Auditory localization should be considered as a sign of minimally conscious state based on multimodal findings.

Auditory localization (i.e. turning the head and/or the eyes towards an auditory stimulus) is often part of the clinical evaluation of patients recovering from coma. The objective of this study is to determine whether auditory localization could be considered as a new sign of minimally conscious state, using a multimodal approach. The presence of auditory localization and the clinical outcome at 2 years of follow-up were evaluated in 186 patients with severe brain injury, including 64 with unresponsive wakefulness syndrome, 28 in minimally conscious state minus, 71 in minimally conscious state plus and 23 who emerged from the minimally conscious state. Brain metabolism, functional connectivity and graph theory measures were investigated by means of F-fluorodeoxyglucose positron emission tomography, functional MRI and high-density electroencephalography in two subgroups of unresponsive patients, with and without auditory localization. These two subgroups were also compared to a subgroup of patients in minimally conscious state minus. Auditory localization was observed in 13% of unresponsive patients, 46% of patients in minimally conscious state minus, 62% of patients in minimally conscious state plus and 78% of patients who emerged from the minimally conscious state. The probability to observe an auditory localization increased along with the level of consciousness, and the presence of auditory localization could predict the level of consciousness. Patients with auditory localization had higher survival rates (at 2-year follow-up) than those without localization. Differences in brain function were found between unresponsive patients with and without auditory localization. Higher connectivity in unresponsive patients with auditory localization was measured between the fronto-parietal network and secondary visual areas, and in the alpha band electroencephalography network. Moreover, patients in minimally conscious state minus significantly differed from unresponsive patients without auditory localization in terms of brain metabolism and alpha network centrality, whereas no difference was found with unresponsive patients who presented auditory localization. Our multimodal findings suggest differences in brain function between unresponsive patients with and without auditory localization, which support our hypothesis that auditory localization should be considered as a new sign of minimally conscious state. Unresponsive patients showing auditory localization should therefore no longer be considered unresponsive but minimally conscious. This would have crucial consequences on these patients' lives as it would directly impact the therapeutic orientation or end-of-life decisions usually taken based on the diagnosis.