Epidural cortical stimulation of the left dorsolateral prefrontal cortex for refractory major depressive disorder

Brian Harris Kopell, Jerry Halverson, Christopher R. Butson, Mercedes Dickinson, Julie Bobholz, Harold Harsch, Charles Rainey, Douglas Kondziolka, Robert Howland, Emad Eskandar, Karleyton C. Evans, Darin D. Dougherty

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Background: A significant number of patients with major depressive disorder are unresponsive to conventional therapies. For these patients, neuromodulation approaches are being investigated. Objective: To determine whether epidural cortical stimulation at the left dorsolateral prefrontal cortex is safe and efficacious for major depressive disorder through a safety and feasibility study. Methods: Twelve patients were recruited in this randomized, single-blind, sham-controlled study with a 104-week follow-up period. The main outcome measures were Hamilton Depression Rating Scale-28 (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire. An electrode was implanted over Brodmann area 9/46 in the left hemisphere. The electrode provided long-term stimulation to this target via its connections to an implanted neurostimulator in the chest. Results: During the sham-controlled phase, there was no statistical difference between sham and active stimulation, although a trend toward efficacy was seen with the active stimulation group. In the open-label phase, we observed a significant improvement in outcome scores for the HDRS, MADRS, and GAF but not the QLES (HDRS: df = 7, F = 7.72, P < .001; MADRS: df = 7, F = 8.2, P < .001; GAF: df = 5, F = 16.87, P < .001; QLES: df = 5, F = 1.32, P > .2; repeated measures ANOVA). With regard to the HDRS, 6 patients had ≥ 40% improvement, 5 patients had ≥ 50% improvement, and 4 subjects achieved remission (HDRS < 10) at some point during the study. Conclusion: Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment-refractory major depressive disorder.

Original languageEnglish (US)
Pages (from-to)1015-1029
Number of pages15
Issue number5
StatePublished - Nov 1 2011
Externally publishedYes


  • Cortical stimulation
  • Major depressive disorder
  • Neuromodulation
  • PET

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology


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