A cross-species assessment of behavioral flexibility in compulsive disorders

Nabil Benzina,Karim N'Diaye,Eric Burguière,Antoine Pelissolo,Luc Mallet

doi:10.1038/s42003-020-01611-y

Abstract

Lack of behavioral flexibility has been proposed as one underlying cause of compulsions, defined as repetitive behaviors performed through rigid rituals. However, experimental evidence has proven inconsistent across human and animal models of compulsive-like behavior. In the present study, applying a similarly-designed reversal learning task in two different species, which share a common symptom of compulsivity (human OCD patients and Sapap3 KO mice), we found no consistent link between compulsive behaviors and lack of behavioral flexibility. However, we showed that a distinct subgroup of compulsive individuals of both species exhibit a behavioral flexibility deficit in reversal learning. This deficit was not due to perseverative, rigid behaviors as commonly hypothesized, but rather due to an increase in response lability. These cross-species results highlight the necessity to consider the heterogeneity of cognitive deficits in compulsive disorders and call for reconsidering the role of behavioral flexibility in the aetiology of compulsive behaviors.

Highlights

Lack of behavioral flexibility has been proposed as one underlying cause of compulsions, defined as repetitive behaviors performed through rigid rituals
In order to study the involvement of behavioral flexibility in compulsive behaviors in both OCD patients and the Sapap[3] KO mice, we have developed an innovative, high throughput behavioral setup for mice that allows us to reliably test individual subjects in a non-spatial visual reversal learning task through multiple reversal blocks, as it is commonly performed in human studies
WTs perseverated more after spontaneous strategy changes (SSC), with more SSC errors than “impaired” KO mice (BF10 > 100, d = 1.61 [0.62 2.24]) (Table 1). These difference in response lability were observed only in a reversal context and not during the acquisition phase, both in OCD “checkers” and “impaired” KO mice. This cross-species study assessed the role of behavioral flexibility in compulsive behaviors through a reversal learning task conducted in both humans and mice

Summary

Introduction

Lack of behavioral flexibility has been proposed as one underlying cause of compulsions, defined as repetitive behaviors performed through rigid rituals. Two recent studies[22,23] have challenged this model in a spatial reversal learning task and found that Sapap[3] KO mice had impaired performances compared to controls after reversal event, the type of deficit differed with increased perseveration found in one study[23] but not the other[22]. Both studies found that these deficits were not correlated with the severity of compulsive-like grooming, suggesting that compulsivity and flexibility dimensions may be distinctly affected in this model. We ensured the correct interpretation of our results by recruiting large samples of well characterized and selected subjects in both species, thereby enabling us to investigate intra-group variability in our analyses

Methods

Results

Conclusion