Project Summary

Helen S. Mayberg, M.D. (Distinguished Investigator 2002) of Rotman Research Institute, will pilot the use of Deep Brain Stimulation (DBS), a reversible method of selective brain lesioning, as an alternative to standard functional neurosurgical approaches for treating severe refractory major depression.  The study should provide not only pilot data on a potentially effective and safe treatment option for severely ill patients, but new insights into neural circuitry mediating normal and abnormal mood states.  Literature demonstrates strong evidence that DBS' use to treat Parkinson's disease and other movement disorders is comparable to direct lesioning of the brain, but with reversible physiological and clinical effects.  The target stimulation site for this study will be the subcaudate tract, bilaterally.  The subcaudate tract region and its cortical projections overlap areas showing common response-specific metabolic decreases in her imaging studies of pharmacological and non-pharmacological treatment of major depression.  Similar changes following successful treatment with ECT and subcaudate tractotomy have also been reported.  Across studies, clinical response appears to best correlate with limbic/paralimbic decreases involving the orbital frontal cortex and subgenual cingulate regions.  Based on these findings, Dr. Mayberg hypothesizes that this combination of limbic-paralimbic decreases and dorsal cortical increases are necessary for clinical remission.  The use of the reversible DBS approach combined with longitudinal functional brain imaging provides an opportunity to refine an important clinical treatment option and to test hypotheses regarding which functional pathway changes are necessary for clinical remission.  This combined approach has been extremely productive in refining surgical approaches for refractory Parkinson's disease and in developing DBS as a mainstream treatment for this disorder-now replacing radiofrequency lesioning. 

Program Area: MOOD DISORDERS\Depression (Unipolar)

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