Oscillatory network markers of subcallosal cingulate deep brain stimulation for depression

M Scherer; I E Harmsen; N Samuel; G J B Elias; J Germann; A Boutet; C E MacLeod; P Giacobbe; N C Rowland; A M Lozano; L Milosevic

doi:10.1016/j.brs.2023.11.016

Oscillatory network markers of subcallosal cingulate deep brain stimulation for depression

Brain Stimul. 2023 Nov-Dec;16(6):1764-1775. doi: 10.1016/j.brs.2023.11.016. Epub 2023 Dec 6.

Authors

M Scherer¹, I E Harmsen², N Samuel³, G J B Elias³, J Germann³, A Boutet⁴, C E MacLeod⁵, P Giacobbe⁶, N C Rowland⁷, A M Lozano⁸, L Milosevic⁹

Affiliations

¹ Krembil Brain Institute, University Health Network, Toronto, Canada; Institute of Biomedical Engineering, University of Toronto, Canada.
² Krembil Brain Institute, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada; Mitchell Goldhar MEG Unit, University Health Network, Toronto, Canada.
³ Krembil Brain Institute, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
⁴ Krembil Brain Institute, University Health Network, Toronto, Canada; Joint Department of Medical Imaging, University of Toronto, Canada.
⁵ Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, Ontario, Canada.
⁶ Department of Psychiatry, Sunnybrook Health Sciences, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, USA; Murray Center for Research on Parkinson's Disease and Related Disorders, Medical University of South Carolina, Charleston, SC, USA.
⁸ Krembil Brain Institute, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada; Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Canada.
⁹ Krembil Brain Institute, University Health Network, Toronto, Canada; Institute of Biomedical Engineering, University of Toronto, Canada; Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Canada; KITE Research Institute, University Health Network, Toronto, Canada. Electronic address: luka.milosevic@mail.utoronto.ca.

Abstract

Identifying functional biomarkers related to treatment success can aid in expediting therapy optimization, as well as contribute to a better understanding of the neural mechanisms of the treatment-resistant depression (TRD) and subcallosal cingulate deep brain stimulation (SCC-DBS). Magnetoencephalography data were obtained from 16 individuals with SCC-DBS for TRD and 25 healthy subjects. The first objective of the study was to identify region-specific oscillatory modulations that both (i) discriminate individuals with TRD (with SCC-DBS OFF) from healthy controls, and (ii) discriminate TRD treatment responders from non-responders (with SCC-DBS ON). The second objective of this work was to further explore the effects of stimulation intensity and frequency on oscillatory activity in the identified brain regions of interest. Oscillatory power analyses led to the identification of brain regions that differentiated responders from non-responders based on modulations of increased alpha (8-12 Hz) and decreased gamma (32-116 Hz) power within nodes of the default mode, central executive, and somatomotor networks, Broca's area, and lingual gyrus. Within these nodes, it was also found that low stimulation frequency had stronger effects on oscillatory modulation than increased stimulation intensity. The identified functional network biomarkers implicate modulation of TRD-related activity in brain regions involved in emotional control/processing, motor control, and the interaction between speech, vision, and memory, which have all been implicated in depression. These electrophysiological biomarkers have the potential to be used as functional proxies for therapy optimization. Additional stimulation parameter analyses revealed that oscillatory modulations can be strengthened by increasing stimulation intensity or reducing frequency, which may represent potential avenues of direction in non-responders.

Keywords: Alpha and gamma oscillations; Deep brain stimulation; Magnetoencephalography; Subcallosal cingulate; Treatment-resistant depression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Deep Brain Stimulation*
Depression
Depressive Disorder, Treatment-Resistant* / therapy
Gyrus Cinguli / physiology
Humans
Treatment Outcome

Substances

Biomarkers

Grants and funding

P20 GM109040/GM/NIGMS NIH HHS/United States