Using brain imaging to improve spatial targeting of transcranial magnetic stimulation for depression
Open accessAbstract
Transcranial magnetic stimulation (TMS) is an effective treatment for depression but is limited in that the optimal therapeutic target remains unknown. Early TMS trials lacked a focal target and thus positioned the TMS coil over the prefrontal cortex using scalp measurements. Over time, it became clear that this method leads to variation in the stimulation site and that this could contribute to heterogeneity in antidepressant response. Newer methods allow for precise positioning of the TMS coil over a specific brain location, but leveraging these precise methods requires a more precise therapeutic target. We review how neuroimaging is being used to identify a more focal therapeutic target for depression. We highlight recent studies showing that more effective TMS targets in the frontal cortex are functionally connected to deep limbic regions such as the subgenual cingulate cortex. We review how connectivity might be used to identify an optimal TMS target for use in all patients and potentially even a personalized target for each individual patient. We address the clinical implications of this emerging field and highlight critical questions for future research.
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Most clinical rTMS treatments for MDD occur daily and are applied using scalp-based targeting of DLPFC; these standard treatments are only modestly effective, even in the general MDD population.
“Most clinical rTMS treatments for MDD occur daily (one rTMS session per day) and are applied using scalp-based targeting of DLPFC. These standard treatments are only modestly effective, even in the general MDD population (17, 24–31).”
From Adaptive trial for the treatment of depressive symptoms associated with concussion using accelerated intermittent theta burst stimulation (ADEPT): rationale, design and methods (2025) · cites this paper as [31]
The ‘Targeting TMS Using Scalp Measurements’ section says scalp-based DLPFC targeting was the most common method in randomized trials. The Conclusions table describes a once-daily regimen, and the opening section reports typical response rates of 29–46% and remission rates of 18–31%. However, the paper discusses these outcomes in the context of treatment-resistant depression; it does not establish the same modest effectiveness for the general MDD population. (LLM, conf=0.84)
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Cites
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.11.1905 · Cited by 5,643 · cited 2× · see citing works
“As few as 30% of patients achieve remission with first-line therapies (2).”
BackgroundFunctional connectome fingerprinting: Identifying individuals using patterns of brain connectivity
Finn, E. S., Shen, X., Scheinost, D., Rosenberg, M. D., Huang, J., Chun, M. M., Papademetris, X., & Constable, R. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4135 · Cited by 2,747 · see citing works
Resting-state connectivity biomarkers define neurophysiological subtypes of depression
Drysdale, A. T., Grosenick, L., Downar, J., Dunlop, K., Mansouri, F., Meng, Y., Fetcho, R. N., Zebley, B., Oathes, D. J., Etkin, A., et al. (2017) · Nature Medicine · doi:10.1038/nm.4246 · Cited by 2,170 · see citing works
Self-citationDepression of motor cortex excitability by low-frequency transcranial magnetic stimulation
Chen, R., Classen, J., Gerloff, C., Celnik, P., Wassermann, E. M., Hallett, M., & Cohen, L. G. (1997) · Neurology · doi:10.1212/wnl.48.5.1398 · Cited by 2,128 · see citing works
The connectomics of brain disorders
Fornito, A., Zalesky, A., & Breakspear, M. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3901 · Cited by 1,734 · see citing works
Self-citationA meta‐analytic study of changes in brain activation in depression
Fitzgerald, P. B., Laird, A. R., Maller, J., & Daskalakis, Z. J. (2008) · Human Brain Mapping · doi:10.1002/hbm.20426 · Cited by 903 · see citing works
Self-citationKessler, R. C. (2012) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2011.11.005 · Cited by 871 · see citing works
Time-resolved resting-state brain networks
Zalesky, A., Fornito, A., Cocchi, L., Gollo, L. L., & Breakspear, M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400181111 · Cited by 753 · see citing works
Cortical folding patterns and predicting cytoarchitecture
Fischl, B., Rajendran, N., Busa, E., Augustinack, J., Hinds, O., Yeo, B. T. T., Mohlberg, H., Amunts, K., & Zilles, K. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhm225 · Cited by 737 · see citing works
McClintock, S. M., Reti, I. M., Carpenter, L. L., McDonald, W. M., Dubin, M., Taylor, S. F., Cook, I. A., O’Reardon, J., Husain, M. M., Wall, C., et al. (2018) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.16cs10905 · Cited by 693 · see citing works
An efficient and accurate new method for locating the F3 position for prefrontal TMS applications
Beam, W., Borckardt, J. J., Reeves, S. T., & George, M. S. (2009) · Brain Stimulation · doi:10.1016/j.brs.2008.09.006 · Cited by 626 · see citing works
Fox, M. D., Halko, M. A., Eldaief, M. C., & Pascual-Leone, A. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.03.035 · Cited by 395 · see citing works
Self-citationBakker, N., Shahab, S., Giacobbe, P., Blumberger, D. M., Daskalakis, Z. J., Kennedy, S. H., & Downar, J. (2015) · Brain Stimulation · doi:10.1016/j.brs.2014.11.002 · Cited by 306 · see citing works
Self-citationSalomons, T. V., Dunlop, K., Kennedy, S. H., Flint, A., Geraci, J., Giacobbe, P., & Downar, J. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.222 · Cited by 299 · see citing works
Self-citationIndividual variability of the system-level Organization of the Human Brain
Gordon, E. M., Laumann, T. O., Adeyemo, B., & Petersen, S. E. (2015) · Cerebral Cortex · doi:10.1093/cercor/bhv239 · Cited by 219 · see citing works
Fitzgerald, P. B., Hoy, K. E., Anderson, R. J., & Daskalakis, Z. J. (2016) · Depression and Anxiety · doi:10.1002/da.22503 · Cited by 204 · see citing works
Self-citationDonse, L., Padberg, F., Sack, A. T., Rush, A. J., & Arns, M. (2018) · Brain Stimulation · doi:10.1016/j.brs.2017.11.004 · Cited by 183 · see citing works
Rao, V. R., Sellers, K. K., Wallace, D. L., Lee, M. B., Bijanzadeh, M., Sani, O. G., Yang, Y., Shanechi, M. M., Dawes, H. E., & Chang, E. F. (2018) · Current Biology · doi:10.1016/j.cub.2018.10.026 · Cited by 181 · see citing works
Zrenner, B., Zrenner, C., Gordon, P. C., Belardinelli, P., McDermott, E. J., Soekadar, S. R., Fallgatter, A. J., Ziemann, U., & Müller-Dahlhaus, F. (2020) · Brain Stimulation · doi:10.1016/j.brs.2019.10.007 · Cited by 175 · see citing works
Dunlop, K., Woodside, B., Olmsted, M., Colton, P., Giacobbe, P., & Downar, J. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.292 · Cited by 147 · cited 1× · see citing works
“Connectomics is also increasingly being used to inform rTMS targeting for cognitive applications (31,139,140) and to guide the modulation of corticostriatothalamic loops in obsessive-compulsive disorder (141,142).”
MethodSelf-citationFitzgerald, P. B., Hoy, K., Daskalakis, Z. J., & Kulkarni, J. (2009) · Depression and Anxiety · doi:10.1002/da.20454 · Cited by 147 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 12
- Berlim MT, van den Eynde F, Tovar-Perdomo S, Daskalakis ZJ (2014): Response, remission and drop-out rates following high- frequency repetitive transcranial magnetic stimulation (rTMS) for treating major depression: A systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. Psychol Med 44:225-239.
- Downar J, Daskalakis ZJ (2013): New targets for rTMS in depression: A review of convergent evidence. Brain Stimul 6:231-240.
- Fitzgerald PB, Daskalakis ZJ (2013): Repetitive Transcranial Magnetic Stimulation Treatment for Depressive Disorders: A Practical Guide. Berlin: Springer.
- Brunoni AR, Chaimani A, Moffa AH, Razza LB, Gattaz WF, Daskalakis ZJ, et al. (2017): Repetitive transcranial magnetic stimu- lation for the acute treatment of major depressive episodes: A sys- tematic review with network meta-analysis. JAMA Psychiatry 74:143- 152.
- von Economo CF, Koskinas GN (1925): Die Cytoarchitektonik der Hirnrinde des Erwachsenen Menschen. J. Springer. Improving Spatial Targeting of TMS for Depression Biological Psychiatry --, 2020; -:---www.sobp.org/journal
- Carson AJ, MacHale S, Allen K, Lawrie SM, Dennis M, House A, et al. (2000): Depression after stroke and lesion location: A systematic review. Lancet 356:122-126.
- Elliott ML, Knodt AR, Ireland D, Morris ML, Poulton R, Ramrakha S, et al. (2019): What is the test-retest reliability of common task-fMRI measures? New empirical evidence and a meta-analysis. bioRxiv. https://doi.org/10.1101/681700. · DOI
- Parkes L, Fulcher B, Yucel M, Fornito A (2018): An evaluation of the efficacy, reliability, and sensitivity of motion correction strategies for resting-state functional MRI. Neuroimage 171:415-436. 101. Gratton C, Laumann TO, Nielsen AN, Greene DJ, Gordon EM, Gilmore AW, et al. (2018): Functional brain networks are dominated by stable group and individual factors, not cognitive or daily variation. Neuron 98:439-452.e435. 102. Braga RM, Buckner RL (2017): Parallel interdigitated distributed networks within the individual estimated by intrinsic functional con- nectivity. Neuron 95:457-471.e455. 103. Horien C, Shen X, Scheinost D, Constable RT (2019): The individual functional connectome is unique and stable over months to years. Neuroimage 189:676-687. 104. Cash R, Cocchi L, Lv J, Fitzgerald P, Zalesky A (2020): Toward state- of-the-art connectivity-guided TMS: Personalization, precision & clinical response. Program No. 0047. Proceedings of the Organiza- tion for Human Brain Mapping, June 23-July 3. 105.
- Beynel L, Powers JP, Appelbaum LG (2020): Effects of repetitive transcranial magnetic stimulation on resting-state connectivity: A systematic review. Neuroimage 211:116596. 130.
- Jannati A, Block G, Oberman LM, Rotenberg A, Pascual-Leone A (2017): Interindividual variability in response to continuous theta- burst stimulation in healthy adults. Clin Neurophysiol 128:2268-2278. 146. Miron JP, Feffer K, Cash RFH, Derakhshan D, Kim JMS, Fettes P, et al. (2019): Safety, tolerability and effectiveness of a novel 20 Hz rTMS protocol targeting dorsomedial prefrontal cortex in major depression: An open-label case series. Brain Stimul 12:1319-1321. 147. Xie J, Chen J, Wei Q (2013): Repetitive transcranial magnetic stimu- lation versus electroconvulsive therapy for major depression: A meta- analysis of stimulus parameter effects. Neurol Res 35:1084-1091. 148. Ke J, Zou X, Huang M, Huang Q, Li H, Zhou X (2020): High-frequency rTMS with two different inter-train intervals improves upper limb motor function at the early stage of stroke. J Int Med Res 48(6): 0300060520928737. 149. Cash RF, Murakami T, Chen R, Thickbroom GW, Ziemann U (2016): Augmenting plasticity induction in human motor cortex by disinhibi- tion stimulation. Cereb Cortex 26:58-69. 150. Chung SW, Sullivan CM, Rogasch NC, Hoy KE, Bailey NW, Cash RF, et al. (2018): The effects of individualised intermittent theta burst stimulation in the prefrontal cortex: A TMS-EEG study. Hum Brain Mapp 40:608-627. 151. Cash RF, Mastaglia FL, Thickbroom GW (2013): Evidence for high- fidelity timing-dependent synaptic plasticity of human motor cortex. J Neurophysiol 109:106-112. 152.
- Stefanou MI, Baur D, Belardinelli P, Bergmann TO, Blum C, Gordon PC, et al. (2019): Brain state-dependent brain stimulation with real-time electroencephalography-triggered transcranial mag- netic stimulation. J Vis Exp (150):10.3791/59711. 153. Bergmann TO, Molle M, Schmidt MA, Lindner C, Marshall L, Born J, et al. (2012): EEG-guided transcranial magnetic stimulation reveals rapid shifts in motor cortical excitability during the human sleep slow oscillation. J Neurosci 32:243-253. 154. Bergmann TO, Karabanov A, Hartwigsen G, Thielscher A, Siebner HR (2016): Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives. Neuroimage 140:4-19. 155. · DOI
- Cash, R. F. H., Weigand, A., Zalesky, A., Siddiqi, S. H., Downar, J., Fitzgerald, P. B. & Fox, M. D. (2020). Using Brain Imaging to Improve Spatial Targeting of Transcranial Magnetic Stimulation for Depression.. Biol Psychiatry, https://doi.org/10.1016/j.biopsych.2020.05.033. Persistent Link: http://hdl.handle.net/11343/252492 File Description: Published version License: cc-by-nc-nd
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Cash, R. F. H., Cocchi, L., Lv, J., Fitzgerald, P. B., & Zalesky, A. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.3794 · Cited by 291 · see citing works
Self-citationCaulfield, K. A., Fleischmann, H. H., Cox, C. E., Wolf, J. P., George, M. S., & McTeague, L. M. (2022) · Brain Stimulation · doi:10.1016/j.brs.2022.08.013 · Cited by 145 · see citing works
Sun, X., Sun, J., Lu, X., Dong, Q., Zhang, L., Wang, W., Liu, J., Ma, Q., Wang, X., Wei, D., et al. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.05.021 · Cited by 129 · see citing works
Trapp, N. T., Purgianto, A., Taylor, J. J., Singh, M. K., Oberman, L. M., Mickey, B. J., Youssef, N. A., Solzbacher, D., Zebley, B., Cabrera, L. Y., et al. (2025) · Clinical Neurophysiology · doi:10.1016/j.clinph.2024.12.015 · Cited by 89 · see citing works
Accelerated Theta Burst Stimulation: Safety, Efficacy, and Future Advancements
Cole, E., O’Sullivan, S. J., Tik, M., & Williams, N. R. (2024) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.12.004 · Cited by 79 · see citing works
Dynamic Neural Interactions Supporting the Cognitive Reappraisal of Emotion
Steward, T., Davey, C. G., Jamieson, A. J., Stephanou, K., Soriano-Mas, C., Felmingham, K. L., & Harrison, B. J. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhaa268 · Cited by 52 · see citing works
Qiu, H., Liang, K., Lu, L., Gao, Y., Li, H., Hu, X., Xing, H., Huang, X., & Gong, Q. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.09.060 · Cited by 41 · see citing works
Lan, X.-J., Yang, X.-H., Mo, Y., Deng, C.-J., Huang, X.-B., Cai, D.-B., & Zheng, W. (2024) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2024.104032 · Cited by 32 · see citing works
Cristancho, P., Arora, J., Nishino, T., Berger, J., Carter, A., Blumberger, D., Miller, P., Snyder, A., Barch, D., & Lenze, E. J. (2023) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.5851 · Cited by 19 · see citing works
The use of tractography-based targeting in deep brain stimulation for psychiatric indications
Davidson, B., Lipsman, N., Meng, Y., Rabin, J. S., Giacobbe, P., & Hamani, C. (2020) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2020.588423 · Cited by 15 · see citing works
Synthesizing Multi-Modal Imaging for Enhanced Brain Mapping in Neurology: a State-of-the-art Review
Kumar, P., Mohammad, T. K., Pramod Kumar, A., Kassym, R., A. S., T., & Akmaral, T. (2024) · 2024 5th International Conference on Communications, Information, Electronic and Energy Systems (CIEES) · doi:10.1109/ciees62939.2024.10811448 · Cited by 4 · see citing works
Oberman, L. M., Penafiel, A. I., Dieterich, R., Phan, C. T., Chou, Y.-Y., Pham, D. L., Adamson, M. M., Hines, C. E., Rezaee, Z., Deng, Z.-D., et al. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1605157
- Authors
- Cash, R. F. H., Weigand, A., Zalesky, A., Siddiqi, S. H., Downar, J., Fitzgerald, P. B., & Fox, M. D.
- Affiliations
- The University of Melbourne (AU)
- Beth Israel Deaconess Medical Center (US)
- University of Toronto (CA)
- Epworth Hospital (AU)
- Brigham and Women's Hospital (US)
- Corresponding author
- Cash, Robin F.H.
- Fox, Michael D.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 90
- Issue
- 10
- Pages
- 689-700
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W3033781588
- Cited by
- 366
- References
- 21
- Citations by year
- 2026: 63 · 2025: 83 · 2024: 71 · 2023: 70 · 2022: 47 · 2021: 27 · 2020: 5
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Funders
- BrainsWay
- Klarman Family Foundation
- Canadian Institutes of Health Research
- Nancy Lurie Marks Family Foundation
- Ontario Brain Institute
- Sidney R. Baer, Jr. Foundation
- National Institute of Mental Health
- Brain and Behavior Research Foundation
- National Institutes of Health
- Arrell Family Foundation
- G. Harold and Leila Y. Mathers Charitable Foundation
- H. Lundbeck A/S
- Fondation Brain Canada
- Australian Research Council (DE200101708)
- Weston Family Foundation
- Toronto General and Western Hospital Foundation
- National Health and Medical Research Council (1136649, 1078567)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- transcranial magnetic stimulation, depression, neuroimaging, functional connectivity, subgenual anterior cingulate cortex, prefrontal cortex, personalized treatment
- MeSH terms
- Brain, Depression, Major Depressive Disorder, Depressive Disorder, Major, Humans, Transcranial Magnetic Stimulation, Neuroimaging
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