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Author Notes:

Correspondence: Otis Smart otissmart@gmail.com

Conception and design of the study: OS, KC, PR-P, RG, AW, and HM.

Care of or/and interaction with patients: PR-P, AC, and RG. Acquisition or/and analysis of data: OS, KC, PR-P, VT, AC, JE and JR.

Composition of manuscript text or/and figures: all authors.

Accountable of all aspects of the work: all authors.

The authors thank Dr. Paul E. Holtzheimer for his contribution to the original design of the clinical trial and initial intraoperative testing sessions.

This study was carried out in accordance with the Emory University IRB (Institutional Review Board) with written informed consent from all subjects.

All subjects gave written informed consent in accordance with the Declaration of Helsinki.

The protocol was approved by the Emory IRB.

HM is a consultant with licensed intellectual property to St Jude Medical Corp (now Abbott Labs).

These arrangements were approved by Emory University.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subjects:

Research Funding:

Grants from the Dana Foundation, the Hope for Depression Research Foundation, and the National Institutes of Health (1R01MH102238, 1R01MH106173, UH3NS103550) and devices donated by St. Jude Medical, Inc. and Medtronic supported this study.

RG has received grants from Medtronic Inc., Neuropace and MRI Interventions, honoraria from Medtronic Inc. and MRI Interventions; and is a paid consultant to St Jude Medical Corp., Medtronic Inc., Neuropace, MRI Interventions, Neuralstem and SanBio.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Mathematical & Computational Biology
  • Neurosciences
  • Neurosciences & Neurology
  • depression
  • LFP
  • SCC
  • DBS
  • power spectra
  • tractography
  • VTA/VTR
  • intraoperative
  • MAJOR DEPRESSION
  • GLUCOSE-METABOLISM
  • DISORDER
  • GYRUS
  • CONNECTIVITY
  • VENLAFAXINE
  • PREDICTORS
  • DYNAMICS
  • THERAPY
  • EMOTION

Initial Unilateral Exposure to Deep Brain Stimulation in Treatment-Resistant Depression Patients Alters Spectral Power in the Subcallosal Cingulate

Tools:

Journal Title:

Frontiers in Computational Neuroscience

Volume:

Volume 12

Publisher:

, Pages 43-43

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: High-frequency Deep Brain Stimulation (DBS) of the subcallosal cingulate (SCC) region is an emerging strategy for treatment-resistant depression (TRD). This study examined changes in SCClocal field potentials (LFPs). The LFPs were recorded fromthe DBS leads following transient, unilateral stimulation at the neuroimaging-defined optimal electrode contact. The goal was identifying a putative electrophysiological measure of target engagement during implantation. Methods: Fourteen consecutive patients underwent bilateral SCC DBS lead implantation. LFP recordings were collected from all electrodes during randomized testing of stimulation on each DBS contact (eight total). Analyses evaluated changes in spectral power before and after 3min of unilateral stimulation at the contacts that later facilitated antidepressant response, as a potential biomarker of optimal contact selection in each hemisphere. Results: Lateralized and asymmetric power spectral density changes were detected in the SCC with acute unilateral SCC stimulation at those contacts subsequently selected for chronic, therapeutic stimulation. Left stimulation induced broadband ipsilateral decreases in theta, alpha, beta and gamma bands. Right stimulation effects were restricted to ipsilateral beta and gamma decreases. These asymmetric effects contrasted with identical white matter stimulation maps used in each hemisphere. More variable ipsilateral decreases were seen with stimulation at the adjacent “suboptimal” contacts, but changes were not statistically different from the “optimal” contact in either hemisphere despite obvious differences in impacted white matter bundles. Change in theta power was, however, most robust and specific with left-sided optimal stimulation, which suggested a putative functional biomarker on the left with no such specificity inferred on the right. Conclusion: Hemisphere-specific oscillatory changes can be detected from the DBS lead with acute intraoperative testing at contacts that later engender antidepressant effects. Our approach defined potential target engagement signals for further investigation, particularly left-sided theta decreases following initial exposure to stimulation. More refined models combining tractography, bilateral SCCLFP, and cortical recordings may further improve the precision and specificity of these putative biomarkers. It may also optimize and standardize the lead implantation procedure and provide input signals for next generation closed-loop therapy and/or monitoring technologies for TRD.

Copyright information:

© 2018 Smart, Choi, Riva-Posse, Tiruvadi, Rajendra, Waters, Crowell, Edwards, Gross and Mayberg.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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