Transcranial magnetic stimulation to the dorsolateral prefrontal cortex modulates single-neuron activity in humans

Charles W Dickey; Umair Hassan; Hiroto Kawasaki; Ariane E Rhone; Christopher C Cline; Matthew A Howard; Nicholas T Trapp; Aaron D Boes; Joel I Berger; Corey J Keller

doi:10.64898/2026.03.15.711839

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Transcranial magnetic stimulation to the dorsolateral prefrontal cortex modulates single-neuron activity in humans

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Transcranial magnetic stimulation to the dorsolateral prefrontal cortex modulates single-neuron activity in humans

Charles W Dickey, Umair Hassan, Hiroto Kawasaki, Ariane E Rhone, Christopher C Cline, Matthew A Howard, Nicholas T Trapp, Aaron D Boes, Joel I Berger and Corey J Keller

bioRxiv

03/18/2026

DOI: 10.64898/2026.03.15.711839

PMCID: PMC13015518

PMID: 41889898

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https://doi.org/10.64898/2026.03.15.711839View

Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an FDA-cleared treatment for depression, yet how cortical stimulation influences single neurons in deep brain circuits remains unknown. Using intracranial microelectrode recordings in four neurosurgical patients, we resolved single-neuron spikes as early as 8 ms from 185 single neurons after single-pulse left dlPFC TMS. TMS elicited time-locked firing responses in 46% of neurons across deep cortical and subcortical structures bilaterally. TMS facilitated putative interneuron spiking in striato-thalamic regions from ∼8 ms, peaking at ∼80-100 ms, and lasting to ∼1000 ms, while suppressing putative pyramidal cell spiking with a delayed and slower time course. Trial-by-trial single-neuron modulations were positively correlated with cortico-striato-thalamic network activity and anti-correlated with limbic network activity. These findings reveal that dlPFC TMS facilitates inhibitory firing in executive control networks while suppressing limbic excitatory drive, providing a cellular mechanism for how cortical stimulation modulates distributed brain networks.

Details

Title: Subtitle: Transcranial magnetic stimulation to the dorsolateral prefrontal cortex modulates single-neuron activity in humans
Creators: Charles W Dickey - Stanford University
Umair Hassan - Stanford University
Hiroto Kawasaki - University of Iowa
Ariane E Rhone - University of Iowa
Christopher C Cline - Neurosciences Institute
Matthew A Howard - University of Iowa
Nicholas T Trapp - University of Iowa
Aaron D Boes
Joel I Berger - University of Iowa
Corey J Keller - Stanford University
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.64898/2026.03.15.711839
PMID: 41889898
PMCID: PMC13015518
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: United States
Language: English
Date posted: 03/18/2026
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics); Neurosurgery; Otolaryngology
Record Identifier: 9985148850102771

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