Dysfunctional Activation and Brain Network Profiles in Youth with Obsessive-Compulsive Disorder: A Focus on the Dorsal Anterior Cingulate during Working Memory.

Vaibhav A Diwadkar,Ella Hong,Paul D Arnold,Carrie Rix,David R Rosenberg,Gregory L Hanna,Ashley Burgess

doi:10.3389/fnhum.2015.00149

Abstract

Brain network dysfunction is emerging as a central biomarker of interest in psychiatry, in large part, because psychiatric conditions are increasingly seen as disconnection syndromes. Understanding dysfunctional brain network profiles in task-active states provides important information on network engagement in an experimental context. This in turn may be predictive of many of the cognitive and behavioral deficits associated with complex behavioral phenotypes. Here we investigated brain network profiles in youth with obsessive-compulsive disorder (OCD), contrasting them with a group of age-comparable controls. Network interactions were assessed during simple working memory: in particular, we focused on the modulation by the dorsal anterior cingulate cortex (dACC) of cortical, striatal, and thalamic regions. The focus on the dACC was motivated by its hypothesized role in the pathophysiology of OCD. However, its task-active network signatures have not been investigated before. Network interactions were modeled using psychophysiological interaction, a simple directional model of seed to target brain interactions. Our results indicate that OCD is characterized by significantly increased dACC modulation of cortical, striatal, and thalamic targets during working memory, and that this aberrant increase in OCD patients is maintained regardless of working memory demand. The results constitute compelling evidence of dysfunctional brain network interactions in OCD and suggest that these interactions may be related to a combination of network inefficiencies and dACC hyper-activity that has been associated with the phenotype.

Highlights

Obsessive-compulsive disorder (OCD) is a commonly occurring childhood and adolescent-onset neuropsychiatric disorder
As one of our study aims was to assess whether hyper-activation in FSTC constitutes a domain-general property of brain regions in OCD, these analyses extend the findings beyond the domain of conflict processing and suggest that multiple tasks engaging FSTC are sensitive for detecting activation-related dysfunction
Three principle results are highlighted across both classes of analyses: Activation Profiles: (1a) Activation profiles were highly sensitive to increases in memory load within each group (Figure 2). (1b) Youth with OCD were characterized by aberrantly increased recruitment of frontal and parietal regions during both levels of working memory

Summary

Introduction

Obsessive-compulsive disorder (OCD) is a commonly occurring childhood and adolescent-onset neuropsychiatric disorder. It is characterized by obsessions (recurrent and persistent thoughts that typically induce marked distress) and compulsions (repetitive behaviors aimed at alleviating distress). OCD represents the upper extreme of an underlying continuous trait distribution encompassing obsessive-compulsive behaviors common in the general population that are heritable and cross traditional diagnostic boundaries. The 1-year incidence of OCD and sub-clinical OCD in adolescents is ~0.7 and 8.4%, respectively (Valleni-Basile et al, 1996). These relatively high rates of incidence and the association with a trait evident in the general population emphasize the importance of characterizing biological mechanisms underlying OCD. We aim Abbreviations: dACC, dorsal anterior cingulate cortex; FSTC, frontal striatal thalamic circuits; OCD, obsessive-compulsive disorder; PPI, psychophysiological interaction

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Results

Conclusion