Can Compulsive Behaviors in OCD Be Explained by Impaired Feedback Processing?

What you need to know

• The study looked at whether compulsive behaviors in a mouse model of OCD are related to problems processing feedback signals.
• The researchers found that artificially impairing feedback processing induced compulsive-like behaviors in both normal mice and the OCD model mice.
• However, the OCD model mice did not show enhanced compulsive behaviors compared to normal mice when feedback processing was impaired.
• This suggests that different types of compulsive behaviors may be driven by separate brain mechanisms.

Understanding compulsive behaviors in OCD

Obsessive-compulsive disorder (OCD) is a mental health condition characterized by recurring, unwanted thoughts (obsessions) and repetitive behaviors (compulsions). People with OCD often feel driven to perform certain actions over and over, even when they recognize these behaviors as excessive or irrational.

While the exact causes of compulsive behaviors in OCD are not fully understood, researchers have proposed several theories. One idea is that compulsions may arise from problems processing feedback signals in the brain. According to this theory, people with OCD may have difficulty recognizing when an action has been completed successfully, leading them to repeat behaviors unnecessarily.

To investigate this possibility, researchers at the Netherlands Institute for Neuroscience conducted a study using a mouse model of OCD. They wanted to see if artificially impairing feedback processing would lead to more compulsive behaviors in these mice compared to normal mice.

The signal attenuation task

The researchers used an experimental procedure called the “signal attenuation task” to study feedback processing in mice. This task was originally developed for use in rats, so the first step was to adapt it for mice.

In the signal attenuation task, animals are first trained to perform a simple action (in this case, poking their nose into a hole) to receive a food reward. When they successfully complete the action, they hear a tone and see a light, which signals that food is available.

After the animals learn this association, the researchers “attenuate” or weaken the signal by presenting the tone and light without any food reward. This is meant to simulate a situation where feedback signals become less reliable or meaningful.

Finally, the animals are tested under “extinction” conditions, where performing the nose-poke action no longer produces any reward. Researchers measure how many times the animals continue to poke their noses or check for food, even when no reward is given. More of these “extra” or unnecessary actions are interpreted as compulsive-like behavior.

Implementing the task in mice

The first experiment validated that the signal attenuation task could be successfully used in mice. Normal mice that went through the signal attenuation procedure showed more compulsive-like behaviors in the final test compared to mice that did not have the signal attenuated.

Specifically, mice in the signal attenuation group performed more “uncompleted trials” where they poked their nose but did not check for food. They also made more “extra nose-pokes” during these uncompleted trials. These behaviors suggest the mice had difficulty recognizing when an action was completed and continued to respond unnecessarily.

This demonstrated that artificially impairing feedback processing through signal attenuation can induce compulsive-like behaviors in mice, similar to what had been observed previously in rats.

Testing the OCD model mice

For the main experiment, the researchers used a strain of genetically engineered mice called SAPAP3 knockout mice. These mice lack a protein important for communication between neurons and show OCD-like behaviors, particularly excessive grooming. They are considered a well-established animal model for studying OCD.

The researchers hypothesized that if compulsive grooming in these mice was related to general problems with feedback processing, then the SAPAP3 knockout mice should show even more compulsive behaviors than normal mice in the signal attenuation task.

Both SAPAP3 knockout mice and normal “wild-type” mice were trained on the signal attenuation task. Some mice in each group went through the signal attenuation procedure, while others did not (serving as control groups).

Key findings

Contrary to the researchers’ prediction, the SAPAP3 knockout mice did not show enhanced compulsive behaviors compared to normal mice in the signal attenuation task. Both types of mice responded similarly:

• Mice that went through signal attenuation (both SAPAP3 knockout and normal) showed more compulsive-like behaviors in the final test compared to mice that did not have the signal attenuated.

• However, the SAPAP3 knockout mice did not exhibit more of these behaviors than normal mice under either condition (with or without signal attenuation).

This suggests that the compulsive grooming seen in SAPAP3 knockout mice may not be directly related to general problems processing feedback signals.

The researchers did observe that SAPAP3 knockout mice groomed more than normal mice throughout most of the experiment, confirming their tendency toward excessive grooming. Interestingly, grooming levels were similar between the two types of mice during the final extinction test of the signal attenuation task.

In the signal attenuation condition, there was a positive correlation between grooming and compulsive-like behaviors in the SAPAP3 knockout mice, but not in normal mice. This hints at a potential relationship between grooming and task-induced compulsivity specifically in the OCD model mice under certain conditions.

Implications and conclusions

The results of this study suggest that different forms of compulsive behavior may be driven by separate mechanisms in the brain. The findings indicate that:

• Artificially impairing feedback processing can induce compulsive-like behaviors in mice.
• However, mice genetically predisposed to compulsive grooming (the OCD model) do not show enhanced susceptibility to this experimentally-induced compulsivity.
• The compulsive grooming seen in the OCD model mice appears to arise through different means than the compulsive-like behaviors induced by signal attenuation.

This research highlights the complexity of compulsive behaviors and suggests caution in assuming a single underlying cause. Different manifestations of compulsivity, even within OCD, may have distinct neurobiological origins.

The study also demonstrates the value of animal models in teasing apart the mechanisms behind complex psychiatric symptoms. By allowing for precise manipulation of brain function, animal research can reveal important nuances that may not be apparent from human studies alone.

Conclusions

• Compulsive-like behaviors can be induced in mice by impairing feedback processing through signal attenuation.
• Mice genetically predisposed to compulsive grooming do not show increased susceptibility to experimentally-induced compulsivity.
• Different forms of compulsive behavior may arise from distinct mechanisms in the brain rather than a single common cause.