
==== Front
medRxiv
MEDRXIV
medRxiv
Cold Spring Harbor Laboratory

39185539
10.1101/2024.08.15.24311994
preprint
2
Article
Precision Network Modeling of Transcranial Magnetic Stimulation Across Individuals Suggests Therapeutic Targets and Potential for Improvement
Sun Wendy http://orcid.org/0000-0001-7350-964X

Billot Anne http://orcid.org/0000-0002-6356-2719

Du Jingnan http://orcid.org/0000-0003-1647-6698

Wei Xiangyu http://orcid.org/0000-0002-8774-5296

Lemley Rachel A http://orcid.org/0009-0003-6251-2159

Daneshzand Mohammad http://orcid.org/0000-0002-4237-5535

Nummenmaa Aapo http://orcid.org/0000-0002-6452-7958

Buckner Randy L http://orcid.org/0000-0001-6422-8037

Eldaief Mark C http://orcid.org/0000-0002-4919-2897

23 9 2024
2024.08.15.24311994https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://medrxiv.org/lookup/doi/10.1101/2024.08.15.24311994
nihpp-2024.08.15.24311994.pdf
Higher-order cognitive and affective functions are supported by large-scale networks in the brain. Dysfunction in different networks is proposed to associate with distinct symptoms in neuropsychiatric disorders. However, the specific networks targeted by current clinical transcranial magnetic stimulation (TMS) approaches are unclear. While standard-of-care TMS relies on scalp-based landmarks, recent FDA-approved TMS protocols use individualized functional connectivity with the subgenual anterior cingulate cortex (sgACC) to optimize TMS targeting. Leveraging previous work on precision network estimation and recent advances in network-level TMS targeting, we demonstrate that clinical TMS approaches target different functional networks between individuals. Homotopic scalp positions (left F3 and right F4) target different networks within and across individuals, and right F4 generally favors a right-lateralized control network. We also modeled the impact of targeting the dorsolateral prefrontal cortex (dlPFC) zone anticorrelated with the sgACC and found that the individual-specific anticorrelated region variably targets a network coupled to reward circuitry. Combining individualized, precision network mapping and electric field (E-field) modeling, we further illustrate how modeling can be deployed to prospectively target distinct closely localized association networks in the dlPFC with meaningful spatial selectivity and E-field intensity and retrospectively assess network engagement. Critically, we demonstrate the feasibility and reliability of this approach in an independent cohort of participants (including those with Major Depressive Disorder) who underwent repeated sessions of TMS to distinct networks, with precise targeting derived from a low-burden single session of data. Lastly, our findings emphasize differences between selectivity and maximal intensity, highlighting the need to consider both metrics in precision TMS efforts.
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pmc
