Subgenual Cingulate Functional Connectivity Predicts Neuromodulation Response in Depression: A Systematic Review
10 affiliations
- 1AI for Mental Health Program, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada
- 2Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- 3CRANIA NeuroModulation Institute, University of Toronto, Toronto, Ontario, Canada
- 4Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada
- 5Division of Neurosurgery, Department of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- 6Centre for Depression and Suicide Studies, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada
- 7Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- 8Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
- 9Division of Neurosurgery, Krembil Brain Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
- 10Joint Department of Medical Imaging, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
Abstract
Resting-state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC) may predict the response to neuromodulation in major depressive disorder (MDD). We conducted a systematic review of studies examining pretreatment sgACC rsFC and subsequent neuromodulation outcomes in adults (ages 18–70 years) with MDD. Ovid MEDLINE, Embase, and APA PsycInfo were searched from inception to May 2, 2025 (PROSPERO: CRD420251038212). The primary outcome was the association between pretreatment sgACC rsFC and changes in depressive symptoms. Study quality was assessed using National Institutes of Health tools and established neuroimaging quality checklists. Reported sgACC coordinates were classified descriptively by analytic role; no inferential coordinate-based meta-analysis was performed. Twenty-two studies (N = 1366 participants) met the inclusion criteria. Greater baseline sgACC–right dorsolateral prefrontal cortex rsFC was associated with reduced symptom improvement in some studies, whereas stronger sgACC–medial orbitofrontal cortex rsFC was associated with greater improvement. Associations were reported most often in repetitive transcranial magnetic stimulation (rTMS) studies, particularly with individualized targeting, but several studies were null. Reported sgACC coordinates were predominantly investigator-defined seed or region-of-interest locations and were not treated as response-associated peaks. The methodological quality of magnetic resonance imaging was adequate (mean = 16.1/20, range 13–18). Pretreatment sgACC–prefrontal rsFC may help predict the neuromodulation response in MDD, particularly in rTMS studies using individualized targeting. However, the findings were heterogeneous, and the available coordinate evidence did not support inferential spatial convergence analysis. Larger prospective studies are needed to establish reproducibility and clinical utility.
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BibTeX
@article{demchenko2026subgenual,
title = {{Subgenual Cingulate Functional Connectivity Predicts Neuromodulation Response in Depression: A Systematic Review}},
author = {Ilya Demchenko and Pranay Soma and Hadi Alhasani and Umaya Krishnathas and Madison Hunter and Ishaan Tailor and Fatemeh Gholamali Nezhad and Tom A. Schweizer and Sidney H. Kennedy and Manish K. Jha and Katharine Dunlop and Alexandre Boutet and Andres M. Lozano and Venkat Bhat},
journal = {Biological Psychiatry Global Open Science},
year = {2026},
month = sep,
doi = {10.1016/j.bpsgos.2026.100823},
url = {https://doi.org/10.1016/j.bpsgos.2026.100823},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Subgenual Cingulate Functional Connectivity Predicts Neuromodulation Response in Depression: A Systematic Review
AU - Ilya Demchenko
AU - Pranay Soma
AU - Hadi Alhasani
AU - Umaya Krishnathas
AU - Madison Hunter
AU - Ishaan Tailor
AU - Fatemeh Gholamali Nezhad
AU - Tom A. Schweizer
AU - Sidney H. Kennedy
AU - Manish K. Jha
AU - Katharine Dunlop
AU - Alexandre Boutet
AU - Andres M. Lozano
AU - Venkat Bhat
PY - 2026
DA - 2026/09/09
JO - Biological Psychiatry Global Open Science
DO - 10.1016/j.bpsgos.2026.100823
UR - https://doi.org/10.1016/j.bpsgos.2026.100823
AB - Resting-state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC) may predict the response to neuromodulation in major depressive disorder (MDD). We conducted a systematic review of studies examining pretreatment sgACC rsFC and subsequent neuromodulation outcomes in adults (ages 18–70 years) with MDD. Ovid MEDLINE, Embase, and APA PsycInfo were searched from inception to May 2, 2025 (PROSPERO: CRD420251038212). The primary outcome was the association between pretreatment sgACC rsFC and changes in depressive symptoms. Study quality was assessed using National Institutes of Health tools and established neuroimaging quality checklists. Reported sgACC coordinates were classified descriptively by analytic role; no inferential coordinate-based meta-analysis was performed. Twenty-two studies (N = 1366 participants) met the inclusion criteria. Greater baseline sgACC–right dorsolateral prefrontal cortex rsFC was associated with reduced symptom improvement in some studies, whereas stronger sgACC–medial orbitofrontal cortex rsFC was associated with greater improvement. Associations were reported most often in repetitive transcranial magnetic stimulation (rTMS) studies, particularly with individualized targeting, but several studies were null. Reported sgACC coordinates were predominantly investigator-defined seed or region-of-interest locations and were not treated as response-associated peaks. The methodological quality of magnetic resonance imaging was adequate (mean = 16.1/20, range 13–18). Pretreatment sgACC–prefrontal rsFC may help predict the neuromodulation response in MDD, particularly in rTMS studies using individualized targeting. However, the findings were heterogeneous, and the available coordinate evidence did not support inferential spatial convergence analysis. Larger prospective studies are needed to establish reproducibility and clinical utility.
SN - 2667-1743
ER -