The timing of transcranial magnetic stimulation relative to the phase of prefrontal alpha EEG modulates downstream target engagement

Spiro P Pantazatos; James R Mclntosh; Golbarg T Saber; Xiaoxiao Sun; Jayce Doose; Josef Faller; Yida Lin; Joshua B Teves; Aidan Blankenship; Sarah Huffman; Robin I Goldman; Mark S George; Paul Sajda; Truman R Brown

doi:10.1016/j.brs.2023.05.007

The timing of transcranial magnetic stimulation relative to the phase of prefrontal alpha EEG modulates downstream target engagement

Brain Stimul. 2023 May-Jun;16(3):830-839. doi: 10.1016/j.brs.2023.05.007. Epub 2023 May 13.

Authors

Spiro P Pantazatos¹, James R Mclntosh², Golbarg T Saber³, Xiaoxiao Sun⁴, Jayce Doose⁵, Josef Faller⁴, Yida Lin⁶, Joshua B Teves⁷, Aidan Blankenship⁷, Sarah Huffman⁸, Robin I Goldman⁹, Mark S George¹⁰, Paul Sajda¹¹, Truman R Brown¹²

Affiliations

¹ Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, 10027, USA.
² Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA; Department of Orthopedic Surgery, Columbia University Irving Medical Center, New York, NY, 10032, USA.
³ Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, 29425, USA; Department of Neurology, University of Chicago, Chicago, IL, 60637, USA.
⁴ Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
⁵ Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, 29425, USA.
⁶ Department of Computer Science, Columbia University, New York, NY, 10027, USA.
⁷ Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, 29425, USA.
⁸ Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA.
⁹ Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, 53705, USA.
¹⁰ Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, 29401, USA.
¹¹ Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA; Department of Radiology, Columbia University Irving Medical Center, New York, NY, 10032, USA; Department of Electrical Engineering, Columbia University, New York, NY, 10027, USA; Data Science Institute, Columbia University, New York, NY, 10027, USA. Electronic address: psajda@columbia.edu.
¹² Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, 29425, USA; Department of Computer Science, Columbia University, New York, NY, 10027, USA. Electronic address: brotrr@musc.edu.

PMID: 37187457
DOI: 10.1016/j.brs.2023.05.007

Abstract

Background: The communication through coherence model posits that brain rhythms are synchronized across different frequency bands and that effective connectivity strength between interacting regions depends on their phase relation. Evidence to support the model comes mostly from electrophysiological recordings in animals while evidence from human data is limited.

Methods: Here, an fMRI-EEG-TMS (fET) instrument capable of acquiring simultaneous fMRI and EEG during noninvasive single pulse TMS applied to dorsolateral prefrontal cortex (DLPFC) was used to test whether prefrontal EEG alpha phase moderates TMS-evoked top-down influences on subgenual, rostral and dorsal anterior cingulate cortex (ACC). Six runs (276 total trials) were acquired in each participant. Phase at each TMS pulse was determined post-hoc using single-trial sorting. Results were examined in two independent datasets: healthy volunteers (HV) (n = 11) and patients with major depressive disorder (MDD) (n = 17) collected as part of an ongoing clinical trial.

Results: In both groups, TMS-evoked functional connectivity between DLPFC and subgenual ACC (sgACC) depended on the EEG alpha phase. TMS-evoked DLPFC to sgACC fMRI-derived effective connectivity (EC) was modulated by EEG alpha phase in healthy volunteers, but not in the MDD patients. Top-down EC was inhibitory for TMS pulses during the upward slope of the alpha wave relative to TMS timed to the downward slope of the alpha wave. Prefrontal EEG alpha phase dependent effects on TMS-evoked fMRI BOLD activation of the rostral anterior cingulate cortex were detected in the MDD patient group, but not in the healthy volunteer group.

Discussion: Results demonstrate that TMS-evoked top-down influences vary as a function of the prefrontal alpha rhythm, and suggest potential clinical applications whereby TMS is synchronized to the brain's internal rhythms in order to more efficiently engage deep therapeutic targets.

Keywords: DCM; Dynamic causal modeling; Electroencephalogram; Neurostimulation; Target engagement; Transcranial magnetic stimulation.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alpha Rhythm
Animals
Brain
Depressive Disorder, Major*
Dorsolateral Prefrontal Cortex
Electroencephalography
Humans
Magnetic Resonance Imaging
Prefrontal Cortex
Transcranial Magnetic Stimulation*