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The association between adversity and cognition varies according to the specific adversity, when the adversity was experienced, and the cognitive domains investigated. Disentangling the effect of adversity and the underlying mechanistic pathway is therefore difficult. The association between adversity (i.e., maltreatment) accumulated over the life course and cognitive flexibility, as well as two potential mediators (i.e., intra-individual variability in reaction time and depression) of this association, were investigated. Data stem from the baseline population of the UK Biobank study (N = 73,489,Mdnage = 56,SDage = 7.628, 55.740% of women). Cumulative life course adversity (specifically maltreatment) was measured with items based on the Childhood Trauma Questionnaire (CTS-5) and items adapted from the British Crime Survey. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9). Intra-individual variability in reaction time was measured with a reaction time test “snap game” and the Trail Making Test A and B were used as a measure of cognitive flexibility. A path analysis was performed on these data. Higher cumulative adverse experiences were associated with lower performance in cognitive flexibility (β = .016,p p

Funding: The research of A.M.S. was supported by an ‘INQMINDS’ ERC Starting Grant no. (SEP-210159400). Executive functions (EF) are a core aspect of cognition. Research with adult humans has produced evidence for unity and diversity in the structure of EF. Studies with preschoolers favour a 1-factor model, in which variation in EF tasks is best explained by a single underlying trait on which all EF tasks load. How EF are structured in nonhuman primates remains unknown. This study starts to fill this gap through a comparative, multi-trait multi-method test battery with preschoolers (N = 185) and chimpanzees (N = 55). The battery aimed at measuring working memory updating, inhibition, and attention shifting with three non-verbal tasks per function. For both species the correlations between tasks were low to moderate and not confined to tasks within the same putative function. Factor analyses produced some evidence for the unity of executive functions in both groups, in that our analyses revealed shared variance. However, we could not conclusively distinguish between 1-, 2- or 3-factor models. We discuss the implications of our findings with respect to the ecological validity of current psychometric research. Publisher PDF

Contains fulltext : 218973.pdf (Publisher’s version ) (Open Access) Aging is associated with cognitive decline, specifically in episodic memory. However, there are large individual differences in the extent of this decline and previous research suggests that these are associated with differences in executive functioning (EF). These EF differences, and associated differences in the encoding and retrieval of episodic information, have been linked to differences in the activation of particular brain regions. The "encoding/retrieval flip" (E/R flip) framework assumes deactivation and activation of specific brain regions during successful encoding and retrieval, respectively. The present study assessed whether this framework can be used to explain EF-based individual differences in memory performance of young and older participants. Young adults (N = 19) and older adults (N = 39) performed an incidental semantic encoding and memory recognition task in an fMRI setting, focusing on brain regions that show the E/R flip. The association between an index of EF and fMRI activity in brain regions showing the E/R flip was tested in each age group. EF predicted E/R flip activity in the older, but not young adults. These findings underscore the importance of individual differences in ageing research and provide empirical evidence for the association between EF and the E/R flip. 5 p.

BackgroundChronic pain is associated with emotional problems as well as difficulties in cognitive functioning. Prior experimental studies have shown that optimism, the tendency to expect that good things happen in the future, and positive emotions can counteract pain-induced task performance deficits in healthy participants. More specifically, induced optimism was found to buffer against the negative effects of experimental pain on executive functioning. This clinical experiment examined whether this beneficial effect can be extended to a chronic pain population.MethodsPatients (N=122) were randomized to a positive psychology Internet-based intervention (PPI; n=74) or a waiting list control condition (WLC; n=48). The PPI consisted of positive psychology exercises that particularly target optimism, positive emotions and self-compassion.ResultsResults demonstrated that patients in the PPI condition scored higher on happiness, optimism, positive future expectancies, positive affect, self-compassion and ability to live a desired life despite pain, and scored lower on pain catastrophizing, depression and anxiety compared to patients in the WLC condition. However, executive task performance did not improve following completion of the PPI, compared to the WLC condition.ConclusionsDespite the lack of evidence that positive emotions and optimism can improve executive task performance in chronic pain patients, this study did convincingly demonstrate that it is possible to increase positive emotions and optimism in chronic pain patients with an online positive psychology intervention. It is imperative to further explore amendable psychological factors that may reduce the negative impact of pain on executive functioning.SignificanceWe demonstrated that an Internet-based positive psychology intervention strengthens optimism and positive emotions in chronic pain patients. These emotional improvements are not associated with improved executive task performance. As pain itself often cannot be relieved, it is imperative to have techniques to reduce the burden of living with chronic pain.

Objective This study compared the effectiveness of manualised training, executive, attention, and motor skills (TEAMS) training versus standard treatment in preschool children with attention deficit hyperactivity disorder (ADHD). We conducted a randomised parallel group, single-blinded, superiority trial. The primary outcome was ADHD symptoms and the secondary outcome was functionality. Parents and primary school teachers assessed outcomes at pretreatment, posttreatment, and at one, three, and 6 months follow-up. Results In total, 67 children (aged 3–6 years) were randomised. In the TEAMS group, 32 out of 33 (97%) participants completed the total 8-week program, compared with only 7 out of 26 (27%) in the control group. The repeated-model analyses showed no significant change between the two interventions for ADHD symptoms and functionality levels over time. The mean difference in ADHD symptoms between TEAMS versus standard treatment at posttreatment was 2.18 points (95% confidence interval − 8.62 to 13.0; trial sequential analysis-adjusted confidence interval − 19.3 to 23.7). Trial registration Clinical Trials identifier: NCT01918436 (Retrospectively registered). Registered on 7 August 2013.

Background and purpose Mechanisms underlying cognitive impairment in patients with small vessel disease (SVD) are still unknown. We hypothesized that cognition is affected by the cumulative effect of multiple SVD-related lesions on brain connectivity. We therefore assessed the relationship between the total SVD burden on MRI, global brain network efficiency, and cognition in memory clinic patients with vascular brain injury. Methods 173 patients from the memory clinic of the University Medical Center Utrecht underwent a 3 T brain MRI scan (including diffusion MRI sequences) and neuropsychological testing. MRI markers for SVD were rated and compiled in a previously developed total SVD score. Structural brain networks were reconstructed using fiber tractography followed by graph theoretical analysis. The relationship between total SVD burden score, global network efficiency and cognition was assessed using multiple linear regression analyses. Results Each point increase on the SVD burden score was associated with 0.260 [−0.404 - -0.117] SD units decrease of global brain network efficiency (p, Highlights • Increasing small vessel disease burden (SVD) related to decreasing network efficiency. • Network efficiency mediates association between SVD burden and processing speed. • Cumulative effect of SVD might partly affect cognition through disrupted connectivity.

OBJECTIVE: To summarise the current research on the effectiveness of the Amsterdam Memory and Attention Training for Children (Amat-c).METHODS: A literature search was conducted to find articles published about the Amat-c, using PubMed, psychINFO, and PsychBITE databases. Relevant search terms included Amat-c, attention and memory, and childhood ABI.RESULTS: Our literature search identified 7 articles that described 5 separate studies including 61 children in total (mostly TBI). Only one study had a control group. All results indicated positive effects on memory and attention, although in three of the studies, these results were not statistically tested. Positive results were generally maintained six months follow up.CONCLUSIONS: This review showed that the Amat-c is effective for treating attention and memory disturbances in children with ABI. However, evidence is limited and training material is outdated. We suggest that the Amat-c should be digitised and implemented in a school setting and further evaluated.

OBJECTIVE: To summarise the current research on the effectiveness of the Amsterdam Memory and Attention Training for Children (Amat-c). METHODS: A literature search was conducted to find articles published about the Amat-c, using PubMed, psychINFO, and PsychBITE databases. Relevant search terms included Amat-c, attention and memory, and childhood ABI. RESULTS: Our literature search identified 7 articles that described 5 separate studies including 61 children in total (mostly TBI). Only one study had a control group. All results indicated positive effects on memory and attention, although in three of the studies, these results were not statistically tested. Positive results were generally maintained six months follow up. CONCLUSIONS: This review showed that the Amat-c is effective for treating attention and memory disturbances in children with ABI. However, evidence is limited and training material is outdated. We suggest that the Amat-c should be digitised and implemented in a school setting and further evaluated.

We recently reported that the serotonin transporter polymorphism 5-HTTLPR moderates the relation between stress exposure and attention-deficit/hyperactivity disorder (ADHD) severity. This gene-environment interaction (GxE) has been previously tied to the processing of emotional stimuli, which is increasingly recognized to be a key factor in ADHD-related impairment. The executive control and default mode brain networks play an important role in the regulation of emotion processing, and altered connectivity of these networks has also been associated with ADHD. We therefore investigated whether resting-state connectivity of either of these networks mediates the relation of 5-HTTLPR and stress exposure with ADHD severity. Resting-state functional magnetic resonance imaging, genetic, and stress exposure questionnaire data was available for 425 adolescents and young adults (average age 17.2 years). We found that 5-HTTLPR S-allele carriers showed a more negative relation between stress exposure and connectivity of the executive control network than L-allele homozygotes, specifically in the pre/postcentral gyrus, striatum, and frontal pole. In the default mode network, we found a positive association between the GxE and supramarginal gyrus connectivity. Connectivity of either network did not significantly mediate the effect of this GxE on ADHD. Opposite effects of stress exposure on connectivity in the executive and default mode networks may contribute to findings that stress exposure is associated with lowered cognitive control and heightened levels of rumination and worrying, for S-allele carriers but not L-allele homozygotes. When combined, these effects on connectivity of both networks may relate to the emotional problems seen in individuals with ADHD. Electronic supplementary material The online version of this article (doi:10.1007/s11682-016-9633-3) contains supplementary material, which is available to authorized users.

Antipsychotics are the most widely used medications for the treatment of schizophrenia spectrum disorders. While such drugs generally ameliorate positive symptoms, clinical responses are highly variable in terms of negative symptoms and cognitive impairments. However, predictors of individual responses have been elusive. Here, we report a pharmacogenetic interaction related to a core cognitive dysfunction in patients with schizophrenia. We show that genetic variations reducing dysbindin-1 expression can identify individuals whose executive functions respond better to antipsychotic drugs, both in humans and in mice. Multilevel ex vivo and in vivo analyses in postmortem human brains and genetically modified mice demonstrate that such interaction between antipsychotics and dysbindin-1 is mediated by an imbalance between the short and long isoforms of dopamine D2 receptors, leading to enhanced presynaptic D2 function within the prefrontal cortex. These findings reveal one of the pharmacodynamic mechanisms underlying individual cognitive response to treatment in patients with schizophrenia, suggesting a potential approach for improving the use of antipsychotic drugs.

We performed meta-analyses of studies using the 6 subtests of the neuropsychological test battery, the Behavioural Assessment of the Dysexecutive Syndrome (BADS), in order to assess and compare subdomains of executive dysfunction in stable phase patients with schizophrenia relative to healthy controls. The meta-analyses were performed according to the PRISMA statement. A systematic literature search was performed yielding 10 studies for inclusion (N SCH = 375; N HC = 541). Meta-analyses were done using Stata IC 14. Due to large heterogeneity and the few number of studies a random-effects model was used along with Hedges’ g. Results showed that relative to healthy controls, patients with schizophrenia overall performed significantly worse in all subtests of BADS. However, moderate effect sizes were seen with regard to temporal estimation and strategy-forming, while very large effect sizes were seen regarding complex forward planning, inhibition, cognitive flexibility and novel problem solving. The findings from this meta-analysis demonstrate a significant difference between patients with (primarily) longer lasting schizophrenia and healthy control subjects on all subdomains of executive functions (EF). But some aspects of EF seem to be more severely affected than others. Future research and clinical interventions need to differentiate between subdomains of EF.

Healthy individuals reporting higher (as compared to lower) levels of trait rumination recruit more neural activity in dorso-cortical regions (mostly in the right hemisphere) when inhibiting negative information, possibly to compensate their difficulty to disengage from it. In the present study, we investigated whether these latter neural correlates are causally implicated in cognitive control in these individuals. We administered the Cued Emotional Control Task, a measure of cognitive control indexed by cognitive costs for inhibiting versus providing a habitual response for emotional information, in thirty-five healthy volunteers reporting a broad range of trait rumination levels. Participants completed the task after receiving both real and sham-placebo (counterbalanced order) anodal transcranial Direct Current Stimulation (tDCS) over the right dorsolateral prefrontal cortex (DLPFC). Results reveal that the tDCS induced effects on cognitive costs for emotional information were associated with individual differences in trait rumination: the higher the trait rumination level, the less cognitive costs following real neuromodulation of the right DLPFC. Interestingly, these effects were observed for both positive and negative stimuli, and not only negative information as hypothesized. Overall, the data suggest that the right DLPFC is causally involved in the alteration of cognitive control in healthy individuals who tend to ruminate, possibly by helping them to disengage from emotional material.

Individuals with alcoholism commonly exhibit impaired performance on episodic memory tasks. However, the contribution of their impaired executive functioning to poor episodic memory remains to be clarified. Thirty-six recently detoxified and sober asymptomatic alcoholic men and 36 matched non-alcoholic participants were tested for processing speed, prepotent response inhibition, mental flexibility, coordination of dual-task and a verbal episodic memory task. Compared with non-alcoholic individuals, the alcoholic patients showed impaired executive functions combined with below normal performance on both free and delayed recall. In contrast, processing speed, cued recall and recognition were preserved. Regression analyses revealed that 47% of alcoholics' episodic memory's free recall performance was predicted by mental flexibility and that 49% of their delayed recall performance was predicted by mental flexibility, manipulation of dual-task and prepotent response inhibition. Regarding participants' executive predictors of episodic memory performance, the slopes of β coefficients were significantly different between the two groups, with alcoholics requiring more their executive system than non-alcoholics. Once detoxified, alcoholic patients showed episodic memory deficits mainly characterized by impaired effortful (executive) processes. Compared with controls, patients used effortful learning strategies, which are nonetheless less efficient., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Item does not contain fulltext Objective: The main aim of this study was to investigate the effects of Huntington's disease (HD) on cognitive and affective Theory of Mind (ToM) abilities. The relation of ToM performance and executive functions was also examined. Method: Eighteen HD patients, early in the course of the disease, and 18 healthy volunteers matched for age and educational levels, were given two tasks: a nonverbal cognitive ToM task assessing attribution of intentions to others and a revised version of the 'Reading the Mind in the Eyes' test, which is an affective ToM task assessing the understanding of other people's mental states from their eyes. Participants were also given various executive tests. Results: The two ToM tasks revealed a significant impairment of ToM abilities in HD patients. Executive functioning was impaired in the HD group and ToM performance on the attribution of intentions task was dependent on several executive processes. Conclusions: Our results are consistent with the idea that both cognitive and affective aspects of ToM could be impaired in HD patients, indicating that cortico-subcortical circuits are underlying higher social functions such as ToM. The results are also consistent with the idea that only a few executive mechanisms regulate the ToM abilities we tested in this work. They also provide a basis for the understanding of the disorganized behavior and the breakdown of interpersonal relationships in daily life after HD. 11 p.

Optimal behavior relies on flexible adaptation to environmental requirements, notably based on the detection of errors. The impact of error detection on subsequent behavior typically manifests as a slowing down of RTs following errors. Precisely how errors impact the processing of subsequent stimuli and in turn shape behavior remains unresolved. To address these questions, we used an auditory spatial go/no-go task where continual feedback informed participants of whether they were too slow. We contrasted auditory-evoked potentials to left-lateralized go and right no-go stimuli as a function of performance on the preceding go stimuli, generating a 2 × 2 design with “preceding performance” (fast hit [FH], slow hit [SH]) and stimulus type (go, no-go) as within-subject factors. SH trials yielded SH trials on the following trials more often than did FHs, supporting our assumption that SHs engaged effects similar to errors. Electrophysiologically, auditory-evoked potentials modulated topographically as a function of preceding performance 80–110 msec poststimulus onset and then as a function of stimulus type at 110–140 msec, indicative of changes in the underlying brain networks. Source estimations revealed a stronger activity of prefrontal regions to stimuli after successful than error trials, followed by a stronger response of parietal areas to the no-go than go stimuli. We interpret these results in terms of a shift from a fast automatic to a slow controlled form of inhibitory control induced by the detection of errors, manifesting during low-level integration of task-relevant features of subsequent stimuli, which in turn influences response speed.

Background Anti– N -methyl-D-aspartate receptor (anti-NMDAR) encephalitis has been recently reported as autoimmune/paraneoplastic encephalitis, affecting mostly young females. Objective To describe opsoclonus-myoclonus syndrome in association with anti-NMDAR antibodies. Design Case report. Setting Geneva University Hospital. Patient A 23-year-old woman with opsoclonus-myoclonus syndrome. Results Two weeks after an episode of gastroenteritis, the patient developed symptoms of depression associated with psychomotor slowing, progressive gait instability, and opsoclonus-myoclonus. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis and intrathecal IgG synthesis with oligoclonal bands. The patient's condition worsened rapidly to an akinetic mutism, followed by a period of agitation, delirium, and hallucinations. These gradually subsided; however, a frontal behavior and executive dysfunction persisted 5 months after symptom presentation. No tumor was found. Anti-NMDAR antibodies were found in the cerebrospinal fluid. Conclusions Opsoclonus-myoclonus may occur in patients with anti-NMDAR encephalitis. Prompt diagnosis of this disorder is important because after tumor removal and immunomodulatory therapies it has a relatively good prognosis.

Recent studies have reported specific executive and attentional deficits in preterm children. However, the majority of this research has used multidetermined tasks to assess these abilities, and the interpretation of the results lacks an explicit theoretical backdrop to better understand the origin of the difficulties observed. In the present study, we used the Child Attention Network Task (Child ANT; Rueda et al. 2004) to assess the efficiency of the alerting, orienting and executive control networks. We compared the performance of 25 preterm children (gestational age ≤ 32 weeks) to 25 full-term children, all between 5½ and 6½ years of age. Results showed that, as compared to full-term children, preterm children were slower on all conditions of the Child ANT and had a specific deficit in executive control abilities. We also observed a significantly higher correlation between the orienting and executive control networks in the preterm group, suggesting less differentiation of these two networks in this population. (JINS, 2010, 16, 130–137.)

BACKGROUND: There is a need to find very early markers for pre-clinical Alzheimer's disease as interventions early in the disease process are thought to be most effective. OBJECTIVE: The present study aimed to address the potential relation between cerebrospinal fluid (CSF) biomarkers and reduced cognitive function in a relatively young cohort of memory clinic patients with subjective cognitive decline. METHODS: 122 patients (mean age 63 years) with subjective cognitive decline were recruited from two university memory clinics and followed for two years. RESULTS: The main finding was that the subgroup with objective memory decline during the study period had significantly higher T-tau at baseline than the group with improved memory. Baseline CSF variables showed a trend toward more pathological values in the patients with memory decline compared to those who improved or remained stable. The baseline memory score of those who declined was significantly better than the baseline score of those who improved over two years. The general trend for the whole group was improved memory and executive test scores. There were no differences in cognitive scores based on CSF quartiles at baseline, nor were there differences in cognitive outcome for patients with early amnestic mild cognitive impairment versus average cognitive function at baseline. CONCLUSIONS: The main finding that T-tau rather than amyloid-β was associated with memory decline do not support the prevailing opinion about the chain of events assumed to take place in Alzheimer's disease. In addition, memory decline was not associated with poor baseline memory score. Thus, a memory cut-off indicating low baseline memory would not would have identified the declining group.

Gait control depends in part on cognition. This study aims to examine the separate and combined effects of episodic memory and executive function impairments on the mean value and the coefficient of variation (CoV) of stride time among non-demented older community dwellers. Based on a cross-sectional design, 1458 older community dwellers without dementia (70.6 ± 4.9 years; 49.2 % female) were recruited and separated into cognitively healthy individuals (CHI) and individuals with cognitive impairment. A score ≤5/6 on the Short Mini-Mental State Examination defined episodic memory impairment. Impaired executive function was defined by errors on the clock-drawing test. Mean value and CoV of stride time were measured by the GAITRite® system. A total of 517 participants (35.5 %) had cognitive impairment in at least one cognitive domain. Participants with memory impairment (P = 0.006) and those with combined cognitive impairments (P < 0.001) had greater (i.e., worse gait performance) mean value of stride time (P = 0.006) compared to CHI. Participants with combined cognitive impairment had a greater CoV of stride time (i.e., worse gait performance) compared to CHI (P = 0.004) and to those with separate memory impairment (P = 0.037). Among participants with combined cognitive impairments, mean value and CoV of stride time had the highest effect size (respectively, effect size = 0.49 [95 % confidence interval (CI) 0.27;0.71] and effect size = 0.40 [95 %CI 0.18;0.62]). Participants with episodic memory or executive impairments had a greater mean value and CoV of stride time compared to those with no cognitive impairment. Combined episodic memory and executive impairments exceeded the sum of separate impairments on gait performances, suggesting a complex interplay going beyond a simple additive effect.

Persistent cognitive impairment in the euthymic state of bipolar disorder is increasingly recognized. Mounting evidence also suggests an association between neuroinflammation and cognitive dysfunction. The purpose of this study was to test if cerebrospinal fluid (CSF) markers of neuroinflammation could account for cognitive impairment in bipolar disorder. Hierarchical linear regression models were applied to account for performance in five cognitive domains using CSF neuroinflammatory biomarkers as predictors in patients with bipolar disorder type I and II (N=78). The associations between these biomarkers and cognition were further tested in healthy age- and sex-matched controls (N=86). In patients with bipolar disorder, the CSF biomarkers accounted for a significant proportion of the variance in executive functions (42.8%, p=

Theoretical models of hypnosis have emphasized the importance of attentional processes in accounting for hypnotic phenomena but their exact nature and brain substrates remain unresolved. Individuals vary in their susceptibility to hypnosis, a variability often attributed to differences in attentional functioning such as greater ability to filter irrelevant information and inhibit prepotent responses. However, behavioral studies of attentional performance outside the hypnotic state have provided conflicting results. We used fMRI to investigate the recruitment of attentional networks during a modified flanker task in High and Low hypnotizable participants. The task was performed in a normal (no hypnotized) state. While behavioral performance did not reliably differ between groups, components of the fronto-parietal executive network implicated in monitoring (anterior cingulate cortex; ACC), adjustment (lateral prefrontal cortex; latPFC), and implementation of attentional control (intraparietal sulcus; IPS) were differently activated depending on the hypnotizability of the subjects: the right inferior frontal gyrus (rIFG) was more recruited, whereas IPS and ACC were less recruited by High susceptible individuals compared to Low. Our results demonstrate that susceptibility to hypnosis is associated with particular executive control capabilities allowing efficient attentional focusing, and point to specific neural substrates in right prefrontal cortex. Significance statement We demonstrated that outside hypnosis, low hypnotizable subjects recruited more parietal cortex and anterior cingulate regions during selective attention conditions suggesting a better detection and implementation of conflict. However, outside hypnosis the right inferior frontal gyrus (rIFG) was more recruited by highly hypnotizable subjects during selective attention conditions suggesting a better control of conflict. Furthermore, in highly hypnotizable subjects this region was more connected to the default mode network suggesting a tight dialogue between internally and externally driven processes that may permit higher flexibility in attention and underlie a greater ability to dissociate.

Within preterm-born children, being born male and at a lower gestational age (GA) have both been associated with a heightened risk for developmental difficulties. However, in this population little is known about the combined effect and the influence of these risk factors on cortical structures and executive control. In the present study, 58 preterm-born children (GA ranging from 24.0 to 35.1 weeks) were administered the computerized Child Attention Network Task at 6 years of age. Brain magnetic resonance imaging was performed and analyzed using Voxel-Based Morphometry (VBM) in all children. At a behavioral level, boys born

Objective: It was hypothesized that neuropsychological impairments in children with neurofibromatosis type I (NF1) are associated with brain areas of increased T2-weighted signal intensity on MRI. Systematic and extensive examination of this hypothesis remains however scarce, particularly regarding executive dysfunction whereas hyperintensities are located preferentially in frontal-subcortical networks. In this study, we compared the executive functioning profile with characteristics of brain hyperintensities in children with NF1. Method: A sample of 36 school-age children with NF1 (7–12 years) underwent a detailed examination of executive function, including performancebased tests and child’s behavior rating in daily life. Executive function measures were compared with the characteristics of the T2-weighted hyperintensities on parallel MRI scans. The presence, number, and size of hyperintensities in the whole brain were considered as well as their main cerebral locations. Results: Executive dysfunction including traditional cognitive and ecological measures in children with NF1 is not significantly influenced by T2-weighted hyperintensities, in terms of presence or not, number, size, and location, whether in the whole brain or according to involved specific brain areas. Conclusion: T2-weighted hyperintensities, as they are currently measured, cannot be used as a strong indicator of executive dysfunction in children with NF1. Based on the available NF1 cognitive impairment pathogenesis models, a critical discussion on anatomicalfunctional relationships between hyperintensities and neuropsychological profile is proposed, especially the executive dysfunction.

Models of action selection postulate the critical involvement of the subthalamic nucleus (STN), especially in reactive inhibition processes when inappropriate responses to a sudden stimulus must be overridden. The STN could also play a key role during proactive inhibition, when subjects prepare to potentially suppress their actions. Here, we hypothesized that STN responses to reactive and proactive inhibitory control might be driven by different underlying mechanisms with specific temporal profiles. Direct neural recordings in twelve Parkinson's disease patients during a modified stop signal task (SST) revealed a decrease of beta band activity (βA, 13-35Hz) in the STN during reactive inhibition of smaller amplitude and shorter duration than during motor execution. Crucially, the onset latency of this relative increase of βA took place before the stop signal reaction time. It could thus be thought of as a "stop" signal inhibiting thalamo-cortical activity that would have supported motor execution. Finally, results also revealed a higher level of βA in the STN during proactive inhibition, which correlated with patient's inhibitory performances. We propose that βA in the STN would here participate in the implementation of a "hold your horse" signal to delay motor responses, thus prioritizing accuracy as compared to speed. In brief, our results provide strong electrophysiological support for the hypothesized role of the STN during executive control underlying proactive and reactive response suppression.

International audience; Background Many studies have highlighted the high prevalence of executive disorders in stroke. However, major uncertainties remain due to use of variable and non-validated methods. The objectives of this study were: 1) to characterize the executive disorder profile in stroke using a standardized battery, validated diagnosis criteria of executive disorders and validated framework for the interpretation of neuropsychological data and 2) examine the sensitivity of the harmonization standards protocol proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) for the diagnosis of Vascular Cognitive Impairment. Methods 237 patients (infarct: 57; cerebral hemorrhage: 54; ruptured aneurysm of the anterior communicating artery (ACoA): 80; cerebral venous thrombosis (CVT): 46) were examined by using the GREFEX battery. The patients' test results were interpreted with a validated framework derived from normative data from 780 controls. Results Dysexecutive syndrome was observed in 88 (55.7%; 95%CI: 48-63.4) out of the 156 patients with full cognitive and behavioral data: 40 (45.5%) had combined behavioral and cognitive syndromes, 29 (33%) had a behavioral disorder alone and 19 (21.6%) had a cognitive syndrome alone. The dysexecutive profile was characterized by prominent impairments of initiation and generation in the cognitive domain and by hypoactivity with disinterest and anticipation loss in the behavioral domain. Cognitive impairment was more frequent (p = 0.014) in hemorrhage and behavioral disorders were more frequent (p = 0.004) in infarct and hemorrhage. The harmonization standards protocol underestimated (p = 0.007) executive disorders in CVT or ACoA. Conclusions This profile of executive disorders implies that the assessment should include both cognitive tests and a validated inventory for behavioral dysexecutive syndrome. Initial assessment may be performed with a short cognitive battery, such as the harmonization standards protocol. However, administration of a full cognitive battery is required in selected patients.

The present study investigated the specificity of planning impairments in schizophrenia compared to unipolar major depression. Multiple measures of planning ability were employed to assess the task independence of a planning deficit. Furthermore, the predictive power of planning ability with regard to functional outcome was analyzed. A total of 80 participants completed a comprehensive neuropsychological assessment with an emphasis on executive functions and planning ability. The sample consisted of 28 patients with schizophrenia, 28 patients with depression and 24 healthy controls. Both patient groups were impaired on measures of attention, working memory and planning, but only planning ability differentiated between patient groups. The deficit was evident across different measures of planning ability and was the best overall predictor of functional outcome. These results provide evidence for the relative specificity of a planning deficit in schizophrenia and show that the deficit is not task-specific but likely affects central cognitive control processes critical for planned behavior. The observed relation to functional outcome supports the clinical relevance of planning ability.

In dyslexia, anomalous activations have been described in both left temporo-parietal language cortices and in left ventral visual occipito-temporal cortex. However, the reproducibility, task-dependency, and presence of these brain anomalies in childhood rather than adulthood remain debated. We probed the large-scale organization of ventral visual and spoken language areas in dyslexic children using minimal target-detection tasks that were performed equally well by all groups. In 23 normal and 23 dyslexic 10-year-old children from two different socio-economic status (SES) backgrounds, we compared fMRI activity to visually presented houses, faces, and written strings, and to spoken sentences in the native or in a foreign language. Our results confirm a disorganization of both ventral visual and spoken language areas in dyslexic children. Visually, dyslexic children showed a normal lateral-to-medial mosaic of preferences, as well as normal responses to houses and checkerboards, but a reduced activation to words in the visual word form area (VWFA) and to faces in the right fusiform face area (FFA). Auditorily, dyslexic children exhibited reduced responses to speech in posterior temporal cortex, left insula and supplementary motor area, as well as reduced responses to maternal language in subparts of the planum temporale, left basal language area and VWFA. By correlating these two findings, we identify spoken-language predictors of VWFA activation to written words, which differ for dyslexic and normal readers. Similarities in fMRI deficits in both SES groups emphasize the existence of a core set of brain activation anomalies in dyslexia, regardless of culture, language and SES, without however resolving whether these anomalies are a cause or a consequence of impaired reading.

Background Few studies looked at the association between gait variability and executive subdomains (ESD). The aim of this study was to examine the association between ESD (i.e., information updating and monitoring) and stride time variability among healthy older adults. Methods Seventy-eight healthy older adults (mean age 69.9 ± 0.9 years, 59% women) were divided into 3 groups according to stride time variability (STV) tertiles while steady state walking. Coefficient of variation of stride time was used as a marker of STV. Scores on cognitive tests evaluating information updating and monitoring (Digit Span test), mental shifting (Trail Making Test part A and part B) and cognitive inhibition (Stroop Color Word test) were used as measures of ESD. Results The full adjusted and the stepwise backward logistic regression models showed that the highest tertile (i.e., the worst performance) of STV was only associated with lower Digit Span performance (Odds ratio = 0.78 with P = 0.020 and Odds ratio = 0.81 with P = 0.019). Conclusions Information updating and monitoring are associated with STV in the sample of studied participants, suggesting that walking may be a complex motor task depending specifically of this subdomain of executive functions.

Although it has been shown that adults with attention-deficit hyperactivity disorder (ADHD) have impaired social cognition, no previous study has reported the brain correlates of face valence processing. This study looked for behavioral, neuropsychological, and electrophysiological markers of emotion processing for faces (N170) in adult ADHD compared to controls matched by age, gender, educational level, and handedness. We designed an event-related potential (ERP) study based on a dual valence task (DVT), in which faces and words were presented to test the effects of stimulus type (faces, words, or face-word stimuli) and valence (positive versus negative). Individual signatures of cognitive functioning in participants with ADHD and controls were assessed with a comprehensive neuropsychological evaluation, including executive functioning (EF) and theory of mind (ToM). Compared to controls, the adult ADHD group showed deficits in N170 emotion modulation for facial stimuli. These N170 impairments were observed in the absence of any deficit in facial structural processing, suggesting a specific ADHD impairment in early facial emotion modulation. The cortical current density mapping of N170 yielded a main neural source of N170 at posterior section of fusiform gyrus (maximum at left hemisphere for words and right hemisphere for faces and simultaneous stimuli). Neural generators of N170 (fusiform gyrus) were reduced in ADHD. In those patients, N170 emotion processing was associated with performance on an emotional inference ToM task, and N170 from simultaneous stimuli was associated with EF, especially working memory. This is the first report to reveal an adult ADHD-specific impairment in the cortical modulation of emotion for faces and an association between N170 cortical measures and ToM and EF.

BACKGROUND Gait disorders in patients with idiopathic normal pressure hydrocephalus (iNPH) share similar characteristics found in pathologies presenting with higher level gait disorders that have been specifically associated with gait changes during walking while simultaneously performing an attention demanding task (i.e. dual tasking). The current study assessed the effect of cerebrospinal fluid (CSF) tapping on quantitative gait modification during single and dual tasking in patients with a suspicion of iNPH. METHODS Of 53 patients suspected of iNPH 18 have been included in this study. Gait analysis during single and dual task condition (walking and backward counting) before and after tapping of 40 ml CSF has been performed. RESULTS Gait speed (P < 0.01) and stride length (P < 0.05) were significantly improved during dual task conditions after CSF tapping compared to the gait performance before spinal tapping without such improvement for gait parameters during single tasking. CONCLUSION Dual tasking condition better reveals gait improvement after CSF tapping than single tasking in patients suspected of iNPH.

Several lines of experimental evidence support an association between facial processing and social cognition, but no direct link between cortical markers of facial processing and complex cognitive processes has been reported until now. In the current study, we tested the hypothesis that cortical electrophysiological markers for the processing of facial emotion are associated with individual differences in executive and social cognition skills. We tested for correlations between the amplitude of event-related potentials (N170) in a dual valence task and participants' scores on three neuropsychological assessments (general neuropsychology, executive functioning, and social cognition). N170 was modulated by the stimulus type (face versus word) and the valence of faces (positive versus negative). The neural source of N170 was estimated to be the fusiform gyrus. Robust correlations were found between neuropsychological markers and measures of facial processing. Social cognition skills (as measured by three tests: the Reading the Mind in the Eyes test, the Faux Pas test, and the Iowa Gambling Task) correlated with cortical measures of emotional discrimination. Executive functioning ability also correlated with the cortical discrimination of complex emotional stimuli. Our findings suggest that the cortical processing of facial emotional expression is associated with social cognition skills. © 2011 Elsevier Ireland Ltd. Fil: Petroni, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Canales-Johnson, Andrés. Universidad Diego Portales; Chile Fil: Urquina Sánchez, Hugo Fernando. Universidad Favaloro; Argentina Fil: Guex, Raphael. Universidad de Ginebra; Suiza Fil: Hurtado, Esteban. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile. Universidad Diego Portales; Chile Fil: Blenkmann, Alejandro Omar. Universidad Nacional de La Plata; Argentina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Von Ellenrieder, Nicolás. Universidad Nacional de La Plata; Argentina Fil: Manes, Facundo Francisco. Universidad Favaloro; Argentina Fil: Sigman, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Ibáñez Barassi, Agustín Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Diego Portales; Chile. Universidad Favaloro; Argentina

Deficits in executive functioning are closely related to the level of everyday functioning in patients with schizophrenia. However, many existing neuropsychological measures are limited in their ability to predict functional outcome. To contribute towards closing this gap, we developed a computer-based test of planning ability (“Plan-a-Day”) that requires participants to create daily activity schedules in a simulated work setting. Eighty patients diagnosed with schizophrenia were tested with Plan-a-Day and a battery of cognitive ability tests. Plan-a-Day showed satisfactory psychometric properties in terms of consistency, reliability, and construct validity. Compared to other neuropsychological tests used in this study, it also demonstrated incremental validity with regard to the Global Assessment of Functioning. The Plan-a-Day approach, therefore, seems to represent a valid alternative for measuring planning ability in patients with executive function deficits, occupying a middle ground between traditional neuropsychological tests and real-life assessments. (JINS, 2011,17, 327–335)

The aim of this study was to predict cognitive performance on the basis of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau) and amyloid-β₄₂ (Aβ₄₂) in controls and patients at various impairment levels. Previous studies have found an association of CSF T-tau levels with cognitive symptoms, but it has been difficult to relate Aβ to cognition, and it has thus been hypothesized that Aβ reaches a plateau level prior to cognitive symptoms. A comprehensive battery of neuropsychological tests was subjected to factor analysis to yield aggregated cognitive domains. Linear regression models were performed for the total sample of the Gothenburg MCI study (n = 435) and for each level of impairment. Aβ₄₂ and T-tau accounted for a significant proportion of performance in all cognitive domains in the total sample. In controls (n = 60) and patients with subjective cognitive impairment (n = 105), Aβ₄₂ predicted a significant proportion of semantic and working memory performance. For patients with mild cognitive impairment (n = 170), T-tau had the most pronounced impact across cognitive domains, and more specifically on episodic memory, visuospatial, and speed/executive performance. For patients with dementia (n = 100), the most pronounced impacts of Aβ₄₂ were found in episodic memory and visuospatial functioning, while T-tau was substantially associated with episodic memory. Our results suggest that cognition is related to CSF biomarkers regardless of impairment level. Aβ₄₂ is associated with cognitive functions from a potentially early to a later disease phase, and T-tau is more indicative of performance in a later disease phase.

Patients with peripheral dysgraphia due to impairment at the allographic level produce writing errors that affect the letter-form and are characterized by case confusions or the failure to write in a specific case or style (e.g., cursive). We studied the writing errors of a patient with pure peripheral dysgraphia who had entirely intact oral spelling, but produced many well-formed letter errors in written spelling. The comparison of uppercase print and lowercase cursive spelling revealed an uncommon pattern: while most uppercase errors were case substitutions (e.g., A - a), almost all lowercase errors were letter substitutions (e.g., n - r). Analyses of the relationship between target letters and substitution errors showed that errors were neither influenced by consonant-vowel status nor by letter frequency, though word length affected error frequency in lowercase writing. Moreover, while graphomotor similarity did not predict either the occurrence of uppercase or lowercase errors, visuospatial similarity was a significant predictor of lowercase errors. These results suggest that lowercase representations of cursive letter-forms are based on a description of entire letters (visuospatial features) and are not - as previously found for uppercase letters - specified in terms of strokes (graphomotor features).

Cross-sectional studies in bipolar disorder (BD) suggested the presence of cognitive deficits and subtle magnetic resonance imaging (MRI) changes in limbic areas that may persist at euthymic stages. Whether or not cognitive and MRI changes represent stable attributes of BD or evolve with time is still matter of debate. To address this issue, we performed a 2-year longitudinal study including detailed neuropsychological and magnetic resonance imaging (MRI) analyses of 15 euthymic older BD patients and 15 controls.Neuropsychological evaluation concerned working memory, episodic memory, processing speed, and executive functions. MRI analyses included voxel-based morphometry (VBM) analysis of gray matter including region of interest (ROI) analysis and tract-based spatial statistics (TBSS) analysis of white matter of diffusion tensor imaging derived fractional anisotropy (FA).BD patients displayed significantly lower performances in processing speed and episodic memory but not in working memory and executive functions compared to controls. However, BD patients did not differ from controls in the mean trajectory of cognitive changes during the 2 years follow-up. In the same line, longitudinal gray matter (VBM, ROI) and white matter (TBSS FA) changes did not differ between BD patients and controls.The lack of distinction between BD patients and controls in respect to the 2-year changes in cognition and MRI findings supports the notion that this disorder does not have a significant adverse impact on cognitive and brain aging. From this point of view, the present results convey a message of hope for patients suffering from BD.

A growing number of studies have been addressing the relationship between theory of mind (TOM) and executive functions (EF) in patients with acquired neurological pathology. In order to provide a global overview on the main findings, we conducted a systematic review on group studies where we aimed to (1) evaluate the patterns of impaired and preserved abilities of both TOM and EF in groups of patients with acquired neurological pathology and (2) investigate the existence of particular relations between different EF domains and TOM tasks. The search was conducted in Pubmed/Medline. A total of 24 articles met the inclusion criteria. We considered for analysis classical clinically accepted TOM tasks (first- and second-order false belief stories, the Faux Pas test, Happe's stories, the Mind in the Eyes task, and Cartoon's tasks) and EF domains (updating, shifting, inhibition, and access). The review suggests that (1) EF and TOM appear tightly associated. However, the few dissociations observed suggest they cannot be reduced to a single function; (2) no executive subprocess could be specifically associated with TOM performances; (3) the first-order false belief task and the Happe's story task seem to be less sensitive to neurological pathologies and less associated to EF. Even though the analysis of the reviewed studies demonstrates a close relationship between TOM and EF in patients with acquired neurological pathology, the nature of this relationship must be further investigated. Studies investigating ecological consequences of TOM and EF deficits, and intervention researches may bring further contributions to this question.

Patients with Alzheimer's disease (AD) and schizophrenia display cognitive, behavioural disturbances and morphological abnormalities. Although these latter reflect progressive neurodegeneration in AD, their significance in schizophrenia is still unclear. We explored the patterns of hippocampal and amygdalar atrophy in those patients and their associations with clinical parameters. Structural magnetic resonance imaging was performed in 20 elderly schizophrenia patients, 20 AD and 19 healthy older controls. Hippocampal and amygdalar volumes were obtained by manual segmentation with a standardized protocol and compared among groups. In both schizophrenia and AD patients, left hippocampal and amygdalar volumes were significantly smaller. The hippocampus/amygdala ratio was significantly lower in schizophrenia compared to both AD cases [2.4 bilaterally, 95% C.I. 2.2 to 2.7] and healthy controls bilaterally [2.5, 95% C.I. 2.3 to 2.9 in left and 2.7, 95% C.I. 2.4 to 3.1 in right hemisphere]. In schizophrenia patients, a significant positive correlation was found between age at disease onset and the right hippocampus/amygdala volume ratio (Spearman rho=0.56). Negative symptoms correlated with higher right/left amygdala volume ratio (Spearman's rho=0.43). Our data show that unlike AD, the hippocampus/amygdala ratio is abnormally low and correlates with the age at onset in schizophrenia, being a neurodevelopmental signature of the disease.

The neural processing of reward can be differentiated into two sub-components with different functions, "wanting" (i.e., the expectation of a reward which includes appetitive and motivational components) and "liking" (i.e., the hedonic impact experienced during the receipt of a reward), involving distinct neural systems. We hypothesize that variability in neural reward processing previously observed in healthy subjects could reflect inter-individual differences in personality. Therefore, the aim of this study was to investigate how the neural processing during expectation and reception of a reward depends on interpersonal differences in reward sensitivity, more specifically the tendency to approach vs. avoid reward-related situations. We employed event-related functional magnetic resonance imaging during a monetary incentive delay task. Subjects with a high approach motivation showed more activation of the Ventral Striatum (VS) during the receipt of a reward, and more medial orbitofrontal activity during both the receipt and omission of a reward. Subjects with a high behavioral inhibition showed less activation in the VS during the receipt of a reward. These findings indicate that the tendency to approach or avoid reward-related situations exhibits a distinct relation with neural reward processing. Specifically, subjects with high behavioral approach appear to be sensitive mainly to positive outcomes and to a lesser extent to the omissions of rewards, whereas subjects with low behavioral approach as well as those with a high inhibition tendency display a blunted response to rewards.

The precise role of the dorsolateral prefrontal cortex (DLPFC) in attentional set activation is still not entirely clear. Hence, repetitive transcranial magnetic stimulation (rTMS) can be applied to interfere with neural processing to determine whether a specific brain area is required in task performance. In this study, the influence of one session of high-frequency (HF)-rTMS of the left DLPFC on a reaction task using visual and auditory trials was investigated. Participants were instructed to pay constant attention to the visual stimuli, and they were informed that distracting auditory stimuli could also appear. Participants had to respond to both stimuli. Results indicate that after one session of HF-rTMS of the left DLPFC, performance was improved for the primary task, but not for the distracters. Specifically, we found decreased response time for an endogenous component of attentional control which embodies the online representations of task-relevant information. To conclude, the current results highlight a specific role of the left DLPFC in actively preparing for a specific task in the presence of a distracting task.

BACKGROUND: Deletions and duplications of the 16p11.2 BP4-BP5 locus are prevalent copy number variations (CNVs), highly associated with autism spectrum disorder and schizophrenia. Beyond language and global cognition, neuropsychological assessments of these two CNVs have not yet been reported. METHODS: This study investigates the relationship between the number of genomic copies at the 16p11.2 locus and cognitive domains assessed in 62 deletion carriers, 44 duplication carriers, and 71 intrafamilial control subjects. RESULTS: IQ is decreased in deletion and duplication carriers, but we demonstrate contrasting cognitive profiles in these reciprocal CNVs. Deletion carriers present with severe impairments of phonology and of inhibition skills beyond what is expected for their IQ level. In contrast, for verbal memory and phonology, the data may suggest that duplication carriers outperform intrafamilial control subjects with the same IQ level. This finding is reminiscent of special isolated skills as well as contrasting language performance observed in autism spectrum disorder. Some domains, such as visuospatial and working memory, are unaffected by the 16p11.2 locus beyond the effect of decreased IQ. Neuroimaging analyses reveal that measures of inhibition covary with neuroanatomic structures previously identified as sensitive to 16p11.2 CNVs. CONCLUSIONS: The simultaneous study of reciprocal CNVs suggests that the 16p11.2 genomic locus modulates specific cognitive skills according to the number of genomic copies. Further research is warranted to replicate these findings and elucidate the molecular mechanisms modulating these cognitive performances.

The main diagnostic criteria of the behavioural variant of frontotemporal degeneration (bvFTD) include neurobehavioral and dysexecutive syndromes, but not specific gait characteristics although strong relationship between gait and prefrontal functions are increasingly recognized. Accordingly, we tested the hypothesis that patients with bvFTD would have more gait changes than older healthy controls and demented patients with Alzheimer's disease (AD). Sixty subjects were included in the study: 19 with bvFTD, 19 with AD and 22 healthy controls. Mean values and coefficients of variation (CV) of stride time while just walking (i.e., single tasking) and while walking with backward counting (i.e., dual tasking) were measured using the SMTEC-footswitch system. Stride time, mean value, and CV were significantly increased in both patient groups compared with healthy controls during single task or walking alone (P < 0.001) and during dual tasking (P < 0.001). After adjusting for age, Mini-mental examination, psychoactive drugs, gender, and history of previous fall, only the patients with bvFTD group was associated with an increase of CV of stride time during single walking (P < 0.001) and dual tasking (P < 0.001). These data suggest that gait instability during single and dual tasking could represent a supportive argument for bvFTD. In clinical practice, such a diagnosis should be at least considered in any demented patient with gait instability.

Atypical functional connectivity in the maturing brains of 22q11.2 deletion syndrome (22q11DS) may contribute to the expression of early psychotic symptoms commonly reported by these youths. This study's objective was to examine functional connectivity in cerebral networks at rest (Resting-State Networks; RSNs) and their relationship to symptomatic and neuropsychological characteristics putting them at very high risk factor for developing psychosis. Twenty-seven adolescents with 22q11DS and 33 typically developing control adolescents matched for age, gender and handedness underwent an 8-minute resting state functional MRI session. RSNs identification procedure employed Independent Component Analysis (ICA). We tested for potential group differences in functional connectivity within-networks. Then, we examined relationships between network connectivity and symptomatic/neuropsychological characteristics in the 22q11DS group. A total of nine resting-state networks were identified. Between-group differences suggested both increased and decreased functional connectivity in the 22q11DS group, involving the default-mode, sensorimotor, visuo-spatial, and high level visual networks. Finally, atypical connectivity in the default-mode network, specifically within the left superior frontal gyrus region, correlated with prodromal symptom intensity and neuropsychological performances in the 22q11DS group. The results suggest that atypical functional connectivity may sustain both increased vulnerability to psychosis and characteristic cognitive impairments in 22q11DS. (C) 2012 Elsevier B.V. All rights reserved.