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Mol Psychiatry ; 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30279459


The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.

eNeuro ; 5(4)2018 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30073200


Human adolescence is a period of rapid changes in cognition and goal-directed behavior, and it constitutes a major transitional phase towards adulthood. One of the mechanisms suggested to underlie the protracted maturation of functional brain networks, is the increased network integration and segregation enhancing neural efficiency. Importantly, the increasing coordinated network interplay throughout development is mediated through functional hubs, which are highly connected brain areas suggested to be pivotal nodes for the regulation of neural activity. To elucidate brain hub development during childhood and adolescence, we estimated voxel-wise eigenvector centrality (EC) using functional magnetic resonance imaging (fMRI) data from two different psychological contexts (resting state and a working memory task), in a large cross-sectional sample (n = 754) spanning the age from 8 to 22 years, and decomposed the maps using independent component analysis (ICA). Our results reveal significant age-related centrality differences in cingulo-opercular, visual, and sensorimotor network nodes during both rest and task performance, suggesting that common neurodevelopmental processes manifest across different mental states. Supporting the functional significance of these developmental patterns, the centrality of the cingulo-opercular node was positively associated with task performance. These findings provide evidence for protracted maturation of hub properties in specific nodes of the brain connectome during the course of childhood and adolescence and suggest that cingulo-opercular centrality is a key factor supporting neurocognitive development.

Neurology ; 89(24): 2413-2421, 2017 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-29142090


OBJECTIVE: To compare the effectiveness of upper extremity virtual reality rehabilitation training (VR) to time-matched conventional training (CT) in the subacute phase after stroke. METHODS: In this randomized, controlled, single-blind phase III multicenter trial, 120 participants with upper extremity motor impairment within 12 weeks after stroke were consecutively included at 5 rehabilitation institutions. Participants were randomized to either VR or CT as an adjunct to standard rehabilitation and stratified according to mild to moderate or severe hand paresis, defined as ≥20 degrees wrist and 10 degrees finger extension or less, respectively. The training comprised a minimum of sixteen 60-minute sessions over 4 weeks. The primary outcome measure was the Action Research Arm Test (ARAT); secondary outcome measures were the Box and Blocks Test and Functional Independence Measure. Patients were assessed at baseline, after intervention, and at the 3-month follow-up. RESULTS: Mean time from stroke onset for the VR group was 35 (SD 21) days and for the CT group was 34 (SD 19) days. There were no between-group differences for any of the outcome measures. Improvement of upper extremity motor function assessed with ARAT was similar at the postintervention (p = 0.714) and follow-up (p = 0.777) assessments. Patients in VR improved 12 (SD 11) points from baseline to the postintervention assessment and 17 (SD 13) points from baseline to follow-up, while patients in CT improved 13 (SD 10) and 17 (SD 13) points, respectively. Improvement was also similar for our subgroup analysis with mild to moderate and severe upper extremity paresis. CONCLUSIONS: Additional upper extremity VR training was not superior but equally as effective as additional CT in the subacute phase after stroke. VR may constitute a motivating training alternative as a supplement to standard rehabilitation. CLINICALTRIALSGOV IDENTIFIER: NCT02079103. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with upper extremity motor impairment after stroke, compared to conventional training, VR training did not lead to significant differences in upper extremity function improvement.

Mãos/fisiopatologia , Paresia/reabilitação , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/fisiopatologia , Interface Usuário-Computador , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paresia/etiologia , Paresia/fisiopatologia , Método Simples-Cego , Acidente Vascular Cerebral/complicações , Resultado do Tratamento , Extremidade Superior/fisiopatologia , Adulto Jovem
BMC Neurol ; 14: 186, 2014 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-25261187


BACKGROUND: Novel virtual reality rehabilitation systems provide the potential to increase intensity and offer challenging and motivating tasks. The efficacy of virtual reality systems to improve arm motor function early after stroke has not been demonstrated yet in sufficiently powered studies. The objective of the study is to investigate whether VR training as an adjunct to conventional therapy is more effective in improving arm motor function in the subacute phase after stroke than dose-matched conventional training, to assess patient and therapist satisfaction when working with novel virtual reality training and to calculate cost-effectiveness in terms of resources required to regain some degree of dexterity. METHODS/DESIGN: Randomized controlled observer-blind trial. DISCUSSION: Virtual reality systems are promising tools for rehabilitation of arm motor function after stroke. Their introduction in combination with traditional physical and occupational therapy may enhance recovery after stroke, and at the same time demand little personnel resources to increase training intensity. The VIRTUES trial will provide further evidence of VR-based treatment strategies to clinicians, patients and health economists. TRIAL REGISTRATION: NCT02079103.

Simulação por Computador , Reabilitação do Acidente Vascular Cerebral , Interface Usuário-Computador , Humanos , Terapia Ocupacional/métodos , Modalidades de Fisioterapia , Método Simples-Cego