Striatal circuits, habits, and implications for obsessive-compulsive disorder

Abstract

Increasing evidence implicates abnormalities in corticostriatal circuits in the pathophysiology of obsessive-compulsive disorder (OCD) and OC-spectrum disorders. Parallels between the emergence of repetitive, compulsive behaviors and the acquisition of automated behaviors suggest that the expression of compulsions could in part involve loss of control of such habitual behaviors. The view that striatal circuit dysfunction is involved in OC-spectrum disorders is strengthened by imaging and other evidence in humans, by discovery of genes related to OCD syndromes, and by functional studies in animal models of these disorders. We highlight this growing concordance of work in genetics and neurobiology suggesting that frontostriatal circuits, and their links with basal ganglia, thalamus and brainstem, are promising candidates for therapeutic intervention in OCD.

Figure 1

Hypothetical dysfunctional corticostriatal circuity in OCD. In normal conditions (top), the excitatory corticostriatal projections modulate striatal activity through a balance between excitation and inhibition. Medium spiny neurons (MSNs) are maintained under tonic inhibition by a network of parvalbumin (PV)-positive interneurons (and possibly other interneuron’s not shown here), with the PV interneurons tightly interconnected through gap-junctions. In pathological OCD conditions (bottom), both cortical and striatal regions are hyperactive, possibly due to a decrease in the number and/or function of striatal PV interneurons that could lead to enhancement of MSN excitation by corticostriatal inputs and eventually to an increased activity throughout the affected corticostriatal loops.