Biological and anatomical factors influencing interindividual variability to noninvasive brain stimulation of the primary motor cortex: a systematic review and meta-analysis

Noninvasive brain stimulation (NIBS) modifies corticospinal excitability (CSE) historically in a predictable manner dependent on stimulation parameters. Researchers, however, discuss high degrees of variability between individuals, either responding as expected or not responding as expected. The explanation for this interindividual variability remains unknown with suggested interplay between stimulation parameters and variations in biological, anatomical, and physiological factors. This systematic review and meta-analysis aimed to investigate the effect of variation in inherent factors within an individual (biological and anatomical factors) on CSE in response to NIBS of the primary motor cortex. Twenty-two studies were included investigating genetic variation (n=7), age variation (n=4), gender variation (n=7), and anatomical variation (n=5). The results indicate that variation in brain-derived neurotrophic factor genotypes may have an effect on CSE after NIBS. Variation between younger and older adults also affects CSE after NIBS. Variation between age-matched males and females does not affect CSE after NIBS, but variation across the menstrual cycle does. Variation between skull thickness and brain tissue morphology influences the electric field magnitude that ultimately reaches the primary motor cortex. These findings indicate that biological and anatomical variations may in part account for interindividual variability in CSE in response to NIBS of the primary motor cortex, categorizing individuals as responding as expected (responders) or not responding as expected (nonresponders).