Vagus nerve stimulation (VNS) is used as an adjunctive therapy for treatment-resistant depression (TRD). Its mechanism of action is not fully understood. Longitudinal measurement of changes in brain metabolism associated with VNS can provide insights into this new treatment modality. Eight severely depressed outpatients who were highly treatment-resistant underwent electrical stimulation of the left vagus nerve for approximately one year. The main outcome measures were resting regional brain glucose uptake measured with positron emission tomography (PET) and the 24-item Hamilton Depression Scale. The most significant and extensive change over one year of chronic VNS localized to the ventromedial prefrontal cortex extending from the subgenual cingulate to the frontal pole. This region continued to decline in metabolism even toward the end of the study. Clinically, this cohort showed a trend for improvement. No correlations surfaced between change in glucose uptake and depression scores. However, the sample size was small; none remitted; and the range of depression scores was limited. Chronic VNS as adjunctive therapy in patients with severe TRD produces protracted and robust declines in resting brain activity within the ventromedial prefrontal cortex, a network with dense connectivity to the amygdala and structures monitoring the internal milieu.
Bibliographical noteFunding Information:
Drs. Sheikh and Pardo own a patent related to vagus nerve stimulation in applications other than TRD. The work was sponsored in part by a grant to the Minnesota Veterans Research Institute by Cyberonics, Inc. (Houston, Texas), who is a supplier of VNS devices.
This work was supported in part by NARSAD; an Investigator-Initiated Grant from Cyberonics, Inc., Houston, TX; the Evert E. Bradbury Fund for Neuroimaging of Depression; RO1 AG120852; and the Department of Veterans Affairs. We thank Hemant Shah, M.D., and Ambreen Sattar, M.D., for assistance with data collection; Susan Siefert for proofreadng an earlier version of the manuscript; and our generous volunteer subjects
- Computed tomography
- Deep brain stimulation (DBS)
- Electroconvulsive therapy (ECT)
- Emission (PET)
- Functional magnetic resonance imaging (fMRI)
- Glucose metabolism
- Nucleus accumbens
- Subgenual anterior cingulate
- Treatment-resistant depression
- Ventromedial prefrontal cortex (VMPFC)