In this study, we aimed to investigate the intrinsic brain activity alterations in patients with disorders of consciousness (DOC) using multidimensional resting-state functional magnetic resonance imaging (rs-fMRI) metrics at ultra-high field (7 T) MRI. We enrolled 10 patients with DOC, including those with vegetative state/unresponsive wakefulness syndrome and minimally conscious state, and 11 healthy controls (HCs). We applied various rs-fMRI metrics ranging from neuronal activity to synchronization and coordination of whole-brain activity, including amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC). Patients with DOC exhibited distinct brain activity patterns compared to HCs. The bilateral inferior temporal gyri showed enhanced activity across various metrics (right: ALFF, ReHo, DC; left: ALFF, fALFF, ReHo), while the right precuneus showed decreased activity in patients with DOC (ALFF, DC, PerAF), compared to HCs. Although an initial inverse relationship was observed between the left putamen and CRS-R total scores in DOC patients, this association did not survive multiple comparisons correction (Bonferroni-adjusted threshold: p < 0.0019). Our findings provide new insights into the neural mechanisms underlying DOC, highlighting the importance of the right precuneus and the bilateral inferior temporal gyri in consciousness level. These results can inform the development of diagnostic and therapeutic strategies for DOC.

Fuzzy symbolic convergent cross mapping: A causal coupling measure for EEG signals in disorders of consciousness patients.

Aberrant prefrontal network patterns in post-stroke prolonged disorders of consciousness: Evidence from resting-state fNIRS.

Development and validation of a machine learning model to predict 30-day mortality in ischemic stroke patients with consciousness impairment: Insights from MIMIC-IV database and multicenter ICU data in China.

Background Prolonged disorders of consciousness (pDOC), including vegetative/unresponsive wakefulness state (VS/UWS) and minimally conscious state (MCS), pose significant diagnostic and prognostic challenges. Multimodal neuroimaging has emerged as a promising tool to uncover neural biomarkers that reflect residual brain function and guide management. This pilot feasibility study aimed to preliminarily characterize metabolic, functional, and structural brain alterations in pDOC patients using simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging, and to examine their tentative associations with clinical behavioral responsiveness. Methods Eight pDOC patients and eight matched healthy controls underwent hybrid 18F-FDG PET/MR scanning. Resting-state fMRI, diffusion tensor imaging (DTI), and FDG-PET were processed to assess amplitude of low-frequency fluctuations (ALFF), fractional anisotropy (FA), and glucose metabolism, respectively. Group differences were analyzed, and correlations with Coma Recovery Scale-Revised (CRS-R) scores were evaluated. Multimodal integration was performed across imaging modalities. Results Compared to controls, pDOC patients exhibited reduced ALFF and FDG uptake in the posterior cingulate cortex (PCC) and anterior cingulate cortex (ACC), with exploratory increased ALFF in the visual cortex inversely correlated with visual responsiveness. Functional connectivity analyses revealed attenuated intra- and inter-network connectivity in the DMN, SN, and DAN. FDG-PET identified metabolic hypofunction in the insula, frontal cortex, and cerebellum, while DTI demonstrated widespread white matter FA reductions. Multimodal correspondence revealed partially overlapping abnormalities in the PCC and occipital regions, highlighting candidate hubs that may be relevant to consciousness level and warrant further validation. Conclusion Simultaneous FDG-PET/MR was feasible in this pilot pDOC cohort and provided a convergent, multimodal assessment of metabolic-functional-structural alterations. The PCC and occipital visual cortices emerge as key regions linked to consciousness levels. Given the small sample size and cross-sectional design, these findings are preliminary, and warrant validation in larger longitudinal cohorts before clinical translation.

Association between the endothelial activation and stress index and the risk of severe consciousness disorder and in-hospital mortality in ICU patients with non-traumatic intracerebral hemorrhage: A retrospective analysis based on the MIMIC database.

Emerging evidence suggests that low-frequency neural oscillations are dynamically regulated by consciousness levels, with the recovery of low cortical activity potentially serving as a neurophysiological substrate for conscious emergence. Targeted enhancement of these low-frequency rhythms in patients with disorders of consciousness (DoC) may constitute a promising neuromodulation strategy to facilitate consciousness recovery in severe brain injury. This study systematically examined the neurophysiological effects of intermittent theta-burst stimulation (iTBS), specifically its potential to enhance low-frequency cortical activity and promote consciousness recovery in patients with DoC. Through multimodal neural assessments, we aimed to elucidate the mechanistic relationship between iTBS-induced neural oscillation modulation and behavioral manifestations of consciousness improvement. This prospective cohort study enrolled 30 patients with DoC, of whom 18 completed the full intervention protocol. Two-way repeated-measures analysis of variance revealed significant group × time interaction effects on the Coma Recovery Scale-Revised (CRS-R) scores, F(1, 16) = 6.543, p = 0.021. Post hoc simple effects analysis demonstrated significant temporal improvement in the active transcranial magnetic stimulation (TMS) group, F(1, 16) = 36.463, p < 0.001, with mean CRS-R scores increased from 9.300 ± 1.320 at baseline to 11.700 ± 1.409 post-intervention (p < 0.001). Conversely, sham stimulation revealed statistically nonsignificant changes (9.845 ± 1.476 versus 10.750 ± 1.575, p = 0.067). Neurophysiological assessments revealed emerging neurophysiological changes in the iTBS group, including enhanced resting-state low-frequency oscillations (delta: 21.642% increase, p = 0.449; theta: 6.800% increase, p = 0.789) and augmented auditory-evoked responses (phrase-level 22.917% increase, p = 0.280; syllable-level: 22.963% increase, p = 0.504), suggesting potential neural plasticity mechanisms that require further validation. Collectively, this study established iTBS targeting the left dorsolateral prefrontal cortex as a clinically effective and well-tolerated neuromodulation approach for consciousness rehabilitation in patients with DoC, with therapeutic effects mediated by iTBS-induced enhancement of thalamocortical low-frequency oscillations. https://www. gov. Unique identifier: NCT03385278. Registered on October 24, 2017.

Predictors of successful decannulation in patients with chronic disorders of consciousness and tracheostomy.

Disorders of consciousness (DoC), including vegetative state (VS), unresponsive wakefulness syndrome (UWS), and minimally conscious state (MCS), are characterized by impaired consciousness and have limited therapeutic options. We aimed to perform a systematic review and meta-analysis of individual participant data (IPD) on the efficacy of vagal nerve stimulation (VNS) for DoC. A systematic literature search identified studies on the use of VNS in patients with DoC. IPD were extracted from included studies and pooled for analysis. The primary outcome was improvement in consciousness, assessed clinically using the Coma Recovery Scale-Revised (CRS-R). A total of 10 studies including 112 patients were identified. VNS was associated with significant improvements in consciousness, with a mean increase of 2.78 (95% CI 1.62 to 3.94) in CRS-R. 40.2% of patients demonstrated an improvement in CRS-R score above the minimal clinically important difference (MCID) of 3 or more. Patients in MCS improved more than those in coma or VS/UWS. This IPD meta-analysis provides early evidence for the efficacy of VNS in improving consciousness in patients with DoC. Our results imply the need for high-quality randomized controlled trials for both invasive and non-invasive VNS to better inform its role in DoC neuro-recovery.

Objective: To investigate the clinical characteristics, risk factors and prognosis of children with refractory anti-N-methyl-D-aspartate (NMDA) receptor antibody encephalitis. Methods: A retrospective cohort study was conducted in 149 children diagnosed with NMDA receptor antibody encephalitis in the Department of Pediatric Neurology, XiangYa Hospital of Central South University from February 2014 to March 2024. Clinical data, including demographics, MRI features, electroencephalography (EEG), immunotherapy and prognosis were collected. Children were divided into refractory and non-refractory groups. Intergroup comparisons were performed using the χ² test or Fisher exact test, independent-samples t test or Mann-Whitney U test as appropriate.. Multivariate Logistic regression model was used to identify risk factors for refractoriness. Results: Among 139 children ultimately included in the analysis, there were 53 males and 86 females, with an onset age of (8.5±4.2) years. There were 21 children in the refractory group and 118 children in the non-refractory group. The refractory group exhibited higher proportions of motor disorders, psychiatric symptoms, sleep disorders, language disorders, consciousness disorders, autonomic dysfunction, tumor comorbidity, pediatric intensive care unit admission, modified Rankin scale scores of 4-5 at onset, absent occipital dominant rhythm on EEG, epileptiform discharges on EEG, diffuse β activity EEG, requirement for plasma exchange, and B-lymphocyte percentage than the non-refractory group (all P<0.05). During a follow-up of 31 (17, 47) months, the modified Rankin scale scores of refractory group and non-refractory group at the last follow-up was 1 (0, 3) and 1 (1, 1), the difference had statistically significant (Z=2.13, P=0.033). Two children in the refractory group died, no deaths in the non-refractory group, the difference had statistically significant (χ²=11.40, P<0.01). Independent risk factors for refractoriness included autonomic dysfunction (OR=5.97, 95%CI 1.66-21.52), EEG epileptiform discharges (OR=4.91, 95%CI 1.53-15.78) and absent occipital dominant rhythm on EEG (OR=4.07, 95%CI 1.13-14.64). Conclusions: Children with refractory NMDA receptor antibody encephalitis present with severe clinical manifestations. Autonomic dysfunction, EEG epileptiform discharges and absent occipital dominant rhythm on EEG are independent risk factors for refractoriness. Early identification and intensified immunotherapy are critical for improving outcomes.

The frequency and nature of neurological exams (neuro-checks) in patients with severe acquired brain injury resulting in coma or disorders of consciousness (DoC) remain variable, with limited evidence guiding practice and poor understanding of their role in predicting and preventing neurological deterioration, functional recovery and adverse effects such as delirium. This scoping review aims to explore the frequency of bedside neurological exams within the first 7 days of injury impact on clinical outcomes in adult patients with severe acquired brain injury including mortality, neurological deterioration, long-term function, and delirium. METHODS: A comprehensive literature search was conducted using the PubMed, CINAHL, Medline and EMBASE databases from 2003 to 2023. Search terms captured a range of acute brain injuries and neuro-assessment tools. Eligible studies included adult patients with severe traumatic or non-traumatic brain injury or stroke that addressed frequency of bedside neurological exams within the first 7 days of admission. RESULTS: Of 1327 studies screened, 20 met inclusion criteria, representing over 16,000 patients across 14 countries. Assessment tools varied, but use of the Glasgow Coma Scale was prevalent. Frequency of neuro-checks ranged from hourly to daily. Multiple outcome measures were utilized. Some studies found that continuing hourly neuro-checks beyond the first 48 hours did not provide additional clinical benefit. Others associated excessive assessment with increased stress or delirium. CONCLUSION: There is very low evidence supporting an association between the frequency of neuro-checks and functional outcomes, mortality, length of stay, or delirium. Although early assessments may aid prognostication, excessive exams may not improve outcomes and may contribute to harm. The heterogeneity, lack of evidence, and limited standardization of neuro-check frequency highlight the need for clinical research to guide future practice.

Prognostication of critically ill children appearing acutely comatose remains challenging. Event-related potentials (ERPs) using electroencephalography (EEG) offer a noninvasive method to detect covert consciousness. These include the mismatched negativity (MMN) and P300b responses. We investigated ERPs using the auditory local-global oddball paradigm to assess inattentive or attentive cortical processing in critically ill, clinically unresponsive children. We prospectively enrolled pediatric intensive care unit (PICU) patients undergoing continuous EEG with Glasgow coma scale scores < 8. Each patient underwent testing with the local-global oddball paradigm. In each trial, five brief tones were delivered; the fifth tone was either identical (local-standard) or different (local-deviant). In total, 80% of trials shared the same local structure (global-standard), and 20% deviated (global-deviant). MMN-like responses were assessed by contrasting local-deviant vs. local-standard trials (100-250ms post-stimulus) at frontocentral electrodes; P300b-like responses were assessed by contrasting global-deviant vs. global-standard trials (250-700ms post-stimulus) at centroparietal electrodes. Cluster-based permutation testing identified significant ERPs. Functional outcomes were assessed at 10-12months using the Glasgow outcome scale extended-Pediatrics (GOSE-Peds), and ERP-outcome associations were analyzed using the Mann-Whitney U test. Among 29 children, 6 (20.7%) showed reproducible ERPs-2 (6.9%) with MMN-like responses and 4 (13.8%) with P300b-like responses. Presence of either ERP response was associated with lower GOSE-Peds scores (p = 0.029), indicating more favorable outcomes. ERPs can detect both inattentive and attentive cortical processing in critically ill clinically unresponsive children. The presence of reproducible responses resembling MMN or P300b may be associated with better long-term functional recovery.

To evaluate clinical significance of the FOUR scale for patients with cerebral insufficiency. A prospective single-center study included 200 patients with acute cerebral insufficiency. Analysis employed ROC curves, logistic regression and correlation methods. The FOUR scale demonstrated high prognostic accuracy in comatose patients (AUC=0.944 vs. 0.742 for GCS, p< 0.001). Strong correlations were found between FOUR scores and GOS grades (rs=0.7546, p<0.0001), as well as prediction of mortality (OR=3.4, 95% CI 2.1-5.6). For patients with chronic consciousness disorders, the FOUR scale showed benefits (AUC=0.936 vs. 0.745 for GCS). The FOUR scale represents an optimal monitoring tool for patients with cerebral insufficiency.

The accurate prediction of prognosis in patients with disorders of consciousness (DOC) is a significant challenge in clinical practice. Some studies based on traditional electroencephalography (EEG) features have shown potential for DOC prognosis. However, the underlying mechanisms behind the recovery of patients with DOC still lack in-depth research. In this study, we used mathematical tools to construct digital twin brain models (DTBM) for DOC patients with different outcomes. Then, we trained a support vector machine classifier using model parameters and modal controllability features to distinguish between DOC patients with different outcomes, and assessed the importance of these features. Finally, we used a support vector machine regressor to predict the Coma Recovery Scale-Revised (CRS-R) score at 6-month follow-up. The results showed that the prognosis model based on local model parameters and modal controllability features achieved better performance (AUC = 90.22%, F-score = 86.00%, SEN = 84.31%, SPE = 91.43%) than the prognosis models based on some traditional EEG features. Additionally, a positive prognosis is associated with lower levels of inhibitory gain, higher levels of excitatory gain and modal controllability, particularly in brain regions within the frontoparietal network. In 74% and 70% of UWS and MCS patients, the MAE between the predicted CRS-R score and the actual CRS-R score was less than 5. Overall, our study contributes to enriching the neuromarkers associated with DOC prognosis and further elucidates the neural mechanisms of consciousness recovery.

This study explored the value of nonlinear features extracted from EEG signals to facilitate the assessment of patients with disorders of consciousness (DOC) with limited communication capacity. We utilized a dataset comprising 104 participants, 56 with vegetative state (VS)/unresponsive wakefulness syndrome (UWS) and 48 in a minimally conscious state (MCS). For each participant, we computed channel-wise approximate entropy (ApEn) from EEG time-series data using a sliding window approach under two experimental paradigms: resting state and preferred music stimulation. These nonlinear measures were then spatially interpolated to generate topographical maps. Both resting state and preferred music stimulation data were processed as 1-second epochs using identical convolutional neural networks (CNN) architectures. The classification performance and validity of the CNN were compared against support vector machine (SVM) and generalized regression neural network (GRNN) models. ApEn in the resting state and under stimulation with preferred music correlated with the Coma Recovery Scale-Revised scores in patients with DOC, showing varied regional responses. Notably, the CNNs resulted in a positive diagnostic performance with an accuracy of 90.00% and an AUC of 0.902. The CNN was better than the SVM and GRNN in differentiating between the VS/UWS and MCS states. This study offers a convenient and accurate method for detecting awareness in patients with VS/UWS and MCS using ApEn features in the resting state and under preferred music stimulation using deep learning.

Unveiling clouded consciousness: Broad-band EEG slowing tracks recovery from post-traumatic confusional state.

Revealing EEG signatures of intervention in disorder of consciousness using artificial intelligence: methodology and feasibility.

Spinal cord stimulation improves brain connectivity and consciousness level in patients with disorders of consciousness.

Detecting emotion in individuals with disorders of consciousness: a pilot study of heart rate deceleration on affective auditory stimuli.

In this retrospective essay celebrating the 40th anniversary of the Journal of Head Trauma and Rehabilitation, Dr. Joseph J. Fins traces the evolution of the neuroethics of disorders of consciousness through autobiographical reflections over the past four decades. His memoir highlights his origins as a medical student on the Cornell Neurology Service headed by Dr. Fred Plum, the co-originator of the Persistent Vegetative State with Dr. Bryan Jennett and culminates with his collaboration with Dr. Nicholas Schiff and the clinical and ethical importance of Cognitive Motor Dissociation in clinical care. During this period Fins describes the therapeutic nihilism that followed in the wake of landmark end-of-life cases like Quinlan, Cruzan and Schiavo and how scientific advance and an emerging nosology has begun to envision therapeutic possibility informed by an expanded nosology and neuroimaging. Fins asserts that the disability rights of people with disorders of consciousness need to be accommodated in tandem with access to technological advance in order to more fully integrate these individuals into the nexus of their families and communities. Fins argues that the developments of the past 40 years are a harbinger of further progress but cautions that this will not occur without sustained government support from the National Institutes of Health.