Patients with disorders of consciousness exhibit severe declines in arousal and awareness, alongside anomalous functional brain connections and aberrant neuronal activities. Yet, the diagnostic error of patients' consciousness states can reach up to forty percent, resulting in a worse prognosis. Neuronal mechanisms underlying the disorders are indispensable for identifying objective and intrinsic markers of consciousness. As the principal relay station between the brainstem arousal nuclei and the cerebral cortex, the thalamus has been empirically inferred to maintain consciousness and wakefulness within the brain connectome. Here, we investigated thalamic spiking, brain connections, consciousness states, and outcomes following deep brain stimulation in 29 patients. Our study reveals that thalamic activities can signal their consciousness states. Patients diagnosed with vegetative state/unresponsive wakefulness syndrome exhibited less active neurons with longer and more variable burst discharges compared to those in a minimally conscious state. Furthermore, as a direct deep brain stimulation site, neuronal profiles in the centromedian/parafascicular complex of the thalamus indicated whether electrostimulation here improved outcomes. Stronger tonic firing was associated with enhanced thalamocortical connections and better recovery outcomes in patients. These findings suggest that thalamic spiking signatures, including single-neuron burst discharge and tonic firing, selectively indicate the representation and alteration of consciousness. These findings provide direct neuronal and clinical evidence for understanding of thalamic contributions to disorders of consciousness.

The authors have declared no competing interest.

This study was supported by Beijing Natural Science Foundation grant Z210009 (to Yan Y.); National Science and Technology Innovation 2030 Major Projects, STI2030-Major Projects grant 2022ZD0204800 (to Yan Y.); National Key R&D Program of China grant 2022YFB4700101 (to H.W.); National Natural Science Foundation of China grant 32070987 and 31722025 (to Yan Y.); Chinese Academy of Sciences Key Program of Frontier Sciences grant QYZDB-SSW-SMC019 (to Yan Y.). S.L. is funded as Chairholder from the Canada Excellence Research Chair in Neuroplasticity; as Research Director at the Belgian National Fund for Scientific Research; the European Foundation of Biomedical Research, the Foundation for Research and Rehabilitation of Neurodegenerative Diseases and the National Natural Science Foundation of China (Grant No.: 81920108023).

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The study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (protocol No: KY2017-361-01) and the Ethics Committee of PLA Army General Hospital (protocol No: 2011-0415).

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