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Dissociation between medial temporal lobe and basal ganglia memory systems in schizophrenia.

The purpose of this study was to investigate basal ganglia (BG) and medial temporal lobe (MTL) dependent learning in patients with schizophrenia. Acquired equivalence is a phenomenon in which prior training to treat two stimuli as equivalent (if two stimuli are associated with the same response) increases generalization between them. The learning of stimulus-response pairs is related to the BG, whereas the MTL system participates in stimulus generalization. Forty-three patients with DSM-IV schizophrenia and 28 matched healthy controls participated. Volunteers received the Rutgers acquired equivalence task (face-fish task) by [Myers, C.E., Shohamy, D., Gluck, M.A. et al., 2003. Dissociating hippocampal versus basal ganglia contributions to learning and transfer. J. Cogn. Neurosci. 15, 185-193.], the California Verbal Learning Test (CVLT), and the n-back working memory test. The Rutgers acquired equivalence task investigates BG-dependent processes (stimulus-response learning) and MTL-dependent processes (stimulus generalization) with a single test. Results revealed that patients with schizophrenia showed a selective deficit on stimulus generalization, whereas stimulus-response learning was spared. The stimulus generalization deficit correlated with the CVLT performance (total scores from trials 1-5 and long-delay recall), but not with the n-back test performance. The number of errors during stimulus-response learning correlated with the daily chlorpromazine-equivalent dose of antipsychotics. In conclusion, this is the first study to show that patients with schizophrenia exhibit deficits during MTL-dependent learning, but not during BG-dependent learning within a single task. High-dose first generation antipsychotics may disrupt BG-dependent learning by blocking dopaminergic neurotransmission in the nigro-stiratal system.

Adult↗

Impact of executive dysfunctions on episodic memory abilities in patients with ruptured aneurysm of the anterior communicating artery.

Executive and memory dysfunctions are among the most frequently reported deficits following a ruptured aneurysm of the anterior communicating artery (ACoA). In order to study the impact of the dysexecutive syndrome on episodic and semantic memory, the data obtained from 59 ACoA patients were examined retrospectively. All patients were assessed on a variety of episodic memory tests (Rey Auditory-Verbal Learning Test, Rey Complex Figure Test, Weschler Memory Scale), semantic memory (verbal fluency), and standardized tests of executive functions (Trail Making Test, Maze tests, Wisconsin Card Sorting Test). There was a strong positive correlation between executive dysfunction and retrieval difficulties in episodic and semantic memory tasks. Comparisons of subgroups of patients with high and low frontal lobe functioning on delayed recall and recognition revealed a significant group X condition interaction in addition to significant group and condition main effects. ACoAs patients with low frontal lobe functioning were particularly deficient in free recall (immediate and delayed) while recognition was equally well preserved in the two subgroups. Neither subgroup presented with an abnormal forgetting over time suggesting a retrieval deficit rather than a true retention impairment.

Adult↗

Normative data for eight neuropsychological tests based on a Danish sample.

Normative neuropsychological data have been provided using a sample of 101 persons aged 20 to 54 years. Eighty-seven of the subjects were recruited among patients who had undergone minor surgery, and 14 subjects were volunteers from the staff at the hospital laundry. The measures consisted of seven subjects from the WAIS-R, the trail-making test, symbol digit modalities test, auditory-verbal learning test, story recall test, visual gestalt test, recurring figures test, verbal fluency, and Purdue pegboard test. These measures were selected because of suitability in regard to time taken for testing each subject and their sensitivity to subtle changes in neuropsychological functioning. The sample was arbitrarily divided into three age groups, and for each of the three samples, mean, standard deviation, and range were calculated for each test. The results of the Information and Vocabulary subtests from the WAIS-R, education, and social status were applied as independent variables in linear regression analyses where each of the neuropsychological tests, in turn, was the dependent variable. For the oldest age group, age in addition was used as an independent variable. Significant linear relationships, which accounted for an optimal part of the variance, were selected for clinical application.

Adult↗

Zonisamide (CI-912) and cognition: results from preliminary study.

Nine patients with refractory partial seizures were evaluated in a pilot study of a new anticonvulsant compound, zonisamide (1,2-benzisoxazole-3-methanesulfonamide; CI-912). Cognitive functioning was evaluated prior to treatment with zonisamide and repeated after 12 and 24 weeks of treatment with zonisamide. At minimum steady-state plasma concentrations greater than 30 micrograms/ml, zonisamide appeared to affect specific cognitive functions such as acquisition and consolidation of new information. Previously learned material, such as vocabulary, and psychomotor performance were not affected. Verbal learning was affected, while visual-perceptual learning was unimpaired. These cognitive effects were observed in the absence of the usual clinical signs and symptoms of toxicity. A linear relationship was found between impairment of cognitive abilities and the minimum plasma concentration (r = -0.73; p less than 0.05). Findings also suggest the development of tolerance to the adverse cognitive effects.

Adult↗

Gender differences in memory and learning in children with insulin-dependent diabetes mellitus (IDDM) over a 4-year follow-up interval.

OBJECTIVE: To examine demographic and disease predictors of memory and learning performance for children with diabetes and controls. METHOD: Children with diabetes (N = 95) and demographically similar control children (N = 100) were administered the Rey Auditory Verbal Learning Test (RAVLT) initially and 4 years later. RESULTS: Unlike other groups, boys with diabetes did not make expected developmental gains on the learning trials of the RAVLT. Boys with diabetes showed a plateau in words learned from the primacy position, and girls with diabetes appeared to lose their relative gender advantage for verbal information. Longer disease duration predicted poorer learning over time. CONCLUSIONS: Subtle difficulties were found in learning related to longer disease duration for a predominantly middle-class group of children with diabetes over a 4-year follow-up interval. It will be important to monitor children's educational development to help avoid a cumulative toll on classroom performance.

Adolescent↗

Exploring cognitive complaints in schizophrenia: the subjective scale to investigate cognition in schizophrenia.

While it has become commonplace to test the various components of memory in schizophrenia with paper-and-pencil or in-lab tasks, very little data exist on the subjective complaints of patients regarding their memory. Few instruments have been designed to collect systematically the complaints of patients with schizophrenia. We present a work in progress on the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS), a 21-item, Likert-type scale that is simple and easy to use. It allows a quantitative approach to the subjective and cognitive dimensions of schizophrenia. Stip constructed the scale based on a questionnaire covering several cognitive domains: memory (working memory, explicit long-term memory), attention (divided, distractibility, alertness, sustained), language, and praxia. We evaluated the psychometric properties of the SSTICS in a population of 114 French-speaking patients in Montreal. Patients were recruited in the community and assessed with the Structured Clinical Interview for DSM-III-R (SCID), the Positive and Negative Syndrome Scale (PANSS), and the Extrapyramidal Symptoms Rating Scale (ESRS). Cognition was measured using the Rey Auditory Verbal Learning Test (RAVLT) (long-term memory), Controlled Oral Word Association Test (verbal fluency), and Trails A and B. Preliminary analyses showed very good internal consistency for the global score (alpha=0.88), and alphas varying from 0.57 to 0.72 for the subscales. Stability over time was very good. The principal components analysis accounted for a multiple structure. Correlations between subjective scores and objective cognitive assessment were significant for several domains. Validation of the SSTICS needs to be completed through further exploration of the factorial structure and testing of the English version.

Adult↗

Prenatal tobacco effects on neuropsychological outcomes among preadolescents.

This study evaluated the relationships between maternal smoking during pregnancy and 10-year-old children's performance on measures of learning, memory, and problem-solving. In this prospective cohort study, mothers were recruited from an urban prenatal clinic in 1982 and 1983 and observed from their fourth prenatal month until the time of the study. At the 10-year visit, 593 children and mothers were evaluated. The prevalence of tobacco use was high in this cohort: 54.3%, 53.3%, and 60% of the women smoked in the first trimester, third trimester, and 10-year assessment, respectively. After controlling statistically for other prenatal substance use, current tobacco, other substance use variables, and multiple sociodemographic covariates, prenatal tobacco exposure was significantly associated with deficits in learning and memory. Specifically, prenatal tobacco exposure was associated with deficits in verbal learning and design memory, as well as slowed responding on a test of eye-hand coordination. In addition, these children demonstrated a reduced ability for flexible problem solving and more impulsivity, as indicated by an increase in perseverative responses on a card-sorting test. Prenatally exposed children did not show attention deficits or increased activity on a continuous performance test.

Adult↗

Learning in Parkinson's disease: eyeblink conditioning, declarative learning, and procedural learning.

OBJECTIVE: To assess the degree of learning ability in Parkinson's disease. METHODS: Three different learning tasks: eyeblink classical conditioning with delay and trace paradigms, the California verbal learning test (CVLT), and a serial reaction time task (SRTT) were studied in patients with Parkinson's disease and normal (control) subjects. RESULTS: In the eyeblink conditioning tasks, both patients and normal subjects showed significant learning effects without between group differences. In the CVLT, patients remembered significantly fewer words than normal subjects in both short term and long term cued recall tasks. In the SRTT, normal subjects had significantly reduced response time and error rates across blocks of repeated sequence trials, whereas patients had significantly reduced error, but not response time rates. CONCLUSION: Impairment of nigrostriatal pathways selectively affects performance in complex learning tasks that are competitive and require alertness such as the SRTT, but not in simple learning procedures such as eyeblink conditioning.

Adult↗

Loss of spatial learning in a patient with topographical disorientation in new environments.

The case is described of a patient who, following cerebral hypoxia, developed severe difficulty in orienting himself in new environments in the context of a mild global amnesic syndrome. Some episodes he related suggested that his main difficulty was remembering the spatial/directional value of landmarks he recognised. A neuroradiological examination documented severe bilateral atrophy of the hippocampi associated with atrophic changes in the cerebral hemispheres, most marked in the dorsal regions. Neuropsychological and experimental evaluation showed a severe deficit of spatial learning with substantially preserved ability to learn verbal and visual-object information. He was also virtually unable to learn a route in a maze task based exclusively on spatial data, but the availability of visual cues substantially improved his learning. Finally, he performed within normal limits on various tests investigating knowledge acquired premorbidly regarding famous buildings, routes in the town he had been living in since childhood, and geography. Topographical disorientation may be subtended by a specific difficulty in storing the spatial/directional value of visual landmarks in novel environments. The hippocampus appears to be involved in the acquisition of new topographical spatial knowledge.

Adult↗

The relationship between semantic organization and memory in obsessive-compulsive disorder.

BACKGROUND: A variety of evidence suggests that frontostriatal dysfunction is involved in obsessive-compulsive disorder (OCD). This evidence includes both neuroimaging findings and results from studies using neuropsychological assessments. Previous studies have documented nonverbal memory deficits in individuals with OCD, whereas verbal learning and memory were less affected. METHODS: The present study examined both verbal and nonverbal memory in a sample of 17 untreated outpatients with OCD. We also evaluated the effects of encoding strategies which are believed to be mediated by frontostriatal system functioning. RESULTS: OCD patients were significantly impaired in both verbal and nonverbal memory performance. This deficit was correlated with impairments in organizational and semantic clustering strategies at the time of encoding. CONCLUSIONS: Deficits in organizational strategies are consistent with frontostriatal dysfunction models in OCD.

Adult↗

Verbal and visuospatial learning and memory function in children with moderate prenatal alcohol exposure.

BACKGROUND: This study investigated the effects of moderate prenatal alcohol exposure on learning and memory in 14-year-old adolescents. The Children's Memory Scale was used to assess learning and memory function in the verbal/auditory and visual/spatial domains. In addition, both short- and long-term memory function were assessed. METHODS: Data were collected as part of the Maternal Health Practices and Child Development Project, a longitudinal study including 580 children and their mothers. Women were assessed during each trimester of pregnancy and with their children from birth to 16 years of age. At age 14, memory function was evaluated using the Children's Memory Scale, an assessment tool that measures learning and immediate and delayed memory function in the verbal and visual-spatial domains. RESULTS: Prenatal alcohol exposure during the first trimester predicted deficits in learning, short-term memory, and long-term memory, specifically in the verbal domain. Deficits in performance were specific to learning and memory of word-pairs. In addition, deficits in memory were mediated by learning performance. CONCLUSIONS: Results demonstrated that prenatal alcohol exposure lead to deficits in encoding processes as indicated by deficits in verbal learning. Initial deficits in acquisition were responsible for deficits in immediate and delayed recall of verbal information in children who were exposed to alcohol during pregnancy but did not have fetal alcohol syndrome.

Adolescent↗

Theory of mind, neurocognition, and functional status in schizotypy.

The present study is the first to concurrently examine social cognition, neurocognition, and social functioning in psychometric schizotypes. Screening of 2108 undergraduates with the Schizotypal Personality Questionnaire-Brief (SPQ-B) identified 52 persons high in schizotypy and 40 persons low in schizotypy. All participants were administered a test battery designed to assess two elements of neurocognition, verbal secondary memory (California Verbal Learning Test) and executive functioning (Wisconsin Card Sorting Test), two elements of social cognition, emotion perception (The Awareness of Social Inference Test-Part 1) and theory of mind (The Awareness of Social Inference Test-Parts 2 and 3), and social functioning (Social Adjustment Scale-Self Report). Although the persons with high schizotypy were impaired in social functioning relative to the persons with low schizotypy, they were not impaired in theory of mind, emotion perception, verbal secondary memory, or executive functioning. Theory of mind and verbal secondary memory were correlated in persons with high schizotypy. The present findings suggest that psychometric schizotypes are not impaired in the domains of social cognition and neurocognition examined.

Adolescent↗

Nonverbal amnesia and asymmetric cerebral lesions following encephalitis.

Global amnesia after herpes simplex encephalitis has been typically associated with lesions of anterior and medial temporal lobe, inferior and medial frontal lobe, and insula. The neuropathologic correlates of this disease are usually considered to be bilateral and similar across cases. We describe a 27-year-old woman whose chronic amnesia and cerebral lesions after viral encephalitis indicate a different pattern. Two features distinguish her presentation: (1) markedly asymmetric lesions extensively involving the right temporal lobe but sparing almost all of the same structures on the left and (2) severe compromise of nonverbal learning and a nonverbal retrograde amnesia in contrast to disproportionately small impairments of verbal learning and retention. The findings suggest that encephalitis patients cannot be treated as a homogeneous group and that detailed analysis of variability in their anatomic lesions may be an important explanatory factor in neural accounts of these severe human amnesias.

Adolescent↗

Differentiation of Alzheimer's disease from dementia with Lewy bodies utilizing positron emission tomography with [18F]fluorodeoxyglucose and neuropsychological testing.

We compared the relative utility of neuropsychological testing and positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG) in differentiating Alzheimer's disease (AD) from dementia with Lewy bodies (DLB). We studied 25 patients with AD, 20 with DLB, and 19 normal elderly controls. There was no difference between patient groups for MMSE, confrontational naming, or verbal learning. The DLB group was significantly more impaired than the AD group for verbal fluency, and the AD group was significantly more impaired than the DLB group for verbal delayed recall. The DLB group had greater difficulty than the AD group on a visual discrimination task that does not require motor functioning, but the difference did not reach significance. Family ratings of motor functioning suggested significantly greater impairment in DLB patients than in AD patients. PET studies revealed significantly lower local cerebral metabolic rates for glucose (lCMRglc) for visual cortex (Brodmann areas 17, 18, and 19) in the DLB than the AD group, but no differences for other regions commonly affected in AD, including posterior cingulate, superior parietal lobe, lateral temporal lobe, and the prefrontal region. Motor ratings were significantly correlated with lCMRglc in all areas of cerebral cortex, including Brodmann areas 17, 18, and 19. The results demonstrate a similar profile of cerebral hypometabolism in the two patient groups except in the visual cortex, where the DLB group shows markedly lower lCMRglc than the AD group. Neuropsychological testing also differentiates the groups, and family ratings of motor functioning are as robust as PET in these later stages of the disorders.

Aged↗

The cost to the central nervous system of climbing to extremely high altitude.

To assess the possibility that climbing to extremely high altitude may result in hypoxic injury to the brain, we performed neuropsychological and physiologic testing on 35 mountaineers before and 1 to 30 days after ascent to altitudes between 5488 and 8848 m, and on 6 subjects before and after simulation in an altitude chamber of a 40-day ascent to 8848 m. Neuropsychological testing revealed a decline in visual long-term memory after ascent as compared with before; of 14 visual items of information on the Wechsler Memory Scale, fewer were recalled after ascent by both the simulated-ascent group (a mean [+/- SD] of 10.14 +/- 1.68 items before, as compared with 7.00 +/- 3.35 items after; P less than 0.05) and the mountaineers (12.33 +/- 1.96 as compared with 11.36 +/- 1.88; P less than 0.05). Verbal long-term memory was also affected, but only in the simulated-ascent group; of a total of 10 words, an average of 8.14 +/- 1.86 were recalled before simulated ascent, but only 6.83 +/- 1.47 afterward (P less than 0.05). On the aphasia screening test, on which normal persons make an average of less than one error in verbal expression, the mountaineers made twice as many aphasic errors after ascent (1.03 +/- 1.10) as before (0.52 +/- 0.80; P less than 0.05). A higher ventilatory response to hypoxia correlated with a reduction in verbal learning (r = -0.88, P less than 0.05) and with poor long-term verbal memory (r = -0.99, P less than 0.01) after ascent. An increase in the number of aphasic errors on the aphasia screening test also correlated with a higher ventilatory response to hypoxia in both the simulated-ascent group (r = 0.94, P less than 0.01) and a subgroup of 11 mountaineers (r = 0.59, P less than 0.05). We conclude that persons with a more vigorous ventilatory response to hypoxia have more residual neurobehavioral impairment after returning to lower elevations. This finding may be explained by poorer oxygenation of the brain despite greater ventilation, perhaps because of a decrease in cerebral blood flow caused by hypocapnia that more than offsets the increase in arterial oxygen saturation.

Adult↗

Factorial validation of the Ruff-Light Trail Learning Test (RULIT).

The factorial validity of the Ruff-Light Trail Learning Test (RULIT) was evaluated for its specificity as a test of visuospatial learning and memory. In a sample of 307 normal adults, principal components analyses (PCAs) were calculated on scores from the RULIT and selected neuropsychological tests. The PCAs revealed visuospatial learning and memory components, which included RULIT scores that were empirically distinct from verbal learning and memory components. These results provide support for the RULIT as a measure of visuospatial learning and memory.

Adolescent↗

Stimulus gender and emotional difficulty level: their effect on recognition of facial expressions of affect in children with and without LD.

The ability to recognize emotions that were easily identifiable and those that were more difficult to identify, as expressed by male and female faces, was studied in 48 nondisabled children and 76 children with learning disabilities (LD) ages 9 through 12. On the basis of their performance on the Rey Auditory Verbal Learning Test and the Benton Visual Retention Test, the LD group was divided into three subgroups: those with verbal (VD), nonverbal (NVD), and both verbal and nonverbal (BD) deficits. A shortened version of Ekman and Friesen's Pictures of Facial Affect, including pictures of both men and women, was the measure of ability to identify facial expressions of affect. Children of both genders in all three groups of children with LD, as well as their normally achieving peers, were more accurate in identifying expressions of affect from female faces, notwithstanding differences in sensitivity to such emotional communication in favor of the nondisabled and VD groups. However, a significant interaction was found between gender and emotional recognition difficulty level, with female faces being more expressive for emotions that were difficult to recognize.

Case-Control Studies↗

Selective cognitive deficits in obsessive-compulsive disorder compared to panic disorder with agoraphobia.

OBJECTIVE: Visual-spatial and executive functions deficits have been reported in obsessive-compulsive disorder (OCD). We investigated their specificity comparing cognitive function in OCD, panic disorder with agoraphobia (PD/A) and controls by a comprehensive neuropsychological battery. METHOD: Fifty-five subjects (25 OCD, 15 PD/A, 15 controls) without current depressive episode underwent structured clinical interview for DSM-IV, Yale-Brown Obsessive Compulsive Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale. Neuropsychological battery assessed: executive functions, visual discrimination, spatial memory and learning, verbal memory, general intellectual functioning. RESULTS: OCD showed controlled fluency, visual-spatial construction, learning and memory deficits; PD/A spatial learning impairment. OCD was discriminated from PD/A and controls by three tests scores, predicting group membership for 76.4% of the cases. CONCLUSION: Visual-constructive and controlled fluency deficits seem specific in OCD, while the spatial learning deficit, shared with PD patients, may not be disorder-specific, but anxiety-related. Results support the proposed ventral frontal-striatal circuit involvement in OCD.

Adolescent↗