Dissociation of Centrally and Peripherally Induced Transcranial Magnetic Stimulation Effects in Nonhuman Primates

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation method that is rapidly growing in popularity for studying causal brain-behavior relationships. However, its dose-dependent centrally induced neural mechanisms and peripherally induced sensory costimulation effects remain deba...

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Bibliographic Details
Published in:The Journal of neuroscience 2023-12, Vol.43 (50), p.8649-8662
Main Authors: Perera, Nipun D, Alekseichuk, Ivan, Shirinpour, Sina, Wischnewski, Miles, Linn, Gary, Masiello, Kurt, Butler, Brent, Russ, Brian E, Schroeder, Charles E, Falchier, Arnaud, Opitz, Alexander
Format: Article
Language:English
Subjects:
Animals
Biomarkers
Brain
Circuits
Electroencephalography - methods
Evoked Potentials - physiology
Evoked Potentials, Motor - physiology
Female
Humans
Macaca mulatta
Magnetic fields
Male
Medical imaging
Neuroimaging
Primates
Transcranial magnetic stimulation
Transcranial Magnetic Stimulation - methods
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Summary:Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation method that is rapidly growing in popularity for studying causal brain-behavior relationships. However, its dose-dependent centrally induced neural mechanisms and peripherally induced sensory costimulation effects remain debated. Understanding how TMS stimulation parameters affect brain responses is vital for the rational design of TMS protocols. Studying these mechanisms in humans is challenging because of the limited spatiotemporal resolution of available noninvasive neuroimaging methods. Here, we leverage invasive recordings of local field potentials in a male and a female nonhuman primate (rhesus macaque) to study TMS mesoscale responses. We demonstrate that early TMS-evoked potentials show a sigmoidal dose-response curve with stimulation intensity. We further show that stimulation responses are spatially specific. We use several control conditions to dissociate centrally induced neural responses from auditory and somatosensory coactivation. These results provide crucial evidence regarding TMS neural effects at the brain circuit level. Our findings are highly relevant for interpreting human TMS studies and biomarker developments for TMS target engagement in clinical applications. Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation method to stimulate the human brain. To advance its utility for clinical applications, a clear understanding of its underlying physiological mechanisms is crucial. Here, we perform invasive electrophysiological recordings in the nonhuman primate brain during TMS, achieving a spatiotemporal precision not available in human EEG experiments. We find that evoked potentials are dose dependent and spatially specific, and can be separated from peripheral stimulation effects. This means that TMS-evoked responses can indicate a direct physiological stimulation response. Our work has important implications for the interpretation of human TMS-EEG recordings and biomarker development.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.1016-23.2023