Circuit-targeted modulation of anxiety symptoms in individuals with major depression: A randomized head-to-head TMS trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Transcranial magnetic stimulation (TMS) is effective for major depressive disorder (MDD) despite imprecise scalp-based targeting. Retrospective analyses suggest that targeting one brain circuit improves “dysphoric” symptoms, while targeting a different brain circuit improves “anxiosomatic” symptoms. Here, we tested this hypothesis prospectively. Individuals with moderate-to-severe MDD and moderate-to-severe anxiety (n=40) were randomized to receive TMS with dysphoric circuit targeting (dorsolateral prefrontal cortex) or anxiosomatic circuit targeting (dorsomedial prefrontal cortex). As hypothesized, dysphoric circuit targeting (n=16) improved BDI more than BAI (ratio 1.08, IQR 0.69-2.02), while anxiosomatic circuit targeting (n=20) improved BAI more than BDI (ratio 0.70, IQR 0.01-1.01) (Wilcoxon rank-sum test p=0.0195). This result was driven by larger improvements in anxiety with -anxiosomatic circuit targeting (p=0.0301). Thus, TMS targeting different brain circuits differentially modulates comorbid anxiety and depression symptoms. Symptom- and circuit-specific trial designs may improve power and better control for placebo and non-specific effects.
Source: Molecular Psychiatry
Authors: Joseph J. Taylor, Jing Li, Christopher Lin, Emma Jones, Summer Frandsen, Claudia R. Becker, William Drew, Dania Haj-Darwish, Sandrine Jabbour, Jessica Leach, Stephan Palm, Lauren Sanderson, Emanuella Santos, Lera Sterina, Nicole Chiulli, John Miller, Sheena Barantono, Irene Gonsalvez, Stanley Lyndon, Samuel B. Snider, Michael D. Fox, Shan H. Siddiqi
Institutions: Harvard University, Mass General Brigham, Texas A&M University
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Treating hyperexcitability in Alzheimer's disease with levetiracetam to improve brain function and cognition, Personalized circuit-based neuromodulation targets for depression, G1630641404, Targeted modulation of symptom-specific brain circuits with transcranial magnetic stimulation, Reliability of Repetitive TMS-induced Modulation of Cortical Excitability, Ketamine for the treatment for alcohol use disorder in the emergency department: A pilot double-blind, placebo-controlled randomized clinical trial, G5032782408, Transdiagnostic memory, mood and motor circuits in Alzheimer's and neurodegenerative disease, Deriving TMS Targets for Mood Valence and Mood Stabilization in Bipolar Disorder, Using human brain connectivity to identify the causal neuroanatomical substrate of depression symptoms
OpenAlex ID: W7143346128