A5044518952- Functional Brain Connectivity Studies
- Genetic Associations and Epidemiology
- Schizophrenia research and treatment
- Advanced Neuroimaging Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- Folate and B Vitamins Research
- Mental Health Research Topics
- Birth, Development, and Health
- Epigenetics and DNA Methylation
- Bipolar Disorder and Treatment
- Health, Environment, Cognitive Aging
- Mental Health and Psychiatry
- Genomic variations and chromosomal abnormalities
- Neural dynamics and brain function
- Bioinformatics and Genomic Networks
- Maternal Mental Health During Pregnancy and Postpartum
- Advanced MRI Techniques and Applications
- Tryptophan and brain disorders
- Genetics, Bioinformatics, and Biomedical Research
- Obsessive-Compulsive Spectrum Disorders
- Congenital heart defects research
- Attention Deficit Hyperactivity Disorder
- Neuroscience and Neuropharmacology Research
- Neurological disorders and treatments
- Diet and metabolism studies
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Athinoula A. Martinos Center for Biomedical Imaging
2012-2024
Lemuel Shattuck Hospital
2024
Health Affairs
2019-2024
Imaging Center
2022
Center for Human Genetics
2022
Stanley Foundation
2019
Broad Institute
2019
Universidad de Extremadura
2017
Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within visual system. Other patterns, particularly association areas, suggest presence of large-scale circuits without clear relations. In this study organization networks human cerebrum was explored using resting-state functional MRI. Data from 1,000 subjects were registered surface-based alignment. A...
The striatum is connected to the cerebral cortex through multiple anatomical loops that process sensory, limbic, and heteromodal information. Tract-tracing studies in monkey reveal these corticostriatal connections form stereotyped patterns striatum. Here organization of was explored human with resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered nonlinear deformation combination surface-based alignment cortex. fcMRI maps derived seed regions placed...
The goal of the Brain Genomics Superstruct Project (GSP) is to enable large-scale exploration links between brain function, behavior, and ultimately genetic variation. To provide broader scientific community data probe these associations, a repository structural functional magnetic resonance imaging (MRI) scans linked information was constructed from sample healthy individuals. initial release, detailed in present manuscript, encompasses quality screened cross-sectional 1,570 participants...
Individual differences in affective and social processes may arise from variability amygdala-medial prefrontal (mPFC) circuitry related genetic heterogeneity. To explore this possibility humans, we examined the structural correlates of trait negative affect a sample 1050 healthy young adults with no history psychiatric illness. Analyses revealed that heightened was associated increased amygdala volume reduced thickness left mPFC region encompassing subgenual rostral anterior cingulate...
Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns extent to which epigenetic signatures measured more accessible tissues such as blood can serve surrogate marker for brain. Here, we aimed (1) investigate blood-brain correspondence DNA methylation using within-subject design and (2) identify changes brain-related biological pathways schizophrenia.We obtained paired temporal lobe biopsy samples simultaneously from 12 epilepsy patients during...
Significance Historically, most research on the biological origins of psychiatric illness has focused individual diagnostic categories, studied in isolation. Mounting evidence indicates that nominally distinct diagnoses are not separated by clear neurobiological boundaries. Here, we derive functional connectomic signatures over 1,000 individuals, including patients presenting with different categories impairment (psychosis), clinical diagnoses, and severity as reflected treatment seeking....
Volume deficits of the hippocampus in schizophrenia have been consistently reported. However, is anatomically heterogeneous; it remains unclear whether certain portions are affected more than others schizophrenia. In this study, we aimed to determine volume confined specific subfields and measure subfield trajectories over course illness. Magnetic resonance imaging scans were obtained from Data set 1: 155 patients with (mean duration illness 7 years) 79 healthy controls, 2: an independent...
Individuals vary widely in their tendency to seek stimulation and act impulsively, early developing traits with genetic origins. Failures regulate these behaviors increase risk for maladaptive outcomes including substance abuse. Here, we explored the neuroanatomical correlates of sensation seeking impulsivity healthy young adults. Our analyses revealed links between reduced cortical thickness that were preferentially localized regions implicated cognitive control, anterior cingulate middle...
Article Abstract Objective: Specific genetic or biological markers may predict inadequate response to therapy for major depressive disorder (MDD). The objective of the current post hoc analysis was evaluate effect specific and on antidepressant efficacy adjunctive l-methylfolate 15 mg versus placebo from a trial responders selective serotonin reuptake inhibitors (SSRIs). Method: double-blind, randomized, placebo-controlled used sequential parallel comparison design. Outpatients with...
More effective treatments are needed for negative symptoms of schizophrenia, which typically chronic, disabling, and costly. Negative have previously been associated with reduced blood folate levels, especially among patients low-functioning variants in genes that regulate metabolism, suggesting the potential utility supplementation.To determine whether folic acid plus vitamin B12 supplementation reduces schizophrenia functional folate-related influence treatment response.Parallel-group,...
Abstract Higher-order cognition emerges through the flexible interactions of large-scale brain networks, an aspect temporal coordination that may be impaired in psychosis. Here, we map dynamic functional architecture cerebral cortex healthy young adults, leveraging this atlas transient network configurations (states), to identify state- and network-specific disruptions patients with schizophrenia psychotic bipolar disorder. We demonstrate connectivity profiles are reliable within...
Abstract In the dawning era of large-scale biomedical data, multidimensional phenotype vectors will play an increasing role in examining genetic underpinnings brain features, behaviour and disease. For example, shape measurements derived from MRI scans are geometric descriptions structure provide alternate class phenotypes that remains largely unexplored studies. Here we extend concept heritability to traits, present first comprehensive analysis neuroanatomical across ensemble structures...
Understanding how risk genes cumulatively impair brain function in schizophrenia could provide critical insights into its pathophysiology. Working memory impairment has been associated with abnormal dopamine signaling the prefrontal cortex, which is likely under complex genetic control. The catechol- O -methyltransferase (COMT) 158Val → Met polymorphism (rs4680), affects availability of signaling, consistently stratifies activation during working performance. However, low-dopamine COMT...
Significance Practical tools for high-dimensional heritability-based screening are invaluable prioritizing phenotypes genetic studies with the dramatic expansion of available phenotypic data. Classical estimates heritability require twin or pedigree data, which can be costly and difficult to acquire. Alternative methods based on whole-genome data from unrelated individuals exist but computationally expensive. Here we present a novel, fast, accurate statistical method massively expedited...
Background Depression is a common source of human disability for which etiologic insights remain limited. Although abnormalities monoamine neurotransmission, including dopamine, are theorized to contribute the pathophysiology depression, evidence linking dopamine-related genes depression has been mixed. The current study sought address this knowledge-gap by examining whether combined effect dopamine polymorphisms was associated with depressive symptomatology in both healthy individuals and...
Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of scale the level cortical networks and coordinate their interplay during memory. Among network territories, mean D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, density...
Patients with schizophrenia (SCZ) experience chronic cognitive deficits. Histone deacetylases (HDACs) are enzymes that regulate circuitry; however, the role of HDACs in disorders, including SCZ, remains unknown humans. We previously determined HDAC2 mRNA levels were lower dorsolateral prefrontal cortex (DLPFC) tissue from donors SCZ compared controls. Here we investigated relationship between vivo HDAC expression and impairment patients matched healthy controls using [11C]Martinostat...