MRI Mapping Improves Deep Brain Stimulation Response in Resistant Depression

Research studies have shown that deep brain stimulation (DBS) within the brain’s subcallosal cingulate (SCC) white matter is an effective therapy for many patients with treatment-resistant depression. Response rates to date have been between 41% and 64% across published studies. One of the proposed mechanisms of action is through modulation of a network of brain regions connected to the SCC. Identifying the critical connections within this network for successful antidepressant response is a significant next step.

A new study using magnetic resonance imaging (MRI) analysis of the white matter connections examined the network’s architecture in patients who demonstrated significant response to SCC DBS. Researchers discovered that all responders showed a common pattern defined by three distinct white matter bundles passing through the SCC. Non-responders did not show this pattern.

The study was published online April 11, 2014, in the journal Biological Psychiatry. “This study shows that successful DBS therapy is not due solely to local changes at the site of stimulation but also in those regions in direct communication with the SCC,” stated senior author of the article, Helen Mayberg, MD, a professor of psychiatry, neurology and radiology, and chair of psychiatric imaging and therapeutics at Emory University School of Medicine (Atlanta, GA, USA). “Precisely delineating these white matter connections appears to be very important to a successful outcome with this procedure. From a practical point of view, these results may help us to choose the optimal contact for stimulation and eventually to better plan the surgical placement of the DBS electrodes.”

Led by researchers from Emory University Case Western Reserve University (Cleveland, OH, USA), and Dartmouth University (Hanover, NH, USA), the study included 16 patients with treatment-resistant depression who previously received SCC DBS at Emory. Computed tomography (CT) scanning was used postoperatively to localize the DBS contacts on each electrode. The activation volumes around the active contacts were modeled for each patient. Sophisticated neuroimaging combined with computerized analysis was used to derive and visualize the specific white matter fibers affected by ongoing DBS.

Therapeutic outcome was evaluated at six months and at two years. Six of the patients had responded positively to DBS at six months, and by two years these six in addition to six more patients responded positively. All shared common involvement of three distinct white matter bundles: the forceps minor, cingulum, and the uncinate fasciculus. The conversion of six of the patients who were not responding at six months to being responders at two years was clarified by the inclusion of all three bundles due to alterations in stimulation settings. Nonresponders at both six months and two years revealed incomplete involvement of these three tracts.

“In the past, placement of the electrode relied solely on anatomical landmarks with contact selection and stimulation parameter changes based on a trial-and-error method,” stated Patricio Riva-Posse, MD, assistant professor of psychiatry and behavioral sciences at Emory and first author of the article. “These results suggest that clinical outcome can be significantly influenced by optimally modulating the response network defined by tractography. This obviously will need to be tested prospectively in additional subjects here and by other teams exploring the use of this experimental treatment.”

“This new information will allow us to develop a refined algorithm for guiding surgical implantation of electrodes and optimizing the response through fine tuning of stimulation parameters,” noted Dr. Mayberg. “That said, improving anatomical precision alone doesn’t account for all nonresponders, so that is an important next focus of our research.”

The researchers now plan to study DBS therapy in a prospective group of similar treatment-resistant depressed patients, using presurgical mapping of an individual patient’s network structure, precisely targeting the three SCC fiber bundles, and systematically testing the stimulation contacts.

Related Links:
Emory University School of Medicine
Case Western Reserve University
Dartmouth University