Abstract
Background At the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test-retest reliability at the individual level. Individualized resting-state network mapping (RSNM) can reliably map inter-individual variability in brain network organization.
Objective To identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile.
Methods We used RSNM to identify network-based rTMS targets in 10 healthy controls and 13 individuals with traumatic brain injury-associated depression (TBI-D). These “RSNM targets” were compared with consensus structural targets and targets based on individualized anti-correlation with a group-mean-derived sgACC region (“anti-group-mean sgACC targets”). The TBI-D cohort was randomized to receive active (n=9) or sham (n=4) rTMS to RSNM targets.
Results The group-mean sgACC connectivity profile was reliably estimated by individualized correlation with default mode network (DMN) and anti-correlation with dorsal attention network (DAN). Individualized RSNM targets were then identified based on DAN anti-correlation and DMN correlation. Counterintuitively, anti-correlation with the group-mean sgACC connectivity profile was stronger and more reliable for RSNM-derived targets than for “anti-group-mean sgACC targets”. Improvement in depression after RSNM-targeted rTMS was predicted by target anti-correlation with the portions of sgACC. Active treatment led to increased connectivity within and between several relevant regions.
Conclusions RSNM may enable reliable individualized rTMS targeting, although further research is needed to determine whether this personalized approach can improve clinical outcomes.
Competing Interest Statement
SHS serves as a clinical consultant for Kaizen Brain Center. SHS has received research support from Neuronetics Inc. The present work was not supported by any of these entities. DLB has served as a consultant for Pfizer Inc, Intellectual Ventures, Signum Nutralogix, Kypha Inc, Sage Therapeutics, iPerian Inc, Navigant, Avid Radiopharmaceuticals (Eli Lilly & Co), the St Louis County Public Defender, the United States Attorney Office, the St Louis County Medical Examiner, GLG, Stemedica, and Luna Innovations. DLB holds equity in the company Inner Cosmos. DLB receives royalties from sales of Concussion Care Manual (Oxford University Press). No conflicts of interest with the presented work. DLB is an employee of the Department of Defense; the views expressed here do not reflect those of the Uniformed Services University of the Health Sciences, the US Department of Defense, or the US Government. ECL holds equity in the companies Neurolutions and Inner Cosmos. CDH, ECL, and SHS hold intellectual property related to the use of RSNM to target TMS. The remaining authors report no conflicts of interest.
Footnotes
↵* Co-senior authors