Emerging research suggests expanded use of technology can aid the specific placement of electrodes to maximize the beneficial effective of deep-brain stimulation among individuals with treatment-resistant depression.
Studies have shown that deep brain stimulation (DBS) within the subcallosal cingulate (SCC) white matter of the brain is an effective treatment for many patients with depression that does not respond to traditional therapies.
Response rates are between 41 percent and 64 percent across published studies to date. Researchers believe the intervention may modulate a network of brain regions connected to the SCC.
However, identifying the critical connections within this network for successful antidepressant response is necessary for improved efficacy of the intervention.
A new study using magnetic resonance imaging (MRI) analysis of the white matter connections examined the architecture of this network in patients who demonstrated significant response to SCC DBS.
Researchers found 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, “Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression,” is published online 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,” said Helen Mayberg, M.D., senior author of the article at Emory University School of Medicine. “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.”
Researchers at Emory, Case Western Reserve and Dartmouth universities followed 16 patients with treatment-resistant depression who previously received SCC DBS at Emory.
Computerized tomography was used post-operatively to localize the DBS contacts on each electrode. Sophisticated neuroimaging combined with computerized analysis was used to derive and visualize the specific white matter fibers affected by ongoing DBS.
Researchers evaluated therapeutic outcomes 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 plus six more patients responded positively.
All shared common involvement of three distinct white matter bundles: the cingulum, the forceps minor, 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 explained by the inclusion of all three bundles due to changes in stimulation settings.
Non-responders at both six months and two years showed 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,” said Patricio Riva-Posse, M.D., Emory assistant professor of psychiatry and behavioral sciences and first author of the paper.
“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.”
The researchers now plan to study DBS therapy in a prospective protocol 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.
Source: Emory University