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Cited by 296Transcranial Magnetic Stimulation StudiesNeurological disorders and treatmentsFunctional Brain Connectivity Studies

Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease

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Siddiqi, Shan H., Schaper, Frederic L. W. V. J., Horn, Andreas, Hsu, Joey, Padmanabhan, Jaya L., Brodtmann, Amy, Cash, Robin F. H., Corbetta, Maurizio +19 more·2021·Nature Human Behaviour
DOI 10.1038/s41562-021-01161-1PMC PMC8688172
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Abstract

Damage to specific brain circuits can cause specific neuropsychiatric symptoms. Therapeutic stimulation to these same circuits may modulate these symptoms. To determine whether these circuits converge, we studied depression severity after brain lesions (n = 461, five datasets), transcranial magnetic stimulation (n = 151, four datasets) and deep brain stimulation (n = 101, five datasets). Lesions and stimulation sites most associated with depression severity were connected to a similar brain circuit across all 14 datasets (P < 0.001). Circuits derived from lesions, deep brain stimulation and transcranial magnetic stimulation were similar (P < 0.0005), as were circuits derived from patients with major depression versus other diagnoses (P < 0.001). Connectivity to this circuit predicted out-of-sample antidepressant efficacy of transcranial magnetic stimulation and deep brain stimulation sites (P < 0.0001). In an independent analysis, 29 lesions and 95 stimulation sites converged on a distinct circuit for motor symptoms of Parkinson's disease (P < 0.05). We conclude that lesions, transcranial magnetic stimulation and DBS converge on common brain circuitry that may represent improved neurostimulation targets for depression and other disorders.

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  • Two recent papers found that clinical efficacy of rTMS for depression was greater when the scalp-targeted stimulation site was incidentally closer to the optimal rsfMRI-derived site.

    “Two recent papers found that clinical efficacy of rTMS for depression was greater when the scalp-targeted stimulation site was incidentally closer to the optimal rsfMRI-derived site (38, 39).”

    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 [39]

    The Results (no page number available) report that connectivity of stimulation sites to a depression circuit predicted clinical outcomes in TMS datasets. The Methods also describe incidentally variable stimulation-site locations. But the paper does not establish the claimed relationship between efficacy and the physical closeness of scalp-targeted sites to an optimal rsfMRI-derived site. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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References 54 · Cited by 296

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Authors
Siddiqi, S. H., Schaper, F. L. W. V. J., Horn, A., Hsu, J., Padmanabhan, J. L., Brodtmann, A., Cash, R. F. H., Corbetta, M., Choi, K. S., Dougherty, D. D., Egorova, N., Fitzgerald, P. B., George, M. S., Gozzi, S. A., Irmen, F., Kuhn, A. A., Johnson, K. A., Naidech, A. M., Pascual-Leone, A., Phan, T. G., Rouhl, R. P. W., Taylor, S. F., Voss, J. L., Zalesky, A., Grafman, J. H., Mayberg, H. S., & Fox, M. D.
Affiliations
  • Brigham and Women's Hospital (US)
  • University of Pittsburgh (US)
  • The University of Melbourne (AU)
  • University of Padua (IT)
  • Icahn School of Medicine at Mount Sinai (US)
  • Harvard University (US)
  • Epworth Hospital (AU)
  • Medical University of South Carolina (US)
  • Monash Health (AU)
  • Florida State University (US)
  • Northwestern University (US)
  • Maastricht University Medical Centre (NL)
  • University of Michigan (US)
Corresponding author
Siddiqi, Shan H.
ORCID
Venue
Nature Human Behaviour
Publisher
Springer Science and Business Media LLC
Published
2021-07-08
Volume
5
Issue
12
Pages
1707-1716
ISSN
2397-3374 (ISSN-L)
DOI
10.1038/s41562-021-01161-1
PMC
PMC8688172
OpenAlex
W3181719595
Cited by
296
References
54
Citations by year
2026: 66 · 2025: 70 · 2024: 61 · 2023: 58 · 2022: 36 · 2021: 5
FWCI
16.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Human Behaviour (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
  • Research Publications (Maastricht University) (submittedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (K23MH121657, R01MH113929, R21MH099196, R01MH115949)
  • Brain and Behavior Research Foundation
  • Sidney R. Baer, Jr. Foundation
Topics
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Keywords
depression, brain circuits, transcranial magnetic stimulation, deep brain stimulation, brain lesions, antidepressant response prediction, human connectome
MeSH terms
Mental Disorders, Brain, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Deep Brain Stimulation, Transcranial Magnetic Stimulation

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