Electrical field based dosing improves non-invasive brain stimulation

Abstract Non-invasive brain stimulation (NIBS) methods, such as transcranial magnetic stimulation (TMS), are invaluable tools to modulate cortical activity and behavior, but high within- and between-subject variability limit their efficacy and reliability. Here, we explore the potential of electrical field (e-field) based NIBS dosing to reduce its variability and discuss current challenges as well as future pathways. In contrast to previous dosing approaches, e-field dosing optimally matches the stimulation strength across cortical areas, both within and across individuals. Challenges include methodological uncertainties of the e-field calculation, target definitions, and comparability of different stimulation thresholds across cortical areas and NIBS protocols. Despite these challenges, e-field dosing promises to substantially improve NIBS applications in neuroscientific research and personalized medicine. Outstanding Questions Box Outstanding Questions Does the cortical threshold for effective stimulation differ between primary regions and higher-level association areas? How large is the impact of cytoarchitectonic differences between regions on a stimulation threshold? Do cortical stimulation thresholds differ across individuals? Are thresholds stable within an individual across the lifespan? What are the physiological factors influencing these thresholds? Can a cortical stimulation threshold measured with single-pulse TMS be transferred to repetitive TMS protocols for the study of cognition? How does the cortical stimulation threshold interact with the current brain state? Graphical abstract