Multimodal evidence for hippocampal engagement and modulation by functional connectivity-guided parietal TMS

Zhuoran Li; Nicholas T Trapp; Joel Bruss; Xianqing Liu; Kang Wu; Ziyan Chen; Amit Etkin; Matthew A Howard; Aaron D Boes; Jing Jiang

doi:10.1038/s41467-026-70346-x

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Multimodal evidence for hippocampal engagement and modulation by functional connectivity-guided parietal TMS

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Multimodal evidence for hippocampal engagement and modulation by functional connectivity-guided parietal TMS

Zhuoran Li, Nicholas T Trapp, Joel Bruss, Xianqing Liu, Kang Wu, Ziyan Chen, Amit Etkin, Matthew A Howard, Aaron D Boes and Jing Jiang

Nature communications

03/08/2026

DOI: 10.1038/s41467-026-70346-x

PMID: 41794924

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Abstract

Hippocampal activity supports memory and many other brain functions. Transcranial magnetic stimulation (TMS) guided by hippocampal functional connectivity (FC) shows promise in improving memory, but direct neural evidence of its capacity to engage and modulate hippocampal activity is lacking. Here we combined TMS with intracranial electroencephalography (iEEG) in 8 neurosurgical patients and with functional magnetic resonance imaging (fMRI) in 79 neurologically healthy participants. We identified that (1) single-pulse TMS to individualized parietal cortex guided by hippocampal-FC preferentially evoked distinct temporal and spectral activity patterns in the hippocampus, (2) variability in TMS-evoked hippocampal responses related to individual differences in parietal-hippocampus FC strength, and (3) repetitive TMS to hippocampal-FC-guided parietal cortex selectively suppressed hippocampal theta oscillations. These findings provide multimodal causal neural evidence and important mechanistic insights supporting the development of personalized neuromodulation strategies aimed at improving hippocampus-dependent functions.

Details

Title: Subtitle: Multimodal evidence for hippocampal engagement and modulation by functional connectivity-guided parietal TMS
Creators: Zhuoran Li - University of Iowa
Nicholas T Trapp - University of Iowa
Joel Bruss - University of Iowa
Xianqing Liu - University of Iowa
Kang Wu - University of Iowa, Stead Family Department of Pediatrics
Ziyan Chen - University of Iowa, Stead Family Department of Pediatrics
Amit Etkin - Alto Neuroscience (United States)
Matthew A Howard - University of Iowa
Aaron D Boes - University of Iowa
Jing Jiang - University of Iowa
Resource Type: Journal article
Publication Details: Nature communications
DOI: 10.1038/s41467-026-70346-x
PMID: 41794924
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: Springer Nature
Grant note: R01MH103324 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) R21MH120441, R01NS114405 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01MH132074 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) 1K23MH125145, R01MH125160, R01MH132074 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) 29441 / Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) 31275 / Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) R01MH136197 / U.S. Department of Health & Human Services | National Institutes of Health (NIH)
Language: English
Electronic publication date: 03/08/2026
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: 9985141896702771

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