Precision non-invasive transcranial electromagnetic stimulation: a thematic review of optimizing spatial, temporal, and dose dimensions

Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) have been extensively used in experimental and clinical research in psychiatry, neurology, and rehabilitation. Several advanced approaches for delivering transcranial electromagnetic stimulation have been proposed to maximize the temporal and spatial precision of conventional stimulation protocols or to optimize stimulation parameters for enhanced efficacy during neuromodulation. Here, we thematically reviewed several advanced neuromodulatory approaches: (1) using prior or real-time brain states to guide the delivery of stimulation through priming protocols or brain-state-dependent stimulation interfaces (temporal precision); (2) facilitating the stimulation target engagement, either from a single brain region to an interregional brain connection using cortico-cortical paired associative stimulation or dual-site in/anti-phase transcranial alternating current stimulation, or from a superficial brain target to a deep brain region using temporal interference stimulation (spatial precision); and (3) strengthening or accelerating the plasticity modulation outcomes using high-dose protocols (dose optimization). While results from these efforts are promising, challenges exist in terms of the optimal timing of brain states and stimulation parameters, treatment durability, as well as the complexity in aggregating different advanced approaches. Future research should focus on exploring the underlying mechanisms, optimizing parameters, and assessing the efficacy in well-designed proof-of-concept experiments and clinical trials.