P 23. Safety aspects of anodal transcranial direct current stimulation: Dose–response effects on EEG and sensory evoked potentials

Introduction Anodal transcranial direct-current stimulation (tDCS) has been shown to modulate cortical excitability and to improve motor learning (Nitsche and Paulus, 2000; Reis et al., 2009). The human studies on tDCS generally use low stimulation intensities-approximately 0.4–0.8A/m 2 -to ensure safe levels. However, the dose–response relationship of tDCS on functional measures of cortical excitability and possible adverse effects of tDCS have not yet been investigated. Objective In this in vivo animal model of tDCS dose-dependent effects of anodal tDCS on cortical excitability were investigated and safety limits for safe application were determined. Methods Adult male Sprague–Dawley rats were equipped with electrodes for tDCS stimulation at the left primary motor cortex and the chest region. Furthermore, EEG electrodes were surgically placed above the somatosensory cortices and the cerebellum (grounding electrode). In separate sessions, the rats were then exposed to anodal tDCS of different intensities (between 2 and 31.8A/m 2 ) for 20min. EEG and sensory evoked potentials were continuously recorded prior to, during and after tDCS, in freely moving (EEG) or anaesthetised (SEP) animals. Results EEG data clearly showed that low stimulation intensities did not affect EEG patterns. Mild EEG alterations-showing more spiky waves and increased amplitudes-were present at the lowest stimulation intensity of 2A/m 2 , while at an intensity of 31.8A/m 2 EEG seizure patterns were observed, also associated with clinical seizures (facial twitch, head nodding, i.e. stage 1–2 on the Racine seizure scale). The calculated threshold (ED1, effective dose 1%) for first occurrence of EEG alterations was 1.35A/m 2 , the ED50 was estimated at 9.2A/m 2 . SEP data are currently under investigation. Conclusions Since only a high stimulation intensity, approximately 40 times higher than that applied to humans, was found to cause seizures, the stimulation intensities applied in human studies are unlikely to be harmful. This suggests that higher stimulation intensities could be applied in human studies, thereby possibly further improving plasticity, i.e. learning, without putting the brain at risk.