Non-Invasive Rhythmic Musical-Electric Trigeminal Nerve Stimulation Improves Consciousness in Patients with Disorders of Consciousness

Abstract Disorders of consciousness (DOC) are often accompanied by aberrant oscillatory neural activity in the thalamus and cerebral cortex. Patient-friendly non-invasive treatments targeting this functional anomaly are still missing. We propose and validate a novel approach that aims to restore DOC patients’ thalamocortical oscillations by combining rhythmic trigeminal-nerve stimulation (TNS) with comodulated musical stimulation. In a cluster-randomized, placebo-controlled, double-blinded, pretest-posttest clinical study, we show that application of this multisensory approach for 40 min on five consecutive days reliably leads to long-lasting improvements in DOC patients’ consciousness (assessed with Coma Recovery Scale-Revised) and oscillatory brain activity at the musical-electric TNS frequency (assessed with electroencephalography and a novel rhythmic auditory-speech paradigm). We found diagnostic improvement in 47% of patients in minimally conscious state and a positive relationship between patients’ behavioral and neural improvements. Based on this evidence we argue that non-invasive musical-electric TNS may serve as an effective patient-friendly DOC treatment and suggest frequency-specific oscillatory neural enhancement as its mode of action.