Biological Psychiatry: Distinct Patterns of Abnormal Lateral Orbitofrontal Cortex Activity During Compulsive Grooming and Reversal Learning Normalize after Fluoxetine

Determining how disrupted neural activity gives rise to compulsive behaviors is vital for understanding obsessive-compulsive disorder (OCD). It is commonly thought that compulsive behaviors and cognitive rigidity share a pathological neural substrate owing to an association between compulsive behavior and abnormal performance and reaction times during reversal learning tasks in OCD. However, it is unknown whether compulsions and reversal learning deficits share a common neural substrate.

Determining whether the same orbitofrontal cortex neurons show disrupted activity during both behaviors can help establish whether abnormal reversal learning and compulsive behaviors share common neural underpinnings.

To answer this question, investigators including Matthew Geramita, MD, PhD (postdoctoral scholar), and Susanne Ahmari, MD, PhD (Associate Professor of Psychiatry), from Pitt Psychiatry, measured neural activity in mice with in vivo calcium imaging of individual lateral orbitofrontal cortex neurons during compulsive grooming and reversal learning before and after fluoxetine treatment.

In a paper published in Biological Psychiatry, the scientists reported that baseline compulsive grooming and reversal learning impairments in the mice improved after fluoxetine treatment. In addition, they observed distinct patterns of abnormal lateral orbitofrontal cortex activity during grooming and reversal learning, both of which normalized after fluoxetine. Finally, reversal learning-associated neurons were distributed randomly among grooming-associated neurons (i.e., the overlap is what would be expected by chance).

“These findings suggest lateral orbitofrontal cortex plays separate roles in pathophysiology/treatment of different perseverative behaviors in OCD. In the future, this could be a useful insight for development of individualized treatments,” said Dr. Ahmari, the study’s senior author.

Distinct patterns of abnormal lateral orbitofrontal cortex activity during compulsive grooming and reversal learning normalize after fluoxetine
Manning EE, Geramita MA, Piantadosi SC, Pierson JL, Ahmari SE. 
Biological Psychiatry. Volume 93, Issue 11, 1 June 2023, Pages 989-999. https://doi.org/10.1016/j.biopsych.2021.11.018