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

Shan H. Siddiqi^*, Frederic L.W.V.J. Schaper, Andreas Horn, Joey Hsu, Jaya L. Padmanabhan, Amy Brodtmann, Robin F.H. Cash, Maurizio Corbetta, Ki Sueng Choi, Darin D. Dougherty, Natalia Egorova, Paul B. Fitzgerald, Mark S. George, Sophia A. Gozzi, Frederike Irmen, Andrea A. Kuhn, Kevin A. Johnson, Andrew M. Naidech, Alvaro Pascual-Leone, Thanh G. PhanRob P.W. Rouhl, Stephan F. Taylor, Joel L. Voss, Andrew Zalesky, Jordan H. Grafman, Helen S. Mayberg, Michael D. Fox

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

100 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1707-1716
Number of pages	10
Journal	Nature human behaviour
Volume	5
Issue number	12
DOIs	https://doi.org/10.1038/s41562-021-01161-1
State	Published - Dec 2021

ASJC Scopus subject areas

Social Psychology
Experimental and Cognitive Psychology
Behavioral Neuroscience

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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., ... Fox, M. D. (2021). Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease. Nature human behaviour, 5(12), 1707-1716. https://doi.org/10.1038/s41562-021-01161-1

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title = "Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease",

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{\textquoteright}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.",

author = "Siddiqi, {Shan H.} and Schaper, {Frederic L.W.V.J.} and Andreas Horn and Joey Hsu and Padmanabhan, {Jaya L.} and Amy Brodtmann and Cash, {Robin F.H.} and Maurizio Corbetta and Choi, {Ki Sueng} and Dougherty, {Darin D.} and Natalia Egorova and Fitzgerald, {Paul B.} and George, {Mark S.} and Gozzi, {Sophia A.} and Frederike Irmen and Kuhn, {Andrea A.} and Johnson, {Kevin A.} and Naidech, {Andrew M.} and Alvaro Pascual-Leone and Phan, {Thanh G.} and Rouhl, {Rob P.W.} and Taylor, {Stephan F.} and Voss, {Joel L.} and Andrew Zalesky and Grafman, {Jordan H.} and Mayberg, {Helen S.} and Fox, {Michael D.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = dec,

doi = "10.1038/s41562-021-01161-1",

language = "English (US)",

volume = "5",

pages = "1707--1716",

journal = "Nature human behaviour",

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Siddiqi, SH, Schaper, FLWVJ, Horn, A, Hsu, J, Padmanabhan, JL, Brodtmann, A, Cash, RFH, Corbetta, M, Choi, KS, Dougherty, DD, Egorova, N, Fitzgerald, PB, George, MS, Gozzi, SA, Irmen, F, Kuhn, AA, Johnson, KA, Naidech, AM, Pascual-Leone, A, Phan, TG, Rouhl, RPW, Taylor, SF, Voss, JL, Zalesky, A, Grafman, JH, Mayberg, HS & Fox, MD 2021, 'Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease', Nature human behaviour, vol. 5, no. 12, pp. 1707-1716. https://doi.org/10.1038/s41562-021-01161-1

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T1 - Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease

AU - Siddiqi, Shan H.

AU - Schaper, Frederic L.W.V.J.

AU - Horn, Andreas

AU - Hsu, Joey

AU - Padmanabhan, Jaya L.

AU - Brodtmann, Amy

AU - Cash, Robin F.H.

AU - Corbetta, Maurizio

AU - Choi, Ki Sueng

AU - Dougherty, Darin D.

AU - Egorova, Natalia

AU - Fitzgerald, Paul B.

AU - George, Mark S.

AU - Gozzi, Sophia A.

AU - Irmen, Frederike

AU - Kuhn, Andrea A.

AU - Johnson, Kevin A.

AU - Naidech, Andrew M.

AU - Pascual-Leone, Alvaro

AU - Phan, Thanh G.

AU - Rouhl, Rob P.W.

AU - Taylor, Stephan F.

AU - Voss, Joel L.

AU - Zalesky, Andrew

AU - Grafman, Jordan H.

AU - Mayberg, Helen S.

AU - Fox, Michael D.

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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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JO - Nature human behaviour

JF - Nature human behaviour

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ER -

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

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