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We studied the latencies, amplitudes, and scalp distributions of the early and late components of the event-related brain potential (ERP) in patients with progressive supranuclear palsy (PSP) and matched normal controls. In separate choice reaction time (RT) tasks, the subjects pressed buttons to visual stimuli presented randomly at probabilities of either 20/80 or 50/50. Compared with normal controls, PSP patients had significantly reduced amplitudes and increased latencies for both the visual P2 and P300 components at all levels of probability. RTs and percent errors were significantly greater in the patients compared with controls. Neither the amplitude nor latency of the visual N1 component was significantly altered in these patients. There were no significant group differences in the distribution of electrical activity over the scalp for any of these ERP components, a finding which suggests that the neural structures responsible for generating these potentials were intact in these patients. The decreased ERP component amplitudes and increased ERP component latencies, combined with intact scalp distributions and increased RTs and error rates, present a pattern of results suggesting that the stimulus identification or categorization processes in these patients are significantly degraded.

We examined script and lexical retrieval in patients with probable Dementia-Alzheimer's Type (DAT), Depressed patients, and normal controls. DAT patient breakdown in script production was structurally similar to their impaired lexical retrieval such that script events of low frequency and low centrality value were lost first. DAT patients also produced more events that fell outside the script boundary as well as more event-order errors. Four cases with DAT were identified on the basis of Z scores whose script production was at least 2 SDs greater than their lexical production or vice versa. This finding suggests that it may be possible to dissociate script and lexical knowledge and production processes. The findings lend partial support for a model of knowledge representation that includes parallel and partially redundant memory networks that are distinctly distributed in the brain.

We recorded event-related brain potentials (ERPs) from 2 groups of human immunodeficiency virus (HIV)-positive men with no physical illness or neurologic involvement: 9 asymptomatic (AS+) and 9 classified as having either acquired immunodeficiency syndrome (AIDS; 7) or AIDS-related complex (ARC; 2). In separate choice reaction time tasks, the subjects pressed buttons to randomly presented auditory or visual stimuli at probabilities of either 20/80 or 50/50. There were no group differences on any of the neuropsychological tests commonly used in screening batteries for HIV patients. In contrast, reduced P300 amplitudes and increased P300 latencies occurred in ARC/AIDS patients in response to both auditory and visual stimuli, while in AS+ patients such alterations occurred only in the visual modality. Significant delays in P2 latency were found only in the auditory modality and then only in ARC/AIDS patients. ARC/AIDS patients alone showed delayed response times, and only in the auditory modality. The P300 results demonstrate alterations in stimulus evaluation and processing speed in the earliest stages of HIV disease, even before cognitive deficits can be detected by more traditional measures.

Body schema disturbances were studied in a 62-yr-old woman with Alzheimer's disease. She was severely impaired in verbal and nonverbal tasks requiring her to localize body parts (on her own body, the examiner's body or a doll's body) even though she correctly named the same parts when pointed at by the examiner. Pointing responses were misdirected mainly to parts contiguous with the target area and, to a lesser extent, to functionally equivalent body parts. We also found that the patient was able to define body part names functionally but not spatially. In another series of tasks, and in contrast to the above results, performances were normal when small objects, attached to the patient's body, served as pointing targets. Furthermore, on subsequent testing she pointed correctly at the remembered position of these objects. The fact that the same point in 'body space' is localized correctly when it corresponds to an external object and erroneously when it corresponds to a body part contradicts the idea of the body schema as a unitary function. Learning the position of objects on the body surface requires access to some form of body-reference system on which this information can be mapped. We argue that such a system can be available in autotopagnosia and is independent from the visuospatial representations of the body structure that are postulated to be damaged or inaccessible in this syndrome. An integrated account of the present results and of those reported by other authors suggests that multiple levels of representation (e.g., sensorimotor, visuospatial, semantic) are involved in the organization of body knowledge.

In this paper the cognitive and psychiatric impairments associated with chronic fatigue syndrome (CFS) and related disorders are reviewed. It is concluded that while acute mononucleosis and infection with Epstein-Barr virus occasionally result in impaired cognition, such changes have not yet been objectively verified in patients with CFS. However, when patients with CFS are carefully studied, concurrent or premorbid psychiatric disorders are revealed at a greater than chance level. Finally, some suggestions are offered regarding improved neuropsychological assessment of fatigue, concentration, and attention for patients with CFS. The findings to date, while suggesting that psychological predisposition may play a role in the expression of CFS, are still inconclusive regarding the etiology of CFS.

The purpose of this study was to determine if patients with focal hand dystonia have any significant psychopathology. We studied 20 patients with hand cramps who were participating in a therapeutic trial of botulinum toxin injections. Patients were interviewed and administered the Minnesota Multiphasic Personality Inventory (MMPI). Beck Depression Inventory, Spielberger State-Trait Anxiety Scale, a finger tapping test, and a choice serial reaction time test. Behavioral ratings were also obtained. Group statistics indicated that all personality scale scores and performances on motor tasks were within normal limits. Four out of 20 patients demonstrated mild depression. Trait anxiety scores were higher than state anxiety scores, suggesting that receiving medical treatment had a beneficial effect on mood. The number of depressive symptoms endorsed on the MMPI was correlated with reaction time speed but not finger dexterity. None of the 20 patients reported a remarkable psychiatric history. These results indicate that hand cramps are not associated with serious psychopathology.

We examined Wisconsin Card Sorting Test performance in a large group of brain-damaged patients and controls. No differences were found between patients with frontal lesions only and those with nonfrontal lesions. Patients with left dorsofrontal and anterior temporal lobe lesions committed the most perseverative errors. More analyses regarding requirements for information processing on the Wisconsin Card Sorting Test are needed.

Two patients with moderately severe AD, when asked directly, could identify their own images in a mirror, but also consistently misidentified their own reflections as that of another person. Both patients were paranoid and mildly depressed at times, but had no evidence of other concurrent psychotic symptoms. It appeared that mood substantially modified the nature of the symptom and the patients' reaction to it over time. These cases illustrate the ability of an organic symptom to be modified by a concurrent affective state, indicating the importance of the interaction between biological and psychological factors in the expression of such symptoms.

We examined patients with Dementia-Alzheimer's Type, depression, and matched controls on tasks designed to compare automatic (monitoring frequency and modality) and effortful (free recall) processing of words and pictures. The results demonstrated that depressed patients performed poorly only when conditions required effortful processing, but DAT patients performed poorly under all conditions. There was almost no overlap in scores between DAT and elderly depressed patients on one of the measures of automatic processing suggesting that this measure may be clinically useful. The results suggest that automatic memory processes can be partially dissociated from effortful memory processes, but that both types of operations are impaired in DAT patients.

Performance on tasks evaluating "executive and attentional" processes presumably subserved by prefrontal cortex were compared in patients with progressive supranuclear palsy and with age- and education-matched control subjects. The results indicated that patients with progressive supranuclear palsy were particularly impaired when a task required sequential movements, conceptual shifting, monitoring the frequency with which stimuli are presented, or rapid retrieval of verbal knowledge. These deficits could not simply be accounted for by slowed information processing or by a deficit in representational knowledge. Conceivably, "weak activation" of frontal lobe representational knowledge characterized by an observed attentional deficit results in the neuropsychological impairments noted in patients with progressive supranuclear palsy. The oral administration of physostigmine, under double-blind placebo-controlled conditions, did not facilitate executive or attentional performance as evaluated by our tasks.

We examined implicit memory using priming and procedural learning tasks in patients with probable Dementia-Alzheimer's Type (DAT) to examine whether priming and procedural processes could be dissociated and whether task specificity was a factor in DAT patient performance. Priming was tested using a word recognition paradigm (perceptual priming) and by repeated administrations of a fragmented objects test (long term priming). Procedural learning was tested using repeated and random sequences on a choice serial reaction time task and by repeated administration of a puzzle map of the United States. DAT patients were compared to hospitalized depressed patients, patients suffering from Progressive Supranuclear Palsy (PSP), and normal controls. We found that DAT patients demonstrated marginal but significant implicit learning on both procedural learning and perceptual priming tasks. DAT patients performed relatively better on the procedural learning task than a perceptual priming task compared to PSP patients, suggesting that priming of meaningful stimuli is subserved by cortical structures whereas procedural motor responses to simple serial visual stimulus patterns can be maintained by subcortical systems. Furthermore, our findings suggest that priming and procedural processes can be dissociated and that task specificity is a factor in interpreting the results of implicit learning paradigms in DAT patients. The implications of these results for models of knowledge representation and memory processes as well as the way they can serve as models for testing nootropic drug effects are discussed.

We have tested a simple and reliable measure of visuospatial ability in Alzheimer patients--the Clock Drawing Test. To determine the usefulness of this measure, we asked 67 Alzheimer patients and 83 normal controls to draw the face of a clock reading the time of 2:45. Six independent observers blindly evaluated the results with ratings from 10 (best) to 1 (worst). The mean performance score of Alzheimer subjects was 4.9 +/- 2.7 compared to 8.7 +/- 1.1 for normal controls (P less than .001). Inter-rater reliability for the clocks drawn by Alzheimer patients was highly significant (r = 0.86; P less than .001), and there was relatively little overlap between ratings for Alzheimer patients and normal controls. Furthermore, correlations were highly significant (P less than .001) between the mean score of clock drawings and three independent global measures of dementia severity. Although the Clock Drawing Test is certainly not a definitive indicator of Alzheimer's disease, the test is easy to administer and provides a useful measure of dementia severity for both research and office settings where sophisticated neuropsychological testing is not available.

Memory may fail in a variety of ways. Patients with Korsakoff's syndrome demonstrate global memory deficits similar to those seen in patients with early progressive dementia. Korsakoff's patients, however, may recall rules and principles for organizing information and can gain access to their previously acquired knowledge (semantic memory), whereas recent memory may be grossly impaired. In contrast, dementia patients may have little access to previously acquired knowledge and therefore have great difficulty in organizing and encoding ongoing events. These contrasting forms of memory failure have implications for understanding the structure and mechanisms of memory and learning, particularly the relationship between episodic and semantic memory, as well as the development of therapeutic strategies for cognitive impairments.

Ten subjects exhibited acquired stuttering that had persisted for 10 to 15 years following penetrating missile wounds sustained during the Vietnam War. None had a history of developmental or chronic adult stuttering. In comparison with other head-injured subjects and normal control subjects, the subjects with acquired stuttering had significant deficits in skilled rapid hand movements and oral and speech movements, suggesting a motor control disorder. The identified brain lesions of the acquired stuttering group were on the right in 5 subjects, on the left in 4, and bilateral in 1. The internal and external capsules, the frontal white matter, and the striatum were more frequently involved in the acquired stuttering group than in other head-injured subjects (p less than or equal to 0.05). This speech rhythm and rate disorder was not associated with evident cortical lesions in either hemisphere but with predominantly unilateral lesions of the subcortical pyramidal and extrapyramidal systems.

Persistent memory problems were reported by a 39-year-old man who suffered a penetrating brain wound while serving in Vietnam 15 years earlier. Neuropsychological testing indicated an unusually isolated memory impairment. Computed tomography revealed transection of the columns of the fornix cerebri with no temporal-lobe involvement and minimal thalamic damage. We suggest that the fornix cerebri has a role in the maintenance of information accessibility to both encoding and recall during post-working memory processing and in the organization of verbal information during encoding and/or retrieval for declarative (recall) purposes. These processes are not essential for verbal recognition but can result in decrements on specific laboratory tasks and in social adjustment.

Four patients with human-immuno-deficiency-virus-associated neurological disease were treated with 3'-azido-3'-deoxythymidine (AZT). Three (two with chronic dementia, and one with chronic dementia and peripheral neuropathy) improved as assessed by clinical examination, psychometric tests, nerve conduction studies, and/or positron emission tomography; there was no improvement in the fourth patient who presented with paraplegia. These results support the hypothesis that certain AIDS-virus-associated neurological abnormalities are reversible by antiretroviral chemotherapy.

Some patients with multiple sclerosis (MS) demonstrate impaired memory. A group of 16 patients with MS who were mildly to moderately affected (Kurtzke Expanded Disability Status Scale Score = 3.8) were studied, and they were compared with a matched control group on tests of "working memory." The working memory system was explored by evaluating the amount of information that can temporarily be held in a buffer system during encoding. Results indicated that patients with MS have difficulty in processing information at the level of a hypothesized articulatory loop in working memory. This deficit was correlated with their retrieval of verbal information from long-term memory, as well as how accurately they processed verbal information presented at a rapid rate. There was no significant relationship between ratings of MS severity or number of plaques visualized on magnetic resonance imaging scans and the degree of working memory deficit.

We compared the neurologic and cognitive performance of 15 young veterans who suffered unilateral penetrating missile wounds to the basal forebrain 15 years ago in the Vietnam War with uninjured controls and patients with lesions elsewhere in the brain. The subjects performed worse on tests of episodic memory, reasoning, and arithmetic and had more prolonged unconsciousness after injury; but their performance usually compared favorably with that of uninjured controls on tests of intelligence, attention, and language and was not consistent with that of a demented patient. The data suggest that the basal forebrain is functionally related to the reticular formation and to the basal forebrain is functionally related to the reticular formation and to the limbic-hippocampal memory system.

Since symptoms of chronic dissociative disorders such as multiple personality disorder (MPD) may be shared by patients with seizure disorders, we investigated the possible relationship between dissociative states and epilepsy. We monitored 6 MPD patients with intensive video-EEG recordings to determine whether epileptic phenomena have any correlation to the dissociative symptoms experienced by these patients. Previously, physicians had diagnosed epilepsy in all 6 patients; however, none proved to have epilepsy. In addition, we studied dissociative symptoms in 71 epileptic patients with the aid of a standardized questionnaire, the Dissociative Experiences Scale, and compared them with age-matched controls. While the group median score of cases with complex partial seizures was higher than that of normal controls, it was significantly lower than that of the psychiatric patients with MPD. Partial seizure patients with dominant hemisphere foci had higher depersonalization subscale scores than those with nondominant foci. Our data suggest that epilepsy is not a primary pathophysiologic mechanism for developing dissociative symptoms.

Among 342 men who survived severe penetrating brain wounds, only 15% had prolonged unconsciousness and 53% had no or momentary unconsciousness after injury, emphasizing the focal nature of these wounds. The left (or language-dominant) hemisphere was dominant for the "wakefulness" component of consciousness. The areas most associated with unconsciousness included the posterior limb of the left internal capsule, left basal forebrain, midbrain, and hypothalamus. Left dominance was not seen for posttraumatic amnesia after elimination of the wakefulness variable, suggesting that wakefulness may be linked to the role of the left hemisphere in verbal memory.

Of 421 veterans who had penetrating brain wounds in Vietnam 15 years ago, 53% had posttraumatic epilepsy, and one-half of those still had seizures 15 years after injury. The relative risk of developing epilepsy dropped from about 580 times higher than the general age-matched population in the first year to 25 times higher after 10 years. Patients with focal neurologic signs or large lesions had increased risk of epilepsy, and site of the lesion may have been more important than size in determining occurrence. Family history of epilepsy or preinjury intelligence had no effect on seizure occurrence. Seizure frequency in the first year predicted future severity of seizures. Phenytoin therapy in the first year after injury did not prevent later seizures.

Verbal memory was compared in 12 patients with progressive supranuclear palsy and 12 healthy control subjects matched for age, sex, and education. Learning, consolidation, and retrieval were significantly impaired in patients with progressive supranuclear palsy. Information scanning, which requires the use of short-term memory processes, remained intact. Duration of symptoms and degree of motor dysfunction correlated with intrusions during learning. No relation between central dopamine metabolism and memory dysfunction could be established.

Sixteen patients with a definitive diagnosis of multiple sclerosis (MS) and an equal number of matched controls were administered tests of memory and information processing speed. Results indicated a significant long-term verbal memory impairment in patients with MS, with spared short-term memory and memory scanning. Speed of information processing was evaluated with the Paced Auditory Serial Addition Test. The results for the two highest rates of presentation revealed significantly impaired processing in the MS group. Performance at the higher rates and retrieval of information from long-term memory were significantly correlated. These results suggest that slowed information processing is a deficit that contributes to long-term memory impairment in patients with MS.

We examined the relationship of preinjury intelligence, a lesion-severity variable (brain-tissue loss volume), and lesion location to the persistence of cognitive deficits in Vietnam veterans with penetrating brain wounds. Using stepwise multiple linear regression procedures, we found that preinjury intelligence predicted a significant amount of the variance on postinjury cognitive testing, being a better predictor for tests requiring a number of complementary cognitive processes (e.g., intelligence tests) than for tests measuring a specific cognitive process (e.g., face recognition). Brain-tissue volume loss was found to play a larger role when a global cognitive measure was used, but a smaller role when a specific cognitive process was measured. Finally, lesion location was shown to be a significant predictor of performance only for specific cognitive processes. Nevertheless, preinjury intelligence/education appears to play an even larger role in postinjury performance than either brain-tissue loss volume or a particular structural loss.

The extent to which intellectual processes are preserved as a function of preinjury 'intelligence' and of size and location of the brain lesions was evaluated in Vietnam war veterans who survived penetrating missile wounds. With regard to an overall postinjury intelligence test score, preinjury intelligence was most predictive, size of lesion was next most predictive and lesion location was least important. For subtest scores from the same intelligence test, lesion location assumed much greater predictive value. Specifically, left temporal and occipital lesions impaired performance on subtests assessing vocabulary and object-function matching ability.

We examined a retired Army General with Progressive Dementia whose initial major presenting complaint was dyscalculia. Our examinations revealed an orderly dissolution of calculation ability with differing dissociations in calculation ability apparent at progressive stages of cognitive decline. For example, we found that number reading and writing errors were qualitatively different from calculation errors. Numerosity knowledge and magnitude comparisons can remain intact even when other arithmetic knowledge and calculation abilities were grossly impaired. His decline in calculation abilities was first demonstrated on more complex problems (e.g., multiplication) and only in later stages on simpler (e.g., addition) problems. The patient was aware that aspects of his performance were impaired, but he was unable to state why--a dissociation between declarative and procedural knowledge.

This article describes the long-term effects of unilateral penetrating hemispheric lesions on contralateral and ipsilateral upper extremity motor performance and functional outcome. Activities-of-daily-living skill and gross motor performance contralateral to the lesions were compared among 32 left-sided and 19 right-sided hemiplegic subjects using analysis of variance and chi-square techniques. Ipsilateral to the damaged hemisphere, fine motor tasks of simple visual motor reaction time, grip and pinch strength, finger tapping, and Purdue Pegboard performance were tested. Analysis of covariance compared each ipsilateral task to performance in the corresponding hand of 70 matched controls. Results indicate similar long-term functional ADL outcome in right and left hemisphere-damaged subjects, despite more severe contralateral functional motor deficits following lesions of the left hemisphere. Right hemisphere lesions led to ipsilateral decrements in reaction time, and lesions of either hemisphere diminished grip or pinch strength, finger tapping, and pegboard performance ipsilaterally. These results demonstrate that unilateral brain damage involving the motor areas of either hemisphere has detrimental effects on ipsilateral upper extremity motor function. Findings are discussed and related to the concept that the left hemisphere is specialized or has greater neuronal representation for bilateral motor processes. Physical therapists involved in the treatment of patients with hemiplegia should be aware that motor functions of the ipsilateral, nonparetic upper extremity may also be affected adversely by unilateral brain lesions.

A group of Vietnam veterans with penetrating brain wounds to the orbitofrontal, dorsofrontal, and nonfrontal cortex were compared with a stratified control group of self-report and observed measures of mood state and cognition. In particular, hypotheses regarding the regulation of anxiety by frontal cortical mechanisms were evaluated. Results indicated that patients with right orbitofrontal lesions were prone to abnormally increased 'edginess'/anxiety and depression, whereas patients with left dorsofrontal lesions were prone to abnormally increased anger/hostility. A working model of mood state regulation is presented which represents the thesis that mood sensations are subject to numerous cognitive and biological influences that result in a variety of expressions of a particular mood disorder.

Acalculia is a loss of calculating abilities occurring as a result of cerebral damage. This paper reviews the development of the notion of acalculia from an expected concomitant of aphasia or dementia to that of a sometimes autonomous disorder. Current evidence indicates that acalculia tends to occur particularly in lesions of the left posterior hemispheric areas.

This study was designed to examine the effects of penetrating head injury upon face discrimination and memory in 213 brain-injured Vietnam veterans and 49 normal controls. Impairment on tests of face memory was most associated with bilateral lesions and with unilateral lesions of the temporal lobe. Impairment on a test of face discrimination was most associated with right hemisphere, and with bilateral lesions which included either frontal or parietal lobe involvement. Performance on these tasks appeared independent of other visuospatial or verbal tasks. Cluster analysis revealed a dissociation between performance on facial memory and facial discrimination tasks.

3'-Azido-2',3'-dideoxythymidine (AZT) has been administered to 7 patients with human immunodeficiency virus-associated neurological disease: 3 with dementia, 2 with peripheral neuropathy, 1 with dementia and peripheral neuropathy, and 1 with T-10 paraplegia. Six of the patients showed improvement in their neurological dysfunction on being administered AZT, as assessed by clinical evaluation, neuropsychological testing, nerve conduction studies, and/or positron emission tomographic scans. Three of these 6 patients showed sustained improvement 5 to 18 months after the initiation of AZT therapy. These results suggest that certain human immunodeficiency virus-associated neurological abnormalities are at least partially reversible following the administration of antiretroviral therapy and provide a rationale for further studies using antiretroviral chemotherapy.

It has been suggested that hemisphere-damaged patients with calculation disorders can be subdivided into 3 groups: agraphia or alexia for numbers, spatial dyscalculia and anarithmetia. The purpose of the present study was to evaluate the role played by visuospatial disorders and by anarithmetia in subjects with impaired calculation abilities. Seventy-six patients with focal hemispheric lesions and 26 normal controls with demonstrated ability to read and write numbers were given a written calculation task, the Token Test, the Crosses Test, a test of Constructional Apraxia and Raven's Progressive Matrices. In the calculation task, a quantitative score represented the number of digits that were correct numerically and put in correct position. A qualitative score with emphasis on visuospatial factors was obtained by scoring each problem with the criteria used in Benton's Visual Retention Test. Analysis of the results showed that both left and right hemisphere-damaged patients performed significantly worse than controls and that patients with left posterior lesions were particularly impaired even after correction of the acalculia scores by the results of the other neuropsychological tests. These results suggest that even though different factors may contribute to calculation disorders (impairment of intelligence, visuoconstructive difficulties and above all aphasia), left posterior lesions are particularly prone to produce an impairment in calculating abilities which is partially independent from the above disorders.

The relationship of preinjury left-hand dominance for motor performance to postinjury distal motor skills following penetrating brain wounds in patients without overt hemiplegia was examined. We studied 13 controls, 13 right-hemisphere brain-damaged patients, and 11 left-hemisphere brain-damaged patients on motor tasks measuring reaction time, strength, and coordination. Our results indicated that no persistent deficits were seen on distal motor tasks in left-handed adults who suffered a penetrating brain wound. These findings are compatible with the relative sparing of persistent neuropsychological deficits in left-handers following brain damage.

Using data derived from a 15-year follow-up study of 520 veterans surviving penetrating brain wounds received in the Vietnam war, we have developed a predictive formula and tables for posttraumatic epilepsy based on time elapsed postinjury and presence of specific clinical and computed tomographic scan risk factors. Such patients remain at some increased risk for epilepsy even ten to 15 years postinjury, although most can be 95% certain of avoiding epilepsy if they have been seizure free for three years posttrauma. Epilepsy onset latency was independent of any risk factors identified.