Full access
Articles
Published Online: 12 March 2020

Distinct Symptom-Specific Treatment Targets for Circuit-Based Neuromodulation

Shan H. Siddiqi, M.D. [email protected], Stephan F. Taylor, M.D., Danielle Cooke, B.S., Alvaro Pascual-Leone, M.D., Ph.D., Mark S. George, M.D., and Michael D. Fox, M.D., Ph.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 177, Number 5
https://doi.org/10.1176/appi.ajp.2019.19090915
Track CitationsAdd to favorites
PDF/EPUBFormats

Abstract

Objective:

Treatment of different depression symptoms may require different brain stimulation targets with different underlying brain circuits. The authors sought to identify such targets, which could improve the efficacy of therapeutic brain stimulation and facilitate personalized therapy.

Methods:

The authors retrospectively analyzed two independent cohorts of patients who received left prefrontal transcranial magnetic stimulation (TMS) for treatment of depression (discovery sample, N=30; active replication sample, N=81; sham replication sample, N=87). Each patient’s TMS site was mapped to underlying brain circuits using functional connectivity MRI from a large connectome database (N=1,000). Circuits associated with improvement in each depression symptom were identified and then clustered based on similarity. The authors tested for reproducibility across data sets and whether symptom-specific targets derived from one data set could predict symptom improvement in the other independent cohort.

Results:

The authors identified two distinct circuit targets effective for two discrete clusters of depressive symptoms. Dysphoric symptoms, such as sadness and anhedonia, responded best to stimulation of one circuit, while anxiety and somatic symptoms responded best to stimulation of a different circuit. These circuit maps were reproducible, predicted symptom improvement in independent patient cohorts, and were specific to active compared with sham stimulation. The maps predicted symptom improvement in an exploratory analysis of stimulation sites from 14 clinical TMS trials.

Conclusions:

Distinct clusters of depressive symptoms responded better to different TMS targets across independent retrospective data sets. These symptom-specific targets can be prospectively tested in a randomized clinical trial. This data-driven approach for identifying symptom-specific targets may prove useful for other disorders and facilitate personalized neuromodulation therapy.

Formats available

You can view the full content in the following formats:

View PDF/EPUBView Full Text

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 177 • Number 5 • May 01, 2020
Pages: 435 - 446
PubMed: 32160765

History

Received: 5 September 2019
Revision received: 12 November 2019
Accepted: 23 December 2019
Published online: 12 March 2020
Published in print: May 01, 2020

Keywords

  1. Cognitive Neuroscience
  2. Neuromodulation
  3. Plasticity
  4. Brain Imaging
  5. TMS

Authors

Details

Shan H. Siddiqi, M.D. [email protected]
Department of Psychiatry (Siddiqi) and Department of Neurology (Pascual-Leone, Fox), Harvard Medical School, Boston; Berenson-Allen Center for Noninvasive Brain Stimulation (Siddiqi, Cooke, Fox), and Cognitive Neurology Unit, Department of Neurology (Siddiqi), Beth Israel Deaconess Medical Center, Boston; Division of Neurotherapeutics, McLean Hospital, Belmont, Mass. (Siddiqi); Department of Psychiatry, Washington University School of Medicine, St. Louis (Siddiqi); Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md. (Siddiqi); Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor (Taylor); Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, Boston (Pascual-Leone); Guttmann Institute, Autonomous University of Barcelona, Barcelona, Spain (Pascual-Leone); Brain Stimulation Lab, Department of Psychiatry, Medical University of South Carolina, Charleston (George); Ralph H. Johnson VA Medical Center, Charleston, S.C. (George); Department of Neurology, Massachusetts General Hospital, Boston (Fox); Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Mass. (Fox).
View all articles by this author
Stephan F. Taylor, M.D.
Department of Psychiatry (Siddiqi) and Department of Neurology (Pascual-Leone, Fox), Harvard Medical School, Boston; Berenson-Allen Center for Noninvasive Brain Stimulation (Siddiqi, Cooke, Fox), and Cognitive Neurology Unit, Department of Neurology (Siddiqi), Beth Israel Deaconess Medical Center, Boston; Division of Neurotherapeutics, McLean Hospital, Belmont, Mass. (Siddiqi); Department of Psychiatry, Washington University School of Medicine, St. Louis (Siddiqi); Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md. (Siddiqi); Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor (Taylor); Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, Boston (Pascual-Leone); Guttmann Institute, Autonomous University of Barcelona, Barcelona, Spain (Pascual-Leone); Brain Stimulation Lab, Department of Psychiatry, Medical University of South Carolina, Charleston (George); Ralph H. Johnson VA Medical Center, Charleston, S.C. (George); Department of Neurology, Massachusetts General Hospital, Boston (Fox); Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Mass. (Fox).
View all articles by this author
Danielle Cooke, B.S.
Department of Psychiatry (Siddiqi) and Department of Neurology (Pascual-Leone, Fox), Harvard Medical School, Boston; Berenson-Allen Center for Noninvasive Brain Stimulation (Siddiqi, Cooke, Fox), and Cognitive Neurology Unit, Department of Neurology (Siddiqi), Beth Israel Deaconess Medical Center, Boston; Division of Neurotherapeutics, McLean Hospital, Belmont, Mass. (Siddiqi); Department of Psychiatry, Washington University School of Medicine, St. Louis (Siddiqi); Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md. (Siddiqi); Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor (Taylor); Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, Boston (Pascual-Leone); Guttmann Institute, Autonomous University of Barcelona, Barcelona, Spain (Pascual-Leone); Brain Stimulation Lab, Department of Psychiatry, Medical University of South Carolina, Charleston (George); Ralph H. Johnson VA Medical Center, Charleston, S.C. (George); Department of Neurology, Massachusetts General Hospital, Boston (Fox); Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Mass. (Fox).
View all articles by this author
Alvaro Pascual-Leone, M.D., Ph.D.
Department of Psychiatry (Siddiqi) and Department of Neurology (Pascual-Leone, Fox), Harvard Medical School, Boston; Berenson-Allen Center for Noninvasive Brain Stimulation (Siddiqi, Cooke, Fox), and Cognitive Neurology Unit, Department of Neurology (Siddiqi), Beth Israel Deaconess Medical Center, Boston; Division of Neurotherapeutics, McLean Hospital, Belmont, Mass. (Siddiqi); Department of Psychiatry, Washington University School of Medicine, St. Louis (Siddiqi); Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md. (Siddiqi); Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor (Taylor); Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, Boston (Pascual-Leone); Guttmann Institute, Autonomous University of Barcelona, Barcelona, Spain (Pascual-Leone); Brain Stimulation Lab, Department of Psychiatry, Medical University of South Carolina, Charleston (George); Ralph H. Johnson VA Medical Center, Charleston, S.C. (George); Department of Neurology, Massachusetts General Hospital, Boston (Fox); Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Mass. (Fox).
View all articles by this author
Mark S. George, M.D.
Department of Psychiatry (Siddiqi) and Department of Neurology (Pascual-Leone, Fox), Harvard Medical School, Boston; Berenson-Allen Center for Noninvasive Brain Stimulation (Siddiqi, Cooke, Fox), and Cognitive Neurology Unit, Department of Neurology (Siddiqi), Beth Israel Deaconess Medical Center, Boston; Division of Neurotherapeutics, McLean Hospital, Belmont, Mass. (Siddiqi); Department of Psychiatry, Washington University School of Medicine, St. Louis (Siddiqi); Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md. (Siddiqi); Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor (Taylor); Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, Boston (Pascual-Leone); Guttmann Institute, Autonomous University of Barcelona, Barcelona, Spain (Pascual-Leone); Brain Stimulation Lab, Department of Psychiatry, Medical University of South Carolina, Charleston (George); Ralph H. Johnson VA Medical Center, Charleston, S.C. (George); Department of Neurology, Massachusetts General Hospital, Boston (Fox); Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Mass. (Fox).
View all articles by this author
Michael D. Fox, M.D., Ph.D.
Department of Psychiatry (Siddiqi) and Department of Neurology (Pascual-Leone, Fox), Harvard Medical School, Boston; Berenson-Allen Center for Noninvasive Brain Stimulation (Siddiqi, Cooke, Fox), and Cognitive Neurology Unit, Department of Neurology (Siddiqi), Beth Israel Deaconess Medical Center, Boston; Division of Neurotherapeutics, McLean Hospital, Belmont, Mass. (Siddiqi); Department of Psychiatry, Washington University School of Medicine, St. Louis (Siddiqi); Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md. (Siddiqi); Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor (Taylor); Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, Boston (Pascual-Leone); Guttmann Institute, Autonomous University of Barcelona, Barcelona, Spain (Pascual-Leone); Brain Stimulation Lab, Department of Psychiatry, Medical University of South Carolina, Charleston (George); Ralph H. Johnson VA Medical Center, Charleston, S.C. (George); Department of Neurology, Massachusetts General Hospital, Boston (Fox); Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Mass. (Fox).
View all articles by this author

Notes

Send correspondence to Dr. Siddiqi ([email protected]).

Competing Interests

Dr. Siddiqi is a consultant for the Kaizen Brain Center and for SigNeuro and owns intellectual property on the use of brain connectivity to guide brain stimulation. Dr. Taylor has received grant support from Boehringer-Ingelheim, Neuronetics, and Otsuka/Vanguard Research Group. Dr. Pascual-Leone serves on the medical and scientific advisory boards of Magstim, Nexstim, and Neuroelectrics, and he is listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and MRI, and on various aspects of brain stimulation methods. Dr. Fox owns intellectual property on the use of brain connectivity to guide brain stimulation. Ms. Cooke and Dr. George report no financial relationships with commercial interests.

Funding Information

National Institute of Mental Healthhttp://dx.doi.org/10.13039/100000025: R01 2017P000514
Sidney R. Baer Foundation:

Metrics & Citations

Metrics

Citations

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format
Citation style
Style
Copy to clipboard
Tips for downloading citations

View Options

View options

PDF/EPUB

View PDF/EPUB

Full Text

View Full Text

Login options

Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.

Personal login Institutional Login Open Athens login
Item saved, go to cart
Purchase Options

Purchase this article to access the full text.

PPV Articles - American Journal of Psychiatry

PPV Articles - American Journal of Psychiatry

Not a subscriber?

Subscribe Now / Learn More

PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

Media

Figures

Other

Tables

Share

Share

Share article link

Share

×

As described within the American Psychiatric Association (APA)'s Privacy Policy and Terms of Use, this website utilizes cookies, including for the purpose of offering an optimal online experience and services tailored to your preferences. Please read the entire Privacy Policy and Terms of Use. By closing this message, browsing this website, continuing the navigation, or otherwise continuing to use the APA's websites, you confirm that you understand and accept the terms of the Privacy Policy and Terms of Use, including the utilization of cookies.