Visual Paired Associate Research Articles

Antipsychotic-induced parkinsonism is associated with working memory deficits in schizophrenia-spectrum disorders.

In view of the significant cognitive deficits in schizophrenia and their impact on patients' social and occupational functioning, and considering that the influence potential influence of antipsychotic-induced extrapyramidal symptoms on cognition in schizophrenia remains poorly understood, the current study sought to identify the clinical, socio-demographic and neurologic predictors of the cognitive performance of schizophrenia patients. Eighty-two schizophrenia-spectrum (DSM-IV criteria) outpatients were recruited. Psychiatric symptoms were evaluated with the Positive And Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Extrapyramidal symptoms were evaluated with the Extrapyramidal Symptoms Rating Scale, while spatial working, planning abilities and visual paired associates learning were evaluated with the CAmbridge Neuropsychological Tests Automated Battery. The Stroop test was also administered. Multivariate hierarchic linear regression analyses were performed. We found that negative symptoms were associated with cognitive flexibility, planning, visual learning and working memory performance in schizophrenia. Age, sex, number of hospitalizations and antipsychotic type also emerged as significant predictors. More importantly, we found a significant association between antipsychotic-induced parkinsonism and working memory performance. The fact that negative symptoms and socio-demographic variables predicted cognitive performance in schizophrenia is consistent with the previous literature on the topic. The finding of an association between parkinsonism and working memory may have clinical implications, since working memory deficits are considered putative endophenotypes of schizophrenia and are known to impair patients' social and occupational functioning. Our results will need to be replicated in longitudinal studies involving larger samples of patients.

Neural compensation in adulthood following very preterm birth demonstrated during a visual paired associates learning task.

Very preterm birth (VPT; < 33 weeks of gestation) is associated with an increased risk of learning disability, which contributes to more VPT-born children repeating grades and underachieving in school. Learning problems associated with VPT birth may be caused by pathophysiological alterations in neurodevelopment resulting from perinatal brain insult; however, adaptive neuroplastic processes may subsequently occur in the developing preterm brain which ameliorate, to an extent, the potential sequelae of altered neurophysiology. Here, we used functional magnetic resonance imaging (fMRI) to compare neuronal activation in 24 VPT individuals and 22 controls (CT) in young adulthood during a learning task consisting of the encoding and subsequent recognition of repeated visual paired associates. Structural MRI data were also collected and analysed in order to explore possible structure-function associations. Whilst the two groups did not differ in their learning ability, as demonstrated by their capacity to recognize previously-seen and previously–unseen visual pairs, between-group differences in linear patterns of Blood Oxygenation Level Dependant (BOLD) activity were observed across the four repeated blocks of the task for both the encoding and recognition conditions, suggesting that the way learning takes place differs between the two groups. During encoding, significant between-group differences in patterns of BOLD activity were seen in clusters centred on the cerebellum, the anterior cingulate gyrus, the midbrain/substantia nigra, medial temporal (including parahippocampal) gyrus and inferior and superior frontal gyri. During the recognition condition, significant between-group differences in patterns of BOLD activity were seen in clusters centred on the claustrum and the posterior cerebellum. Structural analysis revealed smaller grey matter volume in right middle temporal gyrus in VPT individuals compared to controls, however volume in this region was not significantly associated with functional activation. These results demonstrate that although cognitive task performance between VPT individuals and controls may be comparable on certain measures, differences in BOLD signal may also be evident, some of which could represent compensatory neural processes following VPT-related brain insult.

Effect of cholinergic neurotransmission modulation on visual spatial paired associate learning in healthy human adults

Use of cross-species neuropsychological paradigms such as visual-spatial paired associate learning (PAL) may allow for a better understanding of underlying neural substrates of memory. Such paradigms, which are often used to guide models of memory in animals, can then be carried forward into humans to provide a basis for evaluation of pharmacologic compounds designed to ameliorate learning and memory impairments in neurologic and psychiatric morbidities. This double-blind, randomized, crossover trial investigated effects of donepezil, an acetylcholinesterase (AChE) inhibitor, in attenuating scopolamine-induced cognitive impairment using a novel, "process-based" computerized measure of visual-spatial PAL. In healthy male volunteers, scopolamine (0.6mg) induced a time-dependent reduction in visual-spatial PAL, with the greatest impairment (Cohen's d = 1.37) observed 2h after dosing. Cotreatment with donepezil (10mg) significantly ameliorated scopolamine-induced impairment at the 2-h time point (Cohen's d = 0.66). Process-based analyses revealed a significant impairment in both memory (Cohen's d = 1.37 to 0.50) and executive (Cohen's d = 1 .21 to 0.62) aspects of visual-spatial PAL performance following acute scopolamine challenge, and these reductions were ameliorated by donepezil. Acute scopolamine challenge can produce large and robust deficits in visual-spatial PAL, which reflect impairments in both memory and executive processes. Coadministration of a single dose of donepezil can ameliorate these deficits. These results provide support for the use of a visual-spatial PAL test as a pharmacodynamic cognitive marker of central nervous system (CNS)-mediating compounds in humans.

A process‐based approach to characterizing the effect of acute alprazolam challenge on visual paired associate learning and memory in healthy older adults

Alprazolam is a benzodiazepine that, when administered acutely, results in impairments in several aspects of cognition, including attention, learning, and memory. However, the profile (i.e., component processes) that underlie alprazolam-related decrements in visual paired associate learning has not been fully explored. In this double-blind, placebo-controlled, randomized cross-over study of healthy older adults, we used a novel, "process-based" computerized measure of visual paired associate learning to examine the effect of a single, acute 1-mg dose of alprazolam on component processes of visual paired associate learning and memory. Acute alprazolam challenge was associated with a large magnitude reduction in visual paired associate learning and memory performance (d = 1.05). Process-based analyses revealed significant increases in distractor, exploratory, between-search, and within-search error types. Analyses of percentages of each error type suggested that, relative to placebo, alprazolam challenge resulted in a decrease in the percentage of exploratory errors and an increase in the percentage of distractor errors, both of which reflect memory processes. Results of this study suggest that acute alprazolam challenge decreases visual paired associate learning and memory performance by reducing the strength of the association between pattern and location, which may reflect a general breakdown in memory consolidation, with less evidence of reductions in executive processes (e.g., working memory) that facilitate visual paired associate learning and memory.

A prospective study of learning, memory, and executive function in new MDMA users

It is still unclear if cognitive abnormalities in human 3,4-methylenedioxymeth-amphetamine (MDMA) users existed before the beginning of use or if other confounders could explain the deficits. The present study was conducted in order to assess the relationship between beginning MDMA use and subsequent cognitive performance and to overcome previous methodological shortcomings. A prospective cohort study in new MDMA users between 2006 and 2009 with a follow-up duration of 12 months. Of the 149 almost MDMA-naive subjects examined at the initial assessment, 109 subjects participated again after 1 year. During this period, 43 subjects did not use any other illicit substance apart from cannabis; 23 subjects used more than 10 pills MDMA (mean = 33.6). These groups then were compared by means of multivariate analyses of variance. Change scores between the initial examination and follow-up on a neuropsychological test battery including measures of learning, memory, and frontal executive functions [Auditiv-Verbaler Lerntest (AVLT), Lern- und Gedächtnistest (LGT) 3, digit span test, digit symbol test, Stroop task, Trail-making test]. In addition, a comprehensive number of possibly relevant confounders including age, general intelligence, cannabis use, alcohol use, cigarette use, medical treatment, participation in sports, nutrition, sleep patterns and subjective wellbeing was assessed. Groups did not differ in any of the potential confounders. However, significant effects of immediate and delayed recall of a visual paired associates learning task between MDMA users and controls were found (respectively, F ((1,64)) = 11.43, P = 0.001, η(2) = 0.136 and F ((1,64)) = 11.08, P = 0.002, η(2) = 0.144). No significant differences on the other neuropsychological tests were found. MDMA appears to impair visual paired associates learning in new users, suggesting serotonergic dysfunction in hippocampal regions as a consequence of MDMA use.

Clinical Validation of Cambridge Neuropsychological Test Automated Battery in a Norwegian Epilepsy Population

Introduction: Semi-automatic neuropsychological testing has gained a position both in clinical use and in research. Comparison studies with traditional neuropsychological tests are sparse and the role of such semi-automated testing is debated. To integrate semi-automated neuropsychological testing in the established clinical setting the tests must be validated in the patient groups addressed. The aim of this study was to validate Cambridge Neuropsychological Tests Automated Battery (CANTAB) in patients with epilepsy. Material and Methods: Patients scheduled for traditional neuropsychological testing with Category test (CT), Trail Making Test part B (TMT-B), WAIS-III and WMS-R were also asked to complete the CANTAB battery. Our hypothesis was that memory tests from CANTAB (DMS, PAL) would correlate with visual memory tests from WMS-R and that a test of executive functions from CANTAB (SOC) would correlate with functions tested with TMT-B, CT and WAIS-III. Results: Scores from DMS correlated strongly with Visual Paired Associations 1 from WMS-R. From SOC results correlated both with Visual Paired Association 1 & 2, General Memory Index and Full Scale IQ. Results from PAL correlated with several results from the traditional battery: Verbal, Visual and General Memory Index, Paired Associations, Visual Memory Span Backwards, TmtB and Visual IQ. Conclusion: Our results indicate that DMS primarily tests visual matching to sample. SOC tests executive functions and also depends on non-verbal IQ and memory. Numerous correlations between PAL and traditional tests illustrates that PAL is a complex task depending on several cognitive domains, but mainly memory.

Behavioural and electrophysiological effects of visual paired associate context manipulations during encoding and recognition in younger adults, older adults and older cognitively declined adults

The current study examined the EEG of young, old and old declined adults performing a visual paired associate task. In order to examine the effects of encoding context and stimulus repetition, target pairs were presented on either detailed or white backgrounds and were repeatedly presented during both early and late phases of encoding. Results indicated an increase in P300 amplitude in the right parietal cortex from early to late stages of encoding in older declined adults, whereas both younger adults and older controls showed a reduction in P300 amplitude in this same area from early to late phase encoding. In the right hemisphere, stimuli encoded with a white background had larger P300 amplitudes than stimuli presented with a detailed background; however, in the left hemisphere, in the later stages of encoding, stimuli presented with a detailed background had larger amplitudes than stimuli presented with a white background. Behaviourally, there was better memory for congruent stimuli reinstated with a detailed background, but this finding was for older controls only. During recognition, there was a general trend for congruent stimuli to elicit a larger amplitude response than incongruent stimuli, suggesting a distinct effect of context reinstatement on underlying patterns of physiological responding. However, behavioural data suggest that older declined adults showed no memory benefits associated with context reinstatement. When compared with older declined adults, younger adults had larger P100 amplitude responses to stimuli presented during recognition, and overall, younger adults had faster recognition reaction times than older control and older declined adults. Further analysis of repetition effects and context-based hemispheric asymmetry may prove informative in identifying declining memory performance in the elderly, potentially before it becomes manifested behaviourally.

Examining the nature of impairment in visual paired associate learning in amnestic mild cognitive impairment.

Visual spatial learning is impaired in mild cognitive impairment (MCI) although the nature of this impairment is not clear. This study investigated the nature and magnitude of errors made by adults with amnestic MCI (aMCI) when learning pattern-location paired associations in a continuous manner. Visual associate learning was measured using the Continuous Paired Associate Learning (CPAL) task in which 30 adults who met clinical criteria for aMCI and 30 matched controls were required to learn a set of associations between patterns and locations across increasing memory loads (two, four, six, and eight). As hypothesized, the aMCI group made more total errors than controls for all memory loads above two. However, the rate of increase in errors with memory load in the aMCI group was approximately twice that for controls. In controls, errors on the CPAL task reflected almost exclusively difficulty in memory. In the aMCI group, errors on the CPAL reflected limitations in associative learning but also in short-term memory and response monitoring. These results suggest that impairments in specific aspects of executive function and working memory might contribute to poor performance on visual paired associate learning in aMCI.

Understanding failure of visual paired associate learning in amnestic mild cognitive impairment

Impairment in visual paired associate learning occurs often in with amnestic mild cognitive impairment (aMCI), a condition considered to be an early stage of Alzheimer's disease (AD). To date, studies of aMCI have characterized impaired visual paired associate learning only in terms of summary scores such as total errors or total trials to criterion. The aim of this study was to determine the nature and magnitude of errors made on a continuous paired associate learning (CPAL) task designed to allow analysis of the component processes involved in paired associate learning. Twenty-one individuals with aMCI and 54 healthy age-matched older adults (HC) performed the CPAL task in which they had to learn six pattern–location pairings over six trials. Results suggested that aMCI patients performed significantly worse on the CPAL, both in learning rate and in error accumulation. Qualitative analyses of CPAL performance revealed that in aMCI there were significantly more errors on all indices except perseverative errors. When expressed as a percentage of total errors, abnormalities occurred only for within-search and exploratory errors. These findings suggest that poor performance on visual paired associate learning tasks in aMCI reflects impairments in both learning and executive function.

Electroencephalographic coherence, aging, and memory: distinct responses to background context and stimulus repetition in younger, older, and older declined groups

The current study examines the EEG coherence of young, old, and old declined adults performing a visual paired-associates task. In order to examine the effects of encoding context and stimulus repetition, target pairs were presented on either detailed or white backgrounds and were repeatedly presented during both early and late phases of encoding. Younger adults were found to have lower levels of frontal-temporal and temporal-parietal coherence, but higher levels of frontal-parietal coherence, particularly for the gamma frequency band. A number of differential coherence responses to background context and early- versus late-encoding phases were also observed across the groups, particularly for lower alpha and upper alpha frequencies. Coherence-performance maps were generated to further explore topographical differences in the relationship between coherence and performance across groups. Results revealed a more diffuse pattern of negative coherence-performance relations in older declined adults. Results are discussed in light of the literature on age-related cognitive decline.

Unitized representation of paired objects in area 35 of the macaque perirhinal cortex

The perirhinal cortex, which is critical for long-term stimulus-stimulus associative memory, consists of two cytoarchitectonically distinct subdivisions: area 35 (A35) and area 36 (A36). Previous electrophysiological studies suggested that macaque A36 is involved in both association and retrieval processes during a visual pair-association task. However, the neuronal properties of macaque A35 have never been examined because A35 is located in a very narrow region, which makes it difficult to systematically record single-unit activity from there. In the present study, we overcame this technical difficulty for targeting A35 by combining magnetic resonance imaging-guided in-vivo localization with postmortem histological localization. This two-track approach enabled us to record from 181 A35 neurons in two macaque monkeys while they performed a pair-association task. Among these neurons, 64 showed stimulus-selective responses during the cue period (cue-selective neurons), whereas 18 did during the delay period (delay-selective neurons). As in A36, the responses of cue-selective neurons in A35 to paired associates were correlated. In both areas, these correlations were stronger in neurons showing delay selectivity than in those without delay selectivity. Notably, delay-selective neurons in A35 responded similarly to the optimal stimulus and its paired associate, whereas delay-selective neurons in A36 discriminated between them. However, these neurons in both areas discriminated the primary pair, consisting of the optimal stimulus and its paired associate, from other pairs, indicating that selectivity across pairs was maintained between the two areas. These results suggest that delay-selective neurons in A35 represent these paired stimuli as a single unitized item rather than two associated items.

Neural substrates of visual paired associates in young adults with a history of very preterm birth: Alterations in fronto-parieto-occipital networks and caudate nucleus

This study investigated neuronal activation during visuo-perceptual learning processing in adults who were born very preterm (VPT, <33 weeks' gestation). A visual paired associates task was administered during functional magnetic resonance imaging (fMRI) and neuronal activation was compared between 21 VPT-born adults of both sexes and 22 matched controls. The task consisted of 4 conditions (encoding, recognition, same/different discrimination condition (baseline) and a low-level baseline), each containing 8 stimuli pairs. There were no group differences in terms of correctly recognized visual pairs. However, during encoding, VPT-born individuals showed increased BOLD signal response compared to controls in left caudate nucleus, right cuneus (BA 18) and left superior parietal lobule (BA 7), and decreased signal in right inferior frontal gyrus (BA 46). During recognition, VPT-born adults showed increased BOLD signal response compared to controls in right cerebellum and in anterior cingulate gyrus (BA 32) bilaterally. The fMRI data were additionally analyzed controlling for structural differences in the hippocampus bilaterally, where the VPT group showed decreased probability of the absolute amount of grey matter compared to controls. Results of our study suggest that despite good task performance, VPT-born individuals activate different neural networks during mnemonic processing of visuo-perceptual material which may indicate neural compensation for the adult consequences of perinatal brain injury following very preterm birth, as well as maturational delays.

The early diagnosis and differential diagnosis of Alzheimer’s disease with clinical methods

Alzheimer's disease is a progressive and fatal neurodegenerative disorder in which the novel drugs can slow down the progression in the early phase. Our purpose was to find biological markers, which would detect neuropathology in the prodromal and early phase of Alzheimer's disease. Beside the routine diagnostic methods, neuropsychological test, auditory event related potential and special laboratory tests were performed among subjects with Alzheimer's disease, vascular dementia, mild cognitive impairment and major depression compared to a healthy control group. Visual Paired Associate Learning was impaired in all patient groups, in major depression it seemed to be reversible. In amnestic mild cognitive impairment and in dementia a longer latency of late component of auditory evoked potential, P300, was found. Reduced paraoxonase activity in the serum and increased Nepsilon(gamma-glutamyl)lysine isodipeptide concentration in the cerebrospinal fluid were detected in both dementia groups. Characteristic changes of Visual Paired Associate Learning and P300 might predict the conversion to Alzheimer's disease in mild cognitive impairment. The paraoxonase activity and the isodipeptide concentration can be sensitive markers of the pathomechanism of neurodegeneration. A combined use of the above-mentioned methods can help in the early prediction and diagnosis of Alzheimer's disease.

Androgen treatment effects on memory in female-to-male transsexuals

It has been hypothesized that cognitive and memory-related brain function in transsexuals during cross-sex hormonal treatment might be activated towards that of the subjective gender. However, research on this topic has produced inconsistent results, and to the best of our knowledge no studies have investigated memory changes in androgen-treated female-to-male (FM) transsexuals. A total of 33 FM transsexuals underwent neuropsychological testing in order to examine the effects of androgen on memory. We used a longitudinal design in which 14 FM transsexuals were tested twice, before and after receiving 6 months of testosterone treatment. In addition, a cross-sectional design was used to compare 10 individuals off treatment versus 9 individuals on testosterone treatment for at least 6 months. Participants tested before and after 6 months of androgen treatment improved significantly their performance on a visual memory task (visual paired associates, immediate recall, WMS-R). The cross-sectional design confirmed that patients on androgen treatment for at least 6 months performed better than subjects off treatment on the same task and also on another visual memory task (Rey-Osterrieth complex figure test, ROCF; copy and delayed recall). No differences were found in any verbal memory test for either design. The results indicate that androgen has an influence on visual memory, but not on verbal memory. Therefore, for FM transsexuals the data support an activating effect for androgens on visual memory, a domain that generally tends to favour males.

Added ondansetron for stable schizophrenia: A double blind, placebo controlled trial

It is well documented that 5-hydroxytryptamine3 (5-HT3) receptors are involved in the pathogenesis of schizophrenia and cognitive impairment. The purpose of this study was to assess the efficacy of ondansetron, a 5-HT3 receptor antagonist as an adjuvant agent in the treatment of chronic schizophrenia in particular for cognitive impairments. This investigation was a 12-week, double blind study of parallel groups of patients with stable chronic schizophrenia. Thirty patients were recruited from inpatient and outpatient departments. All participants met Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) criteria for schizophrenia. To be eligible, patients were required to have been treated with a stable dose of risperidone as their primary antipsychotic treatment for a minimum period of 8 weeks. The subjects were randomized to receive ondansetron (8 mg/day) or the placebo in addition to risperidone. Clinical psychopathology was assessed with Positive and Negative Syndrome Scale (PANSS). Cognition was measured by a cognitive battery. Patients were assessed at baseline and after 8, and 12 weeks after the medication started. The PANSS scores and cognitive performance were used as the outcome measures. The ondansetron group had significantly greater improvement in the negative symptoms, general psychopathological symptoms and PANSS total scores over the trial. Administration of ondansetron significantly improved visual memory based on improvement on visual reproduction, visual paired associate and figural memory sub tests of Wechsler Memory Scale — Revised. The present study indicates ondansetron as potential adjunctive treatment strategy for chronic schizophrenia particularly for negative symptoms and cognitive impairments.

Apolipoprotein E ɛ4 influences on episodic recall and brain structures in aging pilots

The apolipoprotein (APOE) epsilon4 allele is associated with cognitive deficits and hippocampal atrophy in nondemented middle-aged and older adults. It is not known to what extent this genetic risk factor for Alzheimer's disease (AD) impacts performance in late middle-aged and older workers in cognitively demanding occupations. This cross-sectional analysis examines brain-cognitive-genetic relationships in actively flying general aviation pilots, half of whom are APOE epsilon4 carriers. Fifty pilots were studied with structural MRI and memory tasks. Average visual paired associate memory recall performance was lower in APOE epsilon4 carriers than non-carriers. Memory performance correlated positively with hippocampal volume, but no structural differences were found in hippocampal or frontal volumes with respect to APOE epsilon4 allele. These results were evident in healthy professionals without any presenting memory problems and without selection for a family history of AD. These findings point to basic memory testing as a sensitive tool for detecting APOE epsilon4-related influences on memory in aging workers.

Wechsler Memory Scale Revised Edition: Neural correlates of the visual paired associates subtest adapted for fMRI

Memory deficits in neurological and psychiatric patients are evaluated by neuropsychological tests such as the Wechsler Memory Scale Revised Edition (WMS-R). Neuropsychological data from patients with circumscribed lesions point to single elements of the underlying neural network but fail to identify its whole extent. We report the fMRI adaptation of a subtest of the WMS-R, the Visual Paired Associates. Fifteen healthy, right-handed male volunteers were studied using a 1.5T MRI scanner. The encoding of the combination between a shape and a colour, the assessment of the retrieval of this combination immediately after encoding took place, and the underlying network employed during retrieval a second time after approximately 25 min were investigated. The results show a fronto-parieto-occipital network with left frontal accentuation for encoding and a fronto-parieto-occipital network for immediate and delayed retrieval. Noteworthy is the specific role of the thalamus. During immediate retrieval, the thalamus showed significant bilateral activation; during delayed retrieval, there was no significant activation. The thalami are part of an extended hippocampal–diencephalic system which is critical for efficient encoding and normal retrieval of new episodic information. We describe the probability of thalamocortical connections during retrieval based on the Thalamus Connectivity Atlas. The cerebellum showed significant activation in all conditions; its part in higher cognitive functions such as memory was thereby confirmed.

Evaluation of a Structured Group Format Memory Rehabilitation Program For Adults Following Brain Injury

To evaluate the impact of an 8-session structured group format memory rehabilitation program on impaired memory functioning. Adults with traumatic brain injury (N = 10) or cerebral vascular accidents (N = 2). A waitlist control study with pregroup, postgroup, and 1-month follow-up assessments. WECHSLER MEMORY SCALE-REVISED: Neuropsychological assessments of memory (California Verbal Learning Test, Wechsler Memory Scale-Revised logical memory, visual-paired associates, and Rey Complex Figure) and both self-report and significant other report of behaviors indicative of memory difficulties and the use of memory strategies. Participation in the memory group increased participants' knowledge of memory and memory strategies as well as use of memory aids and strategies; reduced behaviors indicative of memory impairment; and had a positive effect on neuropsychological assessments of memory (eg, delayed recall for words and figures). All significant improvements exceeded change experienced by waiting-list controls and were maintained at 1-month follow-up assessment. While extension of the findings is needed, the memory group has a positive impact on both neuropsychological measures of memory and everyday memory functioning.

Topographic abnormality of slow cortical potentials in schizophrenia.

A recent study from our laboratory has provided evidence for the generation of slow potentials occurring in anticipation to task-performance feedback stimuli, in multiple association cortical areas, consistently including two prefrontal areas. In the present study, we intended to determine whether these slow potentials would indicate some abnormality (topographic) in schizophrenic patients, and thus serve as an indication of abnormal association cortex activity. We recorded slow potentials while subjects performed a paired-associates memory task. A 123-channel EEG montage and common average reference were used for 20 unmedicated schizophrenic (mean duration of illness: 11.3 +/- 9.2 years; mean number of previous hospitalizations: 1.2 +/- 1.9) and 22 healthy control subjects during a visual paired-associates matching task. For the topographic analysis, we used a simple index of individual topographic deviation from normality, corrected for absolute potential intensities. Slow potentials were observed in all subjects. Control subjects showed a simple spatial pattern of voltage extrema (left central positive and right prefrontal negative), whereas schizophrenic patients presented a more complex, fragmented pattern. Topographic deviation was significantly different between groups (P<0.001). The increased topographic complexity in schizophrenics could be visualized in grand averages computed across subjects. Increased topographic complexity could also be seen when grand averages were computed for subgroups of patients assembled either according to task-performance (high versus low) or by their scores on psychopathological scales. There was no significant correlation between topographic deviation and psychopathology scores. We conclude that the slow potential topographic abnormalities of schizophrenia indicate an abnormality in the configuration of large-scale electrical activity in association cortices.

Anatomical organization of forward fiber projections from area TE to perirhinal neurons representing visual long-term memory in monkeys.

A number of studies have shown that the perirhinal (PRh) cortex, which is part of the medial temporal lobe memory system, plays an important role in declarative long-term memory. The PRh cortex contains neurons that represent visual long-term memory. The aim of the present study is to characterize the anatomical organization of forward projections that mediate information flow from visual area TE to memory neurons in the PRh cortex. In monkeys performing a visual pair-association memory task, we conducted an extensive mapping of neuronal responses in the anteroventral part of area TE (TEav) and area 36 (A36) of the PRh cortex. Then, three retrograde tracers were separately injected into A36 and the distribution of retrograde labels in TEav was analyzed. We focused on the degree of divergent projections from TEav to memory neurons in A36, because the highly divergent nature of these forward fiber projections has been implicated in memory function. We found that the degree of divergent projection to memory neurons in A36 was smaller from the TEav neurons selective to learned pictures than from the nonselective TEav neurons. This result demonstrates that the anatomical difference (the divergence) correlates with the physiological difference (selectivity of TEav neurons to the learned pictures). Because the physiological difference is attributed to whether the projections are involved in information transmission required for memory neurons in A36, it can be speculated that the reduced divergent projection resulted from acquisition of visual long-term memory, possibly through retraction of the projecting axon collaterals.