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In recent years, understanding functional brain connectivity has become increasingly important as a scientific tool with potential clinical implications. Statistical methods, such as graphical models and network analysis, have been adopted to construct functional connectivity networks for single subjects. Here we focus on studying the association between functional connectivity networks and clinical characteristics such as psychiatric symptoms and diagnoses. Utilizing machine learning algorithms, we propose a method to examine predictability of functional connectivity networks from clinical characteristics. Our methods can identify salient clinical characteristics predictive of the whole brain network or specific subnetworks. We illustrate our methods on the analysis of fMRI data in the Philadelphia Neurodevelopmental Cohort study, demonstrating clinically meaningful results., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Obsessive-compulsive disorder (OCD) is often associated with pathological uncertainty regarding whether an action has been performed correctly or whether a bad outcome will occur, leading to compulsive "evidence gathering" behaviors aimed at reducing uncertainty. The current study used event-related functional magnetic resonance imaging to investigate neural functioning in OCD patients and controls as subjective certainty was rated in response to sequential pieces of evidence for a decision. Uncertainty was experimentally manipulated so that some decisions were associated with no "objective" uncertainty (all observed evidence pointed to one correct choice), whereas other decisions contained calculable but varying levels of objective uncertainty based on displayed probabilities. Results indicated that OCD patients differed from controls on decisions that contained no objective uncertainty, such that patients rated themselves as more uncertain. Patients also showed greater activation in a network of brain regions previously associated with internally-focused thought and valuation including ventromedial prefrontal cortex, parahippocampus, middle temporal cortex, as well as amygdala and orbitofrontal cortex/ventral anterior insula. In the patient group, a significantly greater number of positive intersubject correlations were found among several of these brain regions, suggesting that this network is more interconnected in patients. OCD patients did not differ from controls on decisions where task parameters led to uncertainty. These results indicate that OCD is associated with hyperactivation in a network of limbic/paralimbic brain regions when making decisions, which may contribute to the greater subjective experience of doubt that characterizes the disorder., (Copyright © 2012 Wiley Periodicals, Inc.)

Individual variability in the location of neural activations poses a unique problem for neuroimaging studies employing group averaging techniques to investigate the neural bases of cognitive and emotional functions. This may be especially challenging for studies examining patient groups, which often have limited sample sizes and increased intersubject variability. In particular, medial frontal cortex (MFC) dysfunction is thought to underlie performance monitoring dysfunction among patients with schizophrenia, yet previous studies using group averaging to compare schizophrenic patients to controls have yielded conflicting results. To examine individual activations in MFC associated with two aspects of performance monitoring, interference and error processing, functional magnetic resonance imaging data were acquired while 17 patients with schizophrenia and 21 healthy controls (HCs) performed an event-related version of the multisource interference task. Comparisons of averaged data revealed few differences between the groups. By contrast, topographic analysis of individual activations for errors showed that control subjects exhibited activations spanning across both posterior and anterior regions of MFC while patients primarily activated posterior MFC, possibly reflecting an impaired emotional response to errors in schizophrenia. This discrepancy between topographic and group-averaged results may be due to the significant dispersion among individual activations, particularly in HCs, highlighting the importance of considering intersubject variability when interpreting the medial frontal response to error commission., (Copyright 2009 Wiley-Liss, Inc)