Circuit interactions within the OCDnet

Project Summary Project 1 The pathophysiology of obsessive compulsive disorder (OCD) is associated with circuit dysfunction in several cortical regions, (rostral anterior cingulate cortex (rACC), dorsal ACC (dACC), ventrolateral prefrontal cortex (vlPFC), orbitofrontal cortex (OFC), insula), and the rostral striatum, that, together integrate information related to behavioral inflexibility, resulting in persistent avoidance. These structures are referred as ‘nodes’ in the OCD network (OCDnet). Anatomically these nodes are interconnected extensively to mutually influence each other. This creates the complex network that underlies the required flexibility for optimizing positive outcomes. Human imaging studies show that ‘hubs’, defined as regions with unusually high and diverse connectivity, exist within distributed networks. These hubs are considered important for integrating and distributing information. However, hubs are defined by imaging which cannot distinguish between inputs to a region that would integrate information, and outputs of a region that would distribute information. P1 combines quantitative anatomic methods with state- of-the-art imaging in both NHP and humans to characterize the complexity of the interconnections of the OCDnet by identifying hub locations, their pathways, and projection zones in the striatum. We hypothesize: 1. that within each node there are specific regions, based on their connectivity profiles, that can be classified as integrative hubs (i-hubs), distributive hubs (d-hubs), or both (central hubs-c-hubs); 2. hub projection zones to the striatum are more expansive compared to nonhub projection zones. Aims 1 & 2 use tracer experiments to locate hubs, delineate their composition, and locate their fibers within the ALIC, CC, and CB. A3 will use this anatomic data, coupled with state-of-the-art structural (dMRI) and functional imaging (rsMRI) in NHPs and humans to determine the location of hubs, their fiber pathways in the ALIC, CC and CB in the human brain.