Neuroimaging studies have suggested an important role for the default mode network (DMN) in disorders of consciousness (DoC). However, the extent to which DMN connectivity can discriminate DoC states-unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS)-is less evident. Particularly, it is unclear whether effective DMN connectivity, as measured indirectly with dynamic causal modelling (DCM) of resting EEG can disentangle UWS from healthy controls and from patients considered conscious (MCS+). Crucially, this extends to UWS patients with potentially \"covert\" awareness (minimally conscious star, MCS*) indexed by voluntary brain activity in conjunction with partially preserved frontoparietal metabolism as measured with positron emission tomography (PET+ diagnosis; in contrast to PET- diagnosis with complete frontoparietal hypometabolism). Here, we address this gap by using DCM of EEG data acquired from patients with traumatic brain injury in 11 UWS (6 PET- and 5 PET+) and in 12 MCS+ (11 PET+ and 1 PET-), alongside with 11 healthy controls. We provide evidence for a key difference in left frontoparietal connectivity when contrasting UWS PET- with MCS+ patients and healthy controls. Next, in a leave-one-subject-out cross-validation, we tested the classification performance of the DCM models demonstrating that connectivity between medial prefrontal and left parietal sources reliably discriminates UWS PET- from MCS+ patients and controls. Finally, we illustrate that these models generalize to an unseen dataset: models trained to discriminate UWS PET- from MCS+ and controls, classify MCS* patients as conscious subjects with high posterior probability (pp > .92). These results identify specific alterations in the DMN after severe brain injury and highlight the clinical utility of EEG-based effective connectivity for identifying patients with potential covert awareness.

OBJECTIVE: The patient being minimally conscious state (MCS) may benefit from wake-up interventions aimed at improving quality of life and have a higher probability of recovering higher level of consciousness compared to patients with the unresponsive wakefulness syndrome (UWS). However, differentiation of the MCS and UWS poses challenge in clinical practice. This study aimed to explore glucose metabolic pattern (GMP) obtained from 18F-labeled-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in distinguishing between UWS and MCS.
METHODS: Fifty-seven patients with disorders of consciousness (21 cases of UWS and 36 cases of MCS) who had undergone repeated standardized Coma Recovery Scale-Revised (CRS-R) evaluations were enrolled in this prospective study. 18F-FDG-PET was carried out in all patients and healthy controls (HCs). Voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was used to generate GMPs. The expression score of whole-brain GMP was obtained, and its diagnostic accuracy was compared with the standardized uptake value ratio (SUVR). The diagnostic efficiency was validated by one-year later clinical outcomes.
RESULTS: UWS-MCS GMP exhibited hypometabolism in the frontal-parietal cortex, along with hypermetabolism in the unilateral lentiform nucleus, putamen, and anterior cingulate gyrus. The UWS-MCS-GMP expression score was significantly higher in UWS compared to MCS patients (0.90 ± 0.85 vs. 0 ± 0.93, p < 0.001). UWS-MCS-GMP expression score achieved an area under the curve (AUC) of 0.77 to distinguish MCS from UWS, surpassing that of SUVR based on the frontoparietal cortex (AUC = 0.623). UWS-MCS-GMP expression score was significantly correlated with the CRS-R score (r = -0.45, p = 0.004) and accurately predicted the one-year outcome in 73.7% of patients.
CONCLUSIONS: UWS and MCS exhibit specific glucose metabolism patterns, the UWS-MCS-GMP expression score significantly distinguishes MCS from UWS, making SSM/PCA a potential diagnostic methods in clinical practice for individual patients.

BACKGROUND: The Patient Right to Autonomy Act (PRAA), implemented in Taiwan in 2019, enables the creation of advance decisions (AD) through advance care planning (ACP). This legal framework allows for the withholding and withdrawal of life-sustaining treatment (LST) or artificial nutrition and hydration (ANH) in situations like irreversible coma, vegetative state, severe dementia, or unbearable pain. This study aims to investigate preferences for LST or ANH across various clinical conditions, variations in participant preferences, and factors influencing these preferences among urban residents.
METHODS: Employing a survey of legally structured AD documents and convenience sampling for data collection, individuals were enlisted from Taipei City Hospital, serving as the primary trial and demonstration facility for ACP in Taiwan since the commencement of the PRAA in its inaugural year. The study examined ADs and ACP consultation records, documenting gender, age, welfare entitlement, disease conditions, family caregiving experience, location of ACP consultation, participation of second-degree relatives, and the intention to participate in ACP.
RESULTS: Data from 2337 participants were extracted from electronic records. There was high consistency in the willingness to refuse LST and ANH, with significant differences noted between terminal diseases and extremely severe dementia. Additionally, ANH was widely accepted as a time-limited treatment, and there was a prevalent trend of authorizing a health care agent (HCA) to make decisions on behalf of participants. Gender differences were observed, with females more inclined to decline LST and ANH, while males tended towards accepting full or time-limited treatment. Age also played a role, with younger participants more open to treatment and authorizing HCA, and older participants more prone to refusal.
CONCLUSIONS: Diverse preferences in LST and ANH were shaped by the public\'s current understanding of different clinical states, gender, age, and cultural factors. Our study reveals nuanced end-of-life preferences, evolving ADs, and socio-demographic influences. Further research could explore evolving preferences over time and healthcare professionals\' perspectives on LST and ANH decisions for neurological patients..

Non-invasive brain stimulation is considered as a promising technology for treating patients with disorders of consciousness (DOC). Various approaches and protocols have been proposed; however, few of them have shown potential effects on patients with vegetative state (VS). This study aimed to explore the neuro-modulation effects of intermittent theta burst stimulation (iTBS) on the brains of patients with VS and to provide a pilot investigation into its possible role in treating such patients.
We conducted a sham-controlled crossover study, a real and a sham session of iTBS were delivered over the left dorsolateral prefrontal cortex of such patients. A measurement of an electroencephalography (EEG) and a behavioral assessment of the Coma Recovery Scale-Revised (CRS-R) were applied to evaluate the modulation effects of iTBS before and after stimulation.
No meaningful changes of CRS-R were found. The iTBS altered the spectrum, complexity and functional connectivity of the patients. The real stimulation induced a trend of decreasing of delta power at T1 and T2 in the frontal region, significant increasing of permutation entropy at the T2 in the left frontal region. In addition, brain functional connectivity, particularly inter-hemispheric connectivity, was strengthened between the electrodes of the frontal region. The sham stimulation, however, did not induce any significant changes of the brain activity.
One session of iTBS significantly altered the oscillation power, complexity and functional connectivity of brain activity of VS patients. It may be a valuable tool on modulating the brain activities of patients with VS.

OBJECTIVE: Assessing recovery potential in patients with disorders of consciousness (DoC) is pivotal for guiding clinical and ethical decisions. We conducted a mega-analysis of individual patient data to understand (1) if a time threshold exists, beyond which regaining consciousness is almost impossible, and (2) how recovery varies based on factors such as diagnosis, etiology, age, sex, and neuropsychological status.
METHODS: A systematic literature search revealed a total of 3290 patients. In this sample, we performed a Cox proportional hazards analysis for interval censored data.
RESULTS: We observed a late saturation of probability to regain consciousness in Kaplan-Meier curves, and the annual rate of recovery was remarkably stable, in that approximately 35% of patients regained consciousness per year. Patients in minimally conscious state (MCS) recovered more frequently than patients in unresponsive wakefulness syndrome (UWS). No significant difference was observed between the recovery dynamics of MCS subgroups: MCS+ and MCS-. Patients with hypoxic brain lesions showed worse recovery rate than patients with traumatic brain injury and patients with vascular brain lesions, while the latter two categories did not differ from each other. Male patients had moderately better chance to regain consciousness. While younger UWS patients recovered more frequently than older patients, it was not the case in MCS.
CONCLUSIONS: Our findings highlight the necessity for neurologists to exercise caution when making negative predictions in individual cases, challenge traditional beliefs regarding recovery timelines, and underscore the importance of conducting detailed and prolonged assessments to better understand recovery prospects in DoC.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been used for the restoration of awareness in patients with a minimal consciousness state (MCS). Most brains of patients in MCS may structurally and electrophysiologically differ from un-damaged brains. Moreover, tDCS is currently contraindicated for patients with craniotomy or skull with metallic implants.
METHODS: We present a case with prolonged MCS over 1 year, who had severe brain damage, ventriculoperitoneal shunt, and cranioplasty with a titanium mesh, which was treated with tDCS which optimized with the simulation of the electric field based on the patient\'s brain MRI. The patient was resulting in emergence from MCS. Six months later, she ate meals orally and started walking with assistance.
UNASSIGNED: This personalized simulation based on MRI would make the treatment available even to patients with severe brain structural changes and metallic instrumentation.

Brain dynamics is highly non-stationary, permanently subject to ever-changing external conditions and continuously monitoring and adjusting internal control mechanisms. Finding stationary structures in this system, as has been done recently, is therefore of great importance for understanding fundamental dynamic trade relationships. Here we analyse electroencephalographic recordings (EEG) of 13 subjects with unresponsive wakefulness syndrome (UWS) during rest and while being influenced by different acoustic stimuli. We compare the results with a control group under the same experimental conditions and with clinically healthy subjects during overnight sleep. The main objective of this study is to investigate whether a stationary correlation pattern is also present in the UWS group, and if so, to what extent this structure resembles the one found in healthy subjects. Furthermore, we extract transient dynamical features via specific deviations from the stationary interrelation pattern. We find that (i) the UWS group is more heterogeneous than the two groups of healthy subjects, (ii) also the EEGs of the UWS group contain a stationary cross-correlation pattern, although it is less pronounced and shows less similarity to that found for healthy subjects and (iii) deviations from the stationary pattern are notably larger for the UWS than for the two groups of healthy subjects. The results suggest that the nervous system of subjects with UWS receive external stimuli but show an overreaching reaction to them, which may disturb opportune information processing.

The assessment of consciousness states, especially distinguishing minimally conscious states (MCS) from unresponsive wakefulness states (UWS), constitutes a pivotal role in clinical therapies. Despite that numerous neural signatures of consciousness have been proposed, the effectiveness and reliability of such signatures for clinical consciousness assessment still remains an intense debate. Through a comprehensive review of the literature, inconsistent findings are observed about the effectiveness of diverse neural signatures. Notably, the majority of existing studies have evaluated neural signatures on a limited number of subjects (usually below 30), which may result in uncertain conclusions due to small data bias. This study presents a systematic evaluation of neural signatures with large-scale clinical resting-state electroencephalography (EEG) signals containing 99 UWS, 129 MCS, 36 emergence from the minimally conscious state, and 32 healthy subjects (296 total) collected over 3 years. A total of 380 EEG-based metrics for consciousness detection, including spectrum features, nonlinear measures, functional connectivity, and graph-based measures, are summarized and evaluated. To further mitigate the effect of data bias, the evaluation is performed with bootstrap sampling so that reliable measures can be obtained. The results of this study suggest that relative power in alpha and delta serve as dependable indicators of consciousness. With the MCS group, there is a notable increase in the phase lag index-related connectivity measures and enhanced functional connectivity between brain regions in comparison to the UWS group. A combination of features enables the development of an automatic detector of conscious states.

BACKGROUND: Family caregivers (FC) contribute to reducing the misdiagnosis rate in patients with disorders of consciousness (DOC). Unfortunately, the recent pandemic of COVID-19 imposed drastic restrictions that limited the access of FC to the sensory/cognitive stimulation protocols. Telemedicine approaches have been implemented to avoid discontinuity in care pathways and to ensure caregivers involvement in rehabilitation programs.
OBJECTIVE: The aim was to investigate whether the presence of FC remotely connected might help clinicians in eliciting higher cortically mediated behavioral responses in patients with DOC.
METHODS: Cross-sectional study.
METHODS: Post-acute Unit of Neurorehabilitation.
METHODS: DOC due to severe brain injury.
METHODS: Consecutive patients with DOC were assessed by means of the Coma Recovery Scale-Revised (CRS-R) by two expert examiners. Each patient underwent to five assessments in two weeks in three different conditions: 1) by the examiner only (standard); 2) with the verbal stimulation given by the FC remotely connected by PC tablet (caregiver in remote); and 3) with the verbal stimulation given by the FC physically present (caregiver in presence).
RESULTS: Thirty patients with DOC (VS/UWS=10; MCS=20; mean age: 51, range: 21-79; vascular: 16; anoxic: 6; TBI=8) and their FC were enrolled. Higher total scores of CRS-R were recorded both in \"caregiver in remote\" and in \"caregiver in presence\" than in standard condition (standard vs. remote, Z=2.942, P=0.003; standard vs. presence, Z=3.736, P<0.001). Furthermore, the administration of the CRS-R with a FC, elicited higher levels of behavioral responses in MCS patients, than CRS-R performed in standard condition. In particular, 2 patients out of 30 (6.66%) showed higher scores and better diagnosis when the CRS-R was administered with FC in remote. Similarly, 5 out of 30 patients (16.66%) showed better diagnoses when the CRS-R was administered with FC in presence. Five patients changed diagnosis between standard and presence conditions (3 MCS- were diagnosed as MCS+; 2 MCS+ were diagnosed as conscious).
CONCLUSIONS: Our findings add new evidence regarding the beneficial role of family members in the diagnosis of DOC, even mediated by telemedicine approach.
CONCLUSIONS: In future guidelines, FC should have an active and supporting role in the diagnostic and rehabilitative process of DOC.

OBJECTIVE: Severe brain injuries can result in disorders of consciousness, such as the Minimally Conscious State (MCS), where individuals display intermittent yet discernible signs of conscious awareness. The varied levels of responsiveness and awareness observed in this state have spurred the progressive delineation of two subgroups within MCS, termed \"plus\" (MCS+) and \"minus\" (MCS-). However, the clinical validity of these classifications remains uncertain. This study aimed to investigate and compare the likelihood of emergence from MCS, as well as the functional independence after emergence, in individuals categorized as in MCS+ and MCS-.
METHODS: Demographic and behavioral data of 80 participants, admitted as either in MCS+ (n = 30) or MCS- (n = 50) to a long-term neurorehabilitation unit, were retrospectively analyzed. The neurobehavioral condition of each participant was evaluated weekly until discharge, demise, or emergence from MCS. The functional independence of those participants who emerged from MCS was assessed 6 months after emergence.
RESULTS: While only about half of the individuals classified as in MCS- (n = 24) emerged from the MCS, all those admitted as in MCS+ did, and in a shorter postinjury period. Despite these differences, all individuals who emerged from the MCS demonstrated similar high disability and low functional independence 6 months after emergence, regardless of their state at admission.
CONCLUSIONS: Individuals classified as MCS+ exhibited a higher likelihood of emergence and a shorter time to emergence compared to those in MCS-. However, the level of functional independence 6 months after emergence was found to be unrelated to the initial state at admission.