A specific deficit in visuospatial simultaneous working memory in Down syndrome

Background   Recent studies have demonstrated that individuals with Down syndrome (DS) present both central and verbal working memory deficits compared with controls matched for mental age, whereas evidence on visuospatial working memory (VSWM) has remained ambiguous. The present paper uses a battery of VSWM tasks to test the hypothesis that individuals with DS can also encounter specific difficulties in VSWM.
Method   Four tasks were administered to 34 children and adolescents with DS and 34 controls matched for verbal mental age. In two of these tasks, participants had to remember a series of locations sequentially presented on a matrix (spatial-sequential WM); in another two, they had to remember locations simultaneously presented (spatial-simultaneous WM).
Results and Conclusions   Results showed that individuals with DS are poorer than controls in the spatial-simultaneous tasks, but not in the spatial-sequential tasks. These findings were not due to a difference in speed of visuospatial processing. In fact, when performances of the two groups in VSWM were compared using speed measures as covariates, differences between groups remained. It is suggested that the simultaneous VSWM deficit of individuals with DS could be due to the request for processing more than one item at a time.     

Neurocognitive impairments and quality of life in unemployed patients with remitted major depressive disorder

Quality of life (QOL) has been reported to be impaired in patients with major depressive disorder (MDD), even after remission according to symptom rating scales. Although a relationship between QOL and neurocognitive dysfunction has been reported during depressive episodes, little is known about this relationship in remitted MDD patients. The aim of the present study was to investigate the relationship between QOL and neurocognitive dysfunction in patients with remitted MDD while controlling for confounding factors. Forty-three remitted MDD patients were assessed with neuropsychological tests and QOL, which was measured by a short-form 36-item health survey. The neurocognitive performances of the patients were compared with those of 43 healthy controls. We next evaluated the relationships between neurocognitive impairments, clinical factors, and QOL. Remitted MDD patients had poorer neurocognitive performances than healthy controls for psychomotor speed, attention, and verbal memory. Residual depressive symptoms were strongly associated with QOL. Delayed verbal recall was associated with general health perceptions, which are part of the QOL assessment, even after the effects of the residual depressive symptoms were considered. The results may indicate that clinicians should try to detect neurocognitive dysfunctions that may interfere with QOL using neurocognitive assessments in their daily practice.     

Visuo–spatial working memory is an important source of domain-general vulnerability in the development of arithmetic cognition

The study of developmental disorders can provide a unique window into the role of domain-general cognitive abilities and neural systems in typical and atypical development. Mathematical disabilities (MD) are characterized by marked difficulty in mathematical cognition in the presence of preserved intelligence and verbal ability. Although studies of MD have most often focused on the role of core deficits in numerical processing, domain-general cognitive abilities, in particular working memory (WM), have also been implicated. Here we identify specific WM components that are impaired in children with MD and then examine their role in arithmetic problem solving. Compared to typically developing (TD) children, the MD group demonstrated lower arithmetic performance and lower visuo-spatial working memory (VSWM) scores with preserved abilities on the phonological and central executive components of WM. Whole brain analysis revealed that, during arithmetic problem solving, left posterior parietal cortex, bilateral dorsolateral and ventrolateral prefrontal cortex, cingulate gyrus and precuneus, and fusiform gyrus responses were positively correlated with VSWM ability in TD children, but not in the MD group. Additional analyses using a priori posterior parietal cortex regions previously implicated in WM tasks, demonstrated a convergent pattern of results during arithmetic problem solving. These results suggest that MD is characterized by a common locus of arithmetic and VSWM deficits at both the cognitive and functional neuroanatomical levels. Unlike TD children, children with MD do not use VSWM resources appropriately during arithmetic problem solving. This work advances our understanding of VSWM as an important domain-general cognitive process in both typical and atypical mathematical skill development.     

Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder

Objectives: Systematic parsing of executive function processes is critical for the development of more specific models of neurobiological processes mediating disturbed cognition in youth with bipolar disorder (BPD). Methods: A sample of 33 children and adolescents with bipolar I disorder (BPD I) (mean age 12.1 ± 3.0 years, 39% female) and 44 demographically matched healthy participants (mean age 12.9 ± 2.8 years, 50% female) completed a neurocognitive battery including measures aimed at detection of disruption in prefrontal cortical circuitry (i.e., working memory, set shifting, and rule attainment). Results: Compared to healthy controls, BPD I children exhibited significant deficits in spatial working memory, visual sequencing and scanning, verbal fluency and abstract problem solving, particularly when a memory component was involved. In our spatial delayed response task, memory set size was parametrically varied; the performance pattern in BPD I children suggested deficits in short‐term memory encoding and/or storage, rather than capacity limitations in spatial working memory. Earlier age at onset of illness and antipsychotic medication usage were associated with poorer performance on speeded information‐processing tasks; however, severity of mood symptomatology and comorbidity with disruptive behavior disorders were not associated with task performance. Conclusions: These results suggest impairment in measures of prefrontal cortical function in juvenile BPD I that are similar to those seen in the adult form of the illness, and implicate both the ventral and dorsolateral prefrontal cortex as loci of pathology in juvenile BPD. As these deficits were not associated with clinical state or comorbidity with other disorders, they may reflect trait‐related impairments, a hypothesis that will be pursued further in longitudinal studies.     

Encoding dysfunctions in a dynamic-static paradigm for visuospatial working memory in first-episode psychosis patients: a 2-year follow-up study

Aim: To investigate static and dynamic visuospatial working memory (VSWM) processes in first‐episode psychosis (FEP) patients and explore the validity of such measures as specific trait markers of schizophrenia. Methods: Twenty FEP patients and 20 age‐, sex‐, laterality‐ and education‐matched controls carried out a dynamic and static VSWM paradigm. At 2‐year follow up 13 patients met Diagnostic and Statistical Manual (of Mental Health Disorders) – Fourth Edition (DSM‐IV) criteria for schizophrenia, 1 for bipolar disorder, 1 for brief psychotic episode and 5 for schizotypal personality disorder. Results: Compared with controls, the 20 FEP patients showed severe impairment in the dynamic VSWM condition but much less impairment in the static condition. No specific bias in stimulus selection was detected in the two tasks. Two‐year follow‐up evaluations suggested poorer baseline scores on the dynamic task clearly differentiated the 13 FEP patients who developed schizophrenia from the seven who did not. Conclusions: Results suggest deficits in VSWM in FEP patients. Specific exploratory analyses further suggest that deficit in monitoring‐manipulation VSWM processes, especially involved in our dynamic VSWM task, can be a reliable marker of schizophrenia.     

Enhanced working and verbal memory after lamotrigine treatment in pediatric bipolar disorder

Pavuluri MN, Passarotti AM, Mohammed T, Carbray JA, Sweeney JA. Enhanced working and verbal memory after lamotrigine treatment in pediatric bipolar disorder.
Bipolar Disord 2010: 12: 213–220. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objective: To examine the treatment impact of lamotrigine on the neurocognitive profile of patients with pediatric bipolar disorder (PBD). Method: Healthy controls (HC) (n = 24; mean age = 12.4 ± 3.3 years) and unmedicated PBD patients with manic, mixed, or hypomanic episodes (n = 34; mean age = 13 ± 3.1 years) were matched for IQ, age, sex, race, and socioeconomic status. A neurocognitive battery was administered at baseline and again after 14 weeks, during which PBD patients were treated with lamotrigine. Results: Clinical symptoms improved with treatment in the patient group with significant change from baseline to follow‐up on the Young Mania Rating Scale (p < 0.001) and the Children’s Depression Rating Scale–Revised (p < 0.001). Global neurocognitive function improved with lamotrigine in PBD patients over time relative to that in HC, although overall performance remained impaired. Working memory and verbal memory significantly improved with treatment in patients, and deficits in these domains were no longer significantly impaired relative to HC at follow‐up. Executive function significantly improved with treatment in the patient group but still lagged behind HC at follow‐up. Performance on attention tests did not improve with treatment. Conclusions: There appears to be significant improvement in cognitive abilities in PBD patients treated with lamotrigine that is most prominent in the areas of working memory and verbal memory and that occurs along with mood stabilization.     

The impact of neurocognitive impairment on occupational recovery of clinically stable patients with bipolar disorder: a prospective study

Bearden CE, Shih VH, Green MF, Gitlin M, Sokolski KN, Levander E, Marusak S, Hammen C, Sugar CA, Altshuler LL. The impact of neurocognitive impairment on occupational recovery of clinically stable patients with bipolar disorder: a prospective study.
Bipolar Disord 2011: 13: 323–333. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objective: Many patients with bipolar disorder do not regain their premorbid level of occupational functioning even after mood episodes have resolved. The reasons for this are not well understood. We evaluated the relationship between neurocognition and occupational function in bipolar disorder patients, following symptomatic recovery. Methods: A total of 79 previously employed adults with bipolar I disorder who achieved symptomatic recovery (i.e., at least six weeks clinically euthymic) following a manic episode underwent a neurocognitive evaluation and assessment of occupational functioning. Study participants were evaluated every three months thereafter for up to nine months. Factor analysis was applied to reduce the initial set of neurocognitive variables to five domains: episodic memory, working memory/attention, executive function, visual scanning, and speed of processing. Multiple logistic regression models were used to examine the joint predictive values of these domains for determining occupational recovery. Results: At the time of symptomatic recovery, four of five neurocognitive factors were significant predictors of concomitant occupational recovery and the fifth, executive function, showed a trend in the same direction. For those not occupationally recovered at baseline, longitudinal analyses revealed that changes between baseline and the three‐month follow‐up timepoint in most cognitive domains were robust and highly significant predictors of occupational recovery at three months. Conclusions: These findings indicate that better neurocognitive function in multiple domains and improvement in these domains over time are strongly predictive of subsequent occupational recovery. Treatments that target cognitive deficit may therefore have potential for improving long‐term vocational functioning in bipolar illness.     

Working memory brain activity and capacity link MAOA polymorphism to aggressive behavior during development

A developmental increase in working memory capacity is an important part of cognitive development, and low working memory (WM) capacity is a risk factor for developing psychopathology. Brain activity represents a promising endophenotype for linking genes to behavior and for improving our understanding of the neurobiology of WM development. We investigated gene–brain–behavior relationships by focusing on 18 single-nucleotide polymorphisms (SNPs) located in six dopaminergic candidate genes (COMT, SLC6A3/DAT1, DBH, DRD4, DRD5, MAOA). Visuospatial WM (VSWM) brain activity, measured with functional magnetic resonance imaging, and VSWM capacity were assessed in a longitudinal study of typically developing children and adolescents. Behavioral problems were evaluated using the Child Behavior Checklist (CBCL). One SNP (rs6609257), located ∼6.6 kb downstream of the monoamine oxidase A gene (MAOA) on human chromosome X, significantly affected brain activity in a network of frontal, parietal and occipital regions. Increased activity in this network, but not in caudate nucleus or anterior prefrontal regions, was correlated with VSWM capacity, which in turn predicted externalizing (aggressive/oppositional) symptoms, with higher WM capacity associated with fewer externalizing symptoms. There were no direct significant correlations between rs6609257 and behavioral symptoms. These results suggest a mediating role of WM brain activity and capacity in linking the MAOA gene to aggressive behavior during development.     

Working memory in schizophrenia and mania: correlation with symptoms during the acute and subacute phases

OBJECTIVE: The aims of this study were to examine working memory in the acute subacute phase of schizophrenia and mania and to examine correlations between working memory and specific symptom domains. METHOD: Visuospatial working memory and symptom profiles were assessed in three groups (schizophrenia group, n= 19; mania, n= 12; controls, n= 19) on two occasions separated by 4 weeks. RESULTS: Both patient groups had significant deficits on working memory compared to the well controls and the schizophrenia and mania groups were equally impaired. All groups showed equivalent improvement over time. In the patient groups, impaired working memory was significantly correlated with the presence of both negative symptoms and positive thought disorder. CONCLUSION: Impaired working memory is found in both schizophrenia and mania during the acute subacute phases. Further research is required in order to clarify the neurocognitive mechanisms linking impaired working memory with both negative symptoms and positive thought disorder.     

A functional MRI study of working memory in adolescents and young adults at genetic risk for bipolar disorder: preliminary findings

Thermenos HW, Makris N, Whitfield‐Gabrieli S, Brown AB, Giuliano AJ, Lee EH, Faraone SV, Tsuang MT, Seidman LJ. A functional MRI study of working memory in adolescents and young adults at genetic risk for bipolar disorder: preliminary findings.
Bipolar Disord 2011: 13: 272–286. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: In this report, we seek to (i) identify a potential neuroimaging endophenotype for bipolar disorder (BD) in emotion regulatory and autonomic circuitry in young first‐degree relatives of persons with BD; and (ii) replicate our previous work identifying the functional neuroanatomy of working memory (WM) in an older sample of relatives of persons with BD. Methods: Ten adolescent and young adult (age 13–24) unmedicated, non‐ill, first‐degree relatives of persons with BD (RELS) and 10 demographically comparable healthy controls performed a 2‐back WM task and a 0‐back control task during functional magnetic resonance imaging (fMRI). fMRI data were collected on a 1.5 Tesla scanner and analyzed using SPM‐2. Mood was assessed on the day of scanning. Results: The groups did not differ on any demographic, neuropsychological, or in‐scanner task performance variables. In contrast to controls, RELS showed (i) weak task‐dependent modulation activity in the cerebellar vermis (CV), insula, and amygdala/parahippocampal region, and (ii) exaggerated modulation of activity in the frontopolar cortex and brainstem, even after controlling for potential confounders. Many of the group differences were driven by differences in activity in the low‐level (0‐back) baseline task. Conclusions: Young, unmedicated RELS exhibited altered task‐dependent modulation of frontopolar, CV, and insula activity during WM, especially during the low‐level (0‐back) baseline task. Results are largely consistent with our initial study of older adult RELS, suggesting these alterations may represent biomarkers of genetic risk for BD.     

Psychopathology and working memory-induced activation of the prefrontal cortex in schizophrenia-like psychosis of epilepsy: Evidence from magnetoencephalography

Aim: The aim of this study was to investigate whether magnetoencephalographic oscillations underlying working memory dysfunction in the dorsolateral prefrontal cortex (DLPFC) are related to psychopathological disturbance in patients with schizophrenia‐like psychosis of epilepsy (SLPE). Methods: Twelve patients with SLPE and 14 non‐psychotic epilepsy controls participated in this study. Magnetoencephalography was recorded while patients performed a visual working memory (WM) task. Psychopathology was assessed using a four‐factor structure of the Brief Psychiatric Rating Scale, and regression analyses were carried out to examine the relative impact of severity of psychopathology on WM‐induced activation of the DLPFC. Results: We found that activation of the WM‐compromising DLPFC, as indicated by increased alpha desynchronization in patients with SLPE compared with their non‐psychotic counterparts, showed a positive linear correlation with disorganization symptom scores. This association remained significant after controlling for confounding factors, including age, task performance, IQ, and duration of psychosis. Conclusion: Our results indicate that abnormal activation in prefrontal areas engaged during working memory may be critical to domains of psychopathology, in particular disorganized thought‐processing in patients with SLPE.     

Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder

Objectives:  Systematic parsing of executive function processes is critical for the development of more specific models of neurobiological processes mediating disturbed cognition in youth with bipolar disorder (BPD).
Methods:  A sample of 33 children and adolescents with bipolar I disorder (BPD I) (mean age 12.1 ± 3.0 years, 39% female) and 44 demographically matched healthy participants (mean age 12.9 ± 2.8 years, 50% female) completed a neurocognitive battery including measures aimed at detection of disruption in prefrontal cortical circuitry (i.e., working memory, set shifting, and rule attainment).
Results:  Compared to healthy controls, BPD I children exhibited significant deficits in spatial working memory, visual sequencing and scanning, verbal fluency and abstract problem solving, particularly when a memory component was involved. In our spatial delayed response task, memory set size was parametrically varied; the performance pattern in BPD I children suggested deficits in short-term memory encoding and/or storage, rather than capacity limitations in spatial working memory. Earlier age at onset of illness and antipsychotic medication usage were associated with poorer performance on speeded information-processing tasks; however, severity of mood symptomatology and comorbidity with disruptive behavior disorders were not associated with task performance.
Conclusions:  These results suggest impairment in measures of prefrontal cortical function in juvenile BPD I that are similar to those seen in the adult form of the illness, and implicate both the ventral and dorsolateral prefrontal cortex as loci of pathology in juvenile BPD. As these deficits were not associated with clinical state or comorbidity with other disorders, they may reflect trait-related impairments, a hypothesis that will be pursued further in longitudinal studies.     

Fronto-temporal dysregulation in remitted bipolar patients: an fMRI delayed-non-match-to-sample (DNMS) study

Objectives:  Bipolar disorder is associated with working memory (WM) impairments that persist during periods of symptomatic remission. However, the neural underpinnings of these deficits are not well understood.
Methods:  Fifteen clinically remitted bipolar patients and 15 demographically matched healthy controls underwent functional magnetic resonance imaging while performing a novel delayed-non-match-to-sample (DNMS) task. This nonverbal DNMS task involves two conditions, one requiring the organization of existing memory traces ('familiarity'), and one involving the formation of new memory traces ('novelty'). These processes are thought to differentially engage the prefrontal cortex and medial temporal lobe, respectively.
Results:  Although behavioral performance did not differ between groups, bipolar patients and controls exhibited significantly different patterns of neural activity during task performance. Patients showed relative hyperactivation in the right prefrontal gyrus and relative hypoactivation in visual processing regions compared to healthy subjects across both task conditions. During the novelty condition, patients showed a pattern of hypoactivation relative to controls in medial temporal regions, with relative hyperactivation in the anterior cingulate.
Conclusions:  These findings suggest that disruption in fronto-temporal neural circuitry may underlie memory difficulties frequently observed in patients with bipolar disorder.     

Increased functional interaction within frontoparietal network during working memory task in major depressive disorder

Abnormal fronto‐parietal activation has been suggested as a neural underpinning of the working memory (WM) deficits in major depressive disorder (MDD). However, the potential interaction within the frontoparietal network during WM processing in MDD remains unclear. This study aimed to examine the role of abnormal functional interactions within frontoparietal network in the neuropathological mechanisms of WM deficits in MDD. A total of 40 MDD patients and 47 demographic matched healthy controls (HCs) were included. Functional magnetic resonance imaging and behavioral data were collected during numeric n‐back tasks. The psychophysiological interaction and dynamic causal modelling methods were applied to investigate the connectivity within the frontoparietal network in MDD during n‐back tasks. The psychophysiological interaction analysis revealed that MDD patients showed increased functional connectivity between the right inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (dlPFC) compared with HCs during the 2‐back task. The dynamic causal modelling analysis revealed that MDD patients had significantly increased forward modulation connectivity from the right IPL to the right dlPFC than HCs during the 2‐back task. Partial correlation was used to calculate the relationship between connective parameters and psychological variables in the MDD group, which showed that the effective connectivity from right IPL to right dlPFC was correlated negatively with the sensitivity index d’ of WM performances and positively with the depressive severity in MDD group. In conclusion, the abnormal functional and effective connectivity between frontal and parietal regions might contribute to explain the neuropathological mechanism of working memory deficits in major depressive disorder.     

Functional network connectivity impairments and core cognitive deficits in schizophrenia

Cognitive deficits contribute to functional disability in patients with schizophrenia and may be related to altered functional networks that serve cognition. We evaluated the integrity of major functional networks and assessed their role in supporting two cognitive functions affected in schizophrenia: processing speed (PS) and working memory (WM). Resting‐state functional magnetic resonance imaging (rsfMRI) data, N = 261 patients and 327 controls, were aggregated from three independent cohorts and evaluated using Enhancing NeuroImaging Genetics through Meta Analysis rsfMRI analysis pipeline. Meta‐ and mega‐analyses were used to evaluate patient‐control differences in functional connectivity (FC) measures. Canonical correlation analysis was used to study the association between cognitive deficits and FC measures. Patients showed consistent patterns of cognitive and resting‐state FC (rsFC) deficits across three cohorts. Patient‐control differences in rsFC calculated using seed‐based and dual‐regression approaches were consistent (Cohen's d: 0.31 ± 0.09 and 0.29 ± 0.08, p < 10^?4). RsFC measures explained 12–17% of the individual variations in PS and WM in the full sample and in patients and controls separately, with the strongest correlations found in salience, auditory, somatosensory, and default‐mode networks. The pattern of association between rsFC (within‐network) and PS (r = .45, p = .07) and WM (r = .36, p = .16), and rsFC (between‐network) and PS (r = .52, p = 8.4 × 10^?3) and WM (r = .47, p = .02), derived from multiple networks was related to effect size of patient‐control differences in the functional networks. No association was detected between rsFC and current medication dose or psychosis ratings. Patients demonstrated significant reduction in several FC networks that may partially underlie some of the core neurocognitive deficits in schizophrenia. The strength of connectivity‐cognition relationships in different networks was strongly associated with network's vulnerability to schizophrenia.     

The neurocognitive signature of psychotic bipolar disorder.

BACKGROUND: Psychotic bipolar disorder may represent a neurobiologically distinct subgroup of bipolar affective illness. We sought to ascertain the profile of cognitive impairment in patients with bipolar disorder and to determine whether a distinct profile of cognitive deficits characterizes bipolar patients with a history of psychosis. METHODS: Sixty-nine outpatients with bipolar I disorder (34 with a history of psychotic symptoms and 35 with no history of psychosis) and 35 healthy comparison subjects underwent a comprehensive neurocognitive battery. All three groups were demographically matched. RESULTS: Despite preserved general intellectual function, bipolar I patients overall showed moderate impairments on tests of episodic memory and specific executive measures (average effect size = .58), and moderate to severe deficits on attentional and processing speed tasks (average effect size = .82). Bipolar I patients with a history of psychosis were impaired on measures of executive functioning and spatial working memory compared with bipolar patients without history of psychosis. CONCLUSIONS: Psychotic bipolar disorder was associated with differential impairment on tasks requiring frontal/executive processing, suggesting that psychotic symptoms may have neural correlates that are at least partially independent of those associated with bipolar I disorder more generally. However, deficits in attention, psychomotor speed, and memory appear to be part of the broader disease phenotype in patients with bipolar disorder.     

Beta band oscillatory deficits during working memory encoding in adolescents with attention‐deficit hyperactive disorder

Attention‐deficit hyperactivity disorder (ADHD) is a neurobehavioural disorder, characterized by symptoms of inattention and/or hyperactivity/impulsivity, in addition to various cognitive deficits, including working memory impairments. This pathology arises from a complex constellation of genetic, structural and neurotransmission abnormalities, which give rise to the aberrant electrophysiological patterns evident in patients with ADHD. Among such, findings have consistently provided support in favour of weaker power across the beta frequency range. Evidence has also emerged that beta rhythmic decrements are linked to working memory encoding. The catecholaminergic modulation of both working memory and beta oscillations may suggest that the link between the two might be rooted at the neurotransmission level. Studies have consistently shown that ADHD involves significant catecholaminergic dysregulation, which is also supported by other clinical studies that demonstrate stimulant‐induced amelioration of ADHD symptomology. In this study, we explore the possible ways that might relate ADHD, working memory, beta rhythms and catecholaminergic signalling altogether by investigating the integrity of encoding‐relevant electroencephalographic beta rhythms in medication‐naïve and stimulant‐medicated adolescent patients. The aberrant parietal and frontal encoding‐related beta rhythm revealed in the ADHD patients together with a working memory (WM) deficit as observed herein was reversed by methylphenidate in the latter case but not with regard to the beta rhythm. This finding per se raises the issue of the role played by beta rhythms in the WM deficits associated with ADHD.     

Deficits of visuospatial working memory and executive function in single- versus multiple-domain amnestic mild cognitive impairment: A combined ERP and sLORETA study

ObjectiveAccording to recent criteria of classification, amnestic mild cognitive impairment (aMCI) could be divided into two categories: single-domain aMCI (sd-aMCI) and multiple-domain aMCI (md-aMCI). The difference between sd-aMCI and md-aMCI needs further exploration. The present study aimed to compare deficits in visuospatial working memory (VSWM) and executive function between sd-aMCI versus md-aMCI patients by use of event-related potentials (ERP) and standardized low-resolution brain electromagnetic tomography analysis (sLORETA).MethodsThe ERP data were measured and analyzed in 26 sd-aMCI, 13 md-aMCI patients and 46 healthy elderly controls (HEC) during VSWM and Go/Nogo processes.ResultsDuring VSWM task, md-aMCI patients showed decreased P300 amplitude compared to HEC and sd-aMCI patients (All p < 0.05). As compared to sd-aMCI, md-aMCI showed a hypoactivation in the right middle frontal gyrus in 1-back task during the P300 time range. During the Go/Nogo task, sd-aMCI and md-aMCI patients showed reduced N200 amplitude, compared to HEC (All p < 0.05). However, md-aMCI patients had decreased N200 amplitude, with respect to sd-aMCI patients. Further, as compared to sd-aMCI patients, md-aMCI patients showed a hypoactivation in the right superior frontal gyrus during the N200 time range.ConclusionsThese findings with a combined ERP and sLORETA study showed more severe deficits in updating operations of WM, detections of the target stimulus and conflict processes in md-aMCI, compared to sd-aMCI patients.SignificanceThe present study showed that a combined ERP and sLORETA study during the VSWM and Go/Nogo tasks could distinguish md-aMCI from sd-aMCI.     

Impaired verbal memory in young adults with unipolar and bipolar depression

Aim: Early stages of severe mood disorders may be accompanied by neurocognitive changes. Specifically, deficits in verbal memory have been linked to depression in young people. This study examined whether young adults with unipolar compared with bipolar depression showed similar neurocognitive deficits. Methods: A total of 57 young adults (16–32 years) were assessed in this study. Twenty with unipolar and 20 with bipolar depression, all currently depressed, were compared with 17 healthy controls. Neuropsychological assessment included psychomotor speed, attention for routine mental operations, attentional switching, executive control and verbal learning and memory. Results: Both unipolar and bipolar subjects showed significant impairments in verbal memory and attentional switching compared with controls. Both mood disorder groups showed no impairments in psychomotor speed, attention for routine mental operations and executive control. Effects size calculations show that the unipolar and bipolar groups do not differ from each other across a range of neurocognitive measures. Conclusion: Neurocognitive deficits in young adults with current depressive syndromes appear to differ from those typically seen in older patients. In early adulthood, both unipolar and bipolar depression may be distinguished by poor verbal memory, despite intact speed of processing, attention and executive functions. This study suggests that there is utility in neuropsychological testing for young adults in the early stages of severe mood disorders. In order to prevent neurobiological changes inherent to the disease, pharmacological and non-pharmacological interventions that target verbal memory deficits may be optimally delivered early in the disease course.     

Memory dysfunction in panic disorder: an investigation of the role of chronic benzodiazepine use

Background: Studies of the neurocognitive effects of long‐term benzodiazepine use have been confounded by the presence of neurocognitive deficits characterizing the clinical conditions for which these medications are taken. Similarly, studies of the neurocognitive effects of anxiety disorders have been confounded by the inclusion of chronically benzodiazepine‐medicated patients. This study was designed to tease apart the potentially confounding effects of long‐term benzodiazepine use and panic disorder (PD) on memory and visuoconstructive abilities. Methods: Twenty chronically benzodiazepine‐medicated and 20 benzodiazepine‐free patients with PD with agoraphobia were compared with a group of 20 normal control participants, group‐matched for age, education, and gender on a battery of neuropsychological tests assessing short‐term, episodic long‐term, and semantic memory, as well as visuoconstructive abilities. Results: Results indicated that benzodiazepine‐free panic patients were relatively impaired in nonverbal short‐term and nonverbal episodic long‐term memory and visuoconstructive abilities, whereas verbal short‐term and verbal episodic memory and semantic memory were preserved. Only limited evidence was found for more pronounced impairments in chronically benzodiazepine‐medicated PD patients. Conclusions: This study provides evidence that patients with PD are characterized by relative impairments in nonverbal memory and visuoconstructive abilities, independent of benzodiazepine use. Nonetheless, we found evidence that chronic treatment with benzodiazepines is associated with intensification of select relative impairments in this realm. Documentation of these deficits raises questions about the broader etiology of neurocognitive impairment in PD as well as its impact on daily functioning. Depression and Anxiety, 2011. © 2011 Wiley Periodicals, Inc.