Visual Memory Deficits Research Articles

Visual memory dysfunction as a neurocognitive endophenotype in bipolar disorder patients and their unaffected relatives. Evidence from a 5-year follow-up Valencia study.

BackgroundScarce research has focused on Visual Memory (VM) deficits as a possible neurocognitive endophenotype of bipolar disorder (BD). The main aim of this longitudinal, family study with healthy controls was to explore whether VM dysfunction represents a neurocognitive endophenotype of BD. MethodsAssessment of VM by Rey–Osterrieth Complex Figure Test (ROCF) was carried out on a sample of 317 subjects, including 140 patients with BD, 60 unaffected first-degree relatives (BD-Rel), and 117 genetically-unrelated healthy controls (HC), on three occasions over a 5-year period (T1, T2, and T3). BD-Rel group scores were analyzed only at T1 and T2. ResultsPerformance of BD patients was significantly worse than the HC group (p < 0.01). Performance of BD-Rel was also significantly different from HC scores at T1 (p < 0.01) and T2 (p = 0.05), and showed an intermediate profile between the BD and HC groups. Only among BD patients, there were significant differences according to sex, with females performing worse than males (p = 0.03). Regarding other variables, education represented significant differences only in average scores of BD-Rel group (p = 0.01). LimitationsImportant attrition in BD-Rel group over time was detected, which precluded analysis at T3. ConclusionsBD patients show significant deficits in VM that remain stable over time, even after controlling sociodemographic and clinical variables. Unaffected relatives also show stable deficits in VM. Accordingly, the deficit in VM could be considered a potential endophenotype of BD, which in turn may be useful as a predictor of the evolution of the disease. Further studies are needed to confirm these findings.

Visual and verbal learning and memory in cystinosis

Cystinosis is a rare genetic lysosomal storage disorder characterized by the accumulation of cystine in lysosomes. Many organ systems are vulnerable to this cystine accumulation including the CNS. A past study demonstrated that children with cystinosis have deficits in visual learning and memory while their verbal learning and memory and global intellectual function are spared (Spilkin, Ballantyne, & Trauner, 2009). However, no related study has been performed to assess the dissociation between visual and verbal learning and memory in adults with cystinosis who have had the benefit of longterm treatment with the cystine-depleting agent, cysteamine. In this study we assessed visual and verbal learning and memory in 15 adults with cystinosis, with a mean age of 30.2 years. The results indicate that adults with cystinosis have no significant deficits in either verbal or visual learning and memory. However, the individuals did perform better on the verbal assessment. The results suggest that if early and continued treatment is given to individuals with cystinosis there is a relative sparing of visual learning and memory that might have otherwise declined. This emphasizes the essential nature of the proper clinical management of cystinosis.

Visual working memory deficits in undergraduates with a history of mild traumatic brain injury.

We investigated whether a history of mild traumatic brain injury (mTBI), or concussion, has any effect on visual working memory (WM) performance. In most cases, cognitive performance is thought to return to premorbid levels soon after injury, without further medical intervention. We tested this assumption in undergraduates, among whom a history of mTBI is prevalent. Notably, participants with a history of mTBI performed worse than their colleagues with no such history. Experiment 1 was based on a change detection paradigm in which we manipulated visual WM set size from one to three items, which revealed a significant deficit at set size 3. In Experiment 2 we investigated whether feedback could rescue WM performance in the mTBI group, and found that it failed. In Experiment 3 we manipulated WM maintenance duration (set size 3, 500-1,500 ms) to investigate a maintenance-related deficit. Across all durations, the mTBI group was impaired. In Experiment 4 we tested whether retrieval demands contributed to WM deficits and showed a consistent deficit across recognition and recall probes. In short, even years after an mTBI, undergraduates perform differently on visual WM tasks than their peers with no such history. Given the prevalence of mTBI, these data may benefit other researchers who see high variability in their data. Clearly, further studies will be needed to determine the breadth of the cognitive deficits in those with a history of mTBI and to identify relevant factors that contribute to positive cognitive outcomes.

Cingulate infarction: A neuropsychological and neuroimaging study

Background and purposeIschemic lesions rarely affect the cingulate cortex (CC) in isolation, restricting human lesion/behavioural change correlational analysis. The aim of this study was to determine clinical, neuropsychological and neuroimaging features of isolated cingulate infarcts. MethodsWe studied, 3800 patients with first-ever ischemic stroke included in our Stroke Registry between 2012 and 2018. Among them we studied 7 patients with an acute isolated cingulate infarct confirmed by MRI. ResultsAmong all patients, 7 patients (0.01%) showed ischemic lesions in the territory of cingulate cortex territory, allowing us to delineate 2 substantial distributions; (1) Anterior cingulate cortex (ACC) infarction (4 patients [57%]) was presented low vigilance level with apathy, mutism, deficits in executive function, attention, and disturbances of working, episodic and verbal memory; (2) Posterior cingulate cortex (PCC) infarction (3 patients [43%]) developed topographic disorientation, visual memory deficit and affective-emotional behavioural changes. ConclusionsAccording rarely seen CC infarction events, we suggest that anterior and posterior CC are functionally separated and differences in clinical presentation are explained by considering; ACC plays a role in executive functions, episodic and working memory, set maintenance, and PCC is focused on spatial and verbal attention, and memory system. We considered that different patterns of cingulate infarcts are the result of variation in cingulate arterial supply or suggest a source of embolism.

Atypical clinical features associated with mixed pathology in a case of non-fluent variant primary progressive aphasia

ABSTRACTA 66-year-old woman presented with agrammatism and apraxia of speech, meeting criteria for non-fluent/agrammatic variant primary progressive aphasia (nfvPPA). However, three years later, she developed frontal/executive, short-term phonological memory, visuospatial, and visual memory deficits suggesting involvement of multiple brain networks. Multimodal neuroimaging showed damage of both fronto-striatal and posterior brain regions. She was found to have multiple pathological processes: corticobasal degeneration (CBD), Alzheimer’s disease (AD), and TAR DNA-binding protein (TDP)-43 type A. We hypothesize that cognitive and neuroimaging findings consistent with damage to multiple brain networks, each associated with vulnerability to certain molecular disease subtypes, could indicate mixed pathology.

RECOVERY OF MEMORY AFTER CEREBRAL ARTERY ANEURYSM SURGERY.

SUMMARYThe principal study objective was to define whether memory deficits (numerical, working, verbal-mechanical, verbal-logical and visual memory) occurred in patients submitted to surgery for brain artery aneurysm and whether significant recovery of memory took place with time. The study sample included 92 patients, i.e. 35 (38%) male and 57 (62%) female patients aged 27 to 76 years. Neuropsychological testing was conducted at Zagreb University Hospital Centre, Department of Neurosurgery, from 1998 to 2012, in two time intervals: first within 11 months following surgery, and then 12 to 48 months after surgery. The obtained results showed that verbal-mechanical, verbal-logical, and visual memory deficits were present in the first testing interval. In the second testing, the verbal-logical and visual memory deficits were still present, while the tests of verbal-mechanical memory showed deficits in capacity and learning curve, but the results for short- and long-term memory were within the normal ranges. Neither the first nor the second testing showed deficits of numerical and working memory. Based on our results, we can conclude that long-term verbal-mechanical and visual short- and long-term memory had recovered to a statistically significant level, whereas other types of memory showed no significant recovery.

Long-Term Cognitive Effects of Kratom (Mitragyna speciosa Korth.) Use

ABSTRACTKratom or Mitragyna speciosa (Korth.) is a medicinal plant of Southeast Asia. As a result of its opioid-like effects, it remains unknown whether consumption of kratom tea is associated with impaired cognitive function. We assessed the cognitive function of 70 regular kratom users and 25 control participants using the Cambridge Neuropsychological Test Automated Battery. Participants performed six neuropsychological tasks that assessed motor, learning and memory, attention and executive function. Relative to control participants, higher consumption (>3 glasses daily or mitragynine doses between 72.5 mg and 74.9 mg) of kratom tea was selectively associated with impaired performance on the Paired Associates Learning task, reflecting deficits in visual episodic memory and new learning. Overall, the performance of kratom users compared to control participants, and the performance of high (>3 glasses per day) as well as low (≤3 glasses per day) kratom using groups, were comparable on all neuropsychological domains. Higher intake of kratom juice (>3 glasses daily) did not appear to impair motor, memory, attention or executive function of regular kratom users.

CIP2A-promoted astrogliosis induces AD-like synaptic degeneration and cognitive deficits

Reactive astrogliosis and early synaptic degeneration are 2 characteristic hallmarks in Alzheimer's disease (AD) brains, but a direct link between the 2 events has not been established. Here, we show that cancerous inhibitor of PP2A (CIP2A), a cancerous protein with high expression level in astrocytes, is upregulated in patients with AD and 3xTg-AD transgenic mice. Overexpression of CIP2A in astrocytes through adeno-associated virus infection both in cultured cells and in mice brains results in activation of astrocytes, increased production of cytokines and Aβ, and synaptic degeneration indicated by decreased levels of synaptic proteins, spine loss, and impairment in long-term potentiation. As a result of synaptic degeneration, CIP2A overexpression in astrocytes in vivo induces significant deficits in visual episodic memory detected by novel objective recognition test and spatial memory detected by Morris water maze. We conclude that CIP2A-promoted astrogliosis induces synaptic degeneration and cognitive deficits in AD.

Memory in children with epilepsy: Utility of the WRAML-2 in generalized and focal epilepsy syndromes

The material-specific model for memory impairment predicts that verbal memory deficits are seen with left temporal seizures, and visual memory deficits are seen with right temporal seizures (Henkin et al., 2005). In pediatric epilepsy, seizure pathology has not always yielded the expected material-specific memory profiles. This study used the Wide Range Assessment of Memory and Learning—Second Edition (WRAML-2) to assess memory functioning among pediatric patients with epilepsy. The WRAML-2 was administered to 180 youth with epilepsy during their neuropsychological evaluations. Memory and recognition scores correlated significantly with epilepsy severity variables. There were no significant differences in verbal and visual memory and recognition index scores among patients with generalized epilepsy or among those with lateralized or localized electroencephalography (EEG) patterns and lesions on imaging. However, clinically meaningful verbal versus visual discrepancy scores were significantly related to lateralized abnormalities on EEG and magnetic resonance imaging (MRI) results. Most patients with right hemisphere pathology showed the expected material-specific visual memory deficits, while fewer than 15% of the left hemisphere cases showed the expected verbal memory deficits. Over one-third of those with identified left-sided pathology showed clinically significant deficits in visual memory. Findings are incongruent with the material-specific memory model and reflect the fact that early developmental neurological insults can lead to functional reorganization/crowding effects in children with left hemisphere epilepsy. On exploratory analyses, there were no significant differences in discrepancy scores among participants with left, right, and bilateral languages on Wada and functional MRI (fMRI). However, those with right and bilateral language dominance were more likely to show discrepancies that were incongruent with the material-specific model.

Distinguishing neurocognitive deficits in adult patients with NP-C from early onset Alzheimer\u2019s dementia

BackgroundNiemann-Pick disease type C (NP-C) is a rare, progressive neurodegenerative disease caused by mutations in the NPC1 or the NPC2 gene. Neurocognitive deficits are common in NP-C, particularly in patients with the adolescent/adult-onset form. As a disease-specific therapy is available, it is important to distinguish clinically between the cognitive profiles in NP-C and primary dementia (e.g., early Alzheimer’s disease; eAD).MethodsIn a prospective observational study, we directly compared the neurocognitive profiles of patients with confirmed NP-C (n = 7) and eAD (n = 15). All patients underwent neurocognitive assessment using dementia screening tests (mini-mental status examination [MMSE] and frontal assessment battery [FAB]) and an extensive battery of tests assessing verbal memory, visuoconstructive abilities, visual memory, executive functions and verbal fluency.ResultsOverall cognitive impairment (MMSE) was significantly greater in eAD vs. NP-C (p = 0.010). The frequency of patients classified as cognitively ‘impaired’ was also significantly greater in eAD vs. NP-C (p = 0.025). Patients with NP-C showed relatively preserved verbal memory, but frequent impairment in visual memory, visuoconstruction, executive functions and in particular, verbal fluency. In the eAD group, a wider profile of more frequent and more severe neurocognitive deficits was seen, primarily featuring severe verbal and visual memory deficits along with major executive impairment. Delayed verbal memory recall was a particularly strong distinguishing factor between the two groups.ConclusionA combination of detailed yet easy-to-apply neurocognitive tests assessing verbal memory, executive functions and verbal fluency may help distinguish NP-C cases from those with primary dementia due to eAD.

Similar profiles of cognitive domain deficits between medication-naïve patients with bipolar II depression and those with major depressive disorder

BackgroundBipolar disorder (BD) II is more likely to be misdiagnosed as major depressive disorder (MDD) than other types of BD, leading to incorrect treatment and poor outcomes. Previous studies have shown inconsistent results regarding the differences in cognitive deficits between the two disorders. To eliminate the compounding effects of medication and aging, we sought to investigate changes in cognitive function in medication-naïve, non-late-life patients with BDII and MDD. MethodsThree subject groups were enrolled: 30 depressed BDII patients, 30 depressed MDD patients and 30 healthy controls. All subjects underwent a battery of cognitive tests to assess 8 cognitive domains. The cognitive domains were compared between the three subject groups. In BDII and MDD, the effect sizes were computed as evaluation parameters, weighing the degree of the cognitive deficits and the correlations between cognitive test deficits and clinical variables were also computed. ResultsCompared with the controls, the BDII and MDD patients were characterized by similar deficits in psychomotor speed, working memory, visual memory, attention switching and verbal fluency. Moderate to severe deficits in the majority of cognitive tests were observed in the BDII and MDD patients. Furthermore, correlations between the modified Wisconsin Card Sorting Test total errors and age of onset in the BDII patients and between correct digit span responses (backward and total) and depressive severity were found in the MDD patients. ConclusionsOur findings suggest that BDII and MDD patients may suffer from similar profiles of cognitive domain deficits that may not assist in distinguishing between the two disorders. In addition, cognitive deficits may be correlated with the age of onset and depressive severity in mood disorders.

A Method to Train Marmosets in Visual Working Memory Task and Their Performance.

Learning and memory processes are similarly organized in humans and monkeys; therefore, monkeys can be ideal models for analyzing human aging processes and neurodegenerative diseases such as Alzheimer’s disease. With the development of novel gene modification methods, common marmosets (Callithrix jacchus) have been suggested as an animal model for neurodegenerative diseases. Furthermore, the common marmoset’s lifespan is relatively short, which makes it a practical animal model for aging. Working memory deficits are a prominent symptom of both dementia and aging, but no data are currently available for visual working memory in common marmosets. The delayed matching-to-sample task is a powerful tool for evaluating visual working memory in humans and monkeys; therefore, we developed a novel procedure for training common marmosets in such a task. Using visual discrimination and reversal tasks to direct the marmosets’ attention to the physical properties of visual stimuli, we successfully trained 11 out of 13 marmosets in the initial stage of the delayed matching-to-sample task and provided the first available data on visual working memory in common marmosets. We found that the marmosets required many trials to initially learn the task (median: 1316 trials), but once the task was learned, the animals needed fewer trials to learn the task with novel stimuli (476 trials or fewer, with the exception of one marmoset). The marmosets could retain visual information for up to 16 s. Our novel training procedure could enable us to use the common marmoset as a useful non-human primate model for studying visual working memory deficits in neurodegenerative diseases and aging.

AB073. Correlations between control of saccadic eye movements and performance in other cognitive tasks in younger adults, older adults and patients with Parkinson’s disease

Background: Cognitive control is defined as the ability to act flexibly in the environment by either behaving automatically or inhibiting said automatic behaviour and it can be measured using an interleaved pro/anti-saccade task. Decline in cognitive control has been attributed to normal aging and neurological illnesses such as Parkinson’s disease (PD) as well as decline in other cognitive abilities. This parallel might highlight the role played by cognitive control in information processing and working memory. However, little is known about the relationship between cognitive control and other cognitive processes such as visual memory, decision making, and visual search. We thus propose to correlate the incidence of impaired cognitive control with deficits in visual memory, decision making and visual search in three groups: younger adults, older adults and patients with idiopathic PD.

P.3.010 - Imbalance in the deployment of neural resources during visual working memory encoding in schizophrenia as a possible intermediate phenotype

Visual working memory (VWM) deficits are a prominent impairment in patients with schizophrenia (SCZ) and are associated with an inefficient encoding process [1] and with neuronal dysfunctions [2]. Both behavioural and neurofunctional impairments can be observed in unaffected first-degree relatives of patients (REL) as well and are thus discussed as a possible intermediate phenotype of the disorder [3,4]. In this study we investigated the characteristics of WM encoding and its neural substrates in SCZ and REL to evaluate their potential role as an intermediate phenotype of the disorder. We examined n = 25 SCZ, n = 22 REL and n = 25 healthy control subjects (CON). All subjects underwent whole brain fMRI scans in a 3 Tesla MR system. During the fMRI scan, a VWM change-detection task was presented, which showed a sample array consisting of 3 red lines of different orientation that should be memorized. After a delay interval of either 100ms, 400ms or 800ms (SOA = stimulus onset asynchrony) a pattern mask was shown, followed by another delay period and a test array. The longer the delay interval until masking, the more durable the VWM representations were expected to be. Response accuracy served as an estimate of the grade of VWM encoding. The behavioural data was analyzed using a two-way univariate ANOVA with repeated measures and post hoc tests. For group statistics of the event-related fMRI data we conducted a random-effects GLM (RFX-GLM) and a subsequent ANOVA with 'group' as a between-subjects factor (3 levels) and 'SOA' as within-subjects factor (3 levels). For behavioural performance in the VWM task we found significant main effects of 'group' (p = 0.026) and 'SOA' (p = 0.013). The longer the SOA interval, the greater the response accuracy across groups (significant linear trend; p = 0.009). Response accuracy was significantly lower in SCZ compared to CON (p = 0.011) and REL (p = 0.041). We observed aberrant neural activation during VWM encoding for both SCZ and REL compared to CON: across SOA conditions SCZ showed widespread neural deactivation, including the DLPFC and precentral gyrus, as well as increased activity of the anterior cingulate. In REL, we observed a shift in neural activation in regard to the length of the SOA interval: at SOA 100 REL showed only decreased activity in the superior frontal gyrus and fusiform gyrus; at SOA 400 we observed decreased activity in the middle frontal gyrus and increased activity in the superior frontal gyrus; and at SOA 800 REL showed only increased activity in the inferior frontal gyrus. The findings indicate that impaired VWM in SCZ may emerge from an insufficient engagement of the functional WM network with concomitant anterior cingulate hyperactivity during encoding. In REL, the shift from decreased to increased activity might reflect a compensatory process: hypoactivity might point towards fundamental neural dysfunctions—at lighter processing demands local hyperactivity might ensure accurate VWM performance. Neural dysfunctions during VWM encoding should thus be considered as a candidate intermediate phenotype of SCZ.

Defense and Veterans Brain Injury Center: The First 25 Years

Defense and Veterans Brain Injury Center: The First 25 Years

A haplotype of the dopamine transporter gene modulates regional homogeneity, gray matter volume, and visual memory in children with attention-deficit/hyperactivity disorder.

The dopamine transporter gene (DAT1) and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine whether a DAT1 haplotype affected functional and structural brain alterations in children with ADHD and whether those alterations were associated with visual memory. We recruited a total of 37 drug-naïve children with ADHD (17 with the DAT1 rs27048 (C)/rs429699 (T) haplotype and 20 without the CT haplotype) and 37 typically developing children (17 with the CT haplotype and 20 without the CT haplotype). Visual memory was assessed by the pattern recognition memory (PRM) and spatial recognition memory (SRM) tasks. We analyzed functional and structural brain architecture with regional homogeneity (ReHo) and gray matter volume (GMV). The CT haplotype was associated with decreased ReHo in the left superior occipital gyrus, cuneus, and precuneus; and decreased GMV in the left superior occipital gyrus, cuneus, and precuneus, and in the right angular gyrus. Significant interactions of ADHD and the CT haplotype were found in the right postcentral gyrus for ReHo and in the right supplementary motor area for GMV. For the ADHD-CT group, we found negative correlations of total correct responses in PRM and SRM and positive correlations of mean latency of correct responses in PRM with the GMV in the left superior occipital gyrus, cuneus, and precuneus. Our findings suggest that the DAT1-related GMV alterations in the posterior cortical regions may contribute to visual memory performance in children with ADHD.

Fregoli Syndrome - A Review Article

Fregoli delusion or the delusion of doubles is a rare disorder in which a person holds a delusional belief that different people are in fact a single person who changes appearance or is in disguise. The syndrome may be related to a brain lesion and is often of a paranoid nature with the delusional person believing themselves persecuted by the person they believe is in disguise. Fregoli caused by Levodopa treatment and traumatic brain injury and exibit the signs and symptoms Delusions, Visual memory deficit, deficit in self-monitoring, deficit in self-awareness, Hallucinations and treatment and mostly utilize the antipsychotic type of drugs as well as antidepressant medication.

Association of GPX1 and GPX4 polymorphisms with episodic memory and Alzheimer’s disease

It is well established that healthy aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD) are associated with substantial declines in episodic memory. However, there is still debate about the roles of GPX1 and GPX4 polymorphisms. The aim of this study was to investigate the association of rs1050450 and rs713041 polymorphisms with memory. This research was composed of a cross-sectional study (334 subjects) and a case-control study (108 healthy controls and 103 with AD-NINCDS/ARDA, DSM-IV-TR criteria). For the association of the genetic polymorphisms with memory or cognitive loss, the phenotypes were analyzed as follows: 1) each memory as a quantitative trait; 2) presence of deficit on a specific memory; 3) presence of MCI; 4) presence of AD. To assess verbal learning and the ability to store new information, we used the Rey Verbal Learning Test. Scores were recorded as a function of age as in the WMS-R testing battery. DNA was obtained from whole blood, and genotypes for GPX1 (rs1050450) and GPX4 (rs713041) were detected by allelic discrimination assay using TaqMan® MGB probes on a real-time PCR system. GPX1 TT homozygotes had lower long-term visual memory scores than CC/CT group (-0.28 ± 1.03 vs. 0.13 ± 1.03, respectively, p = 0.017). For the GPX4 rs713041, the frequency of the TT genotype was higher in the group with normal scores than in the group with long-term visual memory deficits (p = 0.025). In a multivariate logistic regression, GPX1 CC homozygotes had a 2.85 higher chance of developing AD (OR = 2.85, CI95% = 1.04–7.78, p = 0.041) in comparison to the reference genotype. No significant differences were observed regarding the MCI group between genetic variants. This study is one of the first to show that polymorphisms in GPX1 and GPX4 are significantly associated with episodic memory and AD in a South Brazilian population.

Perceived cognitive impairment in people with colorectal cancer who do and do not receive chemotherapy.

Cognitive symptoms are common after cancer, but poorly associated with neuropsychological results. We previously reported colorectal cancer (CRC) patients had more cognitive impairment than controls. Here, we explore relationships between cognitive symptoms and neuropsychological domains. Subjects with CRC (N=362) and 72 healthy controls completed neuropsychological assessments and Functional Assessment of Cancer Therapy-Cognition (FACT-COG) at baseline (pre-chemotherapy) and 6, 12, and 24months. Associations between neuropsychological and FACT-COG scores were explored: perceived cognitive impairment (PCI), perceived cognitive ability (PCA), impact of PCI on quality of life (CogQOL). Of 362CRC subjects, 289 had loco-regional disease and 173 received chemotherapy (CTh+). At baseline, groups did not differ on total FACT-COG, PCI, or PCA scores. All scores, except PCA, were worse at 6months in CTh+. CRC patients not receiving chemotherapy did not differ from controls on FACT-COG domains. PCA associated weakly (r=0.28-0.34) with attention/executive function, visual memory, and global deficit score. There was no association between PCI and neuropsychological domains. Fatigue, anxiety/depression, and poorer quality of life were associated with PCI and CogQOL (r=0.44-0.51) in CRC patients. No association was seen between total FACT-COG or PCI, and neuropsychological domains. A weak-moderate association was found between PCA and attention/executive function and visual memory. The study was registered with clinicaltrials.gov (trial registration: NCT00188331). Cognitive symptoms are associated with fatigue, anxiety/depression, and poorer quality of life, and do not appear to be related to actual cognitive performance. Rates were lower than that reported in breast cancer survivors. Cognitive symptoms were greatest in those who received chemotherapy, with no significant difference between the non-chemotherapy survivors and healthy controls.

Cognitive dysfunction associated with aluminum hydroxide-induced macrophagic myofasciitis: A reappraisal of neuropsychological profile

Patients with macrophagic myofasciitis (MMF) present with diffuse arthromyalgias, chronic fatigue, and cognitive disorder. Representative features of MMF-associated cognitive dysfunction include attentional dysfunction, dysexecutive syndrome, visual memory deficit and left ear extinction. Our study aims to reevaluate the neuropsychological profile of MMF. 105 unselected consecutive MMF patients were subjected to a neuropsychological battery of screen short term and long-term memory, executive functions, attentional abilities, instrumental functions and dichotic listening. From these results, patients were classified in four different groups: Subsymptomatic patients (n=41) with performance above pathological threshold (−1.65 SD) in all tests; Fronto-subcortical patients (n=31) who showed pathological results at executive functions and selective attention tests; Papezian patients (n=24) who showed pathological results in storage, recognition and consolidation functions for episodic verbal memory, in addition to fronto-subcortical dysfunction; and Extinction patients (n=9) who had a left ear extinction at dichotic listening test in association to fronto-subcortical and papezian dysfunction. In addition, inter-test analysis showed that patients with apparently normal cognitive functions (Subsymptomatic group) performed significantly worse to attention tests compared to others. In conclusion, our study shows that (i) most patients have specific cognitive deficits; (ii) all patients with cognitive deficit have impairment of executive functions and selective attention; (iii) patients without measurable cognitive deficits display significant weakness in attention; (iv) episodic memory impairment affects verbal, but not visual, memory; (v) none of the patients show an instrumental dysfunction.