How Does Behavioral Flexibility Relate to Compulsive Behaviors in OCD?

What you need to know

• Behavioral inflexibility is often thought to underlie compulsive behaviors, but evidence has been inconsistent.
• This study compared behavioral flexibility in OCD patients and a mouse model of compulsive behavior.
• Only some OCD patients and mice showed deficits in behavioral flexibility.
• The deficits were due to excessive response changes rather than perseveration.
• Findings highlight the importance of considering individual differences in compulsive disorders.

Behavioral Flexibility and Compulsive Behaviors

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions) that a person feels driven to perform. For example, someone might feel compelled to repeatedly check that doors are locked or wash their hands excessively. Researchers have long thought that difficulties with behavioral flexibility - the ability to adapt one’s behavior when situations change - may contribute to these rigid, repetitive behaviors in OCD.

However, studies examining behavioral flexibility in OCD have produced mixed results. Some find that OCD patients perform worse than healthy individuals on tasks measuring behavioral flexibility, while others find no differences. These inconsistencies have made it difficult to determine if and how behavioral inflexibility relates to compulsive behaviors.

A Cross-Species Approach

To gain new insights into this question, the researchers took an innovative cross-species approach. They compared behavioral flexibility in both humans with OCD and a mouse model that exhibits compulsive-like grooming behaviors. Using similar tasks in both species allowed them to look for consistent patterns across humans and animals.

The study included 40 patients diagnosed with OCD and 40 healthy control participants. For the animal portion, they used mice lacking a gene called Sapap3, which causes them to engage in excessive self-grooming similar to compulsive behaviors in humans. These Sapap3 knockout mice were compared to normal “wild-type” mice.

Measuring Behavioral Flexibility

To assess behavioral flexibility, the researchers used a “reversal learning” task. In this type of task, participants first learn to associate one stimulus (like a particular shape or image) with a reward. Once they’ve learned this association, the rules suddenly change - now a different stimulus leads to the reward. Participants must flexibly adapt their behavior to learn the new rule.

The human and mouse versions of the task were designed to be as similar as possible. Humans saw abstract symbols on a computer screen and pressed buttons to make their choices. Mice saw images on touchscreens in their cages and touched the screens with their noses to respond. Both species had to complete multiple rounds where the rewarded stimulus changed.

Key Findings

No Overall Differences Between Groups

When looking at the OCD patients as a whole compared to healthy controls, there were no significant differences in performance on the reversal learning task. The same was true when comparing all of the Sapap3 knockout mice to the normal mice. This suggests that having OCD or compulsive-like behaviors does not necessarily mean an individual will struggle with behavioral flexibility.

Subgroups Show Deficits

However, when the researchers looked more closely at individuals within each group, they identified subgroups that did show impairments:

• In humans, OCD patients with predominant checking symptoms performed worse on the task compared to other OCD patients and healthy controls.
• In mice, about half of the Sapap3 knockout mice showed deficits, while the other half performed similarly to normal mice.

Importantly, the impaired subgroups in both species needed more trials to learn the new rules after a reversal occurred. This indicates they had more difficulty flexibly adapting their behavior when the situation changed.

Deficits Not Due to Perseveration

A key finding was that the impairments were not caused by perseveration - repeatedly making the same incorrect response. Instead, the impaired individuals showed what the researchers called “excessive response lability.” This means they were more likely to change their response even after receiving positive feedback for a correct choice.

In other words, rather than rigidly sticking with one option, they had trouble maintaining the correct response. This suggests the difficulty may lie more in properly learning or remembering the new rule, rather than an inability to stop the old behavior.

Implications and Future Directions

These findings have several important implications:

1. They highlight the heterogeneity within OCD and animal models of compulsive behavior. Not all individuals with these conditions have the same cognitive profile or deficits.

2. The results call into question the common assumption that behavioral inflexibility in OCD is primarily due to an inability to stop perseverating on previously rewarded behaviors.

3. The similarities between the human and mouse findings suggest the Sapap3 knockout mice may be a useful model for studying the neural mechanisms underlying behavioral flexibility deficits in some types of OCD.

4. For OCD patients, the link between checking symptoms and flexibility impairments provides a potential cognitive marker that could help identify meaningful subgroups within the disorder.

Future research should further investigate what causes some individuals to show these deficits while others do not. This could involve looking at differences in brain structure or function, or other cognitive and behavioral traits. Understanding these individual differences may eventually lead to more personalized and effective treatments for OCD and related conditions.

Additionally, the excessive response lability observed in this study warrants further investigation. It may reflect difficulties with learning or memory, increased sensitivity to uncertainty, or other cognitive processes. Pinpointing the exact nature of this deficit could provide new targets for cognitive interventions.

Conclusions

• Behavioral flexibility deficits are not universal in OCD or animal models of compulsive behavior.
• Some individuals show impairments characterized by difficulty maintaining newly learned responses.
• Findings highlight the importance of considering individual differences when studying cognitive processes in psychiatric disorders.
• Similar patterns in humans and mice suggest promising avenues for future cross-species research on compulsive behaviors.

This study demonstrates the value of using carefully designed, comparable tasks across species to study complex cognitive processes like behavioral flexibility. By revealing similarities and differences between humans and animal models, such approaches can accelerate our understanding of the mechanisms underlying psychiatric symptoms and potentially lead to new treatment strategies.