Diffusion Tensor MRI Mapping of How Brain Fiber Tracts Change after Gamma Knife Capsulotomy for Intractable Obsessive-Compulsive Disorder

Benjamin D. Greenberg, M.D., Ph.D.

Brown University, Butler Hospital

Funded in September, 2000: $100000 for 6 years
LAY SUMMARY . BIOGRAPHY . HYPOTHESIS . SELECTED PUBLICATIONS .

LAY SUMMARY

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Diffusion Tensor MRI Mapping of How Brain Fiber Tracts Change After Gamma Knife Capsulotomy for Intractable Obsessive-Compulsive Disorder

Investigators will employ imaging techniques to help assess the efficacy of surgery being used to treat obsessive-compulsive disorder (OCD) in patients who have not responded to previous medical therapies.

OCD affects about 2% of the population and produces obsessive thoughts, repetitive behaviors, and pathological levels of anxiety that can be extraordinarily incapacitating.  While medications help about 85% of patients, there has been a resurgence in the use of surgical treatment for the remaining 15% of patients.  Surgical lesions are made in a specific brain area of white matter that contains neural circuits thought to be dysfunctional in OCD.  Currently, however, there is no information on the anatomical changes produced by the surgery and their association with symptom improvement.  The investigators will use a new imaging technique, diffusion tensor imaging (DTI), to map the locations of the surgical lesions, determine their effects on the nerve fibers, and correlate this information with patients’ symptoms over the succeeding six months.

The study will provide an accurate correlation between the precise surgical lesion and the degree of symptom improvement.  This information can improve the targeting of surgery and also can contribute to development of another new treatment for OCD, deep brain stimulation.   An additional benefit will be a proven understanding of the circuitry that has gone awry in this disabling condition.  It is increasingly evident that a number of neurological and psychological conditions involve neural circuits within the brain, rather than a specific region of the brain.  The increase in neurosurgical approaches to these conditions, such as OCD or Parkinson’s disease, is aimed at altering the involved circuits to restore them toward normal functioning. 

INVESTIGATOR BIOGRAPHIES

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Benjamin D. Greenberg, M.D., Ph.D.

Associate Professor of Medicine
Brown University, Butler Hospital

HYPOTHESIS

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Hypothesis: 
Patients with intractable Obsessive-Compulsive Disorder (OCD) receiving therapeutic gamma knife capsulotomy will improve more when capsulotomy produces greater interruption in connections between thalamic nuclei and orbitofrontal regions (Brodmann areas 12 and 13) on diffusion tensor MRI (DT-MRI).

Goals: 
To determine how the therapeutic effects of gamma capsulotomy relate to changes in the structure of the thalamus-prefrontal cortex pathways with a new neuroimaging technique called diffusion tensor MRI. The researchers predict that changes in the connections between the thalamus and the orbitofrontal cortex in the brain, which will be visible on DT-MRI but not on conventional MRI, will underlie capsulotomy's therapeutic benefit in OCD. Understanding the changes after surgery that result in the best therapeutic outcomes will allow for the improvement of capsulotomy as a treatment for this debilitating disease. With this information, researchers can refine the targeting of capsulotomy for individual patients, and possibly aid the development of a newer treatment, deep brain stimulation, for intractable OCD. Researchers may also learn more about how the same brain circuits are involved in other psychiatric disorders commonly associated with OCD.

Methods: 
Participants will be adults, ages 18-65, with OCD of disabling severity, refractory to prolonged treatment attempts with conventional medication and behavioral therapies, who have elected to undergo gamma capsulotomy under separate ongoing IRB-approved protocols at Brown University/Butler Hospital. Using a stereotactic frame within the Leksell gamma knife, pairs of lesions, each approximately 4 mm in diameter, are made in the entire ventral half of the anterior limb of the internal capsule at a standard distance rostral to the anterior commissure. Lesion placement is subsequently assessed by conventional MRI obtained 3 months postoperatively. Serial DT-MRI images and symptom ratings will be acquired at presurgical baseline and at 3, 6, and 12 months postsurgery.

SELECTED PUBLICATIONS

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Greenberg B.D., Murphy D.L., and Rasmussen S.A.  Neuroanatomically based approaches to obsessive-compulsive disorder. Neurosurgery and transcranial magnetic stimulation.  Psychiatr Clin North Am. 2000 Sep;23(3):671-86, xii.