Neural correlates of compulsive and perseverative behaviors

Compulsive behaviors are a core feature of OCD and many related disorders, but the neural dysfunction underlying the initiation and persistence of these repetitive actions is unknown. To further understand how compulsive behaviors are generated, sustained, and terminated, we study the neural substrates underlying a variety of naturalistic and instrumental perseverative and compulsive behaviors in mouse models, using calcium imaging and electrophysiology in awake and behaving mice. Current projects are focusing on networks connecting the prefrontal cortex, striatum, and thalamus that have been shown to be dysfunctional in people with OCD.

Developing new tasks to assess OCD-relevant behaviors in animal models

Patients with OCD also show changes in a number of other behavioral domains that can be measured in preclinical mouse models. These include:
Anxiety: measured in mouse models using standard assays such as the elevated plus maze and light/dark tests
Aversive learning: Fear and avoidance conditioning paradigms
Flexible decision-making/Executive functioning: Reversal learning, goal-directed vs habitual behavior, pavlovian instrumental transfer
Sensory processing: prepulse inhibition of the acoustic startle response
Understanding the neural basis of these behaviors in the context of OCD is critical because they significantly contribute to functional impairment, and may also play an important role in the relationship between obsession and compulsions.

Human OCD post-mortem

Though functional imaging studies have identified corticostriatal circuit dysfunction in OCD patients, the molecular underpinnings of this dysfunction are unknown. While genome-wide association studies and post-mortem molecular studies have been conducted in many psychiatric disorders, this foundation for OCD is lacking. In our lab, we have access to valuable human brain tissue from OCD patients and are using molecular biology, RNAseq, and proteomics analysis to investigate consistent, region-specific molecular abnormalities in OCD patients. The long-term goal of these projects is to identify molecular targets for manipulation in animal models, and ultimately inform treatments for patients.