Personalizing Transcranial Electrical Stimulation: Electric Field Insights And Beta Dynamics In Aging And Motor Control

Abstract

Transcranial electrical stimulation (tES) is a promising noninvasive brain stimulation technique for studying the brain and treating clinical disorders. The technique consists of applying electrodes on the scalp, through which a lowintense current then flows, thereby generating an electric field in the brain. However, the effects of tES show significant variability across individuals. This doctoral dissertation aims to optimize tES by addressing two critical sources of variability: anatomy and neurophysiology. In parallel, this work explores the oscillatory dynamics underlying interlimb motor control, an essential part of daily life that is compromised by aging and various clinical disorders. The first section of this dissertation focuses on anatomical variability in tES. Five experiments are presented which employ current flow modeling, a method that simulates the electric fields induced by tES based on head anatomy. A first experiment demonstrates that combining T1w and T2w magnetic resonance imaging data enhances the accuracy of electric field simulations, compared to using solely T1w magnetic resonance imaging data. Second, significant regional differences in the thickness of soft tissues, compact and spongy bone, and cerebrospinal fluid are identified across age groups, sexes, and head regions. These findings highlight the importance of individualized tES paradigms to ensure consistent dosing across populations. Third, to further address anatomical variability, this work evaluates electric field quantification methods, revealing that different methods do not always concur. This has implications for electric field based tES dosing, and underscores the need for standardized practices in current flow modeling. Fourth, a novel dosing strategy is proposed, which prospectively reversecalculates stimulation intensities to account for anatomical variability. This approach significantly reduces interindividual differences in electric fields and is feasible for widespread clinical application. Fifth and finally, an extended head model tailored for extracephalic tES montages (i.e., montages where at least one electrode is placed on a region outside the head, such as the shoulders) is introduced. This head model improves current flow modeling accuracy compared to non-extended models, and enables better tES optimizations for targeting regions such as the cerebellum. In a second section, through a series of three experiments, this dissertation explores neurophysiological variability in the context of interlimb motor control across two motor tasks. The specific focus is on event-related oscillatory electroencephalography data. Across the three experiments, movement-related beta desynchronization (MRβD) emerges as a critical neurophysiological process underpinning interlimb coordination in the context of aging. Furthermore, this work positions MRβD in the right sensorimotor cortex as a critical process during interlimb motor planning, providing causal evidence through the use of beta-band transcranial alternating current, a tES modality involving the use of an alternating current, individualized to the peak beta frequency during the motor planning phase. Collectively, the work presented in this doctoral dissertation advances the development of optimized tES protocols while deepening our understanding of the neurophysiological mechanisms driving motor control. By bridging anatomical and neurophysiological variability, this collection of experiments helps laying the groundwork for precision neuromodulation techniques tailored to diverse populations and clinical needs.