scholarly journals A cross-species assessment of behavioral flexibility in compulsive disorders

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nabil Benzina ◽  
Karim N’Diaye ◽  
Antoine Pelissolo ◽  
Luc Mallet ◽  
Eric Burguière
Keyword(s):  
Reversal Learning ◽  
Cognitive Deficits ◽  
Behavioral Flexibility ◽  
Learning Task ◽  
Repetitive Behaviors ◽  
Common Symptom ◽  
Distinct Subgroup ◽  
Compulsive Behaviors ◽  
Compulsive Disorders

AbstractLack 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.

scholarly journals A cross-species assessment of behavioral flexibility in compulsive disorders

2019 ◽  
Author(s):  
Nabil Benzina ◽  
Karim N’Diaye ◽  
Antoine Pelissolo ◽  
Luc Mallet ◽  
Eric Burguière
Keyword(s):  
Reversal Learning ◽  
Behavioral Flexibility ◽  
Learning Task ◽  
Repetitive Behaviors ◽  
Common Symptom ◽  
Obsessive Compulsive ◽  
Homogeneous Groups ◽  
Impaired Performance ◽  
Compulsive Disorder ◽  
Compulsive Behaviors

ABSTRACTBackgroundCompulsive behaviors, one of the core symptoms of Obsessive-Compulsive Disorder (OCD), are defined as repetitive behaviors performed through rigid rituals. The lack of behavioral flexibility has been as being one of the primary causes of compulsions, but studies exploring this dimension have shown inconsistencies in different tasks performed in human and animal models of compulsive behavior. The aim of this study was so to assess the involvement of behavioral flexibility in compulsion, with a similar approach across different species sharing a common symptom of compulsivity.Methods40 OCD patients, 40 healthy individually matched control subjects, 26 C57BL/6J Sapap3 KO mice and 26 matched wildtype littermates were included in this study. A similar reversal learning task was designed to assess behavioral flexibility in parallel in these two species.ResultsWhen considered as homogeneous groups, OCD patients and KO mice expressing compulsive behaviors did not significantly differ from their controls regarding behavioral flexibility. When clinical subtypes were considered, only patients exhibiting checking compulsions were impaired with more trials needed to reach the reversal criterion. In KO mice, a similarly impaired subgroup was identified. For both species, this impairment did not result in a greater perseveration after reversal, but in a greater lability in their responses in the reversal condition. Moreover, this impairment did not correlate with the severity of compulsive behaviors.ConclusionsIn our cross-species study, we found no consistent link between compulsive behaviors and a lack of behavioral flexibility. However, we showed in both species that the compulsive group was heterogeneous in term of performance in our reversal learning task. Among the compulsive subjects, we identified a subgroup with impaired performance not due to perseverative and rigid behaviors as commonly hypothesized, but rather to an increase in response lability.

Translational approach to study flexibility as an endophenotype of obsessive compulsive disorders

2014 ◽  
Vol 29 (S3) ◽  
pp. 546-546
Author(s):  
N. Benzina ◽  
S.L. Mondragon ◽  
N. Ouarti ◽  
L. Mallet ◽  
E. Burguiere
Keyword(s):  
Reversal Learning ◽  
Behavioral Flexibility ◽  
Repetitive Behaviors ◽  
Reward Contingency ◽  
Neural Basis ◽  
Obsessive Compulsive ◽  
Compulsive Behaviors ◽  
Translational Approach ◽  
Obsessive Compulsive Disorders ◽  
Compulsive Disorders

Behavioral flexibility is the ability of a subject to change its behavior according to contextual cues. In humans, Obsessive Compulsive Disorders (OCD) is characterized by repetitive behavior, performed through rigid rituals. This phenomenological observation has led to explore the idea that OCD patients may have diminished behavioral flexibility. To address this question we developed innovative translational approaches across multiple species, including human patients suffering from obsessive-compulsive disorders, and rodent genetic models of OCD to provide original data in the perspective of enlightening the neurocognitive bases of compulsive behaviors. Behavioral flexibility may be challenged in experimental tasks such as reversal learning paradigms. In these tasks, the subject has to respond to either of two different visual stimuli but only one stimulus is positively rewarded while the other is not. After this first association has been learned, reward contingency are inverted, so that the previously neutral stimulus is now rewarded, while the previously rewarded stimulus is not. Performance in reversal learning is indexed by the number of perseverative errors committed when participants maintain their response towards previously reinforced stimulus in spite of negative reward. Unsurprisingly, this behavioral task has been adapted to mice using various response modalities (T-maze, lever press, nose-poke). Using animal models of compulsive behaviors give much more possibilities to study the deficient functions and their underlying neural basis that could lead to pathological repetitive behaviors. Here we present new behavioral set-ups that we developed in parallel in human (i.e. healthy subjects and OCD patients) and mice (i.e. controls and SAPAP3-KO mice) to study the role of the behavioral flexibility as a possible endophenotype of OCD. We observed that the subjects suffering of compulsive behaviors showed perseverative maladaptive behaviors in these tasks. By comparing the results of a similar task-design in humans and mouse models we will discuss the pertinence of such translational approach to further study the neurocognitive basis of compulsive behaviors.

scholarly journals Inability to activate Rac1-dependent forgetting contributes to behavioral inflexibility in mutants of multiple autism-risk genes

2016 ◽  
Vol 113 (27) ◽  
pp. 7644-7649 ◽  
Author(s):  
Tao Dong ◽  
Jing He ◽  
Shiqing Wang ◽  
Lianzhang Wang ◽  
Yuqi Cheng ◽  
...  
Keyword(s):  
Reversal Learning ◽  
Behavioral Flexibility ◽  
Learning Task ◽  
Repetitive Behaviors ◽  
Loss Of Function ◽  
Risk Genes ◽  
Risk Gene ◽  
Alternative Approach ◽  
Similar Phenotype ◽  
Autistic Symptoms

The etiology of autism is so complicated because it involves the effects of variants of several hundred risk genes along with the contribution of environmental factors. Therefore, it has been challenging to identify the causal paths that lead to the core autistic symptoms such as social deficit, repetitive behaviors, and behavioral inflexibility. As an alternative approach, extensive efforts have been devoted to identifying the convergence of the targets and functions of the autism-risk genes to facilitate mapping out causal paths. In this study, we used a reversal-learning task to measure behavioral flexibility in Drosophila and determined the effects of loss-of-function mutations in multiple autism-risk gene homologs in flies. Mutations of five autism-risk genes with diversified molecular functions all led to a similar phenotype of behavioral inflexibility indicated by impaired reversal-learning. These reversal-learning defects resulted from the inability to forget or rather, specifically, to activate Rac1 (Ras-related C3 botulinum toxin substrate 1)-dependent forgetting. Thus, behavior-evoked activation of Rac1-dependent forgetting has a converging function for autism-risk genes.

Compulsivity and probabilistic reversal learning in OCD and cocaine addiction

2015 ◽  
Vol 30 (S2) ◽  
pp. S110-S111 ◽  
Author(s):  
P. Smith ◽  
N. Benzina ◽  
F. Vorspan ◽  
L. Mallet ◽  
K. N’Diaye
Keyword(s):  
Reversal Learning ◽  
A Priori ◽  
Behavioral Flexibility ◽  
Learning Task ◽  
Repetitive Behaviors ◽  
Cocaine Addiction ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Cocaine Users ◽  
Probabilistic Reversal Learning

Compulsive behavior is a core symptom of both obsessive compulsive disorder (OCD) and cocaine addiction (CA). Across both pathologies, one can identify a priori goal-directed actions (purportedly anxiolytic checking or washing in OCD and pleasure-seeking drug use in addiction) that turn into rigid, ritualized and repetitive behaviors over which the patient loose control. One possible psychopathological mechanism underlying compulsivity is behavioral inflexibility, namely a deficit in the aptitude to dynamically adapt to novel contexts and changing reward rules. The probabilistic reversal learning paradigm allows to objectively assess behavioral flexibility by challenging participants with a task where they have to learn through trials-and-errors which of two stimuli is the most-often rewarded one, while adjusting to sudden inconspicuous contingency reversals. We therefore hypothesized that both OCD and CA would be associated with impaired cognitive flexibility, as measured through perseverative response rate following contingency reversals in this task. Interestingly, impulsivity may also be assessed within this task via the tendency of participants to switch from one stimulus to the other following probabilistic errors. To investigate cognitive inflexibility in relation to CA and OCD respectively, we first compared the performance in a probabilistic reversal learning task of cocaine users, ex cocaine users (abstinent for 2 months or more), and controls, as well as that of participants from the general population whose obsessive-compulsive traits were assessed using the OCI-R, a well-validated self-questionnaire. Our task yielded results similar to those found in the literature: cocaine addicts changed their responses more often, and learned less effectively. Ex-cocaine addicts performed better than addicts but worse than controls, suggesting that addicts’ poor results may be in part explained by reversible cognitive consequences of addiction. Addicts with less cognitive impairments may also be less likely to relapse. Regarding the relationship of flexibility to subclinical OCD traits, we found no link between OCI-R score and perseveration, or between impulsiveness and excessive switching.

scholarly journals Individual differences in behavioral flexibility in a probabilistic reversal learning task: An fMRI study.

2014 ◽  
Vol 7 (4) ◽  
pp. 203-218 ◽  
Author(s):  
Anja Waegeman ◽  
Carolyn H. Declerck ◽  
Christophe Boone ◽  
Ruth Seurinck ◽  
Paul M. Parizel
Keyword(s):  
Individual Differences ◽  
Reversal Learning ◽  
Behavioral Flexibility ◽  
Learning Task ◽  
Fmri Study ◽  
Probabilistic Reversal Learning

scholarly journals The functional role of sequentially neuromodulated synaptic plasticity in behavioural learning

2021 ◽  
Vol 17 (6) ◽  
pp. e1009017
Author(s):  
Grace Wan Yu Ang ◽  
Clara S. Tang ◽  
Y. Audrey Hay ◽  
Sara Zannone ◽  
Ole Paulsen ◽  
...  
Keyword(s):  
Reversal Learning ◽  
Cholinergic Neurons ◽  
Learning Rule ◽  
Computational Prediction ◽  
Learning Task ◽  
Spike Timing ◽  
Weight Changes ◽  
Experimental Findings ◽  
Spatial Learning Task

To survive, animals have to quickly modify their behaviour when the reward changes. The internal representations responsible for this are updated through synaptic weight changes, mediated by certain neuromodulators conveying feedback from the environment. In previous experiments, we discovered a form of hippocampal Spike-Timing-Dependent-Plasticity (STDP) that is sequentially modulated by acetylcholine and dopamine. Acetylcholine facilitates synaptic depression, while dopamine retroactively converts the depression into potentiation. When these experimental findings were implemented as a learning rule in a computational model, our simulations showed that cholinergic-facilitated depression is important for reversal learning. In the present study, we tested the model’s prediction by optogenetically inactivating cholinergic neurons in mice during a hippocampus-dependent spatial learning task with changing rewards. We found that reversal learning, but not initial place learning, was impaired, verifying our computational prediction that acetylcholine-modulated plasticity promotes the unlearning of old reward locations. Further, differences in neuromodulator concentrations in the model captured mouse-by-mouse performance variability in the optogenetic experiments. Our line of work sheds light on how neuromodulators enable the learning of new contingencies.

scholarly journals Greater mindful eating practice is associated with better reversal learning

2017 ◽  
Author(s):  
Lieneke Katharina Janssen ◽  
Iris Duif ◽  
Ilke van Loon ◽  
Jeanne de Vries ◽  
Anne Speckens ◽  
...  
Keyword(s):  
Reversal Learning ◽  
Eating Habits ◽  
Behavioral Flexibility ◽  
Learning Task ◽  
Mindfulness Practice ◽  
Clinical Population ◽  
Group Differences ◽  
Mindful Eating ◽  
Outcome Valence ◽  
Control Intervention

Mindfulness-based interventions are thought to reduce compulsive behavior such as overeating by promoting behavioral flexibility. Here the main aim was to provide support for mindfulness-mediated improvements in reversal learning, a direct measure of behavioral flexibility. We investigated whether an 8-week mindful eating intervention improved outcome-based reversal learning relative to an educational cooking (i.e., active control) intervention in a non-clinical population. Sixty-five healthy participants with a wide BMI range (19–35 kg/m2), who were motivated to change their eating habits, performed a deterministic reversal learning task that enabled the investigation of reward- and punishment-based reversal learning at baseline and following the intervention. No group differences in reversal learning were observed. However, time invested in the mindful eating, but not the educational cooking intervention correlated positively with changes in reversal learning, in a manner independent of outcome valence. These findings suggest that greater amount of mindfulness practice can lead to increased behavioral flexibility, which, in turn, might help overcome compulsive eating in clinical populations.

The role of the cerebellum for feedback processing and behavioral switching in a reversal-learning task

2018 ◽  
Vol 125 ◽  
pp. 142-148 ◽  
Author(s):  
Jutta Peterburs ◽  
David Hofmann ◽  
Michael P.I. Becker ◽  
Alexander M. Nitsch ◽  
Wolfgang H.R. Miltner ◽  
...  
Keyword(s):  
Reversal Learning ◽  
Learning Task ◽  
Feedback Processing ◽  
Behavioral Switching
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