Steady-state visual evoked potentials as diagnostic tool for patients with severe disorders of consciousness - A proof of concept study

The diagnosis of disorders of consciousness (DoC) remains challenging with high rates of misdiagnoses, despite the development of new tools. We developed a new diagnostic paradigm using steady-state visual evoked potentials (SSVEPs) elicited by red-light visual flicker as a proxy for consciousness diagnosis. SSVEPs from 30 Hz and 40 Hz visual flicker stimulation, and the resulting effect on the dominant theta band electroencephalographic (EEG) frequency, were assessed in 13 DoC patients and 8 healthy participants. Analyses of the dominant EEG theta oscillation in 18 patients revealed a significant difference between coma/unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) patients during 40 Hz visual flicker stimulation (Z = -1.86, p = 0.031, d = -1.264), but not during 30 Hz stimulation (Z = 0.477, p = 0.317, d = 0.28). Healthy awake participants showed larger SSVEPs at 40 Hz than 30 Hz, which is reversed in most DoC patients. The ratio of 30/40 Hz SSVEP amplitude was significantly different for healthy participants vs. coma/UWS patients (Z = 2.674, p = 0.004, d = 2.669) and MCS patients (Z = 2.192, p = 0.014, d = 1.242), respectively, but not for coma/UWS vs. MCS patients (Z = 0.905, p = 0.183, d = 0.542). Regarding level of significance, results were equal when using a single CRS-R assessment instead of the best out of five CRS-R assessments for diagnosis. We could show that 40 Hz visual flicker stimulation modulates the ongoing theta oscillations in DoC patients, and that the frequency specific properties of SSVEPs in DoC patients are significantly different from healthy participants, serving as a potential marker of consciousness.