Deep brain stimulation (DBS) in the centromedian-parafascicular complex (CM-pf) has been reported as a potential therapeutic option for disorders of consciousness (DoC). However, the lack of understanding of its electrophysiological characteristics limits the improvement of therapeutic effect. To investigate the CM-pf electrophysiological characteristics underlying disorders of consciousness (DoC) and its recovery. We collected the CM-pf electrophysiological signals from 23 DoC patients who underwent central thalamus DBS (CT-DBS) surgery. Five typical electrophysiological features were extracted, including neuronal firing properties, multiunit activity (MUA) properties, signal stability, spike-MUA synchronization strength (syncMUA), and the background noise level. Their correlations with the consciousness level, the outcome, and the primary clinical factors of DoC were analyzed. 11 out of 23 patients (0/2 chronic coma, 5/13 unresponsive wakefulness syndrome/vegetative state (UWS/VS), 6/8 minimally conscious state minus (MCS-)) exhibited an improvement in the level of consciousness after CT-DBS. In CM-pf, significantly stronger gamma band syncMUA strength and alpha band normalized MUA power were found in MCS- patients. In addition, higher firing rates, stronger high-gamma band MUA power and alpha band normalized power, and more stable theta oscillation were correlated with better outcomes. Besides, we also identified electrophysiological properties that are correlated with clinical factors, including etiologies, age, and duration of DoC. We provide comprehensive analyses of the electrophysiological characteristics of CM-pf in DoC patients. Our results support the 'mesocircuit' hypothesis, one proposed mechanism of DoC recovery, and reveal CM-pf electrophysiological features that are crucial for understanding the pathogenesis of DoC, predicting its recovery, and explaining the effect of clinical factors on DoC.

Objectives: This study investigated the prognostic effect of electroencephalography (EEG) instant effects of single spinal cord stimulation (SCS) on clinical outcome in disorders of consciousness (DOC) and the time‐dependent brain response during the recovery of consciousness prompted by SCS. Methods: Twenty three patients with DOC underwent short‐term SCS (stSCS) implantation operation. Then, all patients received the postoperative EEG test including EEG record before (T1) and after (T2) single SCS session. Subsequently, 2 weeks stSCS treatment was performed and revised coma recovery scale (CRS‐R) and EEG data were collected. Finally, they were classified into effective and ineffective groups at 3‐month follow‐up (T6). Results: The parietal‐occipital (PO) connectivity and clustering coefficients (CC) in the beta band of the effective group at the 1 week after the treatment (T5) were found to be higher than preoperative assessment (T0). Correlation analysis showed that the change in beta CC at T1/T2 was correlated with the change in CRS‐R at T0/T6. In addition, the change in PO connectivity and CC in the beta at T0/T5 were also correlated with the change in CRS‐R at T0/T5. Conclusion: SCS may facilitate the recovery of consciousness by enhancing local information interaction in posterior brain regions. And the recovery can be predicted by beta CC in the EEG test.

Disorders of consciousness (DoC) encompass a range of states characterized by prolonged altered awareness due to heterogeneous brain damage and are associated with highly diverse prognoses. However, the neural mechanisms underlying such diverse recoveries in DoC remain unclear. To address this issue, we analyzed direct recordings from the central thalamus (CeTh), a key hub in arousal regulation, in a series of 23 DoC patients receiving deep brain stimulation treatment (CeTh-DBS). We identified a core set of electrophysiological features of the CeTh, particularly those of the theta rhythm. These features could account for individual recovery outcomes across highly varied etiologies (trauma, brainstem hemorrhage, and anoxia), and across clinical baselines and patient ages. CeTh activities also identified two subgroups of patients with recovery potential, including those with poor initial clinical manifestations but who eventually exhibited functional recovery. A biophysical model further revealed the neurodynamics of the theta rhythm in the CeTh across different brain states correlating with varying consciousness levels. These findings uncover a shared CeTh mechanism underlying diverse recoveries in DoC.

Background: Hyperbaric oxygen (HBO) therapy is an efficacious intervention for patients with prolonged disorders of consciousness (pDOC). Electroencephalographic (EEG) microstate analysis can provide an assessment of the global state of the brain. Currently, the misdiagnosis rate of consciousness‐level assessments in patients with pDOC is high. Therefore, we aimed to assess the consciousness levels and outcomes of patients by analyzing changes in EEG signals during HBO therapy.Methods: EEG data were collected from 32 patients with traumatic brain injury before and after 20 min of HBO therapy. EEG data were obtained during HBO therapy sessions. Modified k‐means clustering was used to segment EEG signals into microstates. A paired sample t test was used to compare the microstate characteristics before and during HBO therapy.Results: The duration, occurrence, and coverage of microstate D significantly increased in the minimally conscious state (MCS) group after therapy. Significant increases in the same parameters were observed in microstate A among patients in the unresponsive wakefulness state group. Furthermore, patients with greater improvements in Coma Recovery Scale‐Revised scores (i.e., improvements of more than three points) showed significant increases in the duration, occurrence, and coverage of microstate D. Both the MCS group and the improvement group presented significant increases in the duration, occurrence, and coverage of microstate D during therapy.Conclusions: Microstate D may be associated with the recovery of consciousness levels in patients. This study verified the safety and feasibility of real‐time EEG during HBO therapy for patients with pDOC. The changes in EEG microstate characteristics during HBO therapy can serve as a significant complement to electroencephalographic assessment indices for patients with pDOC and may be useful for predicting the recovery of consciousness levels.

Introduction: Medical management of disorders of consciousness (DoC) is a growing issue imposing a major burden on families and societies. Recovery rates vary widely among patients with DoC, and recovery predictions strongly influence decisions on medical care. However, the specific mechanisms underlying different etiologies, consciousness levels, and prognoses are still unclear.Methods: We analyzed the comprehensive cerebrospinal fluid (CSF) metabolome through liquid chromatography‐mass spectrometry. Metabolomic analyses were used to identify the metabolic differences between patients with different etiologies, diagnoses, and prognoses.Results: We found that the CSF levels of multiple acylcarnitines were lower in patients with traumatic DoC, suggesting mitochondrial function preservation in the CNS, which might contribute to the better consciousness outcomes of these patients. Metabolites related to glutamate and GABA metabolism were altered and showed a good ability to distinguish the patients in the minimally conscious state and the vegetative state. Moreover, we identified 8 phospholipids as potential biomarkers to predict the recovery of consciousness.Conclusions: Our findings shed light on the differences in physiological activities underlying DoC with different etiologies and identified some potential biomarkers used for DoC diagnosis and prognosis.

SignificanceDisorders of consciousness (DOCs) pose significant challenges for therapeutic intervention. Spinal cord stimulation (SCS) has emerged as a promising neuromodulation technique for treating DOC patients. However, the selection of optimal SCS stimulation parameters, particularly intensity, lacks objective standards, and considerable variations in the configuration of stimulation intensity are evident among different research groups in previous studies.AimWe aim to systematically evaluate the effects of different stimulation intensities of SCS using functional near-infrared spectroscopy (fNIRS) to further optimize the efficacy of SCS.ApproachEleven DOC patients with implanted SCS devices were recruited. Four different stimulation intensities based on individual motor thresholds were used: low (50%), threshold (100%), medium (125%), and high (150%). Hemodynamic responses were recorded using fNIRS, and the mean, peak, and net area under the curve values of hemodynamics, as well as the activated channel count, were analyzed, mainly focusing on two regions of interest: the prefrontal cortex (PFC) and the temporo-parietal junction (TPJ).ResultsAn inverted U-shaped dose–response curve was observed. The medium-intensity group triggered the most significant hemodynamic responses. The high-intensity group evoked less pronounced responses and showed negative responses post-stimulation. The threshold-intensity group exhibited positive responses but less pronounced than the medium- and high-intensity groups. Conversely, the low-intensity SCS evoked a decreased response. The medium-intensity SCS also resulted in the highest number of activated channels and maintained the highest total hemoglobin concentration level during the inter-stimulus interval. Differences in brain region responses to SCS intensity were observed, with the PFC tolerating higher intensities and the TPJ having a narrower therapeutic window.ConclusionsOur findings illustrate that the medium-intensity SCS provides the optimal hemodynamic effect. The observed inverted U-shaped dose–response curve underscores the importance of precise parameter adjustments in SCS for DOC patients to maximize efficacy and to avoid overstimulation or insufficient activation.