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1.
Nat Commun ; 11(1): 5272, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077750

RESUMO

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Espectro Autista/genética , Encéfalo/fisiopatologia , Esquizofrenia/genética , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Cognição , Estudos de Coortes , Variações do Número de Cópias de DNA , Feminino , Deleção de Genes , Duplicação Gênica , Humanos , Imagem por Ressonância Magnética , Masculino , Mutação , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Adulto Jovem
2.
Data Brief ; 31: 105699, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32518809

RESUMO

The impact of multisite acquisition on resting-state functional MRI (rsfMRI) connectivity has recently gained attention. We provide consistency values (Pearson's correlation) between rsfMRI connectivity maps of an adult volunteer (Csub) scanned 25 times over 3.5 years at 13 sites using the Canadian Dementia Imaging Protocol (CDIP, www.cdip-pcid.ca). This dataset was generated as part of the following article: Multivariate consistency of resting-state fMRI connectivity maps acquired on a single individual over 2.5 years, 13 sites and 3 vendors [1]. Acquired on three 3T scanner vendors (GE, Siemens and Philips), the Csub dataset is part of an ongoing effort to monitor the quality and comparability of MRI data collected across the Canadian Consortium on Neurodegeneration in Aging (CCNA) imaging network. The participant was scanned 25 times in the above-mentioned article: multiple times at six sites over a period of 2.5 years, and once at the remaining seven sites. Since then the participant was scanned an additional 45 times, allowing us to extend the dataset to 70 rsfMRI scans over a period of >4 years. In addition, we provide intra- and inter-subject consistency values of rsfMRI connectivity maps derived from 26 adult participants belonging to the publicly released Hangzhou Normal University dataset (HNU1). All HNU1 participants underwent 10 rsfMRI scans over one month on a single 3T scanner (GE). Connectivity maps of seven canonical networks were generated for each scan in the two datasets (Csub and HNU1). All consistency values, along with the scripts used to preprocess the rsfMRI data and generate connectivity maps and pairwise consistency values, have been made available on two public repositories, Github and Zenodo. We have also made available four Jupyter notebooks that use the provided consistency values to (a) generate interactive graphical summaries - 1 notebook, (b) perform statistical analyses - 2 notebooks, and (c) perform data-driven cluster analysis for the recovery of subject identity (i.e. rsfMRI fingerprinting) - 1 notebook. In addition, we provide two interactive dashboards that allow visualization of individual connectivity maps from the two datasets. Finally, we also provide minimally preprocessed rsfMRI data in Brain Imaging Data Standard (BIDS) format on all 70 scans in the extended dataset.

3.
Neuroimage ; 205: 116210, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31593793

RESUMO

Studies using resting-state functional magnetic resonance imaging (rsfMRI) are increasingly collecting data at multiple sites in order to speed up recruitment or increase sample size. The main objective of this study was to assess the long-term consistency of rsfMRI connectivity maps derived at multiple sites and vendors using the Canadian Dementia Imaging Protocol (CDIP, www.cdip-pcid.ca). Nine to 10 min of functional BOLD images were acquired from an adult cognitively healthy volunteer scanned repeatedly at 13 Canadian sites on three scanner makes (General Electric, Philips and Siemens) over the course of 2.5 years. The consistency (spatial Pearson's correlation) of rsfMRI connectivity maps for seven canonical networks ranged from 0.3 to 0.8, with a negligible effect of time, but significant site and vendor effects. We noted systematic differences in data quality (i.e. head motion, number of useable time frames, temporal signal-to-noise ratio) across vendors, which may also confound some of these results, and could not be disentangled in this sample. We also pooled the long-term longitudinal data with a single-site, short-term (1 month) data sample acquired on 26 subjects (10 scans per subject), called HNU1. Using randomly selected pairs of scans from each subject, we quantified the ability of a data-driven unsupervised cluster analysis to match two scans of the same subjects. In this "fingerprinting" experiment, we found that scans from the Canadian subject (Csub) could be matched with high accuracy intra-site (>95% for some networks), but that the accuracy decreased substantially for scans drawn from different sites and vendors, even falling outside of the range of accuracies observed in HNU1. Overall, our results demonstrate good multivariate stability of rsfMRI measures over several years, but substantial impact of scanning site and vendors. How detrimental these effects are will depend on the application, yet our results demonstrate that new methods for harmonizing multisite analysis represent an important area for future work.

4.
Gigascience ; 8(5)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31077314

RESUMO

BACKGROUND: Clinical trials in Alzheimer's disease need to enroll patients whose cognition will decline over time, if left untreated, in order to demonstrate the efficacy of an intervention. Machine learning models used to screen for patients at risk of progression to dementia should therefore favor specificity (detecting only progressors) over sensitivity (detecting all progressors), especially when the prevalence of progressors is low. Here, we explore whether such high-risk patients can be identified using cognitive assessments and structural neuroimaging by training machine learning tools in a high-specificity regime. RESULTS: A multimodal signature of Alzheimer's dementia was first extracted from the ADNI1 dataset. We then validated the predictive value of this signature on ADNI1 patients with mild cognitive impairment (N = 235). The signature was optimized to predict progression to dementia over 3 years with low sensitivity (55.1%) but high specificity (95.6%), resulting in only moderate accuracy (69.3%) but high positive predictive value (80.4%, adjusted for a "typical" 33% prevalence rate of true progressors). These results were replicated in ADNI2 (N = 235), with 87.8% adjusted positive predictive value (96.7% specificity, 47.3% sensitivity, 85.1% accuracy). CONCLUSIONS: We found that cognitive measures alone could identify high-risk individuals, with structural measurements providing a slight improvement. The signature had comparable receiver operating characteristics to standard machine learning tools, yet a marked improvement in positive predictive value was achieved over the literature by selecting a high-specificity operating point. The multimodal signature can be readily applied for the enrichment of clinical trials.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Cognição , Diagnóstico por Computador/métodos , Neuroimagem/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Atrofia , Encéfalo/patologia , Encéfalo/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Aprendizado de Máquina , Masculino
5.
Brain ; 141(6): 1871-1883, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29688388

RESUMO

See Tijms and Visser (doi:10.1093/brain/awy113) for a scientific commentary on this article.Alzheimer's disease is preceded by a lengthy 'preclinical' stage spanning many years, during which subtle brain changes occur in the absence of overt cognitive symptoms. Predicting when the onset of disease symptoms will occur is an unsolved challenge in individuals with sporadic Alzheimer's disease. In individuals with autosomal dominant genetic Alzheimer's disease, the age of symptom onset is similar across generations, allowing the prediction of individual onset times with some accuracy. We extend this concept to persons with a parental history of sporadic Alzheimer's disease to test whether an individual's symptom onset age can be informed by the onset age of their affected parent, and whether this estimated onset age can be predicted using only MRI. Structural and functional MRIs were acquired from 255 ageing cognitively healthy subjects with a parental history of sporadic Alzheimer's disease from the PREVENT-AD cohort. Years to estimated symptom onset was calculated as participant age minus age of parental symptom onset. Grey matter volume was extracted from T1-weighted images and whole-brain resting state functional connectivity was evaluated using degree count. Both modalities were summarized using a 444-region cortical-subcortical atlas. The entire sample was divided into training (n = 138) and testing (n = 68) sets. Within the training set, individuals closer to or beyond their parent's symptom onset demonstrated reduced grey matter volume and altered functional connectivity, specifically in regions known to be vulnerable in Alzheimer's disease. Machine learning was used to identify a weighted set of imaging features trained to predict years to estimated symptom onset. This feature set alone significantly predicted years to estimated symptom onset in the unseen testing data. This model, using only neuroimaging features, significantly outperformed a similar model instead trained with cognitive, genetic, imaging and demographic features used in a traditional clinical setting. We next tested if these brain properties could be generalized to predict time to clinical progression in a subgroup of 26 individuals from the Alzheimer's Disease Neuroimaging Initiative, who eventually converted either to mild cognitive impairment or to Alzheimer's dementia. The feature set trained on years to estimated symptom onset in the PREVENT-AD predicted variance in time to clinical conversion in this separate longitudinal dataset. Adjusting for participant age did not impact any of the results. These findings demonstrate that years to estimated symptom onset or similar measures can be predicted from brain features and may help estimate presymptomatic disease progression in at-risk individuals.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Transtornos Cognitivos/etiologia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Mapeamento Encefálico , Transtornos Cognitivos/diagnóstico por imagem , Disfunção Cognitiva , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
6.
Schizophr Res ; 192: 167-171, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28601499

RESUMO

Our objective was to assess the generalizability, across sites and cognitive contexts, of schizophrenia classification based on functional brain connectivity. We tested different training-test scenarios combining fMRI data from 191 schizophrenia patients and 191 matched healthy controls obtained at 6 scanning sites and under different task conditions. Diagnosis classification accuracy generalized well to a novel site and cognitive context provided data from multiple sites were used for classifier training. By contrast, lower classification accuracy was achieved when data from a single distinct site was used for training. These findings indicate that it is beneficial to use multisite data to train fMRI-based classifiers intended for large-scale use in the clinical realm.


Assuntos
Encéfalo/diagnóstico por imagem , Generalização Psicológica/fisiologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Imagem por Ressonância Magnética , Masculino , Oxigênio/sangue , Adulto Jovem
7.
Alzheimers Dement (Amst) ; 8: 73-85, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28560308

RESUMO

INTRODUCTION: We performed a systematic review and meta-analysis of the Alzheimer's disease (AD) literature to examine consistency of functional connectivity alterations in AD dementia and mild cognitive impairment, using resting-state functional magnetic resonance imaging. METHODS: Studies were screened using a standardized procedure. Multiresolution statistics were performed to assess the spatial consistency of findings across studies. RESULTS: Thirty-four studies were included (1363 participants, average 40 per study). Consistent alterations in connectivity were found in the default mode, salience, and limbic networks in patients with AD dementia, mild cognitive impairment, or in both groups. We also identified a strong tendency in the literature toward specific examination of the default mode network. DISCUSSION: Convergent evidence across the literature supports the use of resting-state connectivity as a biomarker of AD. The locations of consistent alterations suggest that highly connected hub regions in the brain might be an early target of AD.

8.
Neuroimage ; 149: 220-232, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28161310

RESUMO

Connectivity studies using resting-state functional magnetic resonance imaging are increasingly pooling data acquired at multiple sites. While this may allow investigators to speed up recruitment or increase sample size, multisite studies also potentially introduce systematic biases in connectivity measures across sites. In this work, we measure the inter-site effect in connectivity and its impact on our ability to detect individual and group differences. Our study was based on real, as opposed to simulated, multisite fMRI datasets collected in N=345 young, healthy subjects across 8 scanning sites with 3T scanners and heterogeneous scanning protocols, drawn from the 1000 functional connectome project. We first empirically show that typical functional networks were reliably found at the group level in all sites, and that the amplitude of the inter-site effects was small to moderate, with a Cohen's effect size below 0.5 on average across brain connections. We then implemented a series of Monte-Carlo simulations, based on real data, to evaluate the impact of the multisite effects on detection power in statistical tests comparing two groups (with and without the effect) using a general linear model, as well as on the prediction of group labels with a support-vector machine. As a reference, we also implemented the same simulations with fMRI data collected at a single site using an identical sample size. Simulations revealed that using data from heterogeneous sites only slightly decreased our ability to detect changes compared to a monosite study with the GLM, and had a greater impact on prediction accuracy. However, the deleterious effect of multisite data pooling tended to decrease as the total sample size increased, to a point where differences between monosite and multisite simulations were small with N=120 subjects. Taken together, our results support the feasibility of multisite studies in rs-fMRI provided the sample size is large enough.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Vias Neurais/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Método de Monte Carlo , Estudos Multicêntricos como Assunto , Descanso , Máquina de Vetores de Suporte , Adulto Jovem
9.
Neural Comput ; 29(4): 990-1020, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28095191

RESUMO

Mixture of autoregressions (MoAR) models provide a model-based approach to the clustering of time series data. The maximum likelihood (ML) estimation of MoAR models requires evaluating products of large numbers of densities of normal random variables. In practical scenarios, these products converge to zero as the length of the time series increases, and thus the ML estimation of MoAR models becomes infeasible without the use of numerical tricks. We propose a maximum pseudolikelihood (MPL) estimation approach as an alternative to the use of numerical tricks. The MPL estimator is proved to be consistent and can be computed with an EM (expectation-maximization) algorithm. Simulations are used to assess the performance of the MPL estimator against that of the ML estimator in cases where the latter was able to be calculated. An application to the clustering of time series data arising from a resting state fMRI experiment is presented as a demonstration of the methodology.

10.
J Psychiatry Neurosci ; 42(1): 17-26, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27091719

RESUMO

BACKGROUND: Schizophrenia has been defined as a dysconnection syndrome characterized by aberrant functional brain connectivity. Using task-based fMRI, we assessed to what extent the nature of the cognitive context may further modulate abnormal functional brain connectivity. METHODS: We analyzed data matched for motion in patients with schizophrenia and healthy controls who performed 3 different tasks. Tasks 1 and 2 both involved emotional processing and only slighlty differed (incidental encoding v. memory recognition), whereas task 3 was a much different mental rotation task. We conducted a connectome-wide general linear model analysis aimed at identifying context-dependent and independent functional brain connectivity alterations in patients with schizophrenia. RESULTS: After matching for motion, we included 30 patients with schizophrenia and 30 healthy controls in our study. Abnormal connectivity in patients with schizophrenia followed similar patterns regardless of the degree of similarity between cognitive tasks. Decreased connectivity was most notable in the medial prefrontal cortex, the anterior and posterior cingulate, the temporal lobe, the lobule IX of the cerebellum and the premotor cortex. LIMITATIONS: A more circumscribed yet significant context-dependent effect might be detected with larger sample sizes or cognitive domains other than emotional and visuomotor processing. CONCLUSION: The context-independence of functional brain dysconnectivity in patients with schizophrenia provides a good justification for pooling data from multiple experiments in order to identify connectivity biomarkers of this mental illness.


Assuntos
Encéfalo/fisiopatologia , Emoções/fisiologia , Reconhecimento Psicológico/fisiologia , Esquizofrenia/fisiopatologia , Percepção Espacial/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Conectoma , Feminino , Humanos , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Rotação , Esquizofrenia/diagnóstico por imagem , Psicologia do Esquizofrênico
11.
Neuroimage ; 147: 532-541, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28011254

RESUMO

Resting-state functional connectivity (RSFC) studies have provided strong evidences that visual deprivation influences the brain's functional architecture. In particular, reduced RSFC coupling between occipital (visual) and temporal (auditory) regions has been reliably observed in early blind individuals (EB) at rest. In contrast, task-dependent activation studies have repeatedly demonstrated enhanced co-activation and connectivity of occipital and temporal regions during auditory processing in EB. To investigate this apparent discrepancy, the functional coupling between temporal and occipital networks at rest was directly compared to that of an auditory task in both EB and sighted controls (SC). Functional brain clusters shared across groups and cognitive states (rest and auditory task) were defined. In EBs, we observed higher occipito-temporal correlations in activity during the task than at rest. The reverse pattern was observed in SC. We also observed higher temporal variability of occipito-temporal RSFC in EB suggesting that occipital regions in this population may play the role of a multiple demand system. Our study reveals how the connectivity profile of sighted and early blind people is differentially influenced by their cognitive state, bridging the gap between previous task-dependent and RSFC studies. Our results also highlight how inferring group-differences in functional brain architecture solely based on resting-state acquisition has to be considered with caution.


Assuntos
Córtex Auditivo/fisiopatologia , Percepção Auditiva/fisiologia , Cegueira/fisiopatologia , Conectoma/métodos , Córtex Visual/fisiopatologia , Adulto , Córtex Auditivo/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Descanso , Córtex Visual/diagnóstico por imagem , Adulto Jovem
12.
Data Brief ; 9: 1122-1129, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27924300

RESUMO

We present group eight resolutions of brain parcellations for clusters generated from resting-state functional magnetic resonance images for 99 cognitively normal elderly persons and 129 patients with mild cognitive impairment, pooled from four independent datasets. This dataset was generated as part of the following study: Common Effects of Amnestic Mild Cognitive Impairment on Resting-State Connectivity Across Four Independent Studies (Tam et al., 2015) [1]. The brain parcellations have been registered to both symmetric and asymmetric MNI brain templates and generated using a method called bootstrap analysis of stable clusters (BASC) (Bellec et al., 2010) [2]. We present two variants of these parcellations. One variant contains bihemisphereic parcels (4, 6, 12, 22, 33, 65, 111, and 208 total parcels across eight resolutions). The second variant contains spatially connected regions of interest (ROIs) that span only one hemisphere (10, 17, 30, 51, 77, 199, and 322 total ROIs across eight resolutions). We also present maps illustrating functional connectivity differences between patients and controls for four regions of interest (striatum, dorsal prefrontal cortex, middle temporal lobe, and medial frontal cortex). The brain parcels and associated statistical maps have been publicly released as 3D volumes, available in .mnc and .nii file formats on figshare and on Neurovault. Finally, the code used to generate this dataset is available on Github.

13.
Sci Rep ; 6: 34948, 2016 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-27725727

RESUMO

Motor memory consolidation is characterized, in part, by a sleep-facilitated decrease in susceptibility to subsequent interfering experiences. Surprisingly, the cerebral substrates supporting this phenomenon have never been examined. We used fMRI to investigate the neural correlates of the influence of sleep on interference to motor memory consolidation. Healthy young adults were trained on a sequential motor task, and subsequently practiced a second competing sequence after an interval including diurnal sleep or wakefulness. Participants were then retested on the initial sequence 8 h and 24 h (including nocturnal sleep) after training. Results demonstrated that a post-training nap significantly protected memory against interference at 8 h and modulated the link between cerebral activity and behavior, such that a smaller post-interference decrease in cortico-striatal activity was associated with better performance. Interestingly, the protective effect of a nap was only transitory, as both groups performed similarly at 24 h. Activity in cortico-striatal areas that was disrupted during the day, presumably due to interference and accentuated in the absence of a nap, was restored overnight. Altogether, our findings offer the first evidence that cortico-striatal areas play a critical role in the transient sleep-facilitated reduction in motor memory vulnerability and in the overnight restoration of previously degraded memories.


Assuntos
Encéfalo/fisiologia , Consolidação da Memória , Atividade Motora , Destreza Motora , Sono , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
14.
Front Pharmacol ; 7: 90, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27148052

RESUMO

In recent years, pharmacovigilance has undergone some major changes. First, the patient's active role in identifying and describing adverse drug reactions (ADRs) has gained recognition. Second, pharmacovigilance has increasingly incorporated information and communications technology (ICT). Patients can now upload their own reports of ADRs online. Data on intensive medication monitoring are now collected via the Internet and smartphones. Worldwide collection of AEs using smart phones might become the leading technique in Low and Middle Income Countries where broad mobile phone service can be managed cheaper than Internet communication. At the same time, researchers are exploring the potential for data sharing via online forums and Internet search engines. In particular we synthetize the Pros and cons of the various methods for gathering pharmacovigilance data (i.e., Web-based spontaneous reporting of adverse drug reactions; Intensive drug monitoring studies; Analysis of online forum postings; Use of mobile phone systems to monitor drug effects). This article describes these advances and highlights their respective contributions.

15.
Sci Data ; 2: 150043, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26504522

RESUMO

We present a test-retest dataset of resting-state fMRI data obtained in 80 cognitively normal elderly volunteers enrolled in the "Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer's Disease" (PREVENT-AD) Cohort. Subjects with a family history of Alzheimer's disease in first-degree relatives were recruited as part of an on-going double blind randomized clinical trial of Naproxen or placebo. Two pairs of scans were acquired ~3 months apart, allowing the assessment of both intra- and inter-session reliability, with the possible caveat of treatment effects as a source of inter-session variation. Using the NeuroImaging Analysis Kit (NIAK), we report on the standard quality of co-registration and motion parameters of the data, and assess their validity based on the spatial distribution of seed-based connectivity maps as well as intra- and inter-session reliability metrics in the default-mode network. This resource, released publicly as sample UM1 of the Consortium for Reliability and Reproducibility (CoRR), will benefit future studies focusing on the preclinical period preceding the appearance of dementia in Alzheimer's disease.


Assuntos
Doença de Alzheimer , Imagem por Ressonância Magnética , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/etiologia , Doença de Alzheimer/prevenção & controle , Estudos de Coortes , Demência/complicações , Demência/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes
16.
Neuroimage ; 123: 212-28, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26241681

RESUMO

A recent trend in functional magnetic resonance imaging is to test for association of clinical disorders with every possible connection between selected brain parcels. We investigated the impact of the resolution of functional brain parcels, ranging from large-scale networks to local regions, on a mass univariate general linear model (GLM) of connectomes. For each resolution taken independently, the Benjamini-Hochberg procedure controlled the false-discovery rate (FDR) at nominal level on realistic simulations. However, the FDR for tests pooled across all resolutions could be inflated compared to the FDR within resolution. This inflation was severe in the presence of no or weak effects, but became negligible for strong effects. We thus developed an omnibus test to establish the overall presence of true discoveries across all resolutions. Although not a guarantee to control the FDR across resolutions, the omnibus test may be used for descriptive analysis of the impact of resolution on a GLM analysis, in complement to a primary analysis at a predefined single resolution. On three real datasets with significant omnibus test (schizophrenia, congenital blindness, motor practice), markedly higher rate of discovery were obtained at low resolutions, below 50, in line with simulations showing increase in sensitivity at such resolutions. This increase in discovery rate came at the cost of a lower ability to localize effects, as low resolution parcels merged many different brain regions together. However, with 30 or more parcels, the statistical effect maps were biologically plausible and very consistent across resolutions. These results show that resolution is a key parameter for GLM-connectome analysis with FDR control, and that a functional brain parcellation with 30 to 50 parcels may lead to an accurate summary of full connectome effects with good sensitivity in many situations.


Assuntos
Encéfalo/fisiologia , Conectoma/métodos , Imagem por Ressonância Magnética/métodos , Processamento de Sinais Assistido por Computador , Adolescente , Adulto , Idoso , Algoritmos , Cegueira/congênito , Cegueira/fisiopatologia , Encéfalo/fisiopatologia , Simulação por Computador , Interpretação Estatística de Dados , Humanos , Processamento de Imagem Assistida por Computador , Aprendizagem/fisiologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor/fisiologia , Reprodutibilidade dos Testes , Esquizofrenia/fisiopatologia , Adulto Jovem
17.
Cereb Cortex ; 25(9): 2658-69, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24729172

RESUMO

Functional magnetic resonance imaging can measure distributed and subtle variations in brain responses associated with task performance. However, it is unclear whether the rich variety of responses observed across the brain is functionally meaningful and consistent across individuals. Here, we used a multivariate clustering approach that grouped brain regions into clusters based on the similarity of their task-evoked temporal responses at the individual level, and then established the spatial consistency of these individual clusters at the group level. We observed a stable pseudohierarchy of task-evoked networks in the context of a delayed sequential motor task, where the fractionation of networks was driven by a gradient of involvement in motor sequence preparation versus execution. In line with theories about higher-level cognitive functioning, this gradient evolved in a rostro-caudal manner in the frontal lobe. In addition, parcellations in the cerebellum and basal ganglia matched with known anatomical territories and fiber pathways with the cerebral cortex. These findings demonstrate that subtle variations in brain responses associated with task performance are systematic enough across subjects to define a pseudohierarchy of task-evoked networks. Such networks capture meaningful functional features of brain organization as shaped by a given cognitive context.


Assuntos
Mapeamento Encefálico , Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Hemodinâmica/fisiologia , Vias Neurais/irrigação sanguínea , Vias Neurais/fisiologia , Adulto , Análise por Conglomerados , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Modelos Neurológicos , Oxigênio/sangue , Desempenho Psicomotor/fisiologia , Adulto Jovem
18.
Front Aging Neurosci ; 7: 242, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26733866

RESUMO

Resting-state functional connectivity is a promising biomarker for Alzheimer's disease. However, previous resting-state functional magnetic resonance imaging studies in Alzheimer's disease and amnestic mild cognitive impairment (aMCI) have shown limited reproducibility as they have had small sample sizes and substantial variation in study protocol. We sought to identify functional brain networks and connections that could consistently discriminate normal aging from aMCI despite variations in scanner manufacturer, imaging protocol, and diagnostic procedure. We therefore combined four datasets collected independently, including 112 healthy controls and 143 patients with aMCI. We systematically tested multiple brain connections for associations with aMCI using a weighted average routinely used in meta-analyses. The largest effects involved the superior medial frontal cortex (including the anterior cingulate), dorsomedial prefrontal cortex, striatum, and middle temporal lobe. Compared with controls, patients with aMCI exhibited significantly decreased connectivity between default mode network nodes and between regions of the cortico-striatal-thalamic loop. Despite the heterogeneity of methods among the four datasets, we identified common aMCI-related connectivity changes with small to medium effect sizes and sample size estimates recommending a minimum of 140 to upwards of 600 total subjects to achieve adequate statistical power in the context of a multisite study with 5-10 scanning sites and about 10 subjects per group and per site. If our findings can be replicated and associated with other established biomarkers of Alzheimer's disease (e.g., amyloid and tau quantification), then these functional connections may be promising candidate biomarkers for Alzheimer's disease.

19.
Med Sci (Paris) ; 27(4): 413-20, 2011 Apr.
Artigo em Francês | MEDLINE | ID: mdl-21524407

RESUMO

This review presents the results of studies carried out in our laboratory that aim to investigate, through functional magnetic resonance imaging (fMRI), the brain plasticity associated with motor sequence learning, defined as our ability to integrate simple stereotyped movements into a single motor representation. Following a brief description of Doyon and colleagues' model (2002, 2005, 2009) of motor skill learning that has guided this work, we then describe the functional changes that occur at the different (rapid, slow, automatization) acquisition phases, and propose specific roles that the putamen, the cerebellum and their motor-related cortical areas, play in this form of motor behavior. Finally, we put forward evidence that post-training, non-REM sleep (and spindles in Stage 2 sleep, in particular) contributes to the consolidation of a motor sequence memory trace, and that increased activity within the striatum and/or the hippocampus mediates this mnemonic process.


Assuntos
Encéfalo/fisiologia , Aprendizagem/fisiologia , Memória/fisiologia , Destreza Motora/fisiologia , Plasticidade Neuronal/fisiologia , Adulto , Mapeamento Encefálico , Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Feminino , Hábitos , Humanos , Imaginação/fisiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Modelos Psicológicos , Transtornos dos Movimentos/fisiopatologia , Fases do Sono/fisiologia , Comportamento Estereotipado/fisiologia
20.
Proc Natl Acad Sci U S A ; 107(41): 17839-44, 2010 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-20876115

RESUMO

This study aimed to investigate, through functional MRI (fMRI), the neuronal substrates associated with the consolidation process of two motor skills: motor sequence learning (MSL) and motor adaptation (MA). Four groups of young healthy individuals were assigned to either (i) a night/sleep condition, in which they were scanned while practicing a finger sequence learning task or an eight-target adaptation pointing task in the evening (test) and were scanned again 12 h later in the morning (retest) or (ii) a day/awake condition, in which they were scanned on the MSL or the MA tasks in the morning and were rescanned 12 h later in the evening. As expected and consistent with the behavioral results, the functional data revealed increased test-retest changes of activity in the striatum for the night/sleep group compared with the day/awake group in the MSL task. By contrast, the results of the MA task did not show any difference in test-retest activity between the night/sleep and day/awake groups. When the two MA task groups were combined, however, increased test-retest activity was found in lobule VI of the cerebellar cortex. Together, these findings highlight the presence of both functional and structural dissociations reflecting the off-line consolidation processes of MSL and MA. They suggest that MSL consolidation is sleep dependent and reflected by a differential increase of neural activity within the corticostriatal system, whereas MA consolidation necessitates either a period of daytime or sleep and is associated with increased neuronal activity within the corticocerebellar system.


Assuntos
Adaptação Fisiológica/fisiologia , Encéfalo/fisiologia , Aprendizagem/fisiologia , Atividade Motora/fisiologia , Destreza Motora/fisiologia , Plasticidade Neuronal/fisiologia , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Sono/fisiologia , Vigília/fisiologia
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