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1.
Hum Brain Mapp ; 43(10): 3062-3085, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35302683

RESUMO

An emerging goal in neuroscience is tracking what information is represented in brain activity over time as a participant completes some task. While electroencephalography (EEG) and magnetoencephalography (MEG) offer millisecond temporal resolution of how activity patterns emerge and evolve, standard decoding methods present significant barriers to interpretability as they obscure the underlying spatial and temporal activity patterns. We instead propose the use of a generative encoding model framework that simultaneously infers the multivariate spatial patterns of activity and the variable timing at which these patterns emerge on individual trials. An encoding model inversion maps from these parameters to the equivalent decoding model, allowing predictions to be made about unseen test data in the same way as in standard decoding methodology. These SpatioTemporally Resolved MVPA (STRM) models can be flexibly applied to a wide variety of experimental paradigms, including classification and regression tasks. We show that these models provide insightful maps of the activity driving predictive accuracy metrics; demonstrate behaviourally meaningful variation in the timing of pattern emergence on individual trials; and achieve predictive accuracies that are either equivalent or surpass those achieved by more widely used methods. This provides a new avenue for investigating the brain's representational dynamics and could ultimately support more flexible experimental designs in the future.


Assuntos
Mapeamento Encefálico , Encéfalo , Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Humanos , Magnetoencefalografia/métodos , Análise Multivariada
2.
Genome Res ; 28(12): 1812-1825, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30446528

RESUMO

While genetic variants are known to be associated with overall gene abundance in stimulated immune cells, less is known about their effects on alternative isoform usage. By analyzing RNA-seq profiles of monocyte-derived dendritic cells from 243 individuals, we uncovered thousands of unannotated isoforms synthesized in response to influenza infection and type 1 interferon stimulation. We identified more than a thousand quantitative trait loci (QTLs) associated with alternate isoform usage (isoQTLs), many of which are independent of expression QTLs (eQTLs) for the same gene. Compared with eQTLs, isoQTLs are enriched for splice sites and untranslated regions, but depleted of sequences upstream of annotated transcription start sites. Both eQTLs and isoQTLs explain a significant proportion of the disease heritability attributed to common genetic variants. At the ERAP2 locus, we shed light on the function of the gene and how two frequent, highly differentiated haplotypes with intermediate frequencies could be maintained by balancing selection. At baseline and following type 1 interferon stimulation, the major haplotype is associated with low ERAP2 expression caused by nonsense-mediated decay, while the minor haplotype, known to increase Crohn's disease risk, is associated with high ERAP2 expression. In response to influenza infection, we found two uncharacterized isoforms expressed from the major haplotype, likely the result of multiple perfectly linked variants affecting the transcription and splicing at the locus. Thus, genetic variants at a single locus could modulate independent gene regulatory processes in innate immune responses and, in the case of ERAP2, may confer a historical fitness advantage in response to virus.


Assuntos
Processamento Alternativo , Aminopeptidases/genética , Predisposição Genética para Doença , Interações Hospedeiro-Patógeno/genética , Vírus da Influenza A , Influenza Humana/genética , Influenza Humana/virologia , Adolescente , Adulto , Mapeamento Cromossômico , Biologia Computacional/métodos , Células Dendríticas/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Testes Genéticos , Variação Genética , Humanos , Interferon Tipo I/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Anotação de Sequência Molecular , Monócitos/metabolismo , Locos de Características Quantitativas , Transcriptoma , Adulto Jovem
3.
Neuroimage ; 158: 332-345, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28711737

RESUMO

OBJECTIVES: Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy. METHODS: High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy. RESULTS: All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -13(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity. INTERPRETATION: These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.


Assuntos
Mapeamento Encefálico/métodos , Estimulação Encefálica Profunda/métodos , Vias Neurais , Doença de Parkinson/terapia , Núcleo Subtalâmico , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino
4.
Cereb Cortex ; 26(2): 807-819, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26564255

RESUMO

Lack of physical engagement, productivity, and initiative-so-called "behavioral apathy"--is a common problem with significant impact, both personal and economic. Here, we investigate whether there might be a biological basis to such lack of motivation using a new effort and reward-based decision-making paradigm, combined with functional and diffusion-weighted imaging. We hypothesized that behavioral apathy in otherwise healthy people might be associated with differences in brain systems underlying either motivation to act (specifically in effort and reward-based decision-making) or in action processing (transformation of an intention into action). The results demonstrate that behavioral apathy is associated with increased effort sensitivity as well as greater recruitment of neural systems involved in action anticipation: supplementary motor area (SMA) and cingulate motor zones. In addition, decreased structural and functional connectivity between anterior cingulate cortex (ACC) and SMA were associated with increased behavioral apathy. These findings reveal that effort sensitivity and translation of intentions into actions might make a critical contribution to behavioral apathy. We propose a mechanism whereby inefficient communication between ACC and SMA might lead to increased physiological cost--and greater effort sensitivity--for action initiation in more apathetic people.


Assuntos
Apatia/fisiologia , Individualidade , Córtex Motor/fisiologia , Adulto , Mapeamento Encefálico , Sinais (Psicologia) , Tomada de Decisões , Retroalimentação Sensorial , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Córtex Motor/irrigação sanguínea , Vias Neurais/irrigação sanguínea , Vias Neurais/fisiologia , Estimulação Luminosa , Psicofísica , Recompensa , Autorrelato , Substância Branca/fisiologia , Adulto Jovem
5.
J Neurosci ; 33(6): 2242-53, 2013 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-23392656

RESUMO

Although damage to the medial frontal cortex causes profound decision-making impairments, it has been difficult to pinpoint the relative contributions of key anatomical subdivisions. Here we use function magnetic resonance imaging to examine the contributions of human ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC) during sequential choices between multiple alternatives--two key features of choices made in ecological settings. By carefully constructing options whose current value at any given decision was dissociable from their longer term value, we were able to examine choices in current and long-term frames of reference. We present evidence showing that activity at choice and feedback in vmPFC and dACC was tied to the current choice and the best long-term option, respectively. vmPFC, mid-cingulate, and posterior cingulate cortex encoded the relative value between the chosen and next best option at each sequential decision, whereas dACC encoded the relative value of adapting choices from the option with the highest value in the longer term. Furthermore, at feedback we identify temporally dissociable effects that predict repetition of the current choice and adaptation away from the long-term best option in vmPFC and dACC, respectively. These functional dissociations at choice and feedback suggest that sequential choices are subject to competing cortical mechanisms.


Assuntos
Comportamento de Escolha/fisiologia , Giro do Cíngulo/fisiologia , Córtex Pré-Frontal/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Vias Neurais/fisiologia , Estimulação Luminosa/métodos , Adulto Jovem
6.
Neuroimage ; 100: 498-506, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24941453

RESUMO

Two long-standing traditions have highlighted cortical decision mechanisms in the parietal and prefrontal cortices of primates, but it has not been clear how these processes differ, or when each cortical region may influence behaviour. Recent data from ventromedial prefrontal cortex (vmPFC) and posterior parietal cortex (PPC) have suggested one possible axis on which the two decision processes might be delineated. Fast decisions may be resolved primarily by parietal mechanisms, whereas decisions made without time pressure may rely on prefrontal mechanisms. Here, we report direct evidence for such dissociation. During decisions under time pressure, a value comparison process was evident in PPC, but not in vmPFC. Value-related activity was still found in vmPFC under time pressure. However, vmPFC represented overall input value rather than compared output value. In contrast, when decisions were made without time pressure, vmPFC transitioned to encode a value comparison while value-related parameters were entirely absent from PPC. Furthermore, under time pressure, decision performance was primarily governed by PPC, while it was dominated by vmPFC at longer decision times. These data demonstrate that parallel cortical mechanisms may resolve the same choices in differing circumstances, and offer an explanation of the diverse neural signals reported in vmPFC and PPC during value-guided choice.


Assuntos
Mapeamento Encefálico/métodos , Comportamento de Escolha/fisiologia , Lobo Parietal/fisiologia , Córtex Pré-Frontal/fisiologia , Recompensa , Adolescente , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
7.
Psychol Sci ; 25(7): 1303-13, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24815611

RESUMO

How do people sustain resources for the benefit of individuals and communities and avoid the tragedy of the commons, in which shared resources become exhausted? In the present study, we examined the role of serotonin activity and social norms in the management of depletable resources. Healthy adults, alongside social partners, completed a multiplayer resource-dilemma game in which they repeatedly harvested from a partially replenishable monetary resource. Dietary tryptophan depletion, leading to reduced serotonin activity, was associated with aggressive harvesting strategies and disrupted use of the social norms given by distributions of other players' harvests. Tryptophan-depleted participants more frequently exhausted the resource completely and also accumulated fewer rewards than participants who were not tryptophan depleted. Our findings show that rank-based social comparisons are crucial to the management of depletable resources, and that serotonin mediates responses to social norms.


Assuntos
Serotonina/fisiologia , Comportamento Social , Normas Sociais , Triptofano/fisiologia , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Análise de Regressão , Recompensa , Autorrelato , Triptofano/administração & dosagem , Adulto Jovem
8.
Neuroimage ; 80: 273-82, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23727318

RESUMO

In recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organization of the brain as well as providing unique insights to abnormalities that underpin disease states. The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome.


Assuntos
Encéfalo/citologia , Encéfalo/fisiologia , Conectoma/métodos , Imagem de Tensor de Difusão/métodos , Aumento da Imagem/métodos , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Humanos , Modelos Anatômicos , Modelos Neurológicos
9.
Proc Natl Acad Sci U S A ; 106(44): 18680-5, 2009 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-19846760

RESUMO

The human MHC represents the strongest susceptibility locus for autoimmune diseases. However, the identification of the true predisposing gene(s) has been handicapped by the strong linkage disequilibrium across the region. Furthermore, most studies to date have been limited to the examination of a subset of the HLA and non-HLA genes with a marker density and sample size insufficient for mapping all independent association signals. We genotyped a panel of 1,472 SNPs to capture the common genomic variation across the 3.44 megabase (Mb) classic MHC region in 10,576 DNA samples derived from patients with systemic lupus erythematosus, Crohn's disease, ulcerative colitis, rheumatoid arthritis, myasthenia gravis, selective IgA deficiency, multiple sclerosis, and appropriate control samples. We identified the primary association signals for each disease and performed conditional regression to identify independent secondary signals. The data demonstrate that MHC associations with autoimmune diseases result from complex, multilocus effects that span the entire region.


Assuntos
Mapeamento Cromossômico , Predisposição Genética para Doença , Doenças do Sistema Imunitário/genética , Complexo Principal de Histocompatibilidade/genética , Complexo Principal de Histocompatibilidade/imunologia , Polimorfismo de Nucleotídeo Único/genética , Polimorfismo de Nucleotídeo Único/imunologia , Bases de Dados Genéticas , Testes Genéticos , Antígenos HLA/genética , Humanos
10.
Gene ; 684: 118-123, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30366082

RESUMO

MOTIVATION: While large-scale whole genome sequencing is feasible the high costs compel investigators to focus on disease subjects. As a result large sequencing datasets of samples with different diseases are often readily available, but not healthy controls to contrast them with. While it is possible to perform an association study using only diseases, the associations could be driven by a disease acting as a control and not the focal disease. METHODS: We developed a genotype-on-phenotype reverse regression with a Bayesian spike and slab prior to enable association testing in datasets with multiple diseases. This method, referred to as revreg, flagged associations (both common and rare) that were driven by diseases that were not of primary interest. RESULTS: Based on simulations, revreg had 80% power to detect an odds ratio of 1.74 for common variants (3500 samples total) and 3.73 for rare variants (14,000 samples total), with minimal type I error. For common variants, we tested this method on 3657 whole genome sequenced samples aimed at discovering variants associated with disease risk of Chronic Obstructive Pulmonary Disease using three other diseases as controls. We demonstrated detection of six highly significant associations likely due to Age-Related Macular Degeneration. In an exome dataset of 8836 samples aimed at characterizing rare variants associated with disease risk of Asthma, using five other diseases as controls, we detected and removed genic regions due to AMD (C3, CFH, CFHR5, CFI, and DNMT3A) and RA (KRTAP13-4).


Assuntos
Estudo de Associação Genômica Ampla/métodos , Análise de Sequência de DNA/métodos , Sequenciamento Completo do Genoma/métodos , Asma/genética , Teorema de Bayes , Estudos de Casos e Controles , Simulação por Computador , Predisposição Genética para Doença , Humanos , Degeneração Macular/genética , Fenótipo
11.
J Neurosci ; 27(14): 3743-52, 2007 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-17409238

RESUMO

The ability to stop motor responses depends critically on the right inferior frontal cortex (IFC) and also engages a midbrain region consistent with the subthalamic nucleus (STN). Here we used diffusion-weighted imaging (DWI) tractography to show that the IFC and the STN region are connected via a white matter tract, which could underlie a "hyperdirect" pathway for basal ganglia control. Using a novel method of "triangulation" analysis of tractography data, we also found that both the IFC and the STN region are connected with the presupplementary motor area (preSMA). We hypothesized that the preSMA could play a conflict detection/resolution role within a network between the preSMA, the IFC, and the STN region. A second experiment tested this idea with functional magnetic resonance imaging (fMRI) using a conditional stop-signal paradigm, enabling examination of behavioral and neural signatures of conflict-induced slowing. The preSMA, IFC, and STN region were significantly activated the greater the conflict-induced slowing. Activation corresponded strongly with spatial foci predicted by the DWI tract analysis, as well as with foci activated by complete response inhibition. The results illustrate how tractography can reveal connections that are verifiable with fMRI. The results also demonstrate a three-way functional-anatomical network in the right hemisphere that could either brake or completely stop responses.


Assuntos
Cognição/fisiologia , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia
12.
Neuroimage Clin ; 18: 130-142, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29387530

RESUMO

The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.


Assuntos
Estimulação Encefálica Profunda , Tremor Essencial/terapia , Doença de Parkinson/terapia , Tálamo/fisiopatologia , Idoso , Imagem de Difusão por Ressonância Magnética , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Tálamo/diagnóstico por imagem
13.
Neurology ; 89(20): 2083-2091, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29030455

RESUMO

OBJECTIVE: To investigate the mechanism of action of deep brain stimulation for refractory chronic cluster headache and the optimal target within the ventral tegmental area. METHODS: Seven patients with refractory chronic cluster headache underwent high spatial and angular resolution diffusion MRI preoperatively. MRI-guided and MRI-verified electrode implantation was performed unilaterally in 5 patients and bilaterally in 2. Volumes of tissue activation were generated around active lead contacts with a finite-element model. Twelve months after surgery, voxel-based morphometry was used to identify voxels associated with higher reduction in headache load. Probabilistic tractography was used to identify the brain connectivity of the activation volumes in responders, defined as patients with a reduction of ≥30% in headache load. RESULTS: There was no surgical morbidity. Average follow-up was 34 ± 14 months. Patients showed reductions of 76 ± 33% in headache load, 46 ± 41% in attack severity, 58 ± 41% in headache frequency, and 51 ± 46% in attack duration at the last follow-up. Six patients responded to treatment. Greatest reduction in headache load was associated with activation in an area cantered at 6 mm lateral, 2 mm posterior, and 1 mm inferior to the midcommissural point of the third ventricle. Average responders' activation volume lay on the trigeminohypothalamic tract, connecting the trigeminal system and other brainstem nuclei associated with nociception and pain modulation with the hypothalamus, and the prefrontal and mesial temporal areas. CONCLUSIONS: We identify the optimal stimulation site and structural connectivity of the deep brain stimulation target for cluster headache, explicating possible mechanisms of action and disease pathophysiology.


Assuntos
Cefaleia Histamínica/terapia , Estimulação Encefálica Profunda/métodos , Vias Neurais/diagnóstico por imagem , Avaliação de Resultados em Cuidados de Saúde , Área Tegmentar Ventral , Cefaleia Histamínica/diagnóstico por imagem , Estimulação Encefálica Profunda/normas , Imagem de Tensor de Difusão , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia Assistida por Computador , Área Tegmentar Ventral/diagnóstico por imagem
14.
Neuron ; 89(6): 1343-1354, 2016 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-26948895

RESUMO

Complex cognitive processes require sophisticated local processing but also interactions between distant brain regions. It is therefore critical to be able to study distant interactions between local computations and the neural representations they act on. Here we report two anatomically and computationally distinct learning signals in lateral orbitofrontal cortex (lOFC) and the dopaminergic ventral midbrain (VM) that predict trial-by-trial changes to a basic internal model in hippocampus. To measure local computations during learning and their interaction with neural representations, we coupled computational fMRI with trial-by-trial fMRI suppression. We find that suppression in a medial temporal lobe network changes trial-by-trial in proportion to stimulus-outcome associations. During interleaved choice trials, we identify learning signals that relate to outcome type in lOFC and to reward value in VM. These intervening choice feedback signals predicted the subsequent change to hippocampal suppression, suggesting a convergence of signals that update the flexible representation of stimulus-outcome associations.


Assuntos
Hipocampo/fisiologia , Aprendizagem/fisiologia , Córtex Pré-Frontal/fisiologia , Adulto , Mapeamento Encefálico , Comportamento de Escolha , Simulação por Computador , Retroalimentação , Feminino , Lateralidade Funcional , Voluntários Saudáveis , Hipocampo/irrigação sanguínea , Humanos , Modelos Lineares , Masculino , Mesencéfalo/irrigação sanguínea , Mesencéfalo/fisiologia , Modelos Biológicos , Vias Neurais/irrigação sanguínea , Vias Neurais/fisiologia , Oxigênio/sangue , Estimulação Luminosa , Valor Preditivo dos Testes , Córtex Pré-Frontal/irrigação sanguínea , Adulto Jovem
15.
Nat Neurosci ; 19(10): 1280-5, 2016 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-27669988

RESUMO

Dorsal anterior cingulate cortex (dACC) carries a wealth of value-related information necessary for regulating behavioral flexibility and persistence. It signals error and reward events informing decisions about switching or staying with current behavior. During decision-making, it encodes the average value of exploring alternative choices (search value), even after controlling for response selection difficulty, and during learning, it encodes the degree to which internal models of the environment and current task must be updated. dACC value signals are derived in part from the history of recent reward integrated simultaneously over multiple time scales, thereby enabling comparison of experience over the recent and extended past. Such ACC signals may instigate attentionally demanding and difficult processes such as behavioral change via interactions with prefrontal cortex. However, the signal in dACC that instigates behavioral change need not itself be a conflict or difficulty signal.


Assuntos
Tomada de Decisões/fisiologia , Giro do Cíngulo/fisiologia , Recompensa , Animais , Atenção/fisiologia , Comportamento de Escolha/fisiologia , Humanos , Aprendizagem/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia
16.
Neurobiol Aging ; 35(6): 1510.e19-26, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24439484

RESUMO

TREM and TREM-like receptors are a structurally similar protein family encoded by genes clustered on chromosome 6p21.11. Recent studies have identified a rare coding variant (p.R47H) in TREM2 that confers a high risk for Alzheimer's disease (AD). In addition, common single nucleotide polymorphisms in this genomic region are associated with cerebrospinal fluid biomarkers for AD and a common intergenic variant found near the TREML2 gene has been identified to be protective for AD. However, little is known about the functional variant underlying the latter association or its relationship with the p.R47H. Here, we report comprehensive analyses using whole-exome sequencing data, cerebrospinal fluid biomarker analyses, meta-analyses (16,254 cases and 20,052 controls) and cell-based functional studies to support the role of the TREML2 coding missense variant p.S144G (rs3747742) as a potential driver of the meta-analysis AD-associated genome-wide association studies signal. Additionally, we demonstrate that the protective role of TREML2 in AD is independent of the role of TREM2 gene as a risk factor for AD.


Assuntos
Doença de Alzheimer/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Mutação de Sentido Incorreto/genética , Receptores Imunológicos/genética , Doença de Alzheimer/prevenção & controle , Biomarcadores/líquido cefalorraquidiano , Cromossomos Humanos Par 6 , Humanos , Metanálise como Assunto , Polimorfismo de Nucleotídeo Único/genética , Receptores Imunológicos/fisiologia , Risco
17.
Front Neuroinform ; 5: 23, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22016733

RESUMO

We have developed a method for automated probabilistic reconstruction of a set of major white-matter pathways from diffusion-weighted MR images. Our method is called TRACULA (TRActs Constrained by UnderLying Anatomy) and utilizes prior information on the anatomy of the pathways from a set of training subjects. By incorporating this prior knowledge in the reconstruction procedure, our method obviates the need for manual interaction with the tract solutions at a later stage and thus facilitates the application of tractography to large studies. In this paper we illustrate the application of the method on data from a schizophrenia study and investigate whether the inclusion of both patients and healthy subjects in the training set affects our ability to reconstruct the pathways reliably. We show that, since our method does not constrain the exact spatial location or shape of the pathways but only their trajectory relative to the surrounding anatomical structures, a set a of healthy training subjects can be used to reconstruct the pathways accurately in patients as well as in controls.

18.
J Cogn Neurosci ; 16(9): 1536-51, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15601517

RESUMO

Neuroimaging studies of number comparison have consistently found activation in the intraparietal sulcus (IPS). Recently, it has been suggested that activations in the IPS vary with the distance between the numbers being compared. In number comparison, the smaller the distance between a number and the reference the longer the reaction time (RT ). Activations in the right or left IPS, however, have also been related to attentional and intentional selection. It is possible, therefore, that activity in this region is a reflection of the more basic stimulus and response-selection processes associated with changes in RT. This fMRI experiment investigated the effect of numerical distance independently from RT. In addition, activations during number comparison of single-digit and double-digit stimuli were compared. During number comparison blocks, subjects had to indicate whether digits were greater or smaller than a reference (5 or 65). In control blocks, they were asked to perform a perceptual task (vertical line present/absent) on either numerical or nonnumerical stimuli. Number comparison versus rest yielded a large bilateral parietal-posterior frontal network. However, no areas showed more activation during number comparison than during the control tasks. Furthermore, no areas were more active during comparison of numbers separated by a small distance than comparisons of those separated by a large distance or vice versa. A left-lateralized parietal-posterior frontal network varied significantly with RT. Our findings suggest that magnitude and numerical-distance-related IPS activations might be difficult to separate from fundamental stimulus and response-selection processes associated with RT changes. As is the case with other parameters, such as space, magnitude may be represented in the context of response selection in the parietal cortex. In this respect, the representation of magnitude in the human IPS may be similar to the representation of magnitude in other nonhuman primates.


Assuntos
Matemática , Movimento/fisiologia , Lobo Parietal/fisiologia , Tempo de Reação/fisiologia , Pensamento/fisiologia , Adulto , Feminino , Lobo Frontal/fisiologia , Humanos , Masculino , Rede Nervosa/fisiologia
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