Improving responsiveness to non-invasive brain stimulation in minimally conscious state patients: a closed-loop approach

Transcranial direct current stimulation (tDCS) applied on the left dorsolateral prefrontal cortex has already been shown to efficiently promote the recovery of conscious awareness in patients with disorders of consciousness following severe brain injury, especially those in minimally conscious state (MCS)1. However, one potential barrier to clinically respond to tDCS is accounting for the timing of the stimulation with regard to the fluctuations of vigilance that characterize this population2. Indeed, the vigilance of MCS patients has periodic average cycles of 70 minutes (range 57-80 minutes)3, potentially preventing them to be in an optimal neural state to benefit from tDCS when applied at random moments. To tackle this issue, we propose a new protocol to optimize the application of tDCS by selectively stimulating at high vigilance and low vigilance states, as measured by real-time spectral entropy (as a marker of vigilance3) and based on pre-identified individual thresholds, in a closed-loop fashion. We will conduct a clinical trial on 36 patients in MCS who will undergo a 4-hour EEG recording beforehand to set individual vigilance thresholds. The patients will then be randomized in three groups based on the moment of tDCS application: high vigilance, low vigilance and sham. These EEG-tDCS sessions will last for 6 hours with a maximum of two tDCS sessions of 20 min at 2 mA. Behavioral effects will be assessed using the Coma Recovery Scale-Revised4 at baseline, after 3 and 6 hours. The device used will be provided by Starlab and enable real-time analysis of EEG dynamics and spectral entropy as well as control of the tDCS stimulator (a customized version of Neuroelectrics’ Startsim 8). This unique and novel approach will provide new insights for the identification of tDCS responders and provide treatment options for the challenging population of patients with disorders of consciousness.