Affiliations : Icahn School of Medicine at Mount Sinai, NY, USA
Journal reference: https://doi.org/10.1038/s41398-020-00892-5
Summary: A range of different therapies are used to treat OCD. This study focuses on interventions aimed at reducing the repetitive behaviours observed in individuals with OCD. Questions arise as to the efficacy of these interventions which are scrutinised from a neurobehavioural perspective.
Obsessive-compulsive disorder (OCD) is a psychiatric illness characterized by repeated intrusive thoughts (obsessions) and maladaptive actions associated with ritualistic behaviors (compulsions). These compulsive behaviors provide some relief that alleviates the stress or anxiety caused by obsessive thoughts and external triggers. OCD-related behaviors often resemble avoidance of perceived danger and can be treated with exposure-with-response prevention (ERP) therapy in which patients are exposed to triggers but are encouraged to refrain from compulsions, to extinguish compulsive responses. However, because many subjects fail to respond to standard treatments such as ERP therapy, there is a pressing need to use animal models to understand the neurobiology of these persistent behaviors.
Method: a behavioral paradigm that models persistent avoidance in rats
OCD compulsions follow repeated exposures to triggers, but little is known about the effects of persistent avoidance on extinction and its neural correlates. To model persistent avoidance in rats, we used the platform-mediated avoidance task, where the rats are conditioned to avoid a tone-signaled shock by stepping onto a nearby platform. Rats were divided into two groups: rats trained for 8 days and rats overtrained for 20 days.
Consequently, we assessed the extent to which overtraining of active avoidance affects subsequent extinction-with-response prevention (Ext-RP) training as a rodent model of ERP. Extensive conditioning of avoidance may resemble prolonged expression of compulsions, which are thought to be reinforced by the reduction in patients’ stress and anxiety. Therefore, to better approximate the long-term expression of compulsions, we tested the effect of avoidance overtraining (20 days vs. 8 days) on Ext-RP.
During Ext-RP, all the rats were extinguished to triggers (tone-shock association) over 4 days, while access to the platform was blocked with a barrier, thereby preventing the avoidance option. Following the last day of Ext-RP, rats receive a single tone with the barrier removed and the time spent on the platform was used as index of persistent avoidance. The brain activity profile of these two groups were compared using c-Fos indexing to characterize the effects of avoidance overtraining on brain circuits signaling after expression and extinction of avoidance.
Results: Overtrained rats exhibited persistent avoidance
Rats from the two groups (8 and 20 days) produced similar avoidance behavior to a tone paired with a shock. However, the majority of overtrained rats (75%) exhibited persistent avoidance (a severe impairment of extinction) following Ext-RP whereas in the 8 days group, only a minority of rats (37%) exhibited persistent avoidance.
Persistent avoidance was associated with elevated neuronal activity in two brain structures (prelimbic cortex and nucleus accumbens) whereas non-persistent rats showed elevated neuronal activity in two other brain areas (insula and thalamus).
Lastly, extending the duration of Ext-RP training prevented the deleterious effects of overtraining on extinction and avoidance and further impacted the neuronal activity levels in the avoidance circuit.
Conclusion: OCD behaviors act as a snowball effect to reduce the effectiveness of extinction-based therapies
These rodent findings suggest that repeated expression of compulsion-like behaviors biases individuals toward persistent avoidance and alters avoidance circuits, thereby reducing the effectiveness of current extinction-based therapies. An interesting future application would be to determine if ERP therapy could be facilitated by activating brain areas that were identified in this study (insular, orbital, or thalamic) with transcranial magnetic or direct current stimulation in individuals exhibiting treatment resistance.