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.
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Data availability
The raw TMS-iEEG data generated in this study have not been deposited in a public repository. They are available under restricted access due to patient privacy protections and ethical restrictions associated with intracranial clinical recordings at the University of Iowa. Access can be obtained by requesting approval through the corresponding author, who will coordinate institutional review and applicable data-use agreements with the University of Iowa. Responses are typically provided within 4–8 weeks, and data access is granted for the duration specified in the approved agreement. The processed TMS-fMRI data generated in this study are available at https://github.com/JingjiangLab/Parietal-Hippocampus.git. The source data required to reproduce all figures generated in this study are provided with this paper in the Source Data file. Source data are provided with this paper.
Code availability
All codes for TMS-iEEG preprocessing are openly available at https://doi.org/10.5281/zenodo.18355225.
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Acknowledgements
This work was supported by National Institutes of Health R01MH136197 (J.J.), 1K23MH125145 (N.T.T.), R01MH125160 (N.T.T.), R01MH103324 (A.E.), R21MH120441 (A.D.B.), R01NS114405 (A.D.B.), R01MH132074 (N.T.T. and A.D.B.), Brain and Behavior Research Foundation Young Investigator grant 29441 (J.J.), Brain and Behavior Research Foundation 31275 (N.T.T.), Magnus Medical, Inc (N.T.T.), Roy J. Carver Trust (A.D.B.) This work was conducted, in part, on an MRI instrument funded by National Institutes of Health 1S10OD025025-01. We would like to acknowledge the patients and families who graciously agreed to participate in this research, as well as research members in the Human Brain Research Laboratory who assisted with data collection and provided feedback on the project, including Ariane Rhone, Haiming Chen, Ben Pace, Brandt Uitermarkt, Kirill Nourski, Joel Berger, Hiroyuki Oya, and Chris Garcia. We are also grateful to Dr. Yingming Sun for valuable feedback and support with the TMS-fMRI data analysis.
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Conceptualization: Z.L., A.D.B., J.J.; Writing—original draft: Z.L., J.J.; Writing—review and editing: Z.L., N.T.T., J.B., X.L., K.W., Z.C., A.E., M.A.H., A.D.B., J.J.; Investigation: Z.L., N.T.T., J.B., M.T., A.D.B., J.J.; Formal analysis: Z.L., J.J.; Methodology: Z.L., J.B., X.L., K.W., Z.C., J.J.; Funding acquisition, resources, and supervision: N.T.T., A.E., M.A.H., A.D.B., J.J.
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Li, Z., Trapp, N.T., Bruss, J. et al. Multimodal evidence for hippocampal engagement and modulation by functional connectivity-guided parietal TMS. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70346-x
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DOI: https://doi.org/10.1038/s41467-026-70346-x
