Progressive decline of decision-making performances during multiple sclerosis.

The purpose of this study was to evaluate longitudinally, using the Iowa Gambling Task (IGT), the dynamics of decision-making capacity at a two-year interval (median: 2.1 years) in a group of patients with multiple sclerosis (MS) (n = 70) and minor neurological disability [Expanded Disability Status Scale (EDSS) < or = 2.5 at baseline]. Cognition (memory, executive functions, attention), behavior, handicap, and perceived health status were also investigated. Standardized change scores [(score at retest-score at baseline)/standard deviation of baseline score] were computed. Results showed that IGT performances decreased from baseline to retest (from 0.3, SD = 0.4 to 0.1, SD = 0.3, p = .005). MS patients who worsened in the IGT were more likely to show a decreased perceived health status and emotional well-being (SEP-59; p = .05 for both). Relapsing rate, disability progression, cognitive, and behavioral changes were not associated with decreased IGT performances. In conclusion, decline in decision making can appear as an isolated deficit in MS.

Musical training intensity yields opposite effects on grey matter density in cognitive versus sensorimotor networks.

Using optimized voxel-based morphometry, we performed grey matter density analyses on 59 age-, sex- and intelligence-matched young adults with three distinct, progressive levels of musical training intensity or expertise. Structural brain adaptations in musicians have been repeatedly demonstrated in areas involved in auditory perception and motor skills. However, musical activities are not confined to auditory perception and motor performance, but are entangled with higher-order cognitive processes. In consequence, neuronal systems involved in such higher-order processing may also be shaped by experience-driven plasticity. We modelled expertise as a three-level regressor to study possible linear relationships of expertise with grey matter density. The key finding of this study resides in a functional dissimilarity between areas exhibiting increase versus decrease of grey matter as a function of musical expertise. Grey matter density increased with expertise in areas known for their involvement in higher-order cognitive processing: right fusiform gyrus (visual pattern recognition), right mid orbital gyrus (tonal sensitivity), left inferior frontal gyrus (syntactic processing, executive function, working memory), left intraparietal sulcus (visuo-motor coordination) and bilateral posterior cerebellar Crus II (executive function, working memory) and in auditory processing: left Heschl's gyrus. Conversely, grey matter density decreased with expertise in bilateral perirolandic and striatal areas that are related to sensorimotor function, possibly reflecting high automation of motor skills. Moreover, a multiple regression analysis evidenced that grey matter density in the right mid orbital area and the inferior frontal gyrus predicted accuracy in detecting fine-grained incongruities in tonal music.

Cognitive features in euthymic bipolar patients in old age.

OBJECTIVES: Studies of cognition in bipolar disorder (BD) have reported impairments in processing speed, working memory, episodic memory, and executive function, but they have primarily focused on young and middle-aged adults. In such studies, the severity of cognitive deficits increases with the duration of illness. Therefore, one would expect more pronounced deficits in patients with longstanding BD. The first aim of the present study was to determine the pattern and the magnitude of cognitive impairment in older euthymic BD patients. The second aim was to explore the interrelationship between these cognitive deficits and determine whether they reflect a single core impairment or the co-occurrence of independent cognitive deficits. METHODS: Twenty-two euthymic elderly BD patients and 22 controls, matched for gender, age, and education, underwent a comprehensive neuropsychological assessment. RESULTS: Compared to controls, BD patients had significantly reduced performance in processing speed, working memory, verbal fluency, and episodic memory, but not in executive function. Hierarchical regression analyses showed that verbal fluency and working memory impairments were fully mediated by changes in processing speed. This was not the case for the episodic memory dysfunction. CONCLUSION: The cognitive profile in older euthymic BD cases is similar to the one described in younger BD cohorts. Our results further suggest that impaired processing speed plays a major role in the cognitive changes observed in BD patients except for deficits in episodic memory, thus providing strong evidence that processing speed and episodic memory are two core deficits in elderly BD patients.

Social capital and cognitive attainment

We review the different meanings that researchers have given to theconcept of social capital, differentiate four types – bridging, bonding,linking, and overheads –, and discuss their different functions as public,club, and common goods.For each form of social capital we distinguish its productivity (acollective characteristic) from the factors that account for individual’sdifferential access to its returns, and propose alternative ways formeasuring each.We show the utility of our theoretical and measuring approach byanalyzing the impact of the each form of social capital on 15 year-oldstudents’ cognitive attainment across OECD countries, using 2006 PISAdata.The results show that students’ cognitive attainments are a direct functionof the richness or productivity of each form of social capital and ofstudents’ degree of access to each.

Visual functions in the healthy and schizophrenic brain : from stimulus control to illusory perceptions using electrical neuroimaging

ABSTRACT (FRENCH)Ce travail de thèse basé sur le système visuel chez les sujets sains et chez les patients schizophrènes, s'articule autour de trois articles scientifiques publiés ou en cours de publication. Ces articles traitent des sujets suivants : le premier article présente une nouvelle méthode de traitement des composantes physiques des stimuli (luminance et fréquence spatiale). Le second article montre, à l'aide d'analyses de données EEG, un déficit de la voie magnocellulaire dans le traitement visuel des illusions chez les patients schizophrènes. Ceci est démontré par l'absence de modulation de la composante PI chez les patients schizophrènes contrairement aux sujets sains. Cette absence est induite par des stimuli de type illusion Kanizsa de différentes excentricités. Finalement, le troisième article, également à l'aide de méthodes de neuroimagerie électrique (EEG), montre que le traitement des contours illusoires se trouve dans le complexe latéro-occipital (LOC), à l'aide d'illusion « misaligned gratings ». De plus il révèle que les activités démontrées précédemment dans les aires visuelles primaires sont dues à des inférences « top- down ».Afin de permettre la compréhension de ces trois articles, l'introduction de ce manuscrit présente les concepts essentiels. De plus des méthodes d'analyses de temps-fréquence sont présentées. L'introduction est divisée en quatre parties : la première présente le système visuel depuis les cellules retino-corticales aux deux voix du traitement de l'information en passant par les régions composant le système visuel. La deuxième partie présente la schizophrénie par son diagnostic, ces déficits de bas niveau de traitement des stimuli visuel et ces déficits cognitifs. La troisième partie présente le traitement des contours illusoires et les trois modèles utilisés dans le dernier article. Finalement, les méthodes de traitement des données EEG seront explicitées, y compris les méthodes de temps-fréquences.Les résultats des trois articles sont présentés dans le chapitre éponyme (du même nom). De plus ce chapitre comprendra les résultats obtenus à l'aide des méthodes de temps-fréquenceFinalement, la discussion sera orientée selon trois axes : les méthodes de temps-fréquence ainsi qu'une proposition de traitement de ces données par une méthode statistique indépendante de la référence. La discussion du premier article en montrera la qualité du traitement de ces stimuli. La discussion des deux articles neurophysiologiques, proposera de nouvelles d'expériences afin d'affiner les résultats actuels sur les déficits des schizophrènes. Ceci pourrait permettre d'établir un marqueur biologique fiable de la schizophrénie.ABSTRACT (ENGLISH)This thesis focuses on the visual system in healthy subjects and schizophrenic patients. To address this research, advanced methods of analysis of electroencephalographic (EEG) data were used and developed. This manuscript is comprised of three scientific articles. The first article showed a novel method to control the physical features of visual stimuli (luminance and spatial frequencies). The second article showed, using electrical neuroimaging of EEG, a deficit in spatial processing associated with the dorsal pathway in chronic schizophrenic patients. This deficit was elicited by an absent modulation of the PI component in terms of response strength and topography as well as source estimations. This deficit was orthogonal to the preserved ability to process Kanizsa-type illusory contours. Finally, the third article resolved ongoing debates concerning the neural mechanism mediating illusory contour sensitivity by using electrical neuroimaging to show that the first differentiation of illusory contour presence vs. absence is localized within the lateral occipital complex. This effect was subsequent to modulations due to the orientation of misaligned grating stimuli. Collectively, these results support a model where effects in V1/V2 are mediated by "top-down" modulation from the LOC.To understand these three articles, the Introduction of this thesis presents the major concepts used in these articles. Additionally, a section is devoted to time-frequency analysis methods not presented in the articles themselves. The introduction is divided in four parts. The first part presents three aspects of the visual system: cellular, regional, and its functional interactions. The second part presents an overview of schizophrenia and its sensoiy-cognitive deficits. The third part presents an overview of illusory contour processing and the three models examined in the third article. Finally, advanced analysis methods for EEG are presented, including time- frequency methodology.The Introduction is followed by a synopsis of the main results in the articles as well as those obtained from the time-frequency analyses.Finally, the Discussion chapter is divided along three axes. The first axis discusses the time frequency analysis and proposes a novel statistical approach that is independent of the reference. The second axis contextualizes the first article and discusses the quality of the stimulus control and direction for further improvements. Finally, both neurophysiologic articles are contextualized by proposing future experiments and hypotheses that may serve to improve our understanding of schizophrenia on the one hand and visual functions more generally.

Troubles cognitifs du patient alcoolo-dépendant. Dépistage et examen neuropsychologique [Cognitive impairment in alcohol addiction].

Alcohol addiction is associated with cognitive impairment of clinically varying intensity and duration, which starts progressively while remaining often underestimated. Progressive brain damage can lead over time to a dementia syndrome. The diagnosis of cognitive deficits is of prime importance since it helps to optimize patient care and to decrease failure in re-insertion programs. Here we propose several screening tests which should give the practitioner the opportunity to make a basic cognitive assessment and to decide whether a comprehensive neuropsychological evaluation is indicated. In alcohol addiction cognitive impairment is dominated by executive dysfunction of varying severity, which is also characteristic of alcohol dementia.

The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample.

Cannabis use is highly prevalent among people with schizophrenia, and coupled with impaired cognition, is thought to heighten the risk of illness onset. However, while heavy cannabis use has been associated with cognitive deficits in long-term users, studies among patients with schizophrenia have been contradictory. This article consists of 2 studies. In Study I, a meta-analysis of 10 studies comprising 572 patients with established schizophrenia (with and without comorbid cannabis use) was conducted. Patients with a history of cannabis use were found to have superior neuropsychological functioning. This finding was largely driven by studies that included patients with a lifetime history of cannabis use rather than current or recent use. In Study II, we examined the neuropsychological performance of 85 patients with first-episode psychosis (FEP) and 43 healthy nonusing controls. Relative to controls, FEP patients with a history of cannabis use (FEP + CANN; n = 59) displayed only selective neuropsychological impairments while those without a history (FEP - CANN; n = 26) displayed generalized deficits. When directly compared, FEP + CANN patients performed better on tests of visual memory, working memory, and executive functioning. Patients with early onset cannabis use had less neuropsychological impairment than patients with later onset use. Together, these findings suggest that patients with schizophrenia or FEP with a history of cannabis use have superior neuropsychological functioning compared with nonusing patients. This association between better cognitive performance and cannabis use in schizophrenia may be driven by a subgroup of "neurocognitively less impaired" patients, who only developed psychosis after a relatively early initiation into cannabis use.

Executive Order Number Seventeen, September 25, 2009

This Executive Order expects the State of Iowa executive agencies and Regent Institutions own, purchase, build and lease property, including office space, worth billions of dollars for educational, correctional, recreational, conservation, transportation, communication, public health, workforce and related public functions and the placement of state offices in historic central business districts "downtown" can strengthen and revitalize Iowa's cities and towns.

Brain dynamics underlying training-induced improvement in suppressing inappropriate action.

Inhibitory control, a core component of executive functions, refers to our ability to suppress intended or ongoing cognitive or motor processes. Mostly based on Go/NoGo paradigms, a considerable amount of literature reports that inhibitory control of responses to "NoGo" stimuli is mediated by top-down mechanisms manifesting ∼200 ms after stimulus onset within frontoparietal networks. However, whether inhibitory functions in humans can be trained and the supporting neurophysiological mechanisms remain unresolved. We addressed these issues by contrasting auditory evoked potentials (AEPs) to left-lateralized "Go" and right NoGo stimuli recorded at the beginning versus the end of 30 min of active auditory spatial Go/NoGo training, as well as during passive listening of the same stimuli before versus after the training session, generating two separate 2 × 2 within-subject designs. Training improved Go/NoGo proficiency. Response times to Go stimuli decreased. During active training, AEPs to NoGo, but not Go, stimuli modulated topographically with training 61-104 ms after stimulus onset, indicative of changes in the underlying brain network. Source estimations revealed that this modulation followed from decreased activity within left parietal cortices, which in turn predicted the extent of behavioral improvement. During passive listening, in contrast, effects were limited to topographic modulations of AEPs in response to Go stimuli over the 31-81 ms interval, mediated by decreased right anterior temporoparietal activity. We discuss our results in terms of the development of an automatic and bottom-up form of inhibitory control with training and a differential effect of Go/NoGo training during active executive control versus passive listening conditions.

Long-term cognitive profile and incidence of dementia after STN-DBS in Parkinson's disease

An effect of subthalamic nucleus deep brain stimulation (STN-DBS) on cognition has been suspected but long-term observations are lacking. The aim of this study was to evaluate the long-term cognitive profile and the incidence of dementia in a cohort of Parkinson's disease (PD) patients treated by STN-DBS. 57 consecutive patients were prospectively assessed by the mean of a neuropsychological battery over 3 years after surgery. Dementia (DSM-IV) and UPDRS I to IV were recorded. 24.5% of patients converted to dementia over 3 years (incidence of 89 of 1,000 per year). This group of patients cognitively continuously worsened over 3 years up to fulfilling dementia criteria (PDD). The rest of the cohort remained cognitively stable (PD) over the whole follow-up. Preoperative differences between PDD and PD included older age (69.2 +/- 5.8 years; 62.6 +/- 8 years), presence of hallucinations and poorer executive score (10.1 +/- 5.9; 5.5 +/- 4.4). The incidence of dementia over 3 years after STN-DBS is similar to the one reported in medically treated patients. The PDD presented preoperative risk factors of developing dementia similar to those described in medically treated patients. These observations suggest dementia being secondary to the natural evolution of PD rather than a direct effect of STN-DBS.

Cognition, mood and fatigue in patients in the early stage of multiple sclerosis.

QUESTION UNDER STUDY: Cognitive impairment occurs during multiple sclerosis (MS) and contributes to the burden of the disease, but its effect in the initial phase of MS still needs to be better understood. METHODS: We prospectively studied 127 early MS patients presenting with a clinically isolated syndrome (CIS) or definite MS, a mean disease duration of 2.6 years, and with minor disability (mean Expanded Disability Status Scale score 1.8). Patients were tested for long-term memory, executive functions, attention, fatigue, mood disorders, functional handicap and quality of life (QoL). Twenty-one CIS patients were excluded from study as the diagnosis of MS could not be confirmed. RESULTS: Over the 106 MS patients analysed, 31 (29.3%) were cognitively impaired (23.6% for memory, 10.4% for attention and 5.7% for executive functions). Cognitive deficits were already present in CIS patients in whom the diagnosis was not yet confirmed (20%). Impaired cognition was associated with anxiety (p = 0.05), depression(p = 0.004), fatigue (p = 0.03), handicap (p <0.001) and a lower QoL (p <0.001). After adjustment for QoL, handicap, depression, anxiety and fatigue were no longer associated with the presence of cognitive deficits. CONCLUSIONS: In this well-defined early MS group one third of the patients already exhibited cognitive deficits, which were usually apparent in an effortful learning situation and were generally mild. Mood disorders, fatigue, handicap and decreased QoL were all associated with the occurrence of cognitive deficits. QoL itself appeared to take all the other factors into account. Our results confirm the existence of an interplay between cognitive, affective and functional changes and fatigue in early MS.

Attention-related potentials allow for a highly accurate discrimination of mild cognitive impairment subtypes.

The three most frequent forms of mild cognitive impairment (MCI) are single-domain amnestic MCI (sd-aMCI), single-domain dysexecutive MCI (sd-dMCI) and multiple-domain amnestic MCI (md-aMCI). Brain imaging differences among single domain subgroups of MCI were recently reported supporting the idea that electroencephalography (EEG) functional hallmarks can be used to differentiate these subgroups. We performed event-related potential (ERP) measures and independent component analysis in 18 sd-aMCI, 13 sd-dMCI and 35 md-aMCI cases during the successful performance of the Attentional Network Test. Sensitivity and specificity analyses of ERP for the discrimination of MCI subgroups were also made. In center-cue and spatial-cue warning stimuli, contingent negative variation (CNV) was elicited in all MCI subgroups. Two independent components (ICA1 and 2) were superimposed in the time range on the CNV. The ICA2 was strongly reduced in sd-dMCI compared to sd-aMCI and md-aMCI (4.3 vs. 7.5% and 10.9% of the CNV component). The parietal P300 ERP latency increased significantly in sd-dMCI compared to md-aMCI and sd-aMCI for both congruent and incongruent conditions. This latency for incongruent targets allowed for a highly accurate separation of sd-dMCI from both sd-aMCI and md-aMCI with correct classification rates of 90 and 81%, respectively. This EEG parameter alone performed much better than neuropsychological testing in distinguishing sd-dMCI from md-aMCI. Our data reveal qualitative changes in the composition of the neural generators of CNV in sd-dMCI. In addition, they document an increased latency of the executive P300 component that may represent a highly accurate hallmark for the discrimination of this MCI subgroup in routine clinical settings.

Neuroanatomical and neuropsychological features of elderly euthymic depressed patients with early- and late-onset.

BACKGROUND: Whether or not cognitive impairment and brain structure changes are trait characteristics of late-life depression is still disputed. Previous studies led to conflicting data possibly because of the difference in the age of depression onset. In fact, several lines of evidence suggest that late-onset depression (LOD) is more frequently associated with neuropsychological deficits and brain pathology than early-onset depression (EOD). To date, no study explored concomitantly the cognitive profile and brain magnetic resonance imaging (MRI) patterns in euthymic EOD and LOD patients. METHOD: Using a cross-sectional design, 41 remitted outpatients (30 with EOD and 11 with LOD) were compared to 30 healthy controls. Neuropsychological evaluation concerned working memory, episodic memory, processing speed, naming capacity and executive functions. Volumetric estimates of the amygdala, hippocampus, entorhinal and anterior cingulate cortex were obtained using both voxel-based and region of interest morphometric methods. White matter hyperintensities were assessed semiquantitatively. RESULTS: Both cognitive performance and brain volumes were preserved in euthymic EOD patients whereas LOD patients showed a significant reduction of episodic memory capacity and a higher rate of periventricular hyperintensities compared to both controls and EOD patients. CONCLUSION: Our results support the dissociation between EOD thought to be mainly related to psychosocial factors and LOD that is characterized by increasing vascular burden and episodic memory decline.

Iowa Plan for Brain Injury: Executive Summary, 2007-2010

Traumatic Brain Injury (TBI) impacts the lives of thousands of Iowans every year. TBI has been described as the “Silent Epidemic” because so often the scars are not visible to others. The affects of brain injury are cognitive, emotional, and social and can result in physical disability. In addition to the overwhelming challenges individuals with brain injury experience, families also face many difficulties in dealing with their loved one’s injury and in navigating a service delivery system that can be confusing and frustrating.

Brain Connectivity Analysis in Children. Effects of Prematurity. and Prenatal Growth Restriction

Introduction: Survival of children born prematurely or with very low birth weight has increased dramatically, but the long term developmental outcome remains unknown. Many children have deficits in cognitive capacities, in particular involving executive domains and those disabilities are likely to involve a central nervous system deficit. To understand their neurostructural origin, we use DTI. Structurally segregated and functionally regions of the cerebral cortex are interconnected by a dense network of axonal pathways. We noninvasively map these pathways across cortical hemispheres and construct normalized structural connection matrices derived from DTI MR tractography. Group comparisons of brain connectivity reveal significant changes in fiber density in case of children with poor intrauterine grown and extremely premature children (gestational age<28 weeks at birth) compared to control subjects. This changes suggest a link between cortico-axonal pathways and the central nervous system deficit. Methods: Sixty premature born infants (5-6 years old) were scanned on clinical 3T scanner (Magnetom Trio, Siemens Medical Solutions, Erlangen, Germany) at two hospitals (HUG, Geneva and CHUV, Lausanne). For each subject, T1-weighted MPRAGE images (TR/TE=2500/2.91,TI=1100, resolution=1x1x1mm, matrix=256x154) and DTI images (30 directions, TR/TE=10200/107, in-plane resolution=1.8x1.8x2mm, 64 axial, matrix=112x112) were acquired. Parent(s) provided written consent on prior ethical board approval. The extraction of the Whole Brain Structural Connectivity Matrix was performed following (Cammoun, 2009 and Hagmann, 2008). The MPARGE images were registered using an affine registration to the non-weighted-DTI and WM-GM segmentation performed on it. In order to have equal anatomical localization among subjects, 66 cortical regions with anatomical landmarks were created using the curvature information, i.e. sulcus and gyrus (Cammoun et al, 2007; Fischl et al, 2004; Desikan et al, 2006) with freesurfer software (http://surfer.nmr.mgh.harvard.edu/). Tractography was performed in WM using an algorithm especially designed for DTI/DSI data (Hagmann et al., 2007) and both information were then combined in a matrix. Each row and column of the matrix corresponds to a particular ROI. Each cell of index (i,j) represents the fiber density of the bundle connecting the ROIs i and j. Subdividing each cortical region, we obtained 4 Connectivity Matrices of different resolution (33, 66, 125 and 250 ROI/hemisphere) for each subject . Subjects were sorted in 3 different groups, namely (1) control, (2) Intrauterine Growth Restriction (IUGR), (3) Extreme Prematurity (EP), depending on their gestational age, weight and percentile-weight score at birth. Group-to-group comparisons were performed between groups (1)-(2) and (1)-(3). The mean age at examination of the three groups were similar. Results: Quantitative analysis were performed between groups to determine fibers density differences. For each group, a mean connectivity matrix with 33ROI/hemisphere resolution was computed. On the other hand, for all matrix resolutions (33,66,125,250 ROI/hemisphere), the number of bundles were computed and averaged. As seen in figure 1, EP and IUGR subjects present an overall reduction of fibers density in both interhemispherical and intrahemispherical connections. This is given quantitatively in table 1. IUGR subjects presents a higher percentage of missing fiber bundles than EP when compared to control subjects (~16% against 11%). When comparing both groups to control subjects, for the EP subjects, the occipito-parietal regions seem less interhemispherically connected whilst the intrahemispherical networks present lack of fiber density in the lymbic system. Children born with IUGR, have similar reductions in interhemispherical connections than the EP. However, the cuneus and precuneus connections with the precentral and paracentral lobe are even lower than in the case of the EP. For the intrahemispherical connections the IUGR group preset a loss of fiber density between the deep gray matter structures (striatum) and the frontal and middlefrontal poles, connections typically involved in the control of executive functions. For the qualitative analysis, a t-test comparing number of bundles (p-value<0.05) gave some preliminary significant results (figure 2). Again, even if both IUGR and EP appear to have significantly less connections comparing to the control subjects, the IUGR cohort seems to present a higher lack of fiber density specially relying the cuneus, precuneus and parietal areas. In terms of fiber density, preliminary Wilcoxon tests seem to validate the hypothesis set by the previous analysis. Conclusions: The goal of this study was to determine the effect of extreme prematurity and poor intrauterine growth on neurostructural development at the age of 6 years-old. This data indicates that differences in connectivity may well be the basis for the neurostructural and neuropsychological deficit described in these populations in the absence of overt brain lesions (Inder TE, 2005; Borradori-Tolsa, 2004; Dubois, 2008). Indeed, we suggest that IUGR and prematurity leads to alteration of connectivity between brain structures, especially in occipito-parietal and frontal lobes for EP and frontal and middletemporal poles for IUGR. Overall, IUGR children have a higher loss of connectivity in the overall connectivity matrix than EP children. In both cases, the localized alteration of connectivity suggests a direct link between cortico-axonal pathways and the central nervous system deficit. Our next step is to link these connectivity alterations to the performance in executive function tests.