Prolonged disorders of consciousness (pDoC) are pathologies in which there is a loss of consciousness for more than 28 days. The number of patients with pDoC is increasing as the level of critical care treatment and monitoring improves. However, clinical trials for patients with pDoC are limited by small sample sizes, lack of placebo groups, and use of heterogeneous outcome measures. As a result, few therapies have strong evidence to support their use. In recent years, ketamine has been used with remarkable success in the treatment of neuropsychiatric disorders by inducing neuroplasticity, increasing neurophysiologic complexity, and expanding functional brain connectivity states. Considering increased brain plasticity as well as brain complexity, it may be beneficial for consciousness recovery. In this study, the investigators aimed to explore the effects of esketamine on brain networks and level of consciousness in patients with pDoC, and to discuss its possible use as a wakefulness-promoting treatment for patients with pDoC.

Patients with prolonged disorders of consciousness:

Inclusion Criteria:

• Age 18 - 65 years old, native Chinese speaker, dextromanual;
• Chronic disorder of consciousness;
• Spinal cord electrical stimulator implantation under general anesthesia;
• Signed informed consent.

Exclusion Criteria:

• Continuous sedation was administered within 72 hours prior to the study;
• Open head injury, parenchymal resection and other damage of brain structural integrity;
• The intracranial compliance decreased due to hydrocephalus and swelling;
• Known hearing impairment;
• Airway stenosis and various causes of severe ventilation or ventilation dysfunction;
• Known or suspected severe cardiac, pulmonary, hepatic, and renal dysfunction;
• History of drug allergy to esketamine;
• Associated with other mental or neurological diseases;
• Other reasons are not suitable to participate in this study.

Healthy brain volunteers:

Inclusion Criteria:

• Age 18 - 65 years old;
• Patients undergoing surgical treatment under elective general anaesthesia;
• American Society of Anesthesiologists (ASA) I-II;
• Native Chinese speaker;
• Dextromanual;
• Signed informed consent.

Exclusion Criteria:

• Previous history of craniocerebral disease, imaging suggests organic brain lesions;
• People with uncontrolled hypertension, hyperthyroidism, elevated intracranial pressure, epileptic seizures;
• History of drug allergy to esketamine;
• Hearing abnormality;
• History of drug and alcohol abuse;
• People with mental and behavioral disorders.