Precision Network Modeling of Transcranial Magnetic Stimulation Across Individuals Suggests Therapeutic Targets and Potential for Improvement

Higher-order cognitive and affective functions are supported by large-scale networks in the brain. Dysfunction in different networks is proposed to associate with distinct symptoms in neuropsychiatric disorders. However, the specific networks targeted by current clinical transcranial magnetic stimulation (TMS) approaches are unclear. While standard-of-care TMS relies on scalp-based landmarks, recent FDA-approved TMS protocols use individualized functional connectivity with the subgenual anterior cingulate cortex (sgACC) to optimize TMS targeting. Leveraging previous work on precision network estimation and modeling of the TMS electric field (E-field), we asked whether various clinical TMS approaches target different functional networks between individuals. Results revealed that modeled homotopic scalp positions (left F3 and right F4) target different networks within and across individuals, and right F4 generally favors a right-lateralized control network. TMS coil positions over the dorsolateral prefrontal cortex (dlPFC) zone anticorrelated with the sgACC most frequently target a network coupled to the ventral striatum (reward circuitry) but largely miss that network in some individuals. We further illustrate how modeling can be used to retrospectively assess the estimated targets achieved in prior TMS sessions and also used to prospectively provide coil positions that can target distinct closely localized dlPFC network regions with spatial selectivity and maximal E-field intensity. In a final study, precision targeting was found to be feasible in participants with Major Depressive Disorder using data derived from a single low-burden MRI session suggesting the methods are applicable to translational efforts where limiting patient burden and ensuring robustness are critical.