Abstract
Background
Patients with obsessive-compulsive disorder (OCD) display disrupted performance and
abnormal lateral orbitofrontal cortex (LOFC) activity during reversal learning tasks.
However, it is unknown whether compulsions and reversal learning deficits share a
common neural substrate. To answer this question, we measured neural activity with
in vivo calcium imaging in LOFC during compulsive grooming and reversal learning before
and after fluoxetine treatment.
Methods
Sapap3 knockout (KO) mice were used as a model for OCD-relevant behaviors. Sapap3 KOs and control littermates were injected with a virus encoding GCaMP6f and implanted
with gradient-index lenses to visualize LOFC activity using miniature microscopes.
Grooming, reversal learning, and neural activity were measured pre- and post-fluoxetine
treatment (18 mg/kg, 4 weeks).
Results
Baseline compulsive grooming and reversal learning impairments in KOs improved after
fluoxetine treatment. In addition, KOs displayed distinct patterns of abnormal LOFC
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., overlap is what would be expected by chance).
Conclusions
In OCD, LOFC is disrupted during both compulsive behaviors and reversal learning,
but whether these behaviors share common neural underpinnings is unknown. We found
that LOFC plays distinct roles in compulsive grooming and impaired reversal learning
and their improvement with fluoxetine. These findings suggest that LOFC plays separate
roles in pathophysiology and treatment of different perseverative behaviors in OCD.
Keywords
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Article Info
Publication History
Published online: November 26, 2021
Accepted:
November 17,
2021
Received in revised form:
November 9,
2021
Received:
March 3,
2021
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Published by Elsevier Inc on behalf of Society of Biological Psychiatry.
