A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei

Recent advances in magnetic resonance imaging methods, including data acquisition, pre-processing and analysis, have benefited research on the contributions of subcortical brain nuclei to human cognition and behavior. At the same time, these developments have led to an increasing need for a high-resolution probabilistic in vivo anatomical atlas of subcortical nuclei. In order to address this need, we constructed high spatial resolution, three-dimensional templates, using high-accuracy diffeomorphic registration of T_1- and T_2- weighted structural images from 168 typical adults between 22 and 35 years old. In these templates, many tissue boundaries are clearly visible, which would otherwise be impossible to delineate in data from individual studies. The resulting delineations of subcortical nuclei complement current histology-based atlases. We further created a companion library of software tools for atlas development, to offer an open and evolving resource for the creation of a crowd-sourced in vivoprobabilistic anatomical atlas of the human brain

A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei

Recent advances in magnetic resonance imaging methods, including data acquisition, pre-processing and analysis, have benefited research on the contributions of subcortical brain nuclei to human cognition and behavior. At the same time, these developments have led to an increasing need for a high-resolution probabilistic in vivo anatomical atlas of subcortical nuclei. In order to address this need, we constructed high spatial resolution, three-dimensional templates, using high-accuracy diffeomorphic registration of T_1- and T_2- weighted structural images from 168 typical adults between 22 and 35 years old. In these templates, many tissue boundaries are clearly visible, which would otherwise be impossible to delineate in data from individual studies. The resulting delineations of subcortical nuclei complement current histology-based atlases. We further created a companion library of software tools for atlas development, to offer an open and evolving resource for the creation of a crowd-sourced in vivoprobabilistic anatomical atlas of the human brain

Reinforcement Learning Atlas

An in vivo atlas of human subcortical nuclei involved in reinforcement learning. Based on a midspace template derived from Human Connectome Project structural MRI

What is typical: Atypical in young childrens attention regulation?: Characterizing the developmental spectrum with the Multidimensional Assessment Profiles-Attention Regulation Infant-Toddler (MAPS-AR-IT) Scale.

While attention dysregulation is a promising early indicator of neurodevelopmental risk, in particular attention-deficit/hyperactivity disorder (ADHD), it is difficult to characterize clinical concern due to its developmental expectability at the transition to toddlerhood. Thus, explicating the typical:atypical continuum of risk indicators is among the key future directions for research to promote early identification and intervention, and prevent decrements in the attainment of developmental milestones into early childhood. In this paper, we present the Multidimensional Assessment Profiles-Attention Regulation Infant-Toddler (MAPS-AR-IT) Scale, a novel parent-report survey of dimensional, developmentally specified indicators of attention (dys)regulation. Item Response Theory was employed to characterize the typical:atypical spectrum of both normative and more concerning dysregulation (including the contexts in which behavior occurs). We provide evidence of the validity of this measure in capturing the full typical:atypical spectrum via a longitudinal sample of typically developing children at 12-18 months of age (baseline) via concurrent scores on well-validated temperament and clinical measures. We also examine longitudinal stability and predictive validity if the MAPS-AR-IT via a clinical interview of ADHD symptoms at 24-30 months (follow-up). While not diagnostic, we present evidence of the utility of the MAPS-AR-IT in explicating individual neurodevelopmental risk and elucidating the broader typicality of behaviors related to attention (dys)regulation

Molecular mechanism of peroxisome proliferator-activated receptor α activation by WY14643: a new mode of ligand recognition and receptor stabilization

Peroxisome proliferator-activated receptors (PPARs) are members of a superfamily of nuclear transcription factors. They are involved in mediating numerous physiological effects in humans, including glucose and lipid metabolism. PPARα ligands effectively treat dyslipidemia and have significant antiinflammatory and antiatherosclerotic activities. These effects and their ligand-dependent activity make nuclear receptors obvious targets for drug design. Here, we present the structure of the human PPARα in complex with WY14643, a member of fibrate class of drug, and a widely used PPAR activator. The crystal structure of this complex suggests that WY14643 induces activation of PPARα in an unusual bipartite mechanism involving conventional direct helix 12 stabilization and an alternative mode that involves a second ligand in the pocket. We present structural observations, molecular dynamics and activity assays that support the importance of the second site in WY14643 action. The unique binding mode of WY14643 reveals a new pattern of nuclear receptor ligand recognition and suggests a novel basis for ligand design, offering clues for improving the binding affinity and selectivity of ligand. We show that binding of WY14643 to PPARα was associated with antiinflammatory disease in a human corneal cell model, suggesting possible applications for PPARα ligands.FAPESPNIH (DK41482