tDCS and local scalp cooling do not change corticomotor and intracortical excitability in healthy humans

•tDCS did not alter the corticomotor and intracortical excitability of the motor cortex in 105 healthy subjects.•Ipsilateral scalp cooling did not affect the motor excitability measured with SICI, ICF and single-pulse TMS.•Fixed-effects and mixed-effects model analysis resulted in distinct tDCS outcomes. Scalp cooling might increase the long-term potentiation (LTP)-like effect of transcranial direct current stimulation (tDCS) by reducing the threshold for after-effects according to metaplasticity and increasing electrical current density reaching the cortical neurons. We aimed to investigate whether priming scalp cooling potentiates the tDCS after-effect on motor cortex excitability. This study had a randomized, parallel-arms, sham-controlled, double-blinded design with an adequately powered sample of 105 healthy subjects. Corticomotor and intracortical excitability were assessed with motor evoked potentials (MEP) from transcranial magnetic stimulation (TMS) in short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) paradigms. Subjects were randomly allocated into six intervention groups, including anodal and cathodal tDCS (1-mA/20-min), scalp cooling, and sham. MEPs were recorded before, immediately, and 15 min after the interventions. We did not observe changes in MEP amplitude from single-pulse TMS, SICI, and ICF with any intervention protocol. Anodal and cathodal tDCS did not have an LTP-like neuromodulatory effect on corticospinal and did not provide detectable GABAergic and glutamatergic neurotransmission changes, which were not influenced by priming scalp cooling. We provide strong evidence that tDCS (1-mA/20-min) does not alter corticomotor and intracortical excitability with or without priming scalp cooling.