Safety and effects on motor cortex excitability of five cathodal transcranial direct current stimulation sessions in 25hours.

Objective: To assess the safety and effects on motor cortex excitability of five cathodal-tDCS sessions (charge density 342.9C/m) delivered over the dominant motor cortex with a return electrode over the ipsilateral shoulder at increasing time intervals in 25hours.

Methods: Safety was operatively defined as absence of serious adverse events related to tDCS including brain tissue alterations documentable by magnetic resonance imaging and spectroscopy. Effects on motor cortex excitability were evaluated by motor evoked potential (MEP) amplitude.

Results: Thirty-two healthy subjects were enrolled. No serious adverse events occurred. Magnetic resonance imaging and spectroscopy did not show alterations. Inter-individual MEP variability was assessed by the standard error of mean at baseline and subjects were classified on the basis of the ratio between normalized MEPs after the first stimulation compared to baseline. Fifty-six percent of subjects responded with reduction of MEP amplitude, 25% were non-responders and 19% were inverse responders. In responders, MEP suppression was 32% one hour after the end of first cathodal-tDCS, 21% three hours after the second, no longer present with increasing stimulation intervals and 38% two and half hours after the fifth stimulation. Intra-individual inter-sessional reliability in response was high (88-92%).

Conclusions: Five cathodal-tDCS sessions in 25hours are safe. Inter-individual variability in MEP suppression is considerable but response to one cathodal-tDCS highly predicts the response to other sessions. Duration of MEP suppression is limited to three hours. These findings should be considered in trials utilizing repeated cathodal-tDCS.