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A generalized workflow for conducting electric field–optimized, fMRI-guided, transcranial magnetic stimulation

Nature Protocols volume 15, pages 3595–3614 (2020)Cite this article

Subjects

Abstract

Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cerebral cortex that has applications in psychiatry, such as in the treatment of depression and anxiety. Although many TMS targeting methods that use figure-8 coils exist, many do not account for individual differences in anatomy or are not generalizable across target sites. This protocol combines functional magnetic resonance imaging (fMRI) and iterative electric-field (E-field) modeling in a generalized approach to subject-specific TMS targeting that is capable of optimizing the stimulation site and TMS coil orientation. To apply this protocol, the user should (i) operationally define a region of interest (ROI), (ii) generate the head model from the structural MRI data, (iii) preprocess the functional MRI data, (iv) identify the single-subject stimulation site within the ROI, and (iv) conduct E-field modeling to identify the optimal coil orientation. In comparison with standard targeting methods, this approach demonstrates (i) reduced variability in the stimulation site across subjects, (ii) reduced scalp-to-cortical-target distance, and (iii) reduced variability in optimal coil orientation. Execution of this protocol requires intermediate-level skills in structural and functional MRI processing. This protocol takes ~24 h to complete and demonstrates how constrained fMRI targeting combined with iterative E-field modeling can be used as a general method to optimize both the TMS coil site and its orientation.

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Fig. 1: Schematic of the steps described in the Procedure.
Fig. 2: Schematic demonstrating the use of the task throughout the targeting and stimulation steps.
Fig. 3: Example masks obtained using anatomical, functional, meta-analytical, and unconstrained methodologies plotted for a single subject’s T1 scan.
Fig. 4: Peak activations and intersubject distance matrices from Sternberg WM BOLD maps using different masks as input.
Fig. 5: Distance metrics of the peak activations from Sternberg WM BOLD maps using different masks as input.
Fig. 6: Changes in the normalized E-field simulated for each target, plotted as a function of coil handle orientation.
Fig. 7: Metrics used to assess E-field models based on input masks and evaluation strategy.

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Data availability

Example data have been uploaded as Supplementary Data.

Code availability

The code has been uploaded to GitHub (https://github.com/balders2/tms_targeting).

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Acknowledgements

This study used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (https://hpc.nih.gov/). This project was supported in part by a 2018 NARSAD Young Investigator Grant from the Brain & Behavior Foundation (N.L.B.). Financial support for this study was provided by the Intramural Research Program of the National Institute of Mental Health (ZIAMH002798; ClinicalTrial.gov Identifier: NCT03027414: Protocol ID 17-M-0042). The authors all work at the National Institutes of Health. The views expressed here are the authors’ own and do not necessarily reflect the views of the NIH, DHHS, or the US federal government.

Author information

Authors and Affiliations

  1. Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    Nicholas L. Balderston, Camille Roberts, Emily M. Beydler, Monique Ernst & Christian Grillon

  2. Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA

    Nicholas L. Balderston

  3. Noninvasive Neuromodulation Unit, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    Zhi-De Deng, Thomas Radman, Bruce Luber & Sarah H. Lisanby

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  1. Nicholas L. Balderston
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Contributions

The study was designed by N.L.B., C.G., M.E., B.L., and S.H.L. The protocol was designed by N.L.B., Z.-D.D., T.R., B.L., and S.H.L. The data were collected by N.L.B., C.R., and E.M.B., and were analyzed by N.L.B. The manuscript was prepared by N.L.B., B.L., S.H.L., M.E., and C.G.

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Correspondence to Nicholas L. Balderston.

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The authors declare no competing interests.

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Peer review information Nature Protocols thanks Thomas Knoesche and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

Key references using this protocol

Balderston N. et al. Transl. Psychiatry 10, 68 (2020): https://doi.org/10.1038/s41398-020-0751-8

Balderston N. et al. Neuropsychopharmacology 45, 694–702 (2020): https://doi.org/10.1038/s41386-019-0583-5

Davis S. W., Luber, B., Murphy, D. L. K., Lisanby, S. H. & Cabeza, R. Hum. Brain Mapp. 38, 5987–6004 (2017): https://doi.org/10.1002/hbm.23803

Supplementary information

Reporting Summary

Supplementary Data

Example data to be used with the protocol.

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Balderston, N.L., Roberts, C., Beydler, E.M. et al. A generalized workflow for conducting electric field–optimized, fMRI-guided, transcranial magnetic stimulation. Nat Protoc 15, 3595–3614 (2020). https://doi.org/10.1038/s41596-020-0387-4

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