Journal article
Fronto-insular circuit mechanisms of accelerated intermittent theta burst stimulation
Cell, Vol.189(10), pp.3071-3090.e27
05/07/2026
DOI: 10.1016/j.cell.2026.04.030
PMID: 42102818
Abstract
Transcranial magnetic stimulation (TMS) is a widely used neuromodulation treatment for depression, but its mechanisms are poorly understood. Indirect clinical evidence suggests that TMS enhances plasticity within the prefrontal cortical target site and engages downstream networks. However, establishing causal mechanisms to help optimize the large stimulation parameter space has been challenging. Using an optogenetic model of accelerated intermittent theta burst stimulation (prelimbic [PL]-aiTBS) that drives rapid antidepressant-like effects, we examined cell type-specific effects on synapse-related gene expression, increased spine density, and increased excitatory currents in prefrontal intratelencephalic projection neurons. Whole-brain c-Fos immunolabeling, fiber photometry, chemogenetic, and projection-specific optogenetic manipulations revealed that PL-aiTBS activates a fronto-insular network that is necessary and sufficient for its antidepressant-like behavioral effects. Finally, we validate a key role for fronto-insular connectivity and TMS-evoked responses in the human insula using intracortical stereo-electroencephalogram (EEG) and resting-state fMRI. These results establish a fronto-insular circuit as a critical mediator of the antidepressant effects of aiTBS.
Details
- Title: Subtitle
- Fronto-insular circuit mechanisms of accelerated intermittent theta burst stimulation
- Creators
- Shane B Johnson - Cornell UniversityDevin Rocks - Cornell UniversityLaura Chalençon - Cornell UniversityKenneth Johnson - Cornell UniversityUmair Hassan - Stanford UniversityAnisul Arefin - Cornell UniversityGülcan Akgül - Cornell UniversityAlexander Donatelle - Cornell UniversityHenry Asher - Cornell UniversityImmanuel Elbau - Cornell UniversityDavid Estrin - Cornell UniversityRebecca Zhang - Cornell UniversityAlexandra Lenz - Cornell UniversityRachel Mikofsky - Cornell UniversityCory Knox - Cornell UniversityRachael Han - Cornell UniversityPooja Suganthan - Cornell UniversityTahrima Chowdhury - Cornell UniversityChristine Kuang - Cornell UniversityDaniel Shaver - Cornell UniversityParsa Nilchian - Cornell UniversityPuja Parekh - Cornell UniversityJacob Roshgadol - Cornell UniversityNatalia DeMarco Garcia - Weill Cornell MedicineMatthew Wright - Cornell UniversityLindsay Victoria - Cornell UniversityBenjamin Zebley - Cornell UniversityJoshua Levitz - Cornell UniversityCorey J Keller - Stanford UniversityAaron D Boes - University of IowaConor Liston - Cornell University
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.189(10), pp.3071-3090.e27
- DOI
- 10.1016/j.cell.2026.04.030
- PMID
- 42102818
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Publisher
- Elsevier
- Language
- English
- Date published
- 05/07/2026
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9985163467302771
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