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Distinct Symptom-Specific Treatment Targets for Circuit-Based Neuromodulation.
Shan H Siddiqi1, Stephan F Taylor1, Danielle Cooke1
1Department 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).
Researchers identified distinct brain circuit targets for different depression symptoms using transcranial magnetic stimulation (TMS). This finding could lead to more personalized and effective depression treatments.
Area of Science:
- Neuroscience
- Psychiatry
- Medical Imaging
Background:
- Depression treatment efficacy can vary based on symptom presentation.
- Identifying specific brain circuits targeted by neuromodulation is crucial for personalized therapy.
Purpose of the Study:
- To identify distinct brain circuit targets for different depression symptom clusters.
- To improve the efficacy of therapeutic brain stimulation for depression.
Main Methods:
- Retrospective analysis of two independent patient cohorts receiving left prefrontal transcranial magnetic stimulation (TMS).
- Mapping TMS sites to brain circuits using functional connectivity MRI and a large connectome database.
- Clustering circuits associated with symptom improvement and testing reproducibility across datasets.
Main Results:
- Two distinct circuit targets were identified for different depressive symptom clusters.
- One circuit target was effective for dysphoric symptoms (sadness, anhedonia), while another targeted anxiety and somatic symptoms.
- Circuit maps were reproducible, predicted symptom improvement in independent cohorts, and distinguished active from sham TMS.
Conclusions:
- Distinct depressive symptom clusters respond to different TMS targets, validated across independent datasets.
- These symptom-specific targets offer potential for personalized neuromodulation therapies.
- This data-driven approach may be applicable to other neurological and psychiatric disorders.
