Serial vagus nerve stimulation functional MRI in treatment-resistant depression

Ziad Nahas, Charlotte Teneback, Jeong Ho Chae, Qiwen Mu, Chris Molnar, Frank A. Kozel, John Walker, Berry Anderson, Jejo Koola, Samet Kose, Mikhail Lomarev, Daryl E. Bohning, Mark S. George

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


Vagus nerve stimulation (VNS) therapy has shown antidepressant effects in open acute and long-term studies of treatment-resistant major depression. Mechanisms of action are not fully understood, although clinical data suggest slower onset therapeutic benefit than conventional psychotropic interventions. We set out to map brain systems activated by VNS and to identify serial brain functional correlates of antidepressant treatment and symptomatic response. Nine adults, satisfying DSM-IV criteria for unipolar or bipolar disorder, severe depressed type, were implanted with adjunctive VNS therapy (MRI-compatible technique) and enrolled in a 3-month, double-blind, placebo-controlled, serial-interleaved VNS/functional MRI (fMRI) study and open 20-month follow-up. A multiple regression mixed model with blood oxygenation level dependent (BOLD) signal as the dependent variable revealed that over time, VNS therapy was associated with ventro-medial prefrontal cortex deactivation. Controlling for other variables, acute VNS produced greater right insula activation among the participants with a greater degree of depression. These results suggest that similar to other antidepressant treatments, BOLD deactivation in the ventro-medial prefrontal cortex correlates with the antidepressant response to VNS therapy. The increased acute VNS insula effects among actively depressed participants may also account for the lower dosing observed in VNS clinical trials of depression compared with epilepsy. Future interleaved VNS/fMRI studies to confirm these findings and further clarify the regional neurobiological effects of VNS.

Original languageEnglish (US)
Pages (from-to)1649-1660
Number of pages12
Issue number8
StatePublished - Aug 2007

Bibliographical note

Funding Information:
Grant support was received from Cyberonics Inc. (DEB), The Dana Foundation (DEB), The Stanley Foundation (CT) and a grant in kind from the Center for Advanced Imaging Research (CAIR) at MUSC. Other support includes NIMH K08 MH070615-01A1 (ZN), NIMH R21 MH065630-01 (CM, ZN), NIMH R01 MH069896-01 A1 (MSG, SK, BA, CM, ZN), NINDS R01 NS40956-01 (DEB, MSG, ZN, JW). ZN and MSG are paid consultants to CYBX. MSG is a member of CYBX Mechanism of Action and Depression Advisory Boards.


  • Antidepressant
  • Depression
  • Vagus nerve stimulation
  • fMRI


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