Characterizing Effects of Deep Brain Stimulation on Medial Frontal and Cingulate Oscillations in Treatment Resistant Depression

Lay Summary

Determining optimal placement of DBS electrodes to treat intractable depression

Researchers will explore the physiological basis for positive benefits in patients with intractable depression from  deep brain stimulation (DBS).

Clinical studies conducted by Emory University investigators using DBS to treat severe depression that is resistant to medical drug treatment are showing promising results. Evidence so far from the study of 80 patients shows that chronic stimulation of electrodes placed in the brain’s subcallosal cingulate white matter (SCC) effectively treats symptoms. The study emanated from initial findings from a Dana Imaging study by Helen Mayberg, M.D. that the brain’s cingulate area 25 was involved in severe depression.  This was followed by the first experimental use of DBS in a small number of patients by Dr. Mayberg and colleagues at the University of Toronto.  In addition to evidence of long-term efficacy, many patients show immediate changes in mood and attention with initial testing of the electrodes during surgery. In fact, placement of electrodes is increasingly guided by patient responses during surgery as surgeons select candidate placement locations, place the electrode, stimulate it, and observe patient responses. Moreover, these short-term responses have been found to frequently predict long-term outcome.

PET imaging studies have demonstrated changes in blood flow and metabolism locally at these DBS electrode sites, and also remotely in other brain areas connected to the SCC.  The PET and Diffusion-tensor imaging studies have provided converging evidence of the anatomical and functional extent of regional changes involved in the antidepressant effects of DBS over time. But the brain changes involved in patients’ behavioral changes from electrode stimulation during DBS surgery are not known, and no studies to date address the explicit processes by which DBS affects treatment-resistant depression at the neuronal level.

The Emory researchers hypothesize that patients with treatment-resistant depression have abnormal neuronal cell firing patterns between the SCC and brain’s prefrontal area, and that DBS exerts its therapeutic effects by altering these dynamics. Researchers will test this hypothesis in 20 patients with treatment-resistant depression by recording electrical activity during surgery to implant the DBS electrodes, and before and after surgery, using two techniques concurrently: local field potentials, and EEG (electroencephalography). Through this process, they will characterize the physiological activity underlying PET and SCC over-activity that has been previously identified in treatment-resistant depression patients. Additionally, they will measure the immediate effect of stimulation-induced behavioral effects in real time.  As recommended by outside reviewers for Dana, the researchers have as part of their team an expert physiologist who will design and analyze these physiological measures.

Significance: The research is anticipated to provide a new strategy for enabling neurosurgeons to place DBS electrodes optimally in patients with treatment-resistant depression, increasing the likelihood of their effective long-term response to chronic DBS stimulation.