Transferability of cathodal tDCS effects from the primary motor to the dorsolateral prefrontal cortex: a multimodal TMS-EEG study

Abstract

Neurophysiological effects of transcranial direct current stimulation (tDCS) have been extensively studied over the primary motor cortex (M1). Much less is however known about its effects over non-motor areas, such as the prefrontal cortex (PFC), which is the neuronal foundation for many high-level cognitive functions and involved in neuropsychiatric disorders. In this study, we, therefore, explored the transferability of cathodal tDCS effects over M1 to the PFC. Eighteen healthy human participants (11 males and 8 females) were involved in eight randomized sessions, in which four cathodal tDCS dosages, low, medium, and high, as well as sham stimulation, were applied over the M1 and PFC. After-effects of tDCS were evaluated via transcranial magnetic stimulation (TMS)-electroencephalography (EEG), and TMS-elicited motor evoked potentials (MEP), for the outcome parameters TMS-evoked potentials (TEP), TMS-evoked oscillations, and MEP amplitude alterations. TEPs were studied both at the regional and global scalp levels. The results indicate a regional dosage-dependent nonlinear neurophysiological effect of M1 tDCS, which is not one-to-one transferable to PFC tDCS. Low and high dosages of M1 tDCS reduced early positive TEP peaks (P30, P60), and MEP amplitudes, while an enhancement was observed for medium dosage M1 tDCS (P30 and MEP amplitudes). In contrast, prefrontal low, medium and high dosage tDCS uniformly reduced the early positive TEP peak amplitudes. Furthermore, for both cortical areas, regional tDCS-induced modulatory effects were not observed for late TEP peaks, nor TMS-evoked oscillations. However, at the global scalp level, widespread effects of tDCS were observed for both, TMS-evoked potentials and oscillations. This study provides the first direct physiological comparison of tDCS effects applied over different brain areas and therefore delivers crucial information for future tDCS applications. SIGNIFICANCE STATEMENTModulatory effects of tDCS over the M1 were largely taken as a template so far for the use of this intervention over non-motor regions. However, the neurophysiological effects of tDCS over non-motor regions, such as the prefrontal cortex (PFC), have been much less explored. In the current study, we, using concurrent transcranial magnetic stimulation- electroencephalography, systematically explored the transferability of cathodal tDCS effects on cortical excitability from M1 to the PFC. The results indicate a dosage-dependent nonlinear neurophysiological effect of motor cortex tDCS, which is not one-to-one transferable to prefrontal tDCS. This study provides the first direct physiological comparison of tDCS effects applied over different brain areas, which will further consolidate the rationale for the extension of tDCS applications at both, basic and clinical levels.