State-dependent effectiveness of cathodal transcranial direct current stimulation on cortical excitability

: The extensive use of transcranial direct current stimulation (tDCS) in experimental and clinical settings does not correspond to an in-depth understanding of its underlying neurophysiological mechanisms. In previous studies, we employed an integrated system of Transcranial Magnetic Stimulation and Electroencephalography (TMS-EEG) to track the effect of tDCS on cortical excitability. At rest, anodal tDCS (a-tDCS) over the right Posterior Parietal Cortex (rPPC) elicits a widespread increase in cortical excitability. In contrast, cathodal tDCS (c-tDCS) fails to modulate cortical excitability, being indistinguishable from sham stimulation. Here we investigated whether an endogenous task-induced activation during stimulation might change this pattern, improving c-tDCS effectiveness in modulating cortical excitability. In Experiment 1, we tested whether performance in a Visuospatial Working Memory Task (VWMT) and a modified Posner Cueing Task (mPCT), involving rPPC, could be modulated by c-tDCS. Thirty-eight participants were involved in a two-session experiment receiving either c-tDCS or sham during tasks execution. In Experiment 2, we recruited sixteen novel participants who performed the same paradigm but underwent TMS-EEG recordings pre- and 10 min post- sham stimulation and c-tDCS. Behavioral results showed that c-tDCS significantly modulated mPCT performance compared to sham. At a neurophysiological level, c-tDCS significantly reduced cortical excitability in a frontoparietal network likely involved in task execution. Taken together, our results provide evidence of the state dependence of c-tDCS in modulating cortical excitability effectively. The conceptual and applicative implications are discussed.