Personalized connectivity‐guided DLPFC‐TMS for depression: Advancing computational feasibility, precision and reproducibility

• Published in: Human brain mapping Vol. 42; no. 13; pp. 4155 - 4172
• Main Authors: Cash, Robin F.H., Cocchi, Luca, Lv, Jinglei, Wu, Yumeng, Fitzgerald, Paul B., Zalesky, Andrew
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.09.2021
• Subjects: Adult; Care and treatment; Computer applications; Computer architecture; connectivity; Connectome - methods; Connectome - standards; Cortex (cingulate); Customization; depression; Depression, Mental; Depressive Disorder, Treatment-Resistant - diagnostic imaging; Depressive Disorder, Treatment-Resistant - therapy; Dorsolateral Prefrontal Cortex - diagnostic imaging; Feasibility; Feasibility Studies; Female; Functional magnetic resonance imaging; Genetic control; Health aspects; Humans; Magnetic fields; Magnetic Resonance Imaging; Male; Mental depression; neuroimaging; personalization; precision psychiatry; Prefrontal cortex; Reproducibility; Reproducibility of Results; Spatial variations; Transcranial magnetic stimulation; Transcranial Magnetic Stimulation - methods; Transcranial Magnetic Stimulation - standards; Young Adult; personalization; precision psychiatry; depression; transcranial magnetic stimulation; connectivity; neuroimaging
• ISSN: 1065-9471; 1097-0193
• DOI: 10.1002/hbm.25330

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for refractory depression, however, therapeutic outcomes vary. Mounting evidence suggests that clinical response relates to functional connectivity with the subgenual cingulate cortex (SGC) at the precise DLPFC stimulation site. Critically, SGC‐related network architecture shows considerable interindividual variation across the spatial extent of the DLPFC, indicating that connectivity‐based target personalization could potentially be necessary to improve treatment outcomes. However, to date accurate personalization has not appeared feasible, with recent work indicating that the intraindividual reproducibility of optimal targets is limited to 3.5 cm. Here we developed reliable and accurate methodologies to compute individualized connectivity‐guided stimulation targets. In resting‐state functional MRI scans acquired across 1,000 healthy adults, we demonstrate that, using this approach, personalized targets can be reliably and robustly pinpointed, with a median accuracy of ~2 mm between scans repeated across separate days. These targets remained highly stable, even after 1 year, with a median intraindividual distance between coordinates of only 2.7 mm. Interindividual spatial variation in personalized targets exceeded intraindividual variation by a factor of up to 6.85, suggesting that personalized targets did not trivially converge to a group‐average site. Moreover, personalized targets were heritable, suggesting that connectivity‐guided rTMS personalization is stable over time and under genetic control. This computational framework provides capacity for personalized connectivity‐guided TMS targets to be robustly computed with high precision and has the flexibly to advance research in other basic research and clinical applications. Transcranial magnetic stimulation (TMS) provides an important therapeutic option for treatment resistant depression. Prior research demonstrates that clinical outcomes to TMS could likely be enhanced by personalized treatment that is targeted to specific brain connections. Here we designed innovative methodology which enables these connections to be identified and targeted using TMS at a person‐specific level with unprecedented precision.