Multimodal response-predictor analysis for three non-invasive brain stimulation protocols

Non-invasive brain stimulation (NIBS) methods such as paired associative stimulation (PAS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) are used to modulate cortical excitability and reduce symptoms in a variety of psychiatric disorders. Recent studies have shown significant inter-individual variability in the physiological response to these techniques when they are applied over the hand representation of primary motor cortex (M1_hand). The goal of the present study was to identify neurophysiological, neuroanatomical, and neurochemical baseline characteristics that may predict response to commonly used NIBS protocols using data from a previously published study (Therrien-Blanchet et al., 2023). To this end, PAS, anodal tDCS, and 20-Hz tACS were administered to healthy participants in a repeated measures design. Pre/Post differences in transcranial magnetic stimulation-induced input-output curves were used to quantify changes in corticospinal excitability. Primary predictors were late I-wave latency, cortical thickness (CT) of M1_hand, and fractional anisotropy of the corticospinal tract (CST_hand) originating from M1_hand. Secondary exploratory analysis was performed with CT in areas outside motor cortex, diffusion MRI (dMRI) metrics of the CST_hand, magnetic resonance spectroscopy measurements of GABA, glutamate, and n-acetyl aspartate of M1_hand, baseline corticospinal excitability, and cranial circumference. Multiple regression analysis showed that none of the primary variables predicted intervention outcome for any of the NIBS protocols. Exploratory analysis revealed no significant correlation between predictor variables and PAS outcome. tDCS and tACS were significantly correlated with some baseline measures. These data suggest that modulation of cortical excitability following several NIBS protocols may not be easily predicted by baseline characteristics, underscoring the need for a better understanding of their mechanism of action. Significant exploratory associations need to be confirmed in larger samples and confirmatory designs.