How Does Capsulotomy Surgery Affect Brain Activity in Obsessive-Compulsive Disorder?

What you need to know

• Capsulotomy surgery can effectively reduce OCD symptoms and improve quality of life in severe, treatment-resistant cases
• After surgery, patients showed decreased brain activity in regions involved in processing negative emotions and fear
• These brain changes may help explain how capsulotomy relieves OCD symptoms
• The affected brain areas overlap with targets of deep brain stimulation, suggesting a common mechanism

Background on OCD and Capsulotomy

Obsessive-compulsive disorder (OCD) is a mental health condition characterized by unwanted, intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions) that a person feels compelled to perform. For some people with severe OCD that does not respond to standard treatments like medication and therapy, brain surgery may be considered as a last resort option.

One such surgical procedure is anterior capsulotomy. This involves creating small lesions in a part of the brain called the anterior limb of the internal capsule. The internal capsule contains nerve fibers connecting areas of the prefrontal cortex to deeper brain structures. The goal of capsulotomy is to disrupt abnormal communication between these brain regions that is thought to contribute to OCD symptoms.

While capsulotomy can be effective for some patients with severe, treatment-resistant OCD, researchers are still working to understand exactly how it affects brain function to provide symptom relief. This study aimed to examine changes in brain activity after capsulotomy to gain insights into its therapeutic mechanisms.

How the Study Was Done

The researchers compared three groups of participants:

1. 27 OCD patients who had undergone capsulotomy at least 6 months prior
2. 33 OCD patients who had not had surgery (OCD controls)
3. 34 healthy individuals without OCD (healthy controls)

All participants completed questionnaires to assess OCD symptoms, mood, anxiety, quality of life, and daily functioning. They also performed cognitive tests measuring abilities like memory, attention, and cognitive flexibility.

The key part of the study involved participants completing tasks in an fMRI brain scanner. The main task was designed to measure brain responses to anticipating and experiencing negative emotional stimuli. Participants saw cues indicating whether they would see a negative or neutral image. They then had to quickly press a button when a target appeared. If they responded correctly to negative cues, they would see a neutral gray image instead of the negative image.

This task allowed the researchers to examine brain activity during:

1. Anticipation of negative vs. neutral stimuli
2. Receipt of negative vs. neutral feedback
3. Extinction - when participants expected a negative image but received neutral feedback instead

The researchers compared brain activation patterns between the three groups during these different phases of the task.

Key Findings

Clinical Outcomes

Compared to OCD patients who had not had surgery, the capsulotomy patients showed:

• Lower scores on a measure of OCD symptom severity
• Better quality of life
• Improved daily functioning
• No significant differences in anxiety or depression symptoms

Brain Activity Changes

During anticipation of negative stimuli, capsulotomy patients showed:

• Decreased activity in the nucleus accumbens, a brain region involved in processing rewarding and aversive stimuli

When receiving negative feedback, capsulotomy patients had:

• Reduced activity in the rostral anterior cingulate cortex, an area involved in emotional processing and fear extinction
• Decreased activity in part of the inferior frontal cortex, which plays a role in cognitive control and saliency detection

During extinction trials, when participants expected a negative image but saw a neutral one instead, capsulotomy patients showed:

• Lower activity in the rostral anterior cingulate cortex compared to both other groups

Brain Connectivity Changes

The researchers also examined how different brain regions communicate with each other. They found:

• Decreased connectivity between the nucleus accumbens and rostral anterior cingulate cortex in capsulotomy patients compared to OCD controls
• This connectivity change was specific to anticipation of negative vs. neutral stimuli

Relationship to Symptoms

Lower activity in the rostral anterior cingulate cortex during extinction trials was associated with greater improvement in obsessive symptoms after capsulotomy.

Conclusions

• Capsulotomy appears to reduce OCD symptoms in part by dampening brain responses to anticipated negative outcomes and improving extinction learning
• The brain regions affected overlap with targets of deep brain stimulation for OCD, suggesting a common mechanism
• These findings provide insights into how capsulotomy may work to relieve OCD and could inform optimization of surgical treatments
• Abnormal processing of negative emotions may be a key factor underlying OCD symptoms that is remediated by capsulotomy

This study sheds light on the brain mechanisms involved in a last-resort surgical treatment for severe OCD. By identifying specific changes in brain activity and connectivity associated with symptom improvement, it provides a deeper understanding of both how OCD affects the brain and how interventions like capsulotomy may help restore normal brain function. This knowledge could potentially lead to more targeted and effective treatments for OCD in the future.