Figure 1. Model for the cortico-striato-thalamo-cortical circuit dysfunction in individuals with OCD.

This model outlines the hypothesis that the cortico-striato-thalamo-cortical circuit is dysfunctional in individuals with OCD. Increased glutamatergic signals from the frontal cortex are hypothesized to increase excitation in the striatum, which increases inhibitory GABA signals to the GPi and SNr. (A) One possibility is that this then decreases the inhibitory output via GABA from the GPi and SNr to the thalamus, resulting in thalamic excitatory glutamatergic output to the frontal cortex. This positive feedback loop leads to repetitive thoughts (obsessions) and behaviors (compulsions). An indirect external loop composed of the GPe and subthalamic nucleus (STN) is postulated to contribute to a steady state of excitation/inhibition in this model. (B) A second possibility is that there is an unknown dysfunction at the striatum and GPe. Decreased inhibition on the GPe leads to increased inhibition of the STN, which decreases its excitation of the GPi/SNr. The GPi/SNr then decreases its inhibitory output on the thalamus, resulting in excitatory output to the frontal cortex (adapted from ref. 67).