memory performance in Parkinson's disease. The present study was designed to address the questions drawn from these hypotheses.
Hypothesis Ia. Based on the previous findings in the literature documenting memory deficits in Parkinson's patients, I hypothesized that subjects in this study would show a deficit in their delayed recognition of newly learned verbal information relative to same age and education peers. This led to the prediction that PD subjects would perform significantly poorer than the NC subjects on the experimental memory tasks.
Hypothesis Ib. Parkinson's patients are capable of
activating both from within (auto-evoked) and from without (exo-evoked) on tasks which require effortful processing
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resulting in greater recognition of verbal material obtained during this increased phasic arousal relative to material acquired at tonic, resting arousal. This hypothesis led to the prediction that PD and NC subjects would demonstrate greater overall recognition on both the Levels of Processing memory test (LOP) and the Self-Rated Arousal memory test (AR) relative to their recognition on the Verbal Recognition Test (VRT). The LOP is a task which requires the subject to actively process various aspects of target words, which consequently increases arousal. The AR task also increases arousal due to the emotionally laden characteristics of the target words. The VRT is a simple word recognition task which does not inherently elicit a change in arousal aside from normal encoding processes.
Hypothesis IIa. Parkinson's patients do not activate in response to external stimuli as efficiently as age matched peers. In support of this, the prediction was made that PD subjects' performance on a reaction time task would not show a significant reduction in response latency following a warning stimulus, as would be seen in the NC group.
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Hypothesis IIb. If impaired activation was shown to exist as proposed by hypothesis IIa, it follows that PD patients would have a deficit in recognition performance of verbal material acquired in association with a phasic change in arousal because of the decreased cognitive efficiency resulting from the decreased activation. This led to the prediction that PD patients would show a similar pattern of benefit on recognition memory reflective of the level of cognitive processing evoked on the Levels of Processing memory task (as predicted from hypothesis Ib), but that their overall recognition accuracy would be reduced relative to NC subjects since the efficiency of their activation processes are impaired. The prediction was also made that EDR measured at acquisition would mirror the levels effect seen behaviorally (i.e. recognition memory), but that the overall level of responsivity would be reduced for PD subjects relative to NC subjects, as physiological support that activation was impaired in this population.
Hypothesis III. Exo-evoked arousal is relatively intact in Parkinson's patients compared to NC patients reflected in an identical benefit in recognition of verbal
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material acquired during this phasic arousal period. While it follows from Hypothesis I that the overall level of recognition of PD subjects would be reduced relative to NC, this still led to the prediction that PD subjects would show a greater difference in the level of recognition memory between arousing and non-arousing words on the Self-Rated Arousal memory test, with significantly greater recognition accuracy seen for arousing words.
METHOD
Subjects
Subjects for the experimental group were 12 persons with Parkinson's disease (PD). The mean age was 66.2 (sd
6.1) ranging from 56 to 79 years, 4 were female and 8 were male. Mean education was 15.3 (sd 5.5) years, with a range from 8 to 20 years. The diagnosis of PD was confirmed by their physician either through direct referral or from information in their medical record. The duration of illness ranged from 2 to 10 years according to the patients self-report of the onset of symptoms, and the degree of severity, which ranged from mild to moderate, was determined by their attending physician. Subjects were receiving a variety of anti-parkinsonian medication. Due to the difficulty in monitoring medication on an outpatient basis, no systematic effort was made to control for the type of medication, dosage, or time since last administration, although this information was recorded. All subjects were ambulatory. Subjects were noncompensated volunteers, recruited from three sources: a community PD
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support group, University of Florida, Shands Outpatient Clinic, and outpatients from the Gainesville, VA Medical Center. Subjects with a history of significant neurological or psychiatric illness (in addition to PD), or with reported substance abuse (as defined by DSM-III criteria; APA, 1980) were excluded from this study.
The control group included 12 persons with no known history of significant medical, neurological, or psychiatric illness. The mean age for this group was 61.5 (sd 5.6), with a range from 54 to 72 years. Mean education for these subjects was 14.8 years (sd 2.1), with a range from 12 to 18 years. All subjects were noncompensated volunteers recruited as either spouses of PD patients who participated in this study or through a local newspaper advertisement requesting participants for a "memory study." All control subjects denied a history of substance abuse as defined by DSM-III criteria (APA, 1980).
Materials
Subjects in both the experimental and control groups were administered an identical battery of standardized and experimental measures.
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Standardized Measures
These included a short-form (Satz & Mogel, 1962) of the Verbal subtests (VIQ) from the Wechsler Adult Intelligence Scale-Revised (WAIS-R; Wechsler, 1981). This short-form consists of administration of all the subtests from the WAIS-R, but using only approximately 46% of the items within these subtests. Original research on the WAIS showed a significant correlation, r = 0.99, between full administration and the shortened administration for the Verbal IQ Score. Adams, Smigielski, & Jenkins (1984) showed that there was also a significant positive correlation, r = 0.98, between the short and full administration using the WAIS-R. Other measures included the Wechsler Memory Scale (WMS; Wechsler, 1945) with additional 30 minute, delayed recall for both the Logical Memory and Visual Reproduction subtests, and the Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961).
Experimental Measures
Verbal memory
Word lists Two thirty-item word lists (LOP301 &
LOP302; see Appendices A & B) were constructed for the VRT and LOP memory tests used in this experiment. Each list
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was balanced for frequency and imagibility using the Paivio, Yuille, and Madigan (1968) norms. For half of the subjects in each group, LOP301 was used for VRT and LOP302 was used for LOP. For the other half, the lists were reversed.
For each word, a five-alternative multiple choice item was constructed for use in recognition testing (MLOP301 & MLOP302; see Appendices C & D). Alternatives were balanced for frequency and imagibility with the target item, and were arranged such that the target alternative occurred randomly in positions 2-5 of the item, but never first.
Verbal recognition test (VRT). Word stimuli were
presented individually, in sequence, on a computer screen for a duration of approximately 2 seconds with a 15 second interstimulus interval. The examiner simultaneously read each word aloud to the subject. Subjects were instructed to remember each word and told memory would be tested at a later time. Recognition memory was tested after a 30 minute filled delay. At recognition testing, subjects were presented 30 five-word, forced-choice recognition items on the computer screen and asked to choose the one item they recognized from previous exposure. Only one word in each item was presented at acquisition, and none of the other
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four words appeared on any of the other experimental word lists used in this study. Subjects were given unlimited time to respond, but were encouraged to "guess" on items if they were unable to give a response within a reasonable period of time. Each 5-word item appeared individually on the computer screen, and the next item appeared immediately after their response to the previous item had been recorded.
Self-rated arousal test (AR). This test consisted of a list of 120 words (see Appendix E), 60 of which were previously rated by a group of pilot subjects as "highly" emotionally laden and 60 which were rated neutral. The pilot data was obtained from a cross-section of graduate students and elderly controls. Results from these ratings were not quantitatively analyzed, but it was clear that the instrument contained a sufficient number of LO and HI words to justify its use in the study. This test allowed for the assessment of memory performance related to an increase in arousal, i.e. by nature of the emotional quality of the words (Lynn, 1966). Subjects were given standardized instructions (see Appendix F) to rate each word using a 5-point, Likert-type rating scale for how "arousing" the word was to them. An accompanying visual rating scale, the
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Self-Assessment Manikin (SAM; Hodes, Cook, & Lang, 1985), was provided. This scale depicts a manikin figure across 5 frames of increasing degree of internal arousal (see Appendix G). Subjects completed these ratings at their own pace, and were asked to provide their "best estimate" on items which they had difficulty rating.
When the subjects completed their ratings, the examiner identified the 15 words rated as having the relative "highest" arousing effect (i.e. closest to 5, HI) for that individual, and the 15 words rated the relative "lowest" (i.e. closest to 1, LO). In the event that more than 15 words were rated at the same level, the examiner randomly chose from these items. The 30 words selected were then randomly placed in two blocks of 15 words, such that 8 HI and 7 LO words were in the first block, and 7 HI and 8 LO words were in the second block. After they completed the ratings, subjects were given a 15 minute break, during which time the examiner entered the individualized 30-item word list into the computer for presentation.
The 30 item AR word list was presented to the subjects using the same method and instructions as in the acquisition phase of the VRT paradigm described above. Subjects were told their recognition of these items would
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be tested at a later time. Following a 30 minute filled delay, recognition of the 30 words from the AR paradigm was tested. Subjects were presented a sheet containing the same 120 words that they had previously rated (see Appendix H). These words were in a randomized order relative to their initial presentation. Subjects were reminded that they had seen all the words during the rating phase, and the examiner stressed that they were to choose only those 30 items which they recognized from the presentation 30 minutes prior. Subjects were instructed to "guess" if they were unable to provide all 30 choices. In the event that they endorsed more than 30 items, they were asked to limit their choices to the 30 which they were "most certain of" being correct.
Levels of processing test (LOP; Craik & Lockhart,
1972). This measure was used to assess memory performance as it related to the subjects' ability to perform effortful cognitive processing and exhibit a change in arousal. The test consisted of 30 words balanced for frequency and imagibility according to Paivio et al. (1968) norms. They were presented serially on a computer screen for a duration of approximately 2 seconds with an 18 second interstimulus interval. The examiner simultaneously read a brief
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question requiring the subject to attend to either the physical structure of the word (i.e., "Is this word printed in upper case letters?"), its phonemic quality (i.e., "Does this word rhyme with . .?"), or its semantic quality (i.e., "Is this a type of. .?"). Subjects were directed to respond either "yes" or "no" in reference to the word as quickly as possible after the question was read. The next word was automatically presented regardless of their response latency. No mention of later memory testing for these words was given. An equal number of "yes" and "no" questions were given at each processing level. The examiner noted subjects' response to each of these questions. As these questions were straightforward, a significant number of errors on this task was suggestive of either a comprehension deficit or inattention to the content of the items. Incidental recognition was obtained following a 30 minute filled delay. At recognition testing, subjects were presented thirty 5-word, forced-choice recognition items on the computer screen and asked to choose the word they recognized from previous exposure. Only one word in each item was presented at acquisition, and none of the other 4 words appeared on any other experimental word list presented to them during this
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study. Subjects were given unlimited time to respond, but were encouraged to "guess" on items if they were unable to give a response within a reasonable period of time. Each item appeared individually on the computer screen, and the next item appeared immediately after their response to the previous item had been recorded.
Recordings of electrodermal responsivity (EDR;
described below) were obtained from all subjects during the acquisition phase of the LOP paradigm. Electrodes were attached immediately prior to the acquisition phase of this task, and were removed after it was completed. This measurement allowed for the assessment of a physiological index of arousal related to the level of cognitive processing invoked.
Reaction time task (RXN).
In this task, subjects were seated in front of the computer, with the fingertips of their dominant hand resting on the space bar key, and told that this was a task of their reaction time and motor speed. Subjects are presented the following instructions on the computer:
This is a test of your reaction speed. Press the space bar as quickly as you can when the
star shown below appears. Sometimes this
star will be preceded by a beep just before it appears, other times it will not. Do not
press the space bar before the star appears.
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An example of the imperative stimulus ("star") appeared along with the instructions. A one second, computer generated tone was used as the warning stimulus. This test allowed for the assessment of motor response to phasic changes in arousal elicited by the warning stimulus.
There were 75 separate reaction time trials in all; 25 unwarned, 25 with an auditory warning stimulus 200 milliseconds prior to presentation of the imperative stimulus, and 25 with an auditory warning stimulus 800 milliseconds prior to presentation of the imperative stimulus. The order of presentation of each of these trials was randomized for each individual. The imperative stimulus remained in view until the subject made a response. The computer screen remained clear during the intertrial interval. Each trial proceeded automatically, beginning approximately 10 seconds after the subject's last response. In the event that the subject responded prior to the onset of the imperative stimulus, the trial was terminated, the subject was presented a verbal reminder on the computer screen to wait for the visual stimulus before making a response, and the paradigm was continued with that trial randomly reinserted later in the task. Response
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latency was determined automatically from the computer's internal timer as the difference between time at stimulus onset and key press response.
Equipment
The automatic presentation of the word lists for the VRT, LOP, and AR paradigms was completed using an IBM PC/XT, microcomputer. Word stimuli appeared in the approximate center of a Quadchrome VGA color monitor. The words were printed approximately one half inch in height. Data storage into the computer was completed manually by the examiner for subject's responses on the VRT and LOP paradigms. Data from the RXN paradigm (response latency on each trial) and EDR measures (EDR on each trial) were obtained automatically by the computer.
Physiological Measures
Subjects' electrodermal response (EDR) was measured during the acquisition phase of the LOP test. EDR was obtained using Ag/AgCl disc electrodes placed on the thenar and hypothenar eminences of the subject's non-dominant palm, with an additional ground electrode on the non-dominant forearm. This constant voltage arrangement
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passed 0.5 volts across the palm during recording. Electrodermal activity was sampled at 20 hertz for 7 seconds prior to word onset (tonic arousal) and 7 seconds past offset (phasic arousal). EDR was defined as the difference between the tonic peak and the mean skin conductance level occurring in the last second of the phasic period.
Procedure
Each subject was comfortably seated during the entire procedure. Informed consent was obtained, and subjects were given the opportunity to ask questions, provided the option to withdraw from participation at any time, and assured that doing so would in no way affect the treatment they may currently be receiving. No subjects chose to discontinue the procedures after they were initiated.
The presentation order of the four paradigms involving a 30 minute delayed memory component (i.e., VRT, LOP, AR, and WMS) was randomized across subjects within each of the two groups. The delayed memory portion of each preceding paradigm was completed prior to beginning the acquisition phase of the next, so that there was no overlap of these tests. During the 30 minute delay from the VRT, LOP, and AR paradigms, the Verbal subtests from the WAIS-R were
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administered, in their standard order. The RXN paradigm was administered during the 30 minute delay for the Logical Memory and Visual Reproduction subtests of the WMS. Breaks were provided upon request, and typically the testing was completed within 2 1/2 to 3 hours. After all the procedures were completed, the subjects were debriefed as to the purpose of the study and given feedback regarding their performance if requested.
RESULTS
Standardized Measures
Data were obtained for each of the standardized
measures from 12 Parkinson disease patients (PD) and 12 normal control (NC) subjects, with the exception of the Wechsler Memory Scale (WMS); one subject in the PD group had recently been administered the revised version of this test during a separate clinical assessment, and since there is no consistent overlap of scores between these two versions, the data for this subject was not included in analyses using the WMS. Analyses comparing age (F [1, 22] = 3.77, D = 0.065) and education levels (F [1, 22] = 0.09, S= 0.772) between the two subject groups showed no significant differences. Mean age for the PD group was 66.17 (SD 6.12) and 61.50 (SD 5.65) for the NC group.
The resulting means and standard deviations for each of the measures, by group, is presented in Table 1. These include Verbal IQ Score from the Wechsler Adult Intelligence Scale-Revised (VIQ), Logical Memory (LM) and Visual Reproduction (VR), with delays (LMD and VRD
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respectively) and Paired Associates (PA) subtests from the Wechsler Memory Scale, and total score from the Beck Depression Inventory (BDI).
Table 1.
Standardized Measures
Means (Standard Deviations)
MEASURE
GROUP VIQ LM LMD VR VRD PA BDI PD 110.75 8.14 5.95 9.09 7.91 20.54 10.5
(18.8) (2.3) (2.4) (3.2) (3.6) (4.8) (5.7)
NC 115.5 9.38 8.46 9.83 10.08 23.25 3.25
(8.9) (2.7) (2.2) (3.7) (4.0) (4.6) (2.8)
Analysis of the paired scores revealed no significant difference for VIQ, LM, VR, VRD, and PA between groups. Significant differences were obtained between groups for LMD and BECK; PD subjects provided significantly lower recall than NC subjects on LMD, t (1, 21) = 2.62, P < .05, and a higher self-rating of depression on the BDI, t (1, 22) = 3.95, R = .001.
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Experimental Memory Tests
Table 2 lists the mean recognition scores (30 possible correct) and standard deviations for each test; Verbal Recognition Test (VRT), Self-Rated Arousal Memory Test
(AR), and the Levels of Processing Test (LOP), by group. The distribution of percent correct recognition for each test across the two subject groups is presented in Figure
1.
Table 2.
Experimental Memory Tests Means (Standard Deviations) TEST
GROUP VRT AR LOP
PD 25.333 21.667 18.75 (4.08) (4.12) (4.31) NC 27.833 23.917 22.083
(1.9) (2.78) (2.43)
Using GROUP membership as the between subject variable and the three experimental TESTs as dependent variables (VRT, AR, LOP), a 2 x 3 Mixed Model Analysis of Variance (Fisher, 1942) was conducted using total-correct recognition scores for each test as the independent
Figure 1. Percent recall on the experimental memory tests by group.
8878T 68"
M PD Reca ll 58 SNc 480-
3828
18
URT AR LOP
Test
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variable. Results from this analysis are presented in Table 3. Significant main effects for both GROUP, f (1, 22) = 5.69, p < .05, and TEST, f (2, 44) = 39.63, p < .001, were found. The interaction between GROUP and TEST was not significant. Since there was only one degree of freedom for the variable, GROUP, determination of the direction of this main effect was made using mean recognition for each group, collapsed across levels of TEST, showing that there was greater overall recognition across tasks for subjects in the NC group.
An analysis of the direction of the main effect TEST,
collapsed across levels of GROUP, using Tukey's studentized range test (Tukey, 1977) revealed that subjects' performance on VRT was significantly greater than both AR (R < .05) and LOP (p < .05). No difference was found in subjects' performance between the AR and LOP tasks.
Table 3.
Analysis of Variance
Experimental Memory Tests
Source MS DF F PR > F GROUP 33.338 1 5.69 <.05 TEST 232.181 2 39.63 <.001 *** GROUP*TEST 1.931 2 0.33 .721 GROUP(SUBJECTS) 5.859 44
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Self-Rated Arousal Memory Test
Additional analyses were conducted from data obtained on AR to examine the effect of the arousal RATING of the words on recognition performance. The data was divided into two levels of RATING; words self-rated as highly arousing in nature (HI) and those rated low (LO). Words were classified at acquisition as HI if the rating received was "4" or "5" on a 5-point Likert-type scale, and LO if their rating was "1" or "2". The analysis was conducted using a 2 x 2 Analysis of Variance design with the grouping factor, GROUP. The results from this analysis are presented in Table 4. A significant main effect across RATING of arousal was found, F (1, 22) = 33.44, p < .001. A determination of the direction of the effect of RATING was made using the mean recognition performances for HI (12.542 of 15) and LO (10.250 of 15), collapsed across groups, revealing that subjects recognized significantly more of the HI arousal than LO arousal words. The main effect of GROUP was not significant although the interaction of GROUP and RATING approached significance. The distribution of mean recognition for each GROUP as a function of word RATING is provided in Figure 2.
Fiqcure 2. Recall (out of 15 correct) by self-rated arousal level of words for each group.
14
1218
Total I PD
* Nc
6-L 4
2
LO HI Rat ing
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Table 4.
Analysis of Variance
Self-Rated Arousal Memory Test
Source DF MS ERROR F PR > F GROUP 1 15.187 6.172 2.46 .131 RATING 1 63.021 1.884 33.44 < .001 *** RATING*GROUP 22 6.021 1.884 3.20 .088
Levels of Processing Test
Separate analyses were conducted on the relationship of the "LEVEL" of processing required and the valence (SIGN) of the correct response for the acquisition questions (i.e. "yes" or "no") to both the subjects' electrodermal response (EDR) and their ability to recognize the words following a delay (SCORE). There were 3 levels of the variable, LEVEL, (CONCRETE, RHYME, and SEMANTIC) and 2 levels of SIGN (POSITIVE--the correct answer was "yes" to the word at acquisition, and NEGATIVE--the correct answer was "no").
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Electrodermal Response (EDR)
An Analysis of Variance with two trial factors (LEVEL and SIGN) was conducted using the EDR data from the LOP task, between the two levels of GROUP. This analysis tested for the differential responsivity of EDR to assess arousal across the varying levels of cognitive processing imposed. The results of this analysis are presented in Table 5. These findings reflect that there was no differential EDR across main effects of GROUP, LEVEL, and SIGN, nor were there any significant effect of the interactions of these variables.
Table 5.
EDR
Analysis of Variance
Levels of Processing Test
Source DF MS ERROR F PR > F GROUP 1 0.001 0.166 0.01 .937 SIGN 1 0.010 0.018 0.52 .478 LEVEL 2 0.009 0.004 2.16 .128 SIGN*GROUP 2 0.018 0.018 0.98 .332 LEVEL*GROUP 2 0.006 0.004 1.43 .250 LEVEL*SIGN 2 0.016 0.012 1.37 .266 LEVEL*SIGN*GROUP 42 0.011 0.012 0.97 .386
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The mean change in EDR for the PD group was 0.0907
micromoles (SD = 0.1340) and for the NC group it was 0.0963 (SD = 0.1934). The means and standard deviations for each LEVEL by GROUP is provided in Table 6.
Table 6.
Levels of Processing
Mean EDR (Standard Deviation)
CONCRETE RHYME SEMANTIC PD 0.0785 0.0815 0.1122
(0.1262) (0.1086) (0.1673)
NC 0.1106 0.0761 0.1023
(0.2272) (0.1473) (0.2056)
A post-hoc analysis examining the degree to which AGE and
EDR covary was completed using an Analysis of Variance, with the results presented in Table 7. These findings reflect that there was no significant effect of AGE of subject on EDR responsivity.
Table 7.
Analysis of Variance
EDR*AGE
Source DF MS ERROR F PR > F GROUP 1 0.023 0.090 0.26 .619 AGE 1 0.008 0.090 0.09 .762 GROUP*AGE 1 0.025 0.090 0.28 .606
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A post-hoc analysis examining the degree to which EDR and SCORE covaried across LEVEL and GROUP was completed. This analysis was used to determine if the subject's physiological responses could be used to predict their recognition performance; in other words, to assess the degree of correlation between EDR and SCORE. An Analysis of Covariance (Winer, 1971) reflected no significant interaction between these two dependent variables, F (1, 133) = 3.19, p = .076.
SCORE
An Analysis of Variance with two trial factors (LEVEL
and SIGN) was conducted using the recognition data from the LOP task (SCORE) using GROUP as the between subjects variable. The results of this analysis are presented in Table 8. Significant effects for the main effects GROUP, F (1, 22) = 5.45, p > .05, LEVEL, f (2, 44) = 15.00, p < .001, and SIGN, F (1, 22) = 12.17, p < .01 were obtained. A significant interaction was observed between the trial factors LEVEL and SIGN, F (2, 44) = 3.41, D < .05. No other interactions were significant.
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Analysis of the main effect, GROUP, revealed that the NC group was significantly greater than the PD group in overall level of recognition collapsed across LEVEL and SIGN, F (1, 22) = 5.45, p < .05; mean recognition for the NC group was 22.08 (SD 2.43) and 18.75 (SD 4.31) for the PD group. The analysis of the main effect, LEVEL, using Tukey's studentized range test revealed that, collapsed across GROUP and SIGN, subjects recognized fewer words in the CONCRETE level than on either the RHYME (R < .05) or SEMANTIC levels (D < .05). Mean recognition collapsed across GROUP for CONCRETE words was 5.58 of 10 (SD 1.49), for RHYME words 7.00 of 10 (SD 2.03), and for SEMANTIC words 7.83 of 10 (SD 1.33). No difference was found in total recognition between RHYME and SEMANTIC levels. Analysis of the main effect, SIGN, revealed that, collapsed across both variable GROUP and LEVEL, subjects recognized significantly more words when they responded positively (mean 11.12 of 15, SD 3.001) at acquisition, than when they responded negatively (mean 9.29 of 15, SD 3.380), f = (1, 22) = 12.17, R < .01. Subjects in both groups were quite accurate in responding to these "yes/no" orienting questions at acquisition; PD subjects had 97.22% correct and NC subjects had 99.44% correct. Accuracy of responding
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was not significantly different between groups (t [1, 22] =
1.74, p =.095), and because of their level of accuracy, analysis of recognition performance related to accuracy of responses at acquisition was not necessary.
Table 8.
Analysis of Variance
LOP SCORE
Source DF MS Error F PR > F GROUP 1 11.111 2.039 5.45 .029 LEVEL 2 15.528 1.035 15.00 <.001 *** SIGN 1 13.444 1.105 12.17 .002 ** LEVEL*SIGN 2 3.444 1.010 3.41 .042 LEVEL*GROUP 2 1.028 1.035 0.99 .379 SIGN*GROUP 1 0.250 1.105 0.23 .639 GROUP*LEVEL*SIGN 2 0.333 1.010 0.33 .721
Analysis of the simple effects for the interaction of LEVEL by SIGN was accomplished using Tukey's studentized range test. The distribution of total correct by LEVEL (C=CONCRETE, R=RHYME, and S=SEMANTIC) and SIGN ("+" = POSITIVE, and "-" = NEGATIVE) is displayed in Figure 3. These analyses revealed that subjects' recognition of words from the SEMANTIC level within the POSITIVE condition was
Figure 3. Percent recall on the Levels of Processing Test by cognitive processing task and response valence, collapsed across groups.
98-
88T 7968
58"- g o" : Recall
48- "Yes"
38
8
:-I
CONCRETE RHYME SEMANTIC Processing Task
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significantly greater than their recognition for both the POSITIVE and NEGATIVE conditions of the CONCRETE level (p < .05), and the NEGATIVE condition within the RHYME level (p < .05). In addition, their recognition of words from the POSITIVE condition of the RHYME level was significantly greater than both the POSITIVE and NEGATIVE conditions of the CONCRETE level (p < .05). No other simple effects were significantly different.
Reaction Time Task
Latency to respond was obtained for all subjects within each GROUP across three levels of TRIAL [Unwarned (UN), 200 millisecond warning (W2), and 800 millisecond warning
(W8)], between the two GROUPs [Parkinson's disease (PD) and normal controls (NC)]. The distribution of reaction time (in thousandths of a second) by TRIAL conditions for each group can be seen in Figure 4. An Analysis of Variance with a grouping factor was conducted on the reaction time data across the within group factor, TRIAL, between the two levels of GROUP. The results from this analysis are presented in Table 9. A significant main effect for TRIAL was obtained, F (2, 44) = 38.99, p < .001, as well as for the interaction of TRIAL by GROUP, F (2, 44) = 4.84, p < .05. The main effect, GROUP, was not significant.
Figure 4. Reaction times (in thousandths of a second) by TRIALS for each group.
8.5-
8.4-
8.3
P PD
Latency (secs)
8.2-
8.1
8 W8 UN 2 Trial Trial
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Table 9.
Analysis of Variance
Reaction Time Task
Source DF MS Error F PR > F GROUP 1 0.004 0.015 0.28 .599 TRIAL 2 0.067 0.002 38.99 <.001 *** GROUP*TRIAL 2 0.008 0.002 4.84 .013 *
Analysis of the main effect, TRIAL, was conducted using Tukey's studentized range test. These results showed that collapsed across groups, subjects' latency to respond on this task was significantly slower in the UN condition (mean = 0.409, SD = 0.0955) than at either the W2 (mean =
0.316, SD = 0.0667) or W8 (mean = 0.318, SD = 0.0607) conditions (p < .05). There was no difference in reaction time between the W2 and W8 trials.
Examination of the simple effects for the interaction of TRIAL by GROUP was also completed using Tukey's studentized range test. These results revealed that PD subjects' latency to respond on the UN (mean 0.438, SD = 0.1272) condition was significantly slower (p < .05) than their own reaction time on both the W2 (mean = 0.3147, SD =
0.0645) and W8 (mean = 0.3135, SD = 0.0664) conditions, and slower (p < .05) than that of the NC subjects on both the
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W2 (mean = 0.3180, SD = 0.0689) and W8 (mean = 0.3225, SD =
0.0549) conditions. No other significant differences existed for the simple effects of the interaction.
Summary of Results
Subjects in the NC and PD group were comparable in both age and level of education. PD subjects provided a significantly higher self-rating of depression on the BDI than NC subjects. Overall, NC subjects' recognition was greater than PD subjects on both the standardized and experimental memory tests.
On the Self-Rated Arousal Test (AR), PD subjects
recognized as many words as NC subjects. Words rated as HI arousal were recognized significantly more than LO arousing words across both subjects groups, with no other interaction effects.
On the Levels of Processing Test (LOP), there was no difference in EDR across the variables GROUP, LEVEL, and SIGN, and no significant interactions were observed either. NC subjects displayed a significantly greater recognition performance than PD subjects on the LOP test. When analyzed across level of processing required at
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acquisition, words acquired emphasizing CONCRETE characteristics were recognized significantly less than when processed for RHYME and SEMANTIC qualities, collapsed across the two groups. No difference was seen between RHYME and SEMANTIC recognition performance, collapsed across groups. Words acquired when the direction of the processing required a positive response ("yes") were recognized significantly more than words associated with a negative response ("no"), collapsed across groups. No significant interactions between the variables on LOP were found.
On the Reaction Time Task (RXN), PD subjects performed comparable to NC subjects overall. When assessed across both groups, response times to unwarned stimuli were significantly slower on the average than to stimuli following either a 200 or 800 millisecond warning. No significant interactions between the variables on RXN were found.
DISCUSSION
Memory Performance in Parkinson's Disease
The results of this study provide support to Hypothesis Ia which stated that Parkinson's subjects' delayed verbal memory performance is impaired relative to normal control subjects. In general, PD subjects displayed poorer recognition on the experimental memory tests administered, findings which are inconsistent with those of Taylor, Saint-Cyr, and Lang (1986a). However, when memory performance is analyzed across tasks, this group difference is only seen on the LOP. Recognition memory performance for PD subjects on the VRT and AR tasks are intact relative to NC subjects, consistent with Taylor's findings.
A gradient of memory performance is demonstrated when data is collapsed across subject groups, but in the direction opposite of that predicted from Hypothesis Ib. All subjects show poorer recognition on the Self-Rated Arousal Memory Test (AR) and Levels of Processing Memory Test (LOP) than they do on the Visual Recognition Test (VRT). One explanation for this finding is related to the
84
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fact that the two latter tests rely on incidental memory, since explicit instructions were given to subjects on the Verbal Recognition Test that they would have to remember the items presented to them, and no mention of later memory testing was mentioned on either the AR or LOP tests. One way to answer this question would be to test a separate group of subjects using explicit instructions on one form of the AR and LOP tests, and to compare recognition performance with that obtained from subjects administered the tests in their original incidental format.
However, it was noted that several subjects reported
that they had anticipated a recognition trial following the acquisition phase for the AR and LOP tests, and since the majority of the measures used during these procedures were memory tasks, it is a reasonable assumption that the AR and LOP tests were, in fact, not incidental for many subjects. This discrepancy may still have contributed to the variance within these tasks, masking the expected effect, and not allowing for a conclusion to be made regarding a differential memory performance within PD subjects across these tasks.
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Subjects in this study were tested for their
recognition on three separate, 30-item, word lists. The design of this study prevented an overlap between lists in that recognition of one list was always completed before another set of words was presented. However, this supersaturation of new information may have inhibited memory performance in several ways. Such a presentation schedule may result in a normal increase in proactive interference. Since the design of the current study prevented an over-lap of word items, proactive interference may not be directly determined. Tweedy, Langer, and McDowell (1982) have noted that PD patients show a delayed release from proactive interference. They found that PD patients did not appear to be more susceptible to interference effects, but instead when normal interference had built up, it took longer for the detrimental effects to dissipate. While the order of word-list presentations was counterbalanced in this study to prevent a bias in performance due to the sequencing of the tests, an increased (and lingering) interference from prior lists may still have occurred, reducing recognition performance and masking any differentiation of performance that may have existed between the memory tests. One would expect that a
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negative interaction between order of test presentation and recognition performance would be observed, in which case analysis of the dependent recognition variables across both independent variables ORDER and GROUP would reveal the significance of this interaction. Unfortunately, information regarding the order of test presentation was not tagged to the subject data itself; a master schedule was kept, from which presentation orders were merely checked off when used for each subject, thereby making it impossible to determine which subjects had a particular order of presentation. An obvious future direction would therefore be to keep record of test presentations for each
subject.
It is possible that a source memory deficit (Squire, 1982) may have confounded the findings on recognition performance in PD subjects. Squire notes that source amnesia, which is a deficit in the subjects ability to discriminate the context or source from which information was acquired, is associated with frontal system dysfunction--pathology which is reported to be involved in Parkinson's disease (Taylor, Saint-Cyr, & Lang, 1986a). While subjects were never required to make a source distinction for the words acquired, it is speculated that a
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breakdown of the borders between word lists may have had a detrimental effect on the delayed recognition of this information. However, since the word lists were specifically designed with no overlap between them, there were no extralist intrusions, and it was not possible to assess directly intrusions which may be indicative of source amnesia. Future studies addressing the questions raised in this study may reduce the possible deterrent influence of proactive interference and deficient source memory by either using longer intervals between completion of one memory test and the acquisition of items from the next, or by giving only one of the three experimental memory tests to a subject and making a comparison of differential effects between subjects.
However, neither of these latter explanations can
account for the decreased performance of NC subjects on AR and LOP relative to VRT. One speculation may be that the additional cognitive processing inherent in the LOP and AR tasks were a distraction at encoding of the verbal material. NC subjects might be expected to perform poorer on the LOP task relative to VRT because the latter is an incidental memory test. The arousing properties of the highly emotionally laden words on the AR task may have
89
distracted the subjects from adequately processing the items. Future studies might not predict a greater recognition on these tasks relative to tasks free of such encoding interference.
The most likely reason for the lack of support for the hypotheses in this study may have been due to the specific method with which memory was assessed. One important differentiation between previous literature examining memory performance in PD and the current study is that the deficit found in these studies have typically been on free recall paradigms (c.f., Helkala et al., 1988; Taylor et al., 1986a). However, all of the memory paradigms in the present study involve recognition memory. These studies have generally found when memory is tested in this manner, PD patients are within the normal range. Benson (1983) stated that the memory deficit associated with subcortical dementia (i.e., PD) is typically a retrieval (/encoding) deficit. Therefore when provided retrieval cues, such as in a recognition memory paradigm, these subjects can display intact performance relative to normals. The use of such cuing in the present study must be considered a major contributory factor in why many of the hypotheses regarding memory impairment were not supported. Future studies using
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recall measures of verbal memory may find a more robust interaction between arousal and memory performance in PD.
Arousal and Memory Performance
The findings from the reaction time task failed to
support Hypothesis IIa; that Parkinson's patients display a deficit in activation. While it was shown that PD subjects were significantly slower than NC subjects to give a response on unwarned reaction time trials, there were no differences between groups when either a 200 or 800 millisecond auditory warning stimuli directly preceded the trial. These results, in fact, suggest that PD subjects have intact activation, in the observation that PD subjects' reaction time following a warning stimuli was equal to that of NC subjects, reflecting the ability of PD subjects to anticipate having to make a response. The observation that PD subjects demonstrated slower response latencies relative to NC subjects on the unwarned trials reflects bradykinesia in the PD population, consistent with the findings of Taylor et al. (1986a). These results suggest that PD subjects maintain a tonic hypoaroused state, but are capable of increasing this level when it is elicited by a change in the environment.
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Since subjects on the warned trials of this task are
dependent on a change in the environment (i.e., an external cue), it can be said that the subject's response to the auditory warning stimulus is similar to an orienting response (OR), which evokes a nonvoluntary increase in arousal (Sokolov, 1966). The OR is assumed to involve an exo-evoked increase in arousal, rather than auto-evoked. Previous studies have reported intact exo-evoked arousal in PD, with behavioral evidence for this as examples of the phenomenon, paradoxical kinesia (Lit, 1968; Schwab, 1972) discussed earlier. Therefore, the present findings may also be considered to reflect that PD subjects are capable of increasing their arousal from an externally elicited orienting reflex to the warning stimuli.
The findings of this present study are contradictory to those of Heilman, Bowers, Watson, and Greer (1976), who showed that while PD subjects improved their reaction time with a warning stimulus, it was still significantly slower than the warned reaction times of NC subjects. One explanation for this discrepancy may be due to the differences in the two studies in the interstimulus intervals used between the presentation of the warning stimulus and onset of the target stimulus. The present
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study used a 200 millisecond warning signal to assess the lag in activation which may be seen in PD relative to NC subjects. It was assumed that NC subjects would not show much of a difference in responding on W2 and W8 trials, but that PD subjects, because of an initiation deficit, would not show as great a benefit on W2 trials as they would on W8 trials. The observation that the reaction time elicited on W8 was not different from that elicited by W2 suggests that the phasic change had already occurred within the shorter interval. Heilman's group also failed to find a difference in response time between the interstimulus intervals they used (0.5 and 1.0 second), suggesting that there was no response gradient based on the duration of the warning interval. Converging the findings from their study and this present one, it appears that the length of delay between warning and target stimuli was not crucial within the range from 0.2 to 1.0 seconds. Therefore, it is not likely that the differences in interstimulus intervals account for the lack of concurrence between these two studies, and it is more likely that the discrepancy is due to some other cause or to random variance.
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AROUSAL AND MEMORY PERFORMANCE IN PARKINSONISM By PHILIP ANDREW HANGER A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 1989
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ACKNOWLEDGMENTS I would like to thank the members of my dissertation committee for their help and guidance, especially Dr. Russell Bauer who has provided invaluable support and direction not only on this investigation, but throughout my graduate training. I wish to dedicate this project to Emily and Victoria, who came to mind whenever I questioned the necessity of my efforts. ii
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TABLE OF CONTENTS ACKNOWLEDGMENTS. . . . . ii V LIST OF TABLES ABSTRACT .. INTRODUCTION vi Parkinson's Disease . . . Pathophysiology of Parkinson's Disease. Cortical/Subcortical Distinctions . Treatment of Parkinson's Disease ...... 1 1 3 6 Neuropsychology of the Basal Ganglia. . Neuropsychology of the Frontal System . 13 Neuropsychology of Parkinson's Disease. 16 J Executive Functions. . . 17 .J Psychomotor Function . . 2 o 8 10 J Memory Functions . . 21 Visuospatial and Visuoperceptual Functions . . . 25 Language Related Functions . Depression in Parkinson's Disease .... 26 28 Arousal . . . . 32 Arousal and Parkinson's Disease ..... Arousal and Memory in Parkinson's Disease .. 37 Hypotheses. . . . . 4 2 METHOD .. Subjects. . . Materials Standardized Measures. Experimental Measures .. Verbal memory Reaction Time Task. Equipment. . Physiological Measures 48 48 49 50 50 50 56 58 58 Procedure . . . . 59 iii 39
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RESULTS 61 Standardized Measures 61 Experimental Memory Tests 63 Self-Rated Arousal Test 67 Levels of Processing Test 7 O Electrodermal Response (EDR) 71 SCORE .. 73 78 82 -J Reaction Time Task Summary of Results DISCUSSION 84 -J Memory Performance in Parkinson's Disease 84 Arousal and Memory Performance. 90 Limitations 100 Conclusions 102 APPENDICES 105 A. LOP3 01 ACQUISITION 106 B. MLOP301 ANSWER SHEET 107 C. LOP302 ACQUISITION 108 D. MLOP302 ANSWER SHEET 109 E. AR RATING LIST 110 F. AR SUBJECT INSTRUCTIONS. 111 G. SAM AROUSAL RATING GUIDE 112 H. AR RECOGNITION LIST 114 REFERENCES BIOGRAPHICAL SKETCH iv 115 12 6
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Table 1. 2. 3. 4. 5. 6. 7. 8. 9. LIST OF TABLES Title Standardized Measures Means (Standard Deviations). Experimental Memory Tests Means (Standard Deviations). Analysis of Variance Experimental Memory Tests. . Analysis of Variance 62 63 66 Self-Rated Arousal Memory Test . 70 Analysis of Variance Levels of Processing Test. . 71 Levels of Processing Mean EDR (Standard Deviation). 72 Analysis of Variance EDR AGE ...... 72 Analysis of Variance LOP SCORE. 75 Analysis of Variance Reaction Time Task. 81 V
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Abstract of Dissertation Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy AROUSAL AND MEMORY PERFORMANCE IN PARKINSONISM By Philip Andrew Hanger August, 1989 Chairman: Russell M. Bauer, Ph.D. Major Department: Clinical and Health Psychology Research has suggested that cognitive deficits are associated with Parkinson's Disease (PD), including impaired verbal memory. PD patients have also shown decreased cognitive and motor initiation relative to normal controls suggesting that resting or tonic arousal may be reduced in PD. Pharmacological evidence has shown that treatment of PD using L-dopa reportedly increases the patient's subjective and behavioral arousal. The present study examined the degree to which arousal, both tonic and phasic, affects memory performance. Recognition of information acquired under tonic arousal was assessed using the Wechsler Memory Scale and the Verbal Recognition Test. vi
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Recognition of information acquired during self-initiated increased arousal (auto-evoked) was assessed using the Levels of Processing Test. Recording of electrodermal responsivity (EDR) was obtained during the acquisition phase of this task to validate the expected change in arousal associated with different cognitive processes involved. Recognition of information acquired during externally elicited increased arousal (exo-evoked) was assessed using the Self-Rated Arousal Test. In addition, the Reaction Time Task was used to assess auto-evoked arousal and resulting motor responding. The results demonstrated that PD subjects display an overall impairment in their delayed verbal recognition. PD subjects' recognition performance acquired during auto-evoked arousal was equivalent to normal controls. Similarly, PD subjects showed a comparable improvement to normal control subjects in reaction times following a warning stimulus. EDR did not differentiate across the different levels of cognitive processing required at acquisition, although examination of this data suggests that these readings may not have been accurate. PD subjects displayed improved recognition of words acquired under increased exo-evoked arousal, similar to normal control subjects. The pattern of recognition performances vil
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suggested that PD patients have relatively intact arousal function, but that their tonic arousal level may be impaired. The results of this study are discussed in terms of their implications for educating PD patients to compensate for their verbal memory deficit with the aid of different learning strategies. viii
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INTRO DU CTI ON Parkinson's Disease James Parkinson first described a "shaking palsy" (p. 845), which would later bear his name, as a movement disorder with intact "senses" (p. 845) and intellect (Parkinson, 1817; cited in Taylor, Saint-Cyr, & Lang, 1986a). However, since this early description, there has been disagreement regarding the presence of dementia in Parkinson's disease (PD). Authors as early as Charcot (cited in Mortimer, Christensen, & Webster, 1975) and as recently as Brown and Marsden (1988) have argued that a dementia of some form is common in the disease, while others have denied the presence of dementia in PD (c.f ., Schwab, Fabing, & Prichard, 1951; Marsden, 1982). Parkinson's disease is a relatively common disorder, with average age of onset over 50 years, affecting approximately 25 of every 10,000 persons within this age range (Mayeux, 1984). A triad of motor dysfunction is commonly seen in the disease: tremor, bradykinesia, and 1
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2 rigidity. However, many patients also exhibit cognitive and emotional changes as well {Taylor et al., 1986a). The cognitive changes that have been reported range from a small cluster of deficits to a more global dementia. Mortimer and associates {Mortimer, Christensen, & Webster, 1985) stated that from 20 to 40% of PD patients have moderate to severe dementia. They report that this dementia is more likely to occur in older patients although motor dysfunction (bradykinesia) is still the predominant symptom. Hietanen and Teravainen {1988) proposed that the probability of dementia associated with PD increases with age. They stated that the age of first onset of the disease does not correlate significantly with the occurrence of dementia, but that duration of the illness is a more crucial factor, and that patients with early onset {prior to age 60) are as likely to develop a dementia as patients with late onset (after age 60). Etiologically, PD exists in postencephalitic, artheriosclerotic, and idiopathic forms, but until recently these have all come under the common diagnostic label, "Parkinson's disease" {Marsden, 1982). However, PD is not a homogeneous disorder, and even within subtypes there is heterogeneity {Taylor et al., 1986a). These authors report
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3 that while there is generally an agreement on the classic triad of motor symptoms associated with PD, progression of these motor symptoms varies considerably among individual patients. Most recent studies generally use subjects classified with the more common, idiopathic diagnosis of PD. Pathophysiology of Parkinson's Disease The pathophysiology of PD has been attributed to a dopaminergic syndrome. Loss of pigmented cells in the substantia nigra, pars compacta (SNpc) responsible for the production of dopamine, was observed in PD patients (Marsden, 1982). The result of this cell loss is a depletion in dopamine transmission along the pathway from the SNpc to the striatum (caudate and putamen) with eventual connections to the globus pallidus, thalamus, and frontal cortex, particularly the supplemental motor area (SMA) and mesial frontal region. While the frontal lobe is not directly involved in this nigrostriatal dopamine system, input to the frontal region via subcortical, dopamine dependent structures is affected since the striatum receives its dopaminergic input almost exclusively from the SN (Moore, Bhatnagar, & Heller, 1971), resulting in disruption of frontal lobe function.
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4 Another group of dopamine producing cells in the ventral tegmental area (VTA) has also been shown to be disrupted in PD (Javoy-Agid & Agid, 1980). This region, along with the medial part of the SN, is linked to the brain's two other major dopamine systems, the mesolimbic and mesocortical systems. Dopamine innervation of such limbic structures as the hypothalamus and the nucleus accumbens originates from both the SN and VTA. In addition, regions of the amygdala, hippocampus, and prefrontal cortex receive fibers from the mesocortical dopamine system that originate predominately in the VTA (Thierry, Tassin, Blanc, & Glowinski, 1978). Mayeux and associates (Mayeux, Stern, Sano, Cote, & Williams, 1987) suggested that an additional alteration in the norepinephrine metabolism within PD is also responsible for cognitive changes associated with the disease. Dubois and his group (Dubois, Danze, Pillon, Cusimano, Lhermitte, & Agid, 1987) suggested that an alteration in the central cholinergic system exists within PD. They detected this transmitter disruption in PD patients who do not display cognitive impairment as of yet.
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5 A greater amount of plaques and neurofibrillary tangles, granulovacuolar degeneration, and cortical cell loss were observed by Hakim and Mathieson (1979) in a number of PD patients compared with sex-and age-matched controls who died of infarct or trauma. The occurrence of these pathological changes typical of dementia, Alzheimer's type (DAT), confounds the estimate of the existence of a dementing process due to PD alone. Boller and his associates (Boller, Mizutani, Roessmann, & Gambetti, 1980) observed that within a group of 29 PD patients, 9 diagnosed with severe dementia also showed a significant degree of plaques and neurofibrillary tangles. Other studies, however, have failed to confirm the percentage of Alzheimer's-like lesions found in PD patients. For example, Jellinger and Grisold (1982) found that out of a series of 100 consecutive PD patients brought to autopsy, only 4 showed lesions characteristic of DAT as well. These same investigators found that lesions characteristic of PD were also found in 7 of 146 cases diagnosed as DAT. These latter findings suggest that, while an overlap between these two disease processes is indeed present, it appears to be somewhat limited. The most common belief is that a small percentage of those
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6 patients with PD also have DAT, although there is evidence to suggest that the type of cognitive deficits seen in these diseases is unique to itself (Taylor et al., 1986a). Cortical/Subcortical Distinctions Although PD primarily involves subcortical disruption, the cortical/subcortical distinction becomes blurred since the pathophysiological changes involve cortical structures as well. For example, Boller et al. (1980) reported similar patterns of cortical degeneration for these diseases. However, another study (Mortimer, Christensen, & Webster, 1985) concluded that, while the frequency of abnormal cortical findings is higher in PD patients than in the general population, there was no convincing direct association between these abnormal cortical findings and the presence of dementia. The term, subcortical dementia, was used to describe a syndrome characterized by inertia, apathy, forgetfulness, defective ability to manipulate knowledge, and slowness in the rate of information processing (Albert, Feldman, & Willis, 1974; Albert, 1978). These symptoms were ascribed to a number of diseases with predominant subcortical pathology, such as PD, Huntington's disease, and progressive supranuclear palsy. The absence of apraxia,
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7 agnosia, and aphasia was typically used to distinguish the subcortical picture from a cortical dementia, such as DAT. Several authors have reported that there are a number of clinical distinctions between these two groups as well (c.f. Benson, 1983, for summary). Huber and associates (Huber, Shuttleworth, Paulson, Bellchambers, & Clapp, 1986) demonstrated the distinction between the cortical (DAT) and subcortical (PD) types of dementia. They concluded that PD was characterized by a mild impairment of memory and visuospatial functions, yet no impairment of language or praxis. They noted that depression was also a frequent symptom. Patients with DAT, on the other hand, performed markedly different, with overall mental function, memory performance and visuospatial functioning more severely impaired. In addition, there was a significant disturbance of language-related functions and praxis. Depression was also present in several patients. Their results suggest that there was a qualitative as well as quantitative difference in the dementias associated with PD and DAT.
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8 Treatment of Parkinson's Disease The demonstration that there exists a depletion of dopamine in the SNpc and striatum of PD patients led to the therapeutic use of L-3, 4-dihydroxyphenylalanine (also known as levodopa or L-dopa), the immediate precursor of dopamine. This precursor is capable of passing the blood-brain barrier, whereas dopamine itself is not. While there is no direct evidence that the functional integrity of the dopaminergic pathway is restored by the administration of L-dopa, studies of cerebrospinal homovanillic acid (HVA), a dopamine metabolite, suggest that an increased synthesis of dopamine in the central nervous system does result from L-dopa administration (Yahr, Duvoisin, Schear, Barrett, & Hoehn, 1969). Johansson and Roos (1965) had earlier reported a marked decrease in the dopamine by-product, HVA, found in the cerebrospinal fluid of untreated PD patients. The assumption made by Yahr and his group was that in PD, the diseased dopaminergic neuron is readily able to synthesize dopamine if presented with the immediate precursor, but that it has difficulty synthesizing dopamine at the natural first stage, using tyrosine, from which L-dopa is derived.
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9 Double-blind studies using L-dopa have demonstrated a marked improvement in the motor symptoms associated with PD, including decreased rigidity, akinesia, and tremor. In addition, mental changes following administration include improvement in memory, stabilization of sleeping pattern, decreased nervousness, and increased arousal (Yahr et al., 1969). One side-effect associated with prolonged use of L-dopa is described as an "on-off phenomenon" (p. 292). This includes rapid, unpredictable fluctuations between akinesia and dyskinesia, usually independent of the frequency of L-dopa doses or L-dopa level within the bloodstream (Marsden & Parkes, 1976). A comparison between the cognitive status during the on and off states revealed a general disinhibition of language, worsened memory, perseverative responding, and a worsening of mood associated with the off state (Delis, Direnfeld, Alexander, & Kaplan, 1982; Girotti, Carella, Grassi, Soliveri, Marano, & Caraceni, 1986).
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10 Neuropsychology of the Basal Ganglia Since PD involves subcortical pathology, it is useful to understand the behavioral manifestation associated with disruption to these structures in the absence of PD. One of the primary structures within the subcortex is the basal ganglia and a set of circumscribed neuropsychological deficits has been attributed to damage in this region. The striatum is situated so as to process sensory-cortical input as well as to influence motor-cortical output. However, most behavioral studies of basal ganglia function have focused on the motor components associated with this region of the brain (c.f. West, Michael, Knowles, Chapin, & Woodward, 1987). Schneider (1987) emphasized that while many studies examining the role of the basal ganglia in motor function regard the system as having a direct influence on spinal motor function, it in fact is several synapses away from these final spinal pathways and must therefore influence movement indirectly. In addition, while the striatum receives input from motor and somatosensory cortex, output from the basal ganglia does not reach the primary motor cortex directly but is instead directed to the SMA and premotor areas (Nauta & Domesick, 1984). The SMA in turn can alter the responsiveness of the precentral motor neurons to sensory
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11 inputs, resulting in modulation of discrete movements of individual body parts (Tanji & Kurata, 1985). The SMA therefore serves as the link between intention formation and the programming and execution of specific actions. Studies of basal ganglia lesions in rats revealed that they had difficulty when required to use somatosensory feedback in the performance of a proprioceptively guided forelimb reaching task. These motoric abnormalities were not evident during spontaneous locomotion, but became apparent when limb movements had to be generated on the basis of somatosensory feedback (Schneider & Olazabal, 1984). The SMA therefore receives sensory information from the body schema for initiating and modifying motor programs. The observation was also made that damage to the SMA results in impairment of intentional action arising out of internal sensory information as opposed to an environmentally contingent, response action. It can therefore be said that the SMA provides the internal drive for intentional movement. The observation has been made that disruption of the dopaminergic system involving the basal ganglia does more than disrupt movement. Patients often respond as if they are not functioning under normal control of internal cues.
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12 Clinical examples are seen in PD patients who demonstrate improved gait when required to step over lines on the floor, without which they would merely take a few steps and then become unable to initiate any further movement. These patients are unable to utilize proper sensorimotor coordination and require additional visual stimulation (e.g. lines on the floor). Lit (1968) suggested that PD patients, under highly emotional stimulation are able to perform movements which they would have great difficulty accomplishing under normal levels of arousal. He describes the PD patient crossing the street with a typical slow, shuffled gait being able to dash to the curb at the sound of an oncoming automobile as an example of "paradoxical kinesia" (p. 865). Memory disturbance typically associated with damage to the basal ganglia, specifically the caudate nucleus, has been described by Butters and his colleagues (Butters, Wolfe, Martone, Granholm, & Cermak, 1985). They differentiate the memory disorder seen in Huntington's Disease (HD), which involves progressive atrophy of the basal ganglia, from cortical amnesia according to reco~nition memory performance and procedural memory (skill learning). These authors state that while both patient
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13 groups display impaired free recall of verbal information relative to normal control subjects, the HD patients memory performance improves significantly, in fact comparably to normal controls on recognition memory testing, whereas the cortical amnesics do not show this benefit. However, they found that the cortical amnesics were able to demonstrate normal acquisition of a cognitive procedural task, but that the HD patients had marked difficulty doing so. They concluded that the learning and retention of skills and general procedures may be dependent on the normal functioning of the basal ganglia. Neuropsychology of the Frontal System While the frontal system is not directly implicated in PD, many of the subcortical structures that are damaged in the disease have direct connection to the frontal cortex (Stuss & Benson, 1984). It is therefore useful to understand the behavioral manifestations which result from damage (and/or disruption of input) to this region. Tilney (1928) proposed that the frontal lobes played a large evolutionary role in separating the human race from that of primates. Halstead (1947) suggested that the frontal association cortex was responsible for the highest
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14 intellectual and moral functions found in man. However, our knowledge of frontal lobe function has remained relatively limited and controversial, and Teuber's (1964) description of frontal lobe function as "a riddle" is still somewhat true today. Part of the reason for this description is the fact that the functions of the frontal lobe are complex and interrelated. In addition, our knowledge of frontal function has been hindered by inadequate test procedures and lack of control over the size and location of cortical lesions in that region (Stuss & Benson, 1984). Several broad (and vague) descriptive statements provided below have been extracted from a summary by Stuss and Benson (p.22, 1984), and are generally accepted as examples of impaired function associated with frontal dysfunction: 1. "Prefrontal damage can separate action (response) from knowledge." This deficit is illustrated by patients who demonstrate understanding (via verbal report) of the expected behavior but are unable to produce said behavior. 2. "Prefrontal damage can impair the ability to handle sequential behaviors." Patients exhibit an inability to put items in an organized sequence, have difficulty making recency judgements on memory tasks, and display impaired performance on sequential motor tasks, resulting in perseverative responding.
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15 3. "Prefrontal damage can impair the ability to establish or change a set." This deficit is apparent on tests requiring sustaining attention or on sorting tasks, with the resultant behavior appearing random and perseverative. 4. "Prefrontal damage can impair the ability to maintain a set in the face of interference." This becomes especially apparent on memory tests which employ an interference paradigm, such as the Brown-Petersen Consonant Trigram Memory Test. 5. "Prefrontal damage impairs the ability to monitor personal behavior." Patients display uncorrected, erroneous actions and do not appear to benefit from feedback regarding their behavior. 6. "Prefrontal damage can produce attitudes of unconcern, unawareness, and apathy." Often times frontal patients will ignore or actively deny many of their deficits. Schacter (1987) provided a further elaboration on the memory deficit associated with frontal lobe pathology. From both a review of the literature as well as his own findings, he concluded that the memory deficits associated with frontal dysfunction were qualitatively different from those in patients who do not exhibit frontal pathology. He described the frontal memory impairment as involving a deficit in remembering certain types of contextual or spatiotemporal information. He concluded that the frontal lobe's influence on amnesia was not solely via deficits in motivational or strategic processes but could also be associated with a failure in a a highly specific memory
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16 function. This deficit is referred to as a "source amnesia" by Squire (p. 568, 1982). Stuss and Benson (1984) caution that rarely are the frontal lobes individually disturbed; instead the deficits seen are often combined with impaired function secondary to damage in other regions of the brain. In addition, many functions localized to the frontal lobes may also involve input from other regions of the cortex and it is therefore not valid to refer to such an impairment as being related to frontal dysfunction alone. Neuropsychology of Parkinson's Disease The issue of whether the cognitive changes observed in PD are related to a cortical versus a subcortical dementing process is complicated by the fact that within the disease there are symptoms consistent with frontal pathology as well as basal ganglia dysfunction. The possibility of an interactive deficit is a reasonable assumption given the work of Lee (1984), who was unable to produce a primate model of PD following lesions to the SNpc. This finding suggests that the subcortical pathology of PD extends beyond the SNpc, possibly including other neuropathological changes or a reorganization of neural circuits. Taylor and her associates (Taylor et al., 1986a) propose that in
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17 nondemented PD patients, the cognitive deficits reflect a prefrontal component resulting from a combination of disturbed caudate outflow and reduced availability of input to the lateral convexity of the prefrontal region. Below are some of the findings within the literature on neuropsychological function typically associated with PD. These findings are grouped according to major theoretical functions and do not necessarily represent anatomical delineations. Executive Functions. Evidence of impaired frontal function in PD patients was reported by Taylor et al. (1986a). Using the Wisconsin Card Sorting Test, they found that PD patients generated significantly fewer categories and required more trials to attain the first category when compared with age-matched control subjects. Patients did not exhibit a perseverative response style on this test. Performance on the Halstead-Reitan Trail Making Test was not significantly different from controls when the groups were equated for motor slowing. PD patients produced significantly fewer responses on a design fluency task, and while they were relatively more prolific on a verbal fluency task (FAS), their overall performance was still below that of normal
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18 control subjects. They also displayed errors of serial position on visual and verbal span tasks. These authors stated that PD patients exhibited an inability to initiate concepts as well as a tendency to verbalize, but not execute correct responses. On a simple reaction time task, PD patients were significantly slower to respond than control subjects (Bloxham, Dick, & Moore, 1987). However, when they were given a warning signal in the same reaction paradigm they were able to allocate attentional resources and respond as quickly as the control group. In a second experiment, subjects were required to simultaneously perform a continuous task with the right hand while making their responses to the reaction time task with the left. In this situation, patients were still slower to respond, but the overall effect of interference from the second task was the same for both patients and controls. An interesting finding in this study was that for the PD patients, the advantage of the warning signal was lost after long intervals(> 200 milliseconds) regardless of whether the second tasks were being performed. These authors suggest that this finding reflects that PD patients were behaving as if they were constantly performing a motor task even when they were apparently at rest.
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19 Taylor et al. (1986a) also reported that PD patients had difficulty with the execution of simultaneous and competing motor tasks. In this study, subjects were required to continuously maintain a finger tapper with one hand while sorting beads by their shape with the other. These authors reported that the tapping component of the task, on which PD patients were impaired, was not under visual guidance as subjects were attending visually to the sorting task. Therefore the tapping required some form of automatic, internal program which was deficient in this group. They cite Goldberg (1986), who proposed that the SMA of the frontal lobe was responsible for the planning of actions which are guided by such internal cues, in concluding that this structure was impaired in PD., Flowers and Robertson (1985) demonstrated that PD patients have difficulty in alternating between conceptual sets on an Odd-Man-Out choice discrimination task. In this task, subjects are required to indicate which of a set of letters or numbers is different from the others on two series of cards, using two rules of classification alternately on successive trials. The number of correct choices on each trial and the kind of errors made indicate the ability of subjects to apply a concept consistently and
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20 to alternate between one response set and another. The difficulty was believed to result from an instability of the cognitive set as opposed to a loss of the patients' reasoning ability, increased perseveration, or distractibility. A similar finding was reported by Iversen and Mishkin (1970) using monkeys with frontal lesions. This study found that subjects had difficulty alternating between two rules when the stimuli remained the same but the rules guiding the correct choice alternated. These authors believed that the deficient performance was due to an inability by the subjects to apply the rule. Psychomotor Function. Researchers generally agree that the movement disorder associated with PD includes akinesia, bradykinesia, and tremor. These deficits show progressive deterioration with the course of the disease (Lieberman, 1974). While primary motor skills reportedly remain intact in PD (Marsden, 1982), an impairment is seen in their ability to execute learned motor programs automatically. This is demonstrated in patients who are only able to execute separate components of complex movements, resulting in slow, inefficient progress. Flowers (1978) reported that when visual cues are provided, their movements approach normal.
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21 Memory Functions. Taylor and her associates (1986a) found that PD patients showed poorer immediate recall of prose material on the Logical Memory subtest of the Wechsler Memory Scale. Interestingly, this deficit was not observed for delayed recall of this material, and since the PD patients were able to retrieve as many elements from long-term storage as normal control subjects did, they concluded that encoding/retrieval processes were adequate in PD. An explanation for the differential performance at immediate recall was that, while the presentation of the information was consistent for all subjects, the rate of presentation may have been too rapid, and therefore the deficit in recall reflected a slowness to encode material. At immediate recall the information is not yet fully processed, but by delayed recall, after a period of consolidation, the information is available. Recall of supraspan verbal lists was impaired for PD patients relative to controls when overall production was the dependent variable (Taylor et al., 1986a). However, when the data were further analyzed, they discovered that the PD group demonstrated comparable recall to controls for
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22 items at the beginning and end of the list (i.e. primacy and recency effects). Recognition memory was not significantly different between the two groups. The authors admit the evidence for frontal lobe involvement in the memory disturbance seen in PD is "meagre" (p. 850). They point out that patients with damage to the hippocampus display poor recall of words from the beginning of a list (primacy deficit), a deficit not observed in their PD patients. In addition, temporal lobe patients display impaired recognition memory, whereas the PD subjects in their study did not. These authors conclude that the areas most likely responsible for the memory deficits observed in their study were the frontal lobes. They base this position on the previous findings as well as the evidence for deficits on other nonmemory tasks sensitive to frontal dysfunction and the spared abilities sensitive to posterior cortical association areas, Tweedy, Langer, and McDowell (1982) found that PD patients showed a delayed release from proactive interference on a word-list learning task as well as an impaired ability to benefit from semantic cueing on this task. Pirozollo et al. (1982) reported impaired visual memory in PD. They found that PD patients had poorer
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23 recall than NC subjects of visually presented geometric figures following a delay. Yet Flowers and associates (Flowers, Pearce, & Pearce, 1984) demonstrated that PD patients were within normal limits on tests of visual recognition, both at immediate and delayed recall. They concluded that PD does not affect learning of this material, but rather its retrieval. Frith, Bloxham, and Carpenter (1986) had PD patients learn two novel skills in which they were required to track a moving target using a joystick. In the first condition, they only had to anticipate the movements of a "semi-predictable" (p. 664) target. While in the second, the movements of the joystick were mirror-reversed in relation to the target. This study showed that PD patients' performance was poorer that control subjects on both tasks. However, PD patients did show evidence of learning, as demonstrated by performance savings, even after a ten minute delay. The major difference between the control and patients groups appeared to be within the first minute of each practice phase, during which the control group tended to show marked improvement while subjects in the PD group showed relatively little increase in accuracy. The authors concluded that this rapid, although
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24 temporary improvement in performance represented the acquisition of a motor set, and that the impaired initial learning seen in PD subjects was due to a difficulty in acquiring such a set. Helkala and colleagues (Helkala, Laulumaa, Soininen, & Riekkinen, (1988) compared PD and DAT patients on recall of Buschke's list learning task and on a test of story recall. They found differences in performance to exist on delayed recall of the Buscke paradigm in that the performance of PD subjects was superior to that seen in DAT subjects, although no difference was found on immediate recall. There was no nonpatient control group for comparison purposes; therefore, the relative ability of PD subjects could not be assessed. However, it appeared from the group means that the DAT subjects displayed a significantly greater decline in performance relative to the mild decline shown by PD subjects. A similar pattern was observed on recall of the prose material, with PD subjects significantly better on delayed recall, but with no difference on immediate recall. The authors concluded that this difference was evidence for better functioning within PD relative to DAT of the entorhinal cortex and hippocampus, which was proposed to be responsible for
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25 long-term storage of information. Interestingly, this study did not provide a non-patient control group, and so the conclusion of intact functioning of these cortical areas could not be made from these data. Visuospatial and Visuoperceptual Functions. There have been several reports suggesting that PD patients have a deficit in spatial orientation. Proctor and associates (Proctor, Riklan, Cooper, & Teuber, 1964) demonstrated that PD patients were impaired in their ability to judge visual-vertical, both when their body was tilted and when in an upright position. PD patients have also been shown to have impaired performance on subtests from the Wechsler Adult Intelligence Scale (WAIS) which require significant visuospatial ability; these include Picture Arrangement, Block Design, Object Assembly, and Digit symbol (Pirozollo et al., 1982). Albert (1978) reported that on the Hooper Test of Visual Organization, PD patients displayed significant difficulty compared with age-matched controls in combining the abstracted visual material into a meaningful whole.
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26 In contrast to the visuospatial deficits reported above, there have been fewer studies that report impaired visuoconstructional abilities in PD (c.f., Bowen, 1976, for review). Matthews and Haaland (1979) argue that many construction tasks require a great deal of manual dexterity in the manipulation of objects and that the motor impairments associated with PD obviously confound the findings making it appear that visuoconstruction functioning was poorer than it actually was. However, Pirozollo et al. (1982) found that when PD patients were given untimed visuospatial tasks that also did not require a great deal of fine motor coordination, their scores were still below those obtained by normal control subjects. Language Related Functions. It is typically assumed that language abilities are grossly intact in PD (Boller, 1980). Levita and Rikland (1973) reported that they found PD and control subjects did not differ in verbal abilities, including verbal fluency. However, there have been scattered reports of language impairments associated with PD within the literature. Matison and associates (Matison, Mayeux, Rosen, & Fahn, 1982) reported naming and verbal fluency deficits in a
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27 group of PD patients who were not otherwise cognitively impaired. In addition, this group reported that PD patients frequently experienced "tip-of-the-tongue" (p. 567) phenomenon, a type of word finding deficit. Pirozollo et al. (1982) demonstrated that PD patients' performance on the Vocabulary subtest of the WAIS was comparable to control subjects, but their performance on the Information subtest was relatively poorer. The Vocabulary subtest is often used as a general indicator of language ability, strongly dependent on education level, and they suggest that the Information subtest requires greater memory involvement for successful performance. Matthew and Haaland (1979) found that PD subjects obtained Verbal IQ Scores on the WAIS which were lower than that of age-matched controls, although this difference did not reach statistical significance. Mortimer and colleagues (Mortimer, Christensen, & Webster, 1985) suggested that the variability of findings regarding language deficits in PD was due partly to a bias in subject selection factors. They proposed that studies generally chose patients on the basis of presence or absence of dementia, which includes screening for language deficits. Since PD subjects in most studies have already
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28 been prescreened to eliminate language deficits, it comes as no surprise that language impairments fail to arise in most of these studies. Depression in Parkinson's Disease Symptoms of depression are commonly associated with PD, with a reported incidence between 40 to 50% of the patient population (Mayeux, 1982; Taylor, Saint-Cyr, & Lang, 1987). One assumption is that the depression is an adjustment reaction to having a chronic illness such as PD. However, a number of findings suggest that this may not completely account for the nature of the mood changes associated with PD. Robins (1976) reported that PD patients have a higher frequency of depressive symptoms than do patients with other chronic disorders having similar physical disabilities. Celesia and Wanamaker (1972) found that severity of the depression bears little relationship to the severity of the motor impairment observed in PD patients. Mayeux et al. (1981) reported that in many PD patients the depressed mood predated the onset of the motor symptoms entirely.
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29 Brown and Wilson (1972) suggested that the etiology of the depression in PD may be related to neurotransmitter systems involving serotonin, dopamine, and norepinephrine, which are reportedly reduced in PD. Mayeux, Williams, Stern, and Cote (1984) studied 50 consecutive idiopathic PD patients and found that 36% of them were depressed according to DSM-III criteria (APA, 1980). In this study, cerebrospinal fluid was obtained from lumbar puncture in 45 of the original patients as well as 15 age-matched, non-depressed neurologic controls. Metabolites of dopamine, serotonin, and noradrenaline were assayed and the results showed that only the metabolite for serotonin was significantly lower in depressed PD patients than in both the control and non-depressed PD groups. Weingarter and his colleagues (Weingarter, Cohen, Murphy, Martello, & Gerdt, 1981) reported changes in the information processing ability of endogenously depressed patients. Using a Levels of Processing technique (Craik & Lockhart, 1972), they identified a weakness in the ability of depressed patients to encode information to be remembered. They concluded that this represented incomplete or insufficient use of strategies in organizing and transferring information to long term memory when the
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30 information was of the episodic type and required conscious effort. In an attempt to replicate the findings of Weingarter et al. (1981) in depressed PD patients, Taylor, Saint-Cyr, and Lang (1986b) used the Beck Depression Inventory (BDI) as a quantitative measure of depression. They found that regardless of whether PD patients reported moderate or severe levels of depression, short term memory performance was not impaired. In contrast, endogenously depressed patients with moderate to severe depression were impaired on several short term memory tasks. The demonstration that PD patients were able to perform within normal limits on these memory tasks regardless of their self-reported level of depression led the authors to conclude that, unlike the endogenous depressed patients, PD patients maintain adequate ability to use encoding strategies. An additional finding from this study (Taylor et al., 1986b) was that few of the depressed PD patients reported self-destructive thoughts, guilt, or experiencing a sense of failure; all of which are characteristic of a negative mood state associated with endogenous depression according to the DSM-III criteria (APA, 1980). However, the majority of PD patients exhibited signs associated with depressed
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31 mood (i.e. tearfulness and agitation) during the study across all level of BDI ratings. The authors noted that this depressive affect was readily elicited in PD patients when stress was introduced during testing sessions. In addition, unlike endogenously depressed individuals who tended to become untestable when affectively aroused, they found they were able to test through the depressed moods displayed by the PD patients. The results of the study by Taylor et al. (1986b) suggest that the depression seen in PD may represent an entity different from that seen in endogenous depression. The authors proposed the possibility that depression in PD represents a similar, transmitter-related deficit which they propose affects the prefrontal region by nature of the deficient nigrostriatal and mesocortical dopaminergic pathways reported in PD. In addition, they note that the regulation of mood has been linked to structures in the prefrontal cortex which rely in part on basal ganglia output (Nauta, 1971). They cite Fibiger (1984) who proposed that the dopamine depletion in the prefrontal cortex of PD patients may predispose them to experience depression, which can be more easily exacerbated by frustration or stress.
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32 Arousal One of the symptoms of subcortical brain damage reported in the literature is impairment of arousal and/or attention (Oscar-Berman, Gade, Feldman, & Saavedra, 1979). Arousal is often used interchangeably with terms such as activation, awareness, emotion, and others (Klove, 1987). Pribram and McGuinness (1975) distinguished between three related neural systems responsible for arousal. They proposed that the first system was responsible for phasic arousal, a change in the level of arousal in response to input stimulation. They suggested that the amygdala was largely responsible for mediating phasic changes in arousal. The second system was responsible for controlling activation or the tonic physiological readiness of the organism to respond. Control of this resting arousal level was believed to involve the basal ganglia. The third system, involving the hippocampus, was responsible for coordinating arousal and activation, and required effort. Increased arousal is detected neurologically as a change in activity in the Reticular Activating System (RAS). When the cortex receives sufficient afferent impulses it is considered to be aroused; in other words,
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33 the critical number of cortical neurons have been brought into activation, resulting in a state of alertness. This arousal is a generalized activation of not only the cortex, but of the autonomic system as well, specifically the sympathetic nervous system. Afferent pathways lead into the RAS and if sufficient impulses are received, the RAS discharges into the cortex to produce the aroused state (Netter, 1975). According to Klove (1987), input from the sensory systems is sent to the cortex but is also sent along collateral fibers to the RAS. These connections to the RAS then result in connections to the thalamus and to wide areas of the cortex thus allowing for the generalized cortical activation. Arousal influences consciousness as well as an individual's emotional state. Kissin (1986) proposed that the electrical activity of the brain associated with consciousness reflected activation, while the energy level of the organism associated with the intensity of the emotional state reflected arousal. The level of arousal is considered to be associated with the ratio of sympathetic to parasympathetic activities. High levels of sympathetic activity produce increased arousal, and high levels of parasympathetic activity result in lowered arousal.
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34 Control of activation on the other hand is accomplished through the influence of the hypothalamus, thalamus, limbic, and nigrostriatal systems upon the RAS. Inhibitory input to the RAS results in a reduction in the level of consciousness, while an increased excitation of the RAS increases the level of activation of the brain, resulting in behavioral excitation (Kissin, 1986). He warns that there is an optimal range for the level of arousal such that activation outside this range may result in impairment. Too high a level of arousal may result in disorganized behavior or distractibility, while an individual with too low a level of arousal may appear drowsy and have difficulty attending. Joseph and associates (Joseph, Forrest, Fiducia, Como, & Siegel, 1981) reported a significant correspondence between electrophysiological measurement of cortical activation and behavioral arousal. These authors discovered that high-and low-active rats (identical strains) displayed significantly different visual evoked potential amplitudes. In addition, behavioral responsiveness to complex (open-versus close-field), novel, and intense forms of stimuli were correlated with cortical activation, as indicated by amplitude of visual evoked potential.
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35 The orienting response (OR) has typically been thought of as an involuntary attentional mechanism which alerts the organism when an unexpected stimulus occurs and is considered an example of an externally elicited, "exo-evoked", change in arousal (p. 128; Sokolov, 1966). Lynn (1966) proposed three types of stimuli which spontaneously evoke the OR; these are novel stimuli, conflicting stimuli, and stimuli with which we have attributed some prior significance. Ohman (1979) proposed that the OR indicated a call for information processing resources required for a deeper analysis of the eliciting stimuli. Support for this view was provided by the research of Simons, Ohman, and Lang (1979) who showed that electrodermal response (EDR) magnitude to a warning stimulus was larger when a high interest, imperative stimulus was expected than when a low interest stimulus was expected. These authors conclude that the change in electrodermal activity reflected a general mobilization of energy for efficient performance of the task, a reaction time measure, which was sensitive to the arousing quality of the imperative stimulus.
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36 Spinks and associates (Spinks, Blowers, & Shek, 1985) suggested that the anticipatory process of the OR was consistent with the functions of the autonomic nervous system: protection, activation, and integration. They found that skin conductance responses to orienting activity was predictive of the anticipated task demands. The OR was stronger the more information was anticipated at a given moment. They proposed that the autonomic nervous system coordinates preparedness in order to optimally deal with future situations. Preparedness at the cognitive level, is considered by Luria (1973) to be representative of adaptive change in cortical "tone" (p. 214), and equivalent with the concept of arousal. Holloway and Parsons (1971) described habituation is a highly labile, reversible process which occurs even when the stimuli are neither meaningful, intense, or when they are expected, and often not at all under conditions of increased alertness. They demonstrated that a group of heterogeneous "brain damaged" (p. 625) patients failed to show normal habituation to the OR using an auditory stimulus. Failure of habituation was thought to reflect disruption in the cortical modulation of lower brain centers which govern autonomic activity.
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37 Arousal and Parkinson's Disease An effective pharmacological treatment for the motor disability seen in PD involves administration of the dopamine precursor, L-dopa. Several studies have reported additional arousing and antidepressant effects associated with this treatment, and the conclusion was made that a deficit in arousal exists in PD and that this decreased arousal likely contributes to neuropsychological deficits observed in PD (Elithorn, Lunzer, & Weinman, 1975; Godwin-Austen, Tomlinson, Frears, & Kok, 1969). The administration of L-dopa is thought to increase the turnover of catecholamines and increase dopamine stores (Hornykiewicz, 1966). The proposed site of action of this increase in dopamine activity is the basal ganglia, and it is through the mesolimbic dopamine system's projections to the midbrain (i.e. RAS) that increased arousal is effected by administration of L-dopa (Horvath & Meares, 1974). These authors observed that PD patients treated with L-dopa demonstrated increased psychophysiological arousal, in terms of a decreased habituation rate, increased OR, and increased levels of electrodermal responsivity (EDR), and behaviorally, in the form of faster reaction times. They
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38 reported that such a delay in habituation of the OR was also representative of a behavioral index of increased arousal. Brown and Marsden (1988) suggested that PD patients have an impairment in their ability to maintain internal attentional control. They propose that the PD patients have reduced resources available in their "Supervisory Attentional System" (p. 332; SAS), a hypothetical construct responsible for determining which of several conflicting, simultaneous tasks take precedence for their attention. These authors stated that our subconscious allows for automatic processing and performance of several different tasks (schemata) simultaneously. But there are times when these schemata conflict, at which point a "scheduler" (p. 338), the SAS, determines which schemata to give precedence to, dependent on the environmental demands. They propose that PD patients are still capable of scheduling their attention, but that when the attentional demands become too great and exceed the limited resources of their SAS, they are not able to function efficiently. These authors propose that the decreased arousal in PD is a reflection of the decreased resources available to the SAS.
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39 Arousal and Memory in Parkinson's Disease Tasks which require the subject to impose organization and an encoding scheme demand considerable cognitive effort requiring an internally elicited increase in arousal, known as auto-evoked arousal (Hernandez-Peon, 1968). On verbal memory tasks that did not require considerable organization and therefore less effort, PD patients' recall was not significantly different from normal controls (Weingartner, Burns, Diebel, & Lewitt, 1984). In this study, PD patients did not appear to be impaired on tasks which require access to acquired knowledge, i.e. semantic memory. In contrast, DAT patients displayed a disruption in their ability to access these semantic stores. These authors believed that the impairment observed in PD patients more closely resembled the pattern of deficits associated with depression; involving impairment of information processing for tasks requiring considerable cognitive capacity and effort/arousal. This suggests that a deficit in auto-evoked arousal may be involved in PD. DAT patients demonstrated impaired recall regardless of the degree of effort required. The conclusion made from these findings was that different mechanisms mediate automatic processing versus demanding, capacity-limited, effortful processing
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40 (auto-evoked arousal), and that automatic processing (exo-evoked arousal) is spared in PD. Brown and his colleagues (Brown, Marsden, Quinn, & Wyke, 1984) found that Parkinson's disease patients who display the on-off phenomenon demonstrate a decrease in arousal and cognitive function in the off phase of this condition. Arousal in this study was assessed by subjects' self-ratings on a scale containing bipolar adjective pairs such as alert-drowsy. Cognitive function was assessed using a test of general reasoning ability for verbal, numerical and spatial material adapted from Heim (1974). The off phase was believed to be associated with decreased dopamine in the striatum, suggesting that a deficit in this neurochemical process may be responsible in part for the reduced arousal seen with PD. Huber and his associates (Huber, Shulman, Paulson, & Shuttleworth, 1987) supported the findings of Brown et al. (1984) by their observation that a fluctuation in memory performance in PD was correlated with fluctuations in plasma dopamine levels associated, not only with patients demonstrating the on-off phenomenon, but in typical PD patients as well. But, Huber's group proposed that the memory impairment reflected a state-dependent effect
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41 related to the dopamine blood levels. They found that when dopamine levels changed in either direction between the time of initial learning and later recall testing, recall performance was impaired relative to conditions when the dopamine level remained constant across these two time periods. These results suggest memory performance in PD is more dependent on the variability in dopamine level than on the absolute level of dopamine. However, one additional finding was that during the acquisition phase, even the PD groups who were at optimal levels of dopamine required more trials to learn the same amount of information compared to normal controls. The authors concluded that while rate of acquisition of new verbal material was impaired in PD, the retention of this material was grossly intact, provided the level of dopamine at recall was similar to what it was at acquisition. As the previous review demonstrates, the term arousal has been used throughout the literature to refer to a variety of different constructs. For purposes of clarity, the present study will refer to arousal as the readiness of the organism to act, its responsiveness. Tasks which elicit more effort (behavioral or cognitive) are therefore associated with greater arousal. An increase in this level
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42 of arousal may be reflected in a facilitation of the organisms ability to respond behaviorally, such as on a reaction time task (c.f., Bloxham et al., 1987) and physiologically, for example as a change in electrodermal responsivity (c.f., Cohen & Waters, 1985). Hernandez-Peon (1968) suggested that a change in the level of arousal (phasic) could be brought about from stimulation outside the organism as well as from internal sources (i.e. will). Auto-evoked changes in arousal are those behavioral or physiological responses which are elicited from within the organism. Conversely, an exo-evoked change in arousal is a change in responsivity which is elicited from an external source such as a warning signal or pain. Hypotheses The preceding discussion has presented evidence in support of the involvement of decreased dopaminergic functioning in the cognitive deficits associated with PD. Several studies suggest that the deficits involve learning and memory (c.f ., Mortimer, Pirozollo, Hansch, & Webster, 1982), and it has also been suggested that cognitive abilities improve with L-dopa treatment (c.f ., Elithorn, Lunzer, & Weinman, 1975). It is difficult to determine
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43 whether these cognitive changes are the result of either a generalized or specific effect (Brown, Marsden, Quinn, & Wyke, 1984). Mohr and associates (Mohr, Fabbrini, Ruggieri, Fedio, & Chase, 1987) reported that PD patients treated with L-dopa manifested relatively selective cognitive changes, disconfirming a generalized alerting effect of L-dopa. In their study, increased performance was only observed on two tests of delayed verbal memory; the Logical Memory and Paired Associates subtests from the Wechsler Memory Scale. Both of these measures assess episodic memory, a function which is impaired in PD (Squire & Cohen, 1984). Weingartner et al. (1984) also reported deficits of episodic memory in PD, especially on tasks requiring effortful processing, which elicit auto-evoked arousal. Cohen and Waters (1985) suggest there is a relationship between the level of arousal related to the cognitive effort associated with processing information and the recall of that information. They stated that previous investigations have examined whether psychophysiological responsivity was related to attentional demands which influence memory performance. The previous review provided evidence supporting impaired memory function and
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44 arousal mechanisms in PD. This line of evidence naturally leads to the question of the interaction of arousal and memory in PD. The current study explored the extent to which arousal elicited from exo-evoked and auto-evoked sources affected memory performance in PD. The previous literature review suggests several hypotheses regarding the interactive relationship of arousal and memory performance in Parkinson's disease. The present study was designed to address the questions drawn from these hypotheses. Hypothesis Ia. Based on the previous findings in the literature documenting memory deficits in Parkinson's patients, I hypothesized that subjects in this study would show a deficit in their delayed recognition of newly learned verbal information relative to same age and education peers. This led to the prediction that PD subjects would perform significantly poorer than the NC subjects on the experimental memory tasks. Hypothesis Ib. Parkinson's patients are capable of activating both from within (auto-evoked) and from without (exo-evoked) on tasks which require effortful processing
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45 resulting in greater recognition of verbal material obtained during this increased phasic arousal relative to material acquired at tonic, resting arousal. This hypothesis led to the prediction that PD and NC subjects would demonstrate greater overall recognition on both the Levels of Processing memory test (LOP) and the Self-Rated Arousal memory test (AR) relative to their recognition on the Verbal Recognition Test (VRT). The LOP is a task which requires the subject to actively process various aspects of target words, which consequently increases arousal. The AR task also increases arousal due to the emotionally laden characteristics of the target words. The VRT is a simple word recognition task which does not inherently elicit a change in arousal aside from normal encoding processes. Hypothesis !Ia. Parkinson's patients do not activate in response to external stimuli as efficiently as age matched peers. In support of this, the prediction was made that PD subjects' performance on a reaction time task would not show a significant reduction in response latency following a warning stimulus, as would be seen in the NC group.
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46 Hypothesis Ilb. If impaired activation was shown to exist as proposed by hypothesis Ila, it follows that PD patients would have a deficit in recognition performance of verbal material acquired in association with aphasic change in arousal because of the decreased cognitive efficiency resulting from the decreased activation. This led to the prediction that PD patients would show a similar pattern of benefit on recognition memory reflective of the level of cognitive processing evoked on the Levels of Processing memory task (as predicted from hypothesis lb), but that their overall recognition accuracy would be reduced relative to NC subjects since the efficiency of their activation processes are impaired. The prediction was also made that EDR measured at acquisition would mirror the levels effect seen behaviorally (i.e. recognition memory), but that the overall level of responsivity would be reduced for PD subjects relative to NC subjects, as physiological support that activation was impaired in this population. Hypothesis III. Exo-evoked arousal is relatively intact in Parkinson's patients compared to NC patients reflected in an identical benefit in recognition of verbal
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47 material acquired during this phasic arousal period. While it follows from Hypothesis I that the overall level of recognition of PD subjects would be reduced relative to NC, this still led to the prediction that PD subjects would show a greater difference in the level of recognition memory between arousing and non-arousing words on the Self-Rated Arousal memory test, with significantly greater recognition accuracy seen for arousing words.
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METHOD Subjects Subjects for the experimental group were 12 persons with Parkinson's disease (PD). The mean age was 66.2 (sd 6.1) ranging from 56 to 79 years, 4 were female and 8 were male. Mean education was 15.3 (sd 5.5) years, with a range from 8 to 20 years. The diagnosis of PD was confirmed by their physician either through direct referral or from information in their medical record. The duration of illness ranged from 2 to 10 years according to the patients self-report of the onset of symptoms, and the degree of severity, which ranged from mild to moderate, was determined by their attending physician. Subjects were receiving a variety of anti-parkinsonian medication. Due to the difficulty in monitoring medication on an outpatient basis, no systematic effort was made to control for the type of medication, dosage, or time since last administration, although this information was recorded. All subjects were ambulatory. Subjects were noncompensated volunteers, recruited from three sources: a community PD 48
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49 support group, University of Florida, Shands Outpatient Clinic, and outpatients from the Gainesville, VA Medical Center. Subjects with a history of significant neurological or psychiatric illness (in addition to PD), or with reported substance abuse (as defined by DSM-III criteria; APA, 1980) were excluded from this study. The control group included 12 persons with no known history of significant medical, neurological, or psychiatric illness. The mean age for this group was 61.5 (sd 5.6), with a range from 54 to 72 years. Mean education for these subjects was 14.8 years (sd 2.1), with a range from 12 to 18 years. All subjects were noncompensated volunteers recruited as either spouses of PD patients who participated in this study or through a local newspaper advertisement requesting participants for a "memory study." All control subjects denied a history of substance abuse as defined by DSM-III criteria (APA, 1980). Materials Subjects in both the experimental and control groups were administered an identical battery of standardized and experimental measures.
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50 Standardized Measures These included a short-form (Satz & Mogel, 1962) of the Verbal subtests (VIQ) from the Wechsler Adult Intelligence Scale-Revised (WAIS-R; Wechsler, 1981). This short-form consists of administration of all the subtests from the WAIS-R, but using only approximately 46% of the items within these subtests. Original research on the WAIS showed a significant correlation, x;: = 0.99, between full administration and the shortened administration for the Verbal IQ Score. Adams, Smigielski, & Jenkins (1984) showed that there was also a significant positive correlation, x;: = 0.98, between the short and full administration using the WAIS-R. Other measures included the Wechsler Memory Scale (WMS; Wechsler, 1945) with additional 30 minute, delayed recall for both the Logical Memory and Visual Reproduction subtests, and the Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961). Experimental Measures Verbal memory Word lists Two thirty-item word lists (LOP301 & LOP302; see Appendices A & B) were constructed for the VRT and LOP memory tests used in this experiment. Each list
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51 was balanced for frequency and imagibility using the Paivio, Yuille, and Madigan (1968) norms. For half of the subjects in each group, LOP301 was used for VRT and LOP302 was used for LOP. For the other half, the lists were reversed. For each word, a five-alternative multiple choice item was constructed for use in recognition testing (MLOP301 & MLOP302; see Appendices C & D). Alternatives were balanced for frequency and imagibility with the target item, and were arranged such that the target alternative occurred randomly in positions 2-5 of the item, but never first. Verbal recognition test (VRT). Word stimuli were presented individually, in sequence, on a computer screen for a duration of approximately 2 seconds with a 15 second interstimulus interval. The examiner simultaneously read each word aloud to the subject. Subjects were instructed to remember each word and told memory would be tested at a later time. Recognition memory was tested after a 30 minute filled delay. At recognition testing, subjects were presented 30 five-word, forced-choice recognition items on the computer screen and asked to choose the one item they recognized from previous exposure. Only one word in each item was presented at acquisition, and none of the other
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52 four words appeared on any of the other experimental word lists used in this study. Subjects were given unlimited time to respond, but were encouraged to "guess" on items if they were unable to give a response within a reasonable period of time. Each 5-word item appeared individually on the computer screen, and the next item appeared immediately after their response to the previous item had been recorded. Self-rated arousal test (AR). This test consisted of a list of 120 words (see Appendix E), 60 of which were previously rated by a group of pilot subjects as "highly" emotionally laden and 60 which were rated neutral. The pilot data was obtained from a cross-section of graduate students and elderly controls. Results from these ratings were not quantitatively analyzed, but it was clear that the instrument contained a sufficient number of LO and HI words to justify its use in the study. This test allowed for the assessment of memory performance related to an increase in arousal, i.e. by nature of the emotional quality of the words (Lynn, 1966). Subjects were given standardized instructions (see Appendix F) to rate each word using a 5-point, Likert-type rating scale for how "arousing" the word was to them. An accompanying visual rating scale, the
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53 Self-Assessment Manikin (SAM; Hodes, Cook, & Lang, 1985), was provided. This scale depicts a manikin figure across 5 frames of increasing degree of internal arousal (see Appendix G). Subjects completed these ratings at their own pace, and were asked to provide their "best estimate" on items which they had difficulty rating. When the subjects completed their ratings, the examiner identified the 15 words rated as having the relative "highest" arousing effect (i.e. closest to 5, HI) for that individual, and the 15 words rated the relative "lowest" (i.e. closest to 1, LO). In the event that more than 15 words were rated at the same level, the examiner randomly chose from these items. The 30 words selected were then randomly placed in two blocks of 15 words, such that 8 HI and 7 LO words were in the first block, and 7 HI and 8 LO words were in the second block. After they completed the ratings, subjects were given a 15 minute break, during which time the examiner entered the individualized 30-item word list into the computer for presentation. The 30 item AR word list was presented to the subjects using the same method and instructions as in the acquisition phase of the VRT paradigm described above. Subjects were told their recognition of these items would
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54 be tested at a later time. Following a 30 minute filled delay, recognition of the 30 words from the AR paradigm was tested. Subjects were presented a sheet containing the same 120 words that they had previously rated (see Appendix H). These words were in a randomized order relative to their initial presentation. Subjects were reminded that they had seen all the words during the rating phase, and the examiner stressed that they were to choose only those 30 items which they recognized from the presentation 30 minutes prior. Subjects were instructed to "guess" if they were unable to provide all 30 choices. In the event that they endorsed more than 30 items, they were asked to limit their choices to the 30 which they were "most certain of" being correct. Levels of processing test (LOP; Craik & Lockhart. 1972). This measure was used to assess memory performance as it related to the subjects' ability to perform effortful cognitive processing and exhibit a change in arousal. The test consisted of 30 words balanced for frequency and imagibility according to Paivio et al. (1968) norms. They were presented serially on a computer screen for a duration of approximately 2 seconds with an 18 second interstimulus interval. The examiner simultaneously read a brief
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55 question requiring the subject to attend to either the physical structure of the word (i.e., "Is this word printed in upper case letters?"), its phonemic quality (i.e., "Does this word rhyme with ?"), or its semantic quality (i.e., "Is this a type of .. ?"). Subjects were directed to respond either "yes" or "no" in reference to the word as quickly as possible after the question was read. The next word was automatically presented regardless of their response latency. No mention of later memory testing for these words was given. An equal number of "yes" and "no" questions were given at each processing level. The examiner noted subjects' response to each of these questions. As these questions were straightforward, a significant number of errors on this task was suggestive of either a comprehension deficit or inattention to the content of the items. Incidental recognition was obtained following a 30 minute filled delay. At recognition testing, subjects were presented thirty 5-word, forced-choice recognition items on the computer screen and asked to choose the word they recognized from previous exposure. Only one word in each item was presented at acquisition, and none of the other 4 words appeared on any other experimental word list presented to them during this
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56 study. Subjects were given unlimited time to respond, but were encouraged to "guess" on items if they were unable to give a response within a reasonable period of time. Each item appeared individually on the computer screen, and the next item appeared immediately after their response to the previous item had been recorded. Recordings of electrodermal responsivity (EDR; described below) were obtained from all subjects during the acquisition phase of the LOP paradigm. Electrodes were attached immediately prior to the acquisition phase of this task, and were removed after it was completed. This measurement allowed for the assessment of a physiological index of arousal related to the level of cognitive processing invoked. Reaction time task (RXN). In this task, subjects were seated in front of the computer, with the fingertips of their dominant hand resting on the space bar key, and told that this was a task of their reaction time and motor speed. Subjects are presented the following instructions on the computer: This is a test of your reaction speed. Press the space bar as quickly as you can when the star shown below appears. Sometimes this star will be preceded by a beep just before it appears, other times it will not. Do not press the space bar before the star appears.
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57 An example of the imperative stimulus ("star") appeared along with the instructions. A one second, computer generated tone was used as the warning stimulus. This test allowed for the assessment of motor response to phasic changes in arousal elicited by the warning stimulus. There were 75 separate reaction time trials in all; 25 unwarned, 25 with an auditory warning stimulus 200 milliseconds prior to presentation of the imperative stimulus, and 25 with an auditory warning stimulus 800 milliseconds prior to presentation of the imperative stimulus. The order of presentation of each of these trials was randomized for each individual. The imperative stimulus remained in view until the subject made a response. The computer screen remained clear during the intertrial interval. Each trial proceeded automatically, beginning approximately 10 seconds after the subject's last response. In the event that the subject responded prior to the onset of the imperative stimulus, the trial was terminated, the subject was presented a verbal reminder on the computer screen to wait for the visual stimulus before making a response, and the paradigm was continued with that trial randomly reinserted later in the task. Response
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58 latency was determined automatically from the computer's internal timer as the difference between time at stimulus onset and key press response. Equipment The automatic presentation of the word lists for the VRT, LOP, and AR paradigms was completed using an IBM PC/XT, microcomputer. Word stimuli appeared in the approximate center of a Quadchrome VGA color monitor. The words were printed approximately one half inch in height. Data storage into the computer was completed manually by the examiner for subject's responses on the VRT and LOP paradigms. Data from the RXN paradigm (response latency on each trial) and EDR measures (EDR on each trial) were obtained automatically by the computer. Physiological Measures Subjects' electrodermal response (EDR) was measured during the acquisition phase of the LOP test. EDR was obtained using Ag/Agel disc electrodes placed on the thenar and hypothenar eminences of the subject's non-dominant palm, with an additional ground electrode on the non-dominant forearm. This constant voltage arrangement
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59 passed 0.5 volts across the palm during recording. Electrodermal activity was sampled at 20 hertz for 7 seconds prior to word onset (tonic arousal) and 7 seconds past off set (phasic arousal). E DR was defined as the difference between the tonic peak and the mean skin conductance level occurring in the last second of the phasic period. Procedure Each subject was comfortably seated during the entire procedure. Informed consent was obtained, and subjects were given the opportunity to ask questions, provided the option to withdraw from participation at any time, and assured that doing so would in no way affect the treatment they may currently be receiving. No subjects chose to discontinue the procedures after they were initiated. The presentation order of the four paradigms involving a 30 minute delayed memory component (i.e., VRT, LOP, AR, and WMS) was randomized across subjects within each of the two groups. The delayed memory portion of each preceding paradigm was completed prior to beginning the acquisition phase of the next, so that there was no overlap of these tests. During the 30 minute delay from the VRT, LOP, and AR paradigms, the Verbal subtests from the WAIS-R were
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60 administered, in their standard order. The RXN paradigm was administered during the 30 minute delay for the Logical Memory and Visual Reproduction subtests of the WMS. Breaks were provided upon request, and typically the testing was completed within 2 1/2 to 3 hours. After all the procedures were completed, the subjects were debriefed as to the purpose of the study and given feedback regarding their performance if requested.
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RESULTS Standardized Measures Data were obtained for each of the standardized measures from 12 Parkinson disease patients (PD) and 12 normal control (NC) subjects, with the exception of the Wechsler Memory Scale (WMS); one subject in the PD group had recently been administered the revised version of this test during a separate clinical assessment, and since there is no consistent overlap of scores between these two versions, the data for this subject was not included in analyses using the WMS. Analyses comparing age (F [1, 22] = 3. 77, 2_ = 0.065) and education levels (F [1, 22] = 0.09, 2_ = 0.772) between the two subject groups showed no significant differences. Mean age for the PD group was 66.17 (SD 6.12) and 61.50 (SD 5.65) for the NC group. The resulting means and standard deviations for each of the measures, by group, is presented in Table 1. These include Verbal IQ Score from the Wechsler Adult Intelligence Scale-Revised (VIQ), Logical Memory (LM) and Visual Reproduction (VR), with delays (LM D and VRD 61
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62 respectively) and Paired Associates (PA) subtests from the Wechsler Memory Scale, and total score from the Beck Depression Inventory (BDI). GROUP PD NC VIQ 110. 75 (18.8) 115.5 (8.9) Table 1. Standardized Measures Means (Standard Deviations) MEASURE LM LMD VR VRD PA BDI 8.14 5.95 9.09 7 .91 20.54 10.5 (2.3) (2.4) (3.2) (3.6) (4.8) (5.7) 9.38 8.46 9.83 10.08 23.25 3.25 (2.7) (2.2) (3.7) (4.0) (4.6) (2.8) Analysis of the paired scores revealed no significant difference for VIQ, LM, VR, VRD, and PA between groups. Significant differences were obtained between groups for LMD and BECK; PD subjects provided significantly lower recall than NC subjects on LMD, .t (1, 21) = 2.62, 12. < .05, and a higher self-rating of depression on the BDI, .t (1, 22) = 3.95, J2. = .001.
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63 Experimental Memory Tests Table 2 lists the mean recognition scores (30 possible correct) and standard deviations for each test; Verbal Recognition Test (VRT), Self-Rated Arousal Memory Test (AR), and the Levels of Processing Test (LOP), by group. The distribution of percent correct recognition for each test across the two subject groups is presented in Figure 1. Table 2. Experimental Memory Tests Means (Standard Deviations) TEST GROUP VRT AR LOP PD 25.333 21.667 18. 75 ( 4. 08) ( 4 .12) ( 4. 31) NC 27 .833 23.917 22.083 (1.9) (2. 78) (2.43) Using GROUP membership as the between subject variable and the three experimental TESTs as dependent variables (VRT, AR, LOP), a 2 x 3 Mixed Model Analysis of Variance (Fisher, 1942) was conducted using total-correct recognition scores for each test as the independent
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Figure 1. Percent recall on the experimental memory tests by group.
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x Recal 1 1001 901 80-78' 60I 501 t = t 10-0 1 Test
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66 variable. Results from this analysis are presented in Table 3. Significant main effects for both GROUP, F (1, 22) = 5.69, 11 < .05, and TEST, F (2, 44) = 39.63, 12. < .001, were found. The interaction between GROUP and TEST was not significant. Since there was only one degree of freedom for the variable, GROUP, determination of the direction of this main effect was made using mean recognition for each group, collapsed across levels of TEST, showing that there was greater overall recognition across tasks for subjects in the NC group. An analysis of the direction of the main effect TEST, collapsed across levels of GROUP, using Tukey's studentized range test (Tukey, 1977) revealed that subjects' performance on VRT was significantly greater than both AR (12. < .05) and LOP (12. < .05). No difference was found in subjects' performance between the AR and LOP tasks. Source GROUP TEST GROUP*TEST GROUP(SUBJECTS) Table 3. Analysis of Variance Experimental Memory Tests MS 33.338 232.181 1.931 5.859 DF 1 2 2 44 F 5.69 39.63 0.33 PR> F <.05 <.001 *** 721
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67 Self-Rated Arousal Memory Test Additional analyses were conducted from data obtained on AR to examine the effect of the arousal RATING of the words on recognition performance. The data was divided into two levels of RATING; words self-rated as highly arousing in nature (HI) and those rated low (LO). Words were classified at acquisition as HI if the rating received was 11411 or 11511 on a 5-point Likert-type scale, and LO if their rating was 11111 or 11211 The analysis was conducted using a 2 x 2 Analysis of Variance design with the grouping factor, GROUP. The results from this analysis are presented in Table 4. A significant main effect across RATING of arousal was found, F (1, 22) = 33.44, R. < .001. A determination of the direction of the effect of RATING was made using the mean recognition performances for HI (12.542 of 15) and LO (10.250 of 15), collapsed across groups, revealing that subjects recognized significantly more of the HI arousal than LO arousal words. The main effect of GROUP was not significant although the interaction of GROUP and RATING approached significance. The distribution of mean recognition for each GROUP as a function of word RATING is provided in Figure 2.
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Figure 2. Recall (out of 15 correct) by self-rated arousal level of words for each group.
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14 Total Rating
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70 Table 4. Analysis of Variance Self-Rated Arousal Memory Test Source DF MS ERROR F PR > F GROUP 1 15.187 6.172 2.46 .131 RATING 1 63.021 1.884 33.44 < .001 *** RATING*GROUP 22 6.021 1.884 3.20 .088 Levels of Processing Test Separate analyses were conducted on the relationship of the "LEVEL" of processing required and the valence (SIGN) of the correct response for the acquisition questions (i.e. "yes" or "no") to both the subjects' electrodermal response (EDR) and their ability to recognize the words following a delay (SCORE). There were 3 levels of the variable, LEVEL, (CONCRETE, RHYME, and SEMANTIC) and 2 levels of SIGN (POSITIVE--the correct answer was "yes" to the word at acquisition, and NEGATIVE--the correct answer was "no").
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71 Electrodermal Response (EDR) An Analysis of Variance with two trial factors (LEVEL and SIGN) was conducted using the EDR data from the LOP task, between the two levels of GROUP. This analysis tested for the differential responsivity of EDR to assess arousal across the varying levels of cognitive processing imposed. The results of this analysis are presented in Table 5. These findings reflect that there was no differential EDR across main effects of GROUP, LEVEL, and SIGN, nor were there any significant effect of the interactions of these variables. Table 5. EDR Analysis of Variance Levels of Processing Test Source OF MS ERROR F PR > F GROUP 1 0.001 0.166 0.01 .937 SIGN 1 0.010 0.018 0.52 .4 78 LEVEL 2 0.009 0.004 2.16 .128 SIGN*GROUP 2 0.018 0.018 0.98 .332 LEVEL*GROUP 2 0.006 0.004 1.43 .250 LEVEL*SIGN 2 0.016 0.012 1.37 .266 LEVEL*SIGN*GROUP 42 0.011 0.012 0.97 .386
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72 The mean change in EDR for the PD group was 0.0907 micromoles (SD = 0.1340) and for the NC group it was 0.0963 (SD= 0.1934). The means and standard deviations for each LEVEL by GROUP is provided in Table 6. PD NC Table 6. Levels of Processing Mean EDR (Standard Deviation) CONCRETE RHYME SEMANTIC 0.0785 0.0815 0.1122 (0.1262) (0.1086) (0.1673) 0.1106 0.0761 0.1023 (0.2272) (0.1473) (0.2056) A post-hoc analysis examining the degree to which AGE and EDR covary was completed using an Analysis of Variance, with the results presented in Table 7. These findings reflect that there was no significant effect of AGE of subject on EDR responsivity. Table 7. Analysis of Variance EDR*AGE Source DF MS ERROR F PR > F GROUP 1 0.023 0.090 0.26 .619 AGE 1 0.008 0.090 0.09 762 GROUP*AGE 1 0.025 0.090 0.28 .606
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73 A post-hoc analysis examining the degree to which EDR and SCORE covaried across LEVEL and GROUP was completed. This analysis was used to determine if the subject's physiological responses could be used to predict their recognition performance; in other words, to assess the degree of correlation between EDR and SCORE. An Analysis of Covariance (Winer, 1971) reflected no significant interaction between these two dependent variables, F (1, 133) = 3.19, 12. = .076. SCORE An Analysis of Variance with two trial factors (LEVEL and SIGN) was conducted using the recognition data from the LOP task (SCORE) using GROUP as the between subjects variable. The results of this analysis are presented in Table 8. Significant effects for the main effects GROUP, F (1, 22) = 5.45, 12. > .05, LEVEL, F (2, 44) = 15.00, 12. < .001, and SIGN, F (1, 22) = 12.17, 12. < .01 were obtained. A significant interaction was observed between the trial factors LEVEL and SIGN, F (2, 44) = 3.41, 12. < .05. No other interactions were significant.
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74 Analysis of the main effect, GROUP, revealed that the NC group was significantly greater than the PD group in overall level of recognition collapsed across LEVEL and SIGN, F (1, 22) = 5.45, 2. < .05; mean recognition for the NC group was 22.08 (SD 2.43) and 18. 75 (SD 4.31) for the PD group. The analysis of the main effect, LEVEL, using Tukey's studentized range test revealed that, collapsed across GROUP and SIGN, subjects recognized fewer words in the CONCRETE level than on either the RHYME (2. < .05) or SEMANTIC levels (2. < .05). Mean recognition collapsed across GROUP for CONCRETE words was 5.58 of 10 (SD 1.49), for RHYME words 7 .00 of 10 (SD 2.03), and for SEMANTIC words 7 .83 of 10 (SD 1.33). No difference was found in total recognition between RHYME and SEMANTIC levels. Analysis of the main effect, SIGN, revealed that, collapsed across both variable GROUP and LEVEL, subjects recognized significantly more words when they responded positively (mean 11.12 of 15, SD 3.001) at acquisition, than when they responded negatively (mean 9.29 of 15, SD 3.380), F = (1, 22) = 12.17, 2. < .01. Subjects in both groups were quite accurate in responding to these "yes/no" orienting questions at acquisition; PD subjects had 97.22% correct and NC subjects had 99.44% correct. Accuracy of responding
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75 was not significantly different between groups (.t. [1, 22] = 1. 74, :g_ =.095), and because of their level of accuracy, analysis of recognition performance related to accuracy of responses at acquisition was not necessary. Table 8. Analysis of Variance LOP SCORE Source DF MS Error F PR> F GROUP 1 11.111 2.039 5.45 .029 LEVEL 2 15.528 1.035 15.00 <.001 *** SIGN 1 13.444 1.105 12.17 .002 ** LEVEL*SIGN 2 3.444 1.010 3.41 .042 LEVEL*GROUP 2 1.028 1.035 0.99 .379 SIGN*GROUP 1 0.250 1.105 0.23 .639 GROUP*LEVEL*SIGN 2 0.333 1.010 0.33 721 Analysis of the simple effects for the interaction of LEVEL by SIGN was accomplished using Tukey's studentized range test. The distribution of total correct by LEVEL (C=CONCRETE, R=RHYME, and S=SEMANTIC) and SIGN ("+" = POSITIVE, and "-" = NEGATIVE) is displayed in Figure 3. These analyses revealed that subjects' recognition of words from the SEMANTIC level within the POSITIVE condition was
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Figure 3. Percent recall on the Levels of Processing Test by cognitive processing task and response valence, collapsed across groups.
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58 % Recall 48 30 0 CONCRETE RHYME Processing Task SEMANTIC ''No'' II "Yes"
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78 significantly greater than their recognition for both the POSITIVE and NEGATIVE conditions of the CONCRETE level (Q. < .05), and the NEGATIVE condition within the RHYME level (Q. < .05). In addition, their recognition of words from the POSITIVE condition of the RHYME level was significantly greater than both the POSITIVE and NEGATIVE conditions of the CONCRETE level (R. < .05). No other simple effects were significantly different. Reaction Time Task Latency to respond was obtained for all subjects within each GROUP across three levels of TRIAL [Unwarned (UN), 200 millisecond warning (W2), and 800 millisecond warning (W8) ], between the two GROUPs [Parkinson's disease (PD) and normal controls (NC)]. The distribution of reaction time (in thousandths of a second) by TRIAL conditions for each group can be seen in Figure 4. An Analysis of Variance with a grouping factor was conducted on the reaction time data across the within group factor, TRIAL, between the two levels of GROUP. The results from this analysis are presented in Table 9. A significant main effect for TRIAL was obtained, F (2, 44) = 38.99, 2. < .001, as well as for the interaction of TRIAL by GROUP, F (2, 44) = 4.84, 2. < 05. The main effect, GROUP, was not significant.
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Figure 4. Reaction times (in thousandths of a second) by TRIALS for each group.
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0 ,51 1 0.3 Latency (secs) 0.2 0.1 UN W2 Trial we C
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81 Table 9. Analysis of Variance Reaction Time Task Source OF MS Error F PR> F GROUP 1 0.004 0.015 0.28 .599 TRIAL 2 0.067 0.002 38.99 <.001 *** GROUP*TRIAL 2 0.008 0.002 4.84 .013 Analysis of the main effect, TRIAL, was conducted using Tukey's studentized range test. These results showed that collapsed across groups, subjects' latency to respond on this task was significantly slower in the UN condition (mean = 0.409, SD = 0.0955) than at either the W2 (mean = 0.316, SD = 0.0667) or W8 (mean = 0.318, SD = 0.0607) conditions (2. < .05). There was no difference in reaction time between the W2 and W8 trials. Examination of the simple effects for the interaction of TRIAL by GROUP was also completed using Tukey's studentized range test. These results revealed that PD subjects' latency to respond on the UN (mean 0.438, SD = 0.1272) condition was significantly slower (2. < .05) than their own reaction time on both the W2 (mean= 0.3147, SD= 0.0645) and W8 (mean = 0.3135, SD = 0.0664) conditions, and slower (2. < .05) than that of the NC subjects on both the
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82 W2 (mean = 0.3180, SD = 0.0689) and W8 (mean = 0.3225, SD = 0.0549) conditions. No other significant differences existed for the simple effects of the interaction. Summary of Results Subjects in the NC and PD group were comparable in both age and level of education. PD subjects provided a significantly higher self-rating of depression on the BDI than NC subjects. Overall, NC subjects' recognition was greater than PD subjects on both the standardized and experimental memory tests. On the Self-Rated Arousal Test (AR), PD subjects recognized as many words as NC subjects. Words rated as HI arousal were recognized significantly more than LO arousing words across both subjects groups, with no other interaction effects. On the Levels of Processing Test (LOP), there was no difference in EDR across the variables GROUP, LEVEL, and SIGN, and no significant interactions were observed either. NC subjects displayed a significantly greater recognition performance than PD subjects on the LOP test. When analyzed across level of processing required at
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83 acquisition, words acquired emphasizing CONCRETE characteristics were recognized significantly less than when processed for RHYME and SEMANTIC qualities, collapsed across the two groups. No difference was seen between RHYME and SEMANTIC recognition performance, collapsed across groups. Words acquired when the direction of the processing required a positive response ("yes") were recognized significantly more than words associated with a negative response ("no"), collapsed across groups. No significant interactions between the variables on LOP were found. On the Reaction Time Task (RXN), PD subjects performed comparable to NC subjects overall. When assessed across both groups, response times to unwarned stimuli were significantly slower on the average than to stimuli following either a 200 or 800 millisecond warning. No significant interactions between the variables on RXN were found.
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DISCUSSION Memory Performance in Parkinson's Disease The results of this study provide support to Hypothesis Ia which stated that Parkinson's subjects' delayed verbal memory performance is impaired relative to normal control subjects. In general, PD subjects displayed poorer recognition on the experimental memory tests administered, findings which are inconsistent with those of Taylor, Saint-Cyr, and Lang (1986a). However, when memory performance is analyzed across tasks, this group difference is only seen on the LOP. Recognition memory performance for PD subjects on the VRT and AR tasks are intact relative to NC subjects, consistent with Taylor's findings. A gradient of memory performance is demonstrated when data is collapsed across subject groups, but in the direction opposite of that predicted from Hypothesis Ib. All subjects show poorer recognition on the Self-Rated Arousal Memory Test (AR) and Levels of Processing Memory Test (LOP) than they do on the Visual Recognition Test (VRT). One explanation for this finding is related to the 84
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85 fact that the two latter tests rely on incidental memory, since explicit instructions were given to subjects on the Verbal Recognition Test that they would have to remember the items presented to them, and no mention of later memory testing was mentioned on either the AR or LOP tests. One way to answer this question would be to test a separate group of subjects using explicit instructions on one form of the AR and LOP tests, and to compare recognition performance with that obtained from subjects administered the tests in their original incidental format. However, it was noted that several subjects reported that they had anticipated a recognition trial following the acquisition phase for the AR and LOP tests, and since the majority of the measures used during these procedures were memory tasks, it is a reasonable assumption that the AR and LOP tests were, in fact, not incidental for many subjects. This discrepancy may still have contributed to the variance within these tasks, masking the expected effect, and not allowing for a conclusion to be made regarding a differential memory performance within PD subjects across these tasks.
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86 Subjects in this study were tested for their recognition on three separate, 30-item, word lists. The design of this study prevented an overlap between lists in that recognition of one list was always completed before another set of words was presented. However, this supersaturation of new information may have inhibited memory performance in several ways. Such a presentation schedule may result in a normal increase in proactive interference. Since the design of the current study prevented an over-lap of word items, proactive interference may not be directly determined. Tweedy, Langer, and McDowell {1982) have noted that PD patients show a delayed release from proactive interference. They found that PD patients did not appear to be more susceptible to interference effects, but instead when normal interference had built up, it took longer for the detrimental effects to dissipate. While the order of word-list presentations was counterbalanced in this study to prevent a bias in performance due to the sequencing of the tests, an increased (and lingering) interference from prior lists may still have occurred, reducing recognition performance and masking any differentiation of performance that may have existed between the memory tests. One would expect that a
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87 negative interaction between order of test presentation and recognition performance would be observed, in which case analysis of the dependent recognition variables across both independent variables ORDER and GROUP would reveal the significance of this interaction. Unfortunately, information regarding the order of test presentation was not tagged to the subject data itself; a master schedule was kept, from which presentation orders were merely checked off when used for each subject, thereby making it impossible to determine which subjects had a particular order of presentation. An obvious future direction would therefore be to keep record of test presentations for each subject. It is possible that a source memory deficit (Squire, 1982) may have confounded the findings on recognition performance in PD subjects. Squire notes that source amnesia, which is a deficit in the subjects ability to discriminate the context or source from which information was acquired, is associated with frontal system dysfunction--pathology which is reported to be involved in Parkinson's disease (Taylor, Saint-Cyr, & Lang, 1986a). While subjects were never required to make a source distinction for the words acquired, it is speculated that a
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88 breakdown of the borders between word lists may have had a detrimental effect on the delayed recognition of this information. However, since the word lists were specifically designed with no overlap between them, there were no extralist intrusions, and it was not possible to assess directly intrusions which may be indicative of source amnesia. Future studies addressing the questions raised in this study may reduce the possible deterrent influence of proactive interference and deficient source memory by either using longer intervals between completion of one memory test and the acquisition of items from the next, or by giving only one of the three experimental memory tests to a subject and making a comparison of differential effects between subjects. However, neither of these latter explanations can account for the decreased performance of NC subjects on AR and LOP relative to VRT. One speculation may be that the additional cognitive processing inherent in the LOP and AR tasks were a distraction at encoding of the verbal material. NC subjects might be expected to perform poorer on the LOP task relative to VRT because the latter is an incidental memory test. The arousing properties of the highly emotionally laden words on the AR task may have
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89 distracted the subjects from adequately processing the items. Future studies might not predict a greater recognition on these tasks relative to tasks free of such encoding interference. The most likely reason for the lack of support for the hypotheses in this study may have been due to the specific method with which memory was assessed. One important differentiation between previous literature examining memory performance in PD and the current study is that the deficit found in these studies have typically been on free recall paradigms (c.f ., Helkala et al., 1988; Taylor et al., 1986a). However, all of the memory paradigms in the present study involve recognition memory. These studies have generally found when memory is tested in this manner, PD patients are within the normal range. Benson (1983) stated that the memory deficit associated with subcortical dementia (i.e., PD) is typically a retrieval (/encoding) deficit. Therefore when provided retrieval cues, such as in a recognition memory paradigm, these subjects can display intact performance relative to normals. The use of such cuing in the present study must be considered a major contributory factor in why many of the hypotheses regarding memory impairment were not supported. Future studies using
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90 recall measures of verbal memory may find a more robust interaction between arousal and memory performance in PD. Arousal and Memory Performance The findings from the reaction time task failed to support Hypothesis IIa; that Parkinson's patients display a deficit in activation. While it was shown that PD subjects were significantly slower than NC subjects to give a response on unwarned reaction time trials, there were no differences between groups when either a 200 or 800 millisecond auditory warning stimuli directly preceded the trial. These results, in fact, suggest that PD subjects have intact activation, in the observation that PD subjects' reaction time following a warning stimuli was equal to that of NC subjects, reflecting the ability of PD subjects to anticipate having to make a response. The observation that PD subjects demonstrated slower response latencies relative to NC subjects on the unwarned trials reflects bradykinesia in the PD population, consistent with the findings of Taylor et al. (1986a). These results suggest that PD subjects maintain a tonic hypoaroused state, but are capable of increasing this level when it is elicited by a change in the environment.
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91 Since subjects on the warned trials of this task are dependent on a change in the environment (i.e., an external cue), it can be said that the subject's response to the auditory warning stimulus is similar to an orienting response (OR), which evokes a nonvoluntary increase in arousal (Sokolov, 1966). The OR is assumed to involve an exo-evoked increase in arousal, rather than auto-evoked. Previous studies have reported intact exo-evoked arousal in PD, with behavioral evidence for this as examples of the phenomenon, paradoxical kinesia (Lit, 1968; Schwab, 1972) discussed earlier. Therefore, the present findings may also be considered to reflect that PD subjects are capable of increasing their arousal from an externally elicited orienting reflex to the warning stimuli. The findings of this present study are contradictory to those of Heilman, Bowers, Watson, and Greer (1976), who showed that while PD subjects improved their reaction time with a warning stimulus, it was still significantly slower than the warned reaction times of NC subjects. One explanation for this discrepancy may be due to the differences in the two studies in the interstimulus intervals used between the presentation of the warning stimulus and onset of the target stimulus. The present
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92 study used a 200 millisecond warning signal to assess the lag in activation which may be seen in PD relative to NC subjects. It was assumed that NC subjects would not show much of a difference in responding on W2 and W8 trials, but that PD subjects, because of an initiation deficit, would not show as great a benefit on W2 trials as they would on W8 trials. The observation that the reaction time elicited on W8 was not different from that elicited by W2 suggests that the phasic change had already occurred within the shorter interval. Heilman's group also failed to find a difference in response time between the interstimulus intervals they used (0.5 and 1.0 second), suggesting that there was no response gradient based on the duration of the warning interval. Converging the findings from their study and this present one, it appears that the length of delay between warning and target stimuli was not crucial within the range from 0.2 to 1.0 seconds. Therefore, it is not likely that the differences in interstimulus intervals account for the lack of concurrence between these two studies, and it is more likely that the discrepancy is due to some other cause or to random variance.
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93 The finding that NC subjects did not demonstrate an increase in arousal, as evidenced by their lack of reduction in reaction time on warned trials suggests that the findings from this paradigm should be viewed with caution. One likely explanation for this was that the task used in this study was not complex enough to demonstrate the expected benefit from a warning stimulus. For example, a more complex, choice-reaction-time task may be useful in future studies demonstrating this effect. However, one significant difference between this study and the work of Heilman et al. (1976) is in regard to the nature of the stimuli used. Heilman's group used a quick-peak incandescent lamp, while this present study used a relatively small, computer generated figure. It could be argued that the target in this present study was weaker than that used by Heilman, making it less effective at eliciting a further reduction in reaction time beyond that which both groups demonstrated following warning stimuli. Future studies should include more potent stimuli to assess reaction time in these populations. Lack of support for Hypothesis IIb came from the observation that PD subjects displayed a levels of processing effect similar to that of NC subjects. This
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94 suggests that activation processes are intact in PD subjects, and can allow for an increase in memory concomitant with increased arousal. It is important to note at this point that arousal is inferred from memory performance. However Cohen and Waters (1985) found a significant positive correlation between psychophysiological indicators of arousal (heart rate and electrodermal activity) and recall performance. In their study there was a greater level of physiological activity associated with deeper levels of cognitive processing (i.e., semantic) and greater delayed recall of this information as well. They concluded that their results demonstrated support for increased arousal associated with increased cognitive effort on a level of processing task. The present data support the findings of previous studies which found poorer delayed recall associated when verbal material was processed according to its orthographic properties relative to when its semantic properties were processed (Craik, 1979; Cacioppo, Petty, and Morris, 1985). Subjects from both groups in the present study displayed greater recognition of words phonemically processed at acquisition relative to orthographically processed words. However, in the present study, there was
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95 no significant difference between recognition of words processed phonemically or semantically, which is contrary to that found by the previous researchers who have found greater recognition associated with semantic relative to phonemic processing at acquisition. Previous studies have relied on incidental memory on levels of processing tasks, a likely element necessary for demonstrating this differentiation in recognition associated with cognitive processing at acquisition. In the present study, subjects were assailed with a number of memory tasks, and it is not at all unlikely that subjects made the assumption that all material presented to them during the procedures was for purposes of testing recognition. Therefore, the levels of processing effect may have been masked, in that subjects put forth increased cognitive effort to recognize the items regardless of the instructions at acquisition. An additional finding of the current study was that subjects in both groups displayed better recognition for words acquired when the orienting question required a correct response of "yes," regardless of the cognitive processing elicited. In other words, subjects recognized more of the words for which they were required to respond "yes" to at acquisition. One theory for this finding is
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96 that subjects are encoding a process-word pair and that a match between the question and the word (i.e., a "yes" response) denotes a successful pairing, and that this additional information, the positive pair, is also encoded along with the word itself, strengthening recognition of words associated with positive valence. One way to assess this in future studies would be to ask subjects to recall the process required at the time of acquisition for that particular item (i.e., "What question did I ask you when you saw this word?" or "Did I ask you about the size of the letters, what it rhymed with, or what type of thing it was?"). If the enhanced recall of the positive conditions was due to this pairing, there should be better recall of the process required on positive trials than for recall of the process on negative trials. There was no significant difference between groups in the number of correct responses to the acquisition questions on the LOP task, suggesting that both groups were as capable of accurately orienting to the process required. This study used electrodermal response (EDR) as an indirect measure of arousal, with the prediction that EDR would correlate with word recognition on the LOP test. The
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97 findings of this study failed to show any differential electrodermal activity across either group as well as across level of processing required. In addition, there was no effect of subject age on EDR for subjects from either group. Cacioppo, Petty, and Morris (1985), using electromyographic (EMG) recording found a differentiation in level of EMG related to the subjects self-reported level of effort for the cognitive processes involved on the acquisition tasks, although EMG failed to predict recall performance. Horvath and Meares (1974) showed that PD patients display reduced electrodermal responsivity relative to normal control subjects. The present study failed to replicate either of these previous findings. A possible explanation for these null results is that the data in this present study contains significant variance from a number of sources including equipment failure or from inadequate contact at the point of the electrode. Examination of the data revealed that baseline electrodermal measures were obtained, but that there did not appear to be substantial changes from these basal levels across trials in either group. A common dermatological condition occurring in older populations is
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98 "dry skin" (p. 469; Gilchrist, 1986). This is seen as a reduction of hydration in the stratum corneum, which is the outer layer of the epidermis. The stratum corneum is made up of keratinocytes that form the major chemical and mechanical barrier of the body. It is this decreased hydration of the corneum in the elderly which Edelberg (1972) proposed was responsible for a general decline in conductivity observed in the elderly population. This phenomenon is the most likely explanation for the apparent floor effect in electrodermal responsivity in the present study, accounting in part for the lack of significant results. Increasing the sensativity of the EDR recording may alleviate this problem to some degree. However, a more plausible solution for future research would be to include additional psychophysiological measures which are not as affected by aging factors to assess arousal in these populations. These measures could include heart rate, respiration rate, and electroencephalogram recordings. Lynn (1966) suggested that stimuli which generate conflict within the individual, such as highly emotional words, would elicit an orienting response; thus an increase in exo-evoked arousal. This increase in phasic arousal during exposure to stimuli has been found to augment
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99 delayed recall performance (Pribram and McGuinness, 1975). The present study replicated these findings and support Hypothesis III, in that PD subjects (as well as NC) demonstrated a greater recognition of words which they self-rated as more emotionally arousing to those rated lower along this dimension. These findings suggest that exo-evoked arousal processes are intact in PD patients. However, the finding that PD subjects' total recognition was not significantly different from that of NC subjects on the AR test when analysis of RATING was utilized, contradicts Hypothesis I which predicted an overall deficit in memory performance for PD subjects. A possible explanation for these findings is that the phasic change elicited by the highly emotionally laden words was of significantly great magnitude to allow PD subjects to overcome their relative memory deficit, and that both NC and PD subjects were observed at a ceiling level of recognition for this measure. It is arguable that this theory is inaccurate in light of the findings that recognition on the Verbal Recognition Test (VRT) is greater than that of the Self-Rated Arousal Memory Test (AR), suggesting that the subjects are in fact not at their maximum level of recognition on AR. However, these two
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100 tests differ in the nature of the cognitive demands involved, which in turn may result in a natural difference in the observed ceiling on these two tests. An alternative explanation is that the lack of a significant difference between PD and NC subjects in overall recognition is due to random variance within the data. Limitations The present study failed to replicate findings observed in previous studies. This included the failure to repeat a levels of processing effect that has been replicated by several researchers (Craik and Tulving, 1975; Cohen and Waters, 1985). The findings for the variable LEVEL on the LOP test were approached significance (R = .128). It is possible that by increasing power in the sample, either by increasing the size, or by selecting a more homogeneous subject pool, a significant effect may be observed in future studies. The current project also failed to replicate the findings of Cohen and Waters (1985) in the correlated changes in EDR associated with cognitive effort concomitant with the level of processing required on the LOP test. As described previously, much of this may lie in the limited
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101 range of recording inherent in the older population used in the present study. Subjects in the study by Cohen and Waters had a mean age of 20.6 (SD 3.4), while mean age for all subjects in this study was 63.8 (SD 5.9). As noted previously (Edelberg, 1972), there are a number of factors associated with normal aging which reduce the range of recording of the EDR. Increasing the sensitivity of the EDR measurement in adjusting for such age effects may allow for replication of the findings of Cohen and Waters. Heilman et al. (1976) found that with and without a warning stimulus, PD patients performed significantly slower than NC subjects on a reaction time task. The failure of the present study to replicate this differentiation between groups on trials when the warning stimulus was used may again be related to decreased power within the study. The patients in the study by Heilman and associates were described as "ten hypokinetic parkisonian patients" (p. 139); a seemingly homogeneous group based on their motor functioning. PD patients in the present study were not selected on the basis of any specific criteria, instead inclusion was based solely on the presence of the diagnosis by a physician, and mild to moderate overall severity of the disease. These selection criteria may have
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102 resulted in a more heterogeneous sample of PD patients in the present study. Future studies which select for PD patients along a more specific set of criteria may increase the power of the data set. One final limitation of the present study is the fact the PD subjects were all currently undergoing some form of dopaminergic agonist therapy. One observed effect of levadopa was increased arousal (Horvath and Meares, 1974). However, a number of other functions have been shown to be affected, directly or indirectly by this medication, including memory (c.f ., Yahr et al., 1969). One solution would be to obtain data from nonmedicated PD subjects to eliminate any masking effect of dopamine agonist medication. Conclusions The results of this study suggest that Parkinson's patients have poorer delayed recognition of verbal material relative to age peers, but that they do show an increase in memory performance associated with certain tasks which effect increases in phasic arousal (e.g., deeper processing during learning or memory for emotionally arousing material). The information from this present study may be useful in educating PD patients on how to optimize their learning potential.
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103 This study provided information regarding the effect of arousal at acquisition on memory performance in PD. However, future research is also needed to determine the benefit in the memory performance of PD subjects from increased arousal at retrieval. A future direction for this research in the future would be to examine the effects of arousal on memory in nonmedicated PD patients. The arousing effects of levadopa may have masked the deficits in tonic and phasic arousal which may have a significant influence on memory performance in PD. Another direction for further research is based on the observation that a significant degree of PD patients report symptoms of depression. In this study, PD subjects provided higher self-ratings of depression on the BDI than the NC group. A systematic analysis of the effect of depression in this patient population on memory performance would be valuable. However, it should be noted that only 3 of the PD subjects had BDI scores which were within the clinically significant range for depression. In addition, the mean score for the NC subjects (3.3, sd 2.8) is well below the mean provided by Beck et al. (1961) for normal subjects (10.9, sd 8.1). it is possible that NC subjects
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104 who were relative of PD subjects used in this study may have under reported their level of depressed symptoms when contrasted with their spouses relative level of health. In addition, since the other NC subjects were noncompensated volunteers, they may not be a valid representation of the elderly population since they would have to have a high level of motivation to put forth the effort to respond for this study, suggestive of a lower level of depression in this subgroup.
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APPENDICES
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APPENDIX A LOP301 ACQUISITION c+ 1. OIUROI Is this printed in upper case letters? y N s+ 2. UNIFORM Is this a type of clothing? y N R-3. float Ibes this rhyme with match? y N s-4. frierrl Is this a type of furniture? y N R+ 5. BEIL Ibes this rhyme with sell? y N c-6. ice Is this printed in upper case letters? y N c-7. flesh Is this printed in upper case letters? y N s+ 8. winter Is this a season? y N R-9. TREASURE Ibes this rhyme with plant? y N R+ 10. kiss lx>es this rhyme with miss? y N s-11. SAI.ARY Is this a type of tool? y N c+ 12. I.EADER Is this printed in upper case letters? y N s+ 13. spoon Is this a type of utensil? y N s-14. CHAIR Is this a type of animal? y N R+ 15. sock lx>es this rhyme with block? y N c-16. gun Is this printed in upper case letters? y N R-17. FENCE Ibes this rhyme with hour? y N c+ 18. FORE.ST Is this printed in upper case letters? y N c+ 19. BRF.AD Is this printed in upper case letters? y N R-20. death Ibes this rhyme with fall? y N s+ 21. AVENUE Is this a type of street? y N R+ 22. FLY Ibes this rhyme with cry? y N s-23. AGE Is this a type of transportation? y N c-24. pipe Is this printed in upper case letters? y N c-25. cloud Is this printed in upper case letters? y N s+ 26. mint Is this a type of herb? y N R-27. beach Ix>es this rhyme with rug? y N R+ 28. I.AD Ibes this rhyme with fad? y N s-29. flute Is this a type of sport? y N c+ 30. SALT Is this printed in upper case letters? y N 106
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1. answer 2. bank 3. power 4. wirrl 5. key 6. woman 7. view 8. cotton 9. storm 10. iron 11. job 12. tent 13. gold 14. deal 15. horse 16. flag 17. earth 18. board 19. past 20. baby 21. action 22. king 23. fur 24. picture 25. poet 26. gift 27. circle 28. barrl 29. fear 30. art APPENDIX B MLOP301 ANSWER SHEET door FLY person AVENUE foot railroad doctor prison hug pack FllJI'E master SRX>N coin murder valley top SOCK oak wheel ticket book nod BREAD TRFA5URE doll cabin height MINI' journal CIDUD coal vessel lamp FOREST egg shadow pupil tear city ocean SALT bill QIAIR bottle party leaf BFAQf FENCE voltnne lie blood home orange car ICE flood amount speech F1.0AT QillRQi hall bag ball flower FLESH star form product air pole SAIJ\RY BELL affair bar fight UNIFORM clock arm rock bow corn roll AGE steam KISS bone towel acre pin 107 market price lAD letter wish rope PIPE week meeting pool term breast DFA'IH cream field fire cellar I.EADER deck bird judge lion FRIEND potato soil plane GUN floor port WINI'ER
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s+ 1. poetry c-2. dtnnmy s+ 3. CDFFEE c+ 4. GARDEN s-5. WEAroN c+ 6. GOBI.EI' R+ 7. money s-8. OJS'IUME R-9. corner R+ 10. VAroR c-11. folder c+ 12. I.ESSON R-13. Ia.JIDER R-14. drama s+ 15. mountain c-16. contract R+ 17. BI.ESSlliG s-18. face c+ 19. CIRaJIT R-20. HOI'EL c-21. session R+ 22. RATlliG s-23. APPLE s+ 24. table R-25. paper c+ 26. WHISTLE s-27. mercy s+ 28. BFAVER R+ 29. tower c-30. tripod APPENDIX C LOP302 ACQUISITION Is this a type of art? Is this printed in upper case leb:ers? Is this a type of beverage? Is this printed in upper case letters? Is this a color? Is this printed in upper case let~ers? Does this rhyme with swmy? Is this a type of plant? Does this rhyme with batch? Does this rhyme with taper? Is this printed in upper case letters? Is this printed in upper case letters? Does this rhyme with feet? Does this rhyme with bait? Is this a type of landscape? Is thi s printed in upper case letters? IxJes this rhyme with missing? Is this a type of food? Is this printed in upper case letters? Does this rhyme with back? Is this printed in upper case letters? IxJes this rhyme with waiting? Is this a type of insect? Is this a type of furniture? Does this rhyme with coat? Is this printed in upper case letters? Is this a type of fruit? Is tl1is a type of animal? IxJes this rhyme with sour? Is this printed in upper case letters? 108 y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N y N
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1. nephew 2. hankerin;;J 3. wall 4. engine 5. extent 6. deduction 7. metal 8. laborer 9. lip 10. battle 11. wheat 12. prayer 13. discussion 14. student 15. dark 16. essence 17. lob 18. fioble 19. vacation 20. battery 21. weakness 22. equity 23. enclosure 24. altar 25. nail 26. anoc>r 27. algebra 28. vodka 29. house 30. brain APPENDIX D MLOP302 ANSWER SHEET ambulance BlFSSING fonnation box genius place flame IDNEY village career stonn FACE waiter radio avoidance upkeep FOIDER dcx:trine river WHISTI.E sugar learning atrophy bankruptcy B:XJI.DER meat wine teeth edge 1FSSON dress TOWER cattle starch GARDEN magazine diligence MERCY observer mFFEE coat lake mouth knob mRNER RATING rubble irony soldier city shock infection misery outsider VAroR belief policeman usage diagram BEAVER I:oE.'TRY unison verdict daffodil research IXJMMY keeper realism 'IRII:oD hour teacher TABLE palace mother truck leIOC>nade tern.ency DRAMA nonsense GOBI.ET pronntion APPLE steam board gate parent lady HOI'EL paint clothin;;J 109 banker CIROJIT nooel troops WF.AIDN residence time SESSION temple desert canal skin landlord buildin;;J lxMl admiral PAPER msIUME vigor horror pioneer cigar basin coast o::>NTRACT ellxM bullet silence MXJNI'AIN cat
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rnYSl'IIL_ ruNDIE_ WHORE_ OOST_ TIDE_ TIMBER_ M:lRI\'.;AGE_ 1\MfUTIITE CIIMERA_ WEDOillG_ TEMro_ FR1\CIURE RELIGION KIIL_ .AMBITION_ PI\.TR_ RETIRE_ sotn!Y_ llJNOI_ STI\W_ DIVORCE vrnr::;m_ BOOIH_ DEFillE_ BASTIIRD VG!IT __ CI\MP_ So-!OIJ\R FOCSI' AUEl_ lnJ<1]ET_ FIITHER WXJL_ FI.MK_ ElID1l\ MUTIIATE __ MUcnJS FIUCTION Tl\XE'3 SEX_ MEDICillE_ ROBBERY_ HIT_ M'.lNKEY_ \ol:)RJ<_ GOD_ INSIINE SOOR_ APPENDIX E AR RATING LIST BIT01_ SlAVE_ Ml\TEIUII.L SORES_ CIISTRl\TE __ Pilll'_ 1-DIFSr ImTERY_ I\WNING_ 'IRIIDE SI\TI\N Nffl!E}{_ rus rnEVIEW 11.IOO_ Sl'IIB_ TIIRCtlE 1\~ rnIDE_ CI\RRY_ JESUS GIORY B\HJO __ PRIES!' PAIN_ SCIEl1CE FECES_ HF' .... wrn_ I\SSIIULT WAR_ I\CCIDllll'_ BIOOI' SODIDM_ a:MIIE_ D,\NCE_ noru:sr GAR/\GE_ CDIDNY_ WRITE OIIID_ PIEr.x;E MISSION 001'1\IN MElRIC_ ro.r:ra1_ IMPIICT STI\NCE_ a:tml\T_ 110 RAPE_ HERPE<;_ Sl'IIBIE_ CI.OOF:1'_ aJIJIURE KJIE_ IOEII_ 1\t:UIJI'ERY_ FUNER1\.L_ OIIVES_ IWl'ON __ INCESI' S'lrol
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APPENDIX F AR SUBJECT INSTRUCTIONS ARCOSAL USUALLY REFERS 'IO AN INI'ERNAL FEELING WE EXPERIENCE IN RESFONSE 'ID EMJI'IONAL OR SHOC'.KING INFORMATION. SOOE TIBES WE FEEL AN INCREASE IN OUR INrERNAL AROOSAL FRCM }OSITIVE EVENTS, LIKE WINNING A C01PEI'ITION, AND OTHER TIBES WE EXPERIENCE AN INCREASE IN ARa.JSAL 'ID NEXiATIVE EVENTS, SUOI AS Lo.SING A ro1PEI'ITI0N. THEREFORE, REX:;ARDI.FSS OF WHEil-IER THESE EVENTS ARE FDSITIVE OR NEXiATIVE, OUR INrERNAL FEELING OF .ARaJSAL INCREASES AS A RESUilI' OF 'IlIEM. ON THIS NEXT TASK, I \UJ1D LIKE YOO 'IO RATE S01E OOROO ACCORDING 'ID HCM .ARaJSING 'IlIEY ARE 'ID YOO. PI.EASE 00 THIS AS QUICKLY AS YOO CAN USING THE FOILCMING 5 ro:rnr SCAI.E (FOINr): IF A OORD MAKES YOO FEEL LI'ITIE OR NO QIANGE IN YOUR INrERNAL .ARaJSAL, YOO MIGHI' RATE IT CLOSE 'ID A 1 (FOINr). ON THE OTHER HAND, A OORD '!HAT IS VERY ARCUSING 'IO YOU MAY RECEIVE A SOORE CI.OSER 'IO 5 (FOINI'). aIHER OOROO MAY FALL BE'IWEEN THIS RANGE FRCM 1, MEANING NO .ARaJSAL, 'ID 5 MEANING HIGH .ARaJSAL (FOINr). REMEMBER '!HAT AN ARCOSING w::>RD, LIKE AN EVENT, CAN BE EITHER FDSITIVE OR NEGATIVE. 111
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APPENDIX G SAM AROUSAL RATING GUIDE
PAGE 121
5 4 3 2
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APPENDIX H AR RECOGNITION LIST l\MBITION_ srAB_ PRIFBT SOD'.Hi_ BRCYIH_ CARRY_ INCFBT __ ACIOR DEFINE PAIR_ AIDS_ DIVORCE FUNETh\L nlIDE_ JESUS_ IWUO_ KIIL_ MDL'l'ERY REl'IRE_ srAIN_ IJJNCH_ RELIGION VIRGIN_ :rus 'IlrnoNE IDEA_ QUVFS_ PREVIEW &\'JON GlDRY_ FATHER_ HF'.J\VEN_ ROBBERY_ GARAGE_ (X)lONY __ IUJQJET_ Fil\SJ<,__ HONESTY_ S1ROKE_ Bioor_ VCMIT_ SOOR_ WRITE_ ~L_ ENEMA_ JIUS&\ND_ NUMBER_ 001'1\MY_ WAR_ MUTIIATE MEDICINE __ FECTS_ Pl\IN_ AfJE{_ ASSJ\ULT SURGERY_ IMPACf_ Bt\STJ\RD_ MJNKEY_ SODIUM_ a!OIR_ MISSION SCAB_ lli\NCE INSANE_. FRICITON_ PIB[X;E C01MIE_ SCIENCE_ CJ\MP_ SOIOIM_ Sl1EF1l_ a::.MBll.T_ BJr1U1_ anm_ 5rl\NCE_ MENU_ Tl\XES __ SEX __ l\OCIDENf_ FroST_ FIDrusr HIT_ CDRI'SE MlJroJS METRIC GOD_ WHE_ ~HK_ 01\.SIS AMFUI'A'IE TIMBER_ BI'IGI_ CRYbi'AL rusr_ PINT_ Rl\PE CillSE'l'. I1JI'l'ERY_ MJIBsr __ Ml\.TERIAL OOITT'GAGE_ rumu:_ 'l'EMFO_ STABIB_ SLAVE_ Sl\Tl\U l\lffllEM_ l\wtrING FRJ\CltJRE SORES_ HERPF.S __ vnlOR.S ___ WEDDING CASTAA'l'E MlJIB_ TIDE TRADE ___ CAMERA ClJL'IURE __ 114
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BIOGRAPHICAL SKETCH Philip Andrew Hanger was born in Cherokee, Iowa, on June 19, 1961. He received his Bachelor of Science degree with honors in psychology from the University of Iowa in May, 1984. He received his Master of Science degree from the Graduate School of the University of Florida in May, 1987. His major field of study was clinical psychology, with a minor focus in neuropsychology. 126
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I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is. fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. Russell M. aiuer: Ph.D. Associate Professor of Clinical and Health Psychology I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. Eileen B. Fennell, Ph.D. Professor of Clinical and Health Psychology I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. Dawn Bowers, Ph.D. Associate Professor of Clinical and Health Psychology I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. Anthony G:reene7 Ph.D. Assistant Professor of Clinical and Health Psychology
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I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is.fully adequate, in scope and quality, as a dissertation for the degre f actor of Philosophy. Edward Valenstein, M.D. Professor of Neurology This dissertation was submitted to the Graduate Faculty of the College of Health Related Professions and to the Graduate School and was accepted as partial fulfillment of the requirements for the degree of Doctor of Philosophy. August, 1989 Dean, College of Health Related 7/lons D~an, Graduate School
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