Anatomical-related factors and outcome of percutaneous short-term spinal cord stimulation electrode shift in patients with disorders of consciousness: a retrospective study.

Background: Disorders of consciousness (DoC) represent a spectrum of neurological conditions that pose significant treatment challenges. Percutaneous short-term spinal cord stimulation (SCS) has emerged as a promising experimental diagnostic treatment to assess and potentially improve consciousness levels. However, the effectiveness of this intervention is frequently compromised by the shift of electrodes, particularly in the cervical region, which can negatively affect therapeutic outcomes. Methods: This retrospective study aimed to study if electrodes shift in percutaneous short-term SCS in patients with DoC would affect the outcome. We analyzed the relationship between electrode shift length and patient outcome, as well as the correlation with various anatomical parameters, including the actual length of the cervical spine, linear length, spinal canal transverse diameter, spinal canal diameter, and C2 cone height, in a cohort of patients undergoing the procedure. Results: Our findings revealed that in patients with better outcome, there are significant less patient with electrode shift (p = 0.019). Further, a linear correlation was found between the length of electrode shift and patients' outcome (Rho = 0.583, p = 0.002), with longer shift lengths associated with poorer outcomes. Contrary to our expectations, there was no significant association between the measured anatomical parameters and the extent of electrode shift. However, a trend was found between the actual length of the cervical spine and the shift of the electrode (p = 0.098). Notably, the shorter spinal canal transverse diameter was found to be significantly associated with better outcome in patients with DoC receiving percutaneous short-term SCS (p = 0.033). Conclusion: These results highlight the clinical importance of electrode stability in the cervical region during SCS treatment for patients with DoC. Ensuring secure placement of electrodes may play a crucial role in enhancing patients' outcome and minimize postoperative complications. Given the lack of association with expected anatomical parameters, future research should investigate other factors that could impact electrode stability to optimize this therapeutic intervention.

Permutation conditional mutual information to quantify TMS-evoked cortical connectivity in disorders of consciousness.

OBJECTIVE: To improve the understanding and diagnostic accuracy of disorders of consciousness (DOC) by quantifying transcranial magnetic stimulation evoked electroencephalography (TMS-EEG) connectivity using Permutation Conditional Mutual Information (PCMI). Approach: PCMI can characterize the functional connectivity between different brain regions. This study employed PCMI to analyze TMS-evoked cortical connectivity (TEC) in 154 DOC patients and 16 normal controls, focusing on optimizing parameter selection for PCMI (Data length, Order length, Time delay). We compared short-range and long-range PCMI values across different consciousness states-unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and normal (NOR)-and assessed various feature selection and classification techniques to distinguish these states. Main Results: 1) PCMI can quantify TEC. We found optimal parameters to be Data length: 500ms; Order: 3; Time delay: 6ms. 2) TMS evoked potentials (TEP) for NOR showed a rich response, while MCS patients showed only a few components, and UWS patients had almost no significant components. The values of PCMI connectivity metrics demonstrated its usefulness for measuring cortical connectivity evoked by TMS. From NOR to MCS to UWS, the number and strength of TEC decreased. Quantitative analysis revealed significant differences in the strength and number of TEC in the entire brain, local regions and inter-regions among different consciousness states. 3) A decision tree with feature selection by mutual information performed the best (balanced accuracy: 87.0% and accuracy: 83.5%). This model could accurately identify NOR (100.0%), but had lower identification accuracy for UWS (86.5%) and MCS (74.1%). Significance: The application of PCMI in measuring TMS-evoked connectivity provides a robust metric that enhances our ability to differentiate between various states of consciousness in DOC patients. This approach not only aids in clinical diagnosis but also contributes to the broader understanding of cortical connectivity and consciousness. .

Conscious care: a proposed model to improve interprofessional care of patients with disorders of consciousness in the acute hospital setting.

BACKGROUND: Forty percent of individuals within the Disorders of Consciousness (DoC) spectrum are misdiagnosed as in a vegetative state/unresponsive wakefulness syndrome (VS/UWS) when in fact they are minimally conscious or emerged, underscoring a need to optimize evaluation techniques and interprofessional care management. PRIMARY OBJECTIVE: Conscious Care is a proposed care model that aims to improve interprofessional care of patients with DoC in the hospital setting. The aim of this paper is to describe this model's key ingredients and various components. CONCLUSIONS: This care model will advance clinician and caregiver preparedness to manage the complexities of this population and advocate for equal access to post-hospital medical and rehabilitative services. Evaluation and treatment of survivors of DoC should incorporate current evidence which drives continuous quality improvement and education to clinicians across the continuum of care. Immediate action must be taken to decrease the vulnerability and neglect of this marginalized population. Conscious Care is an innovative, sustainable solution that will improve interprofessional awareness of best practices and available science, strengthen care, and advocate for the right to quality of life that this population is so often denied.

Individualized music induces theta-gamma phase-amplitude coupling in patients with disorders of consciousness.

Objective: This study aimed to determine whether patients with disorders of consciousness (DoC) could experience neural entrainment to individualized music, which explored the cross-modal influences of music on patients with DoC through phase-amplitude coupling (PAC). Furthermore, the study assessed the efficacy of individualized music or preferred music (PM) versus relaxing music (RM) in impacting patient outcomes, and examined the role of cross-modal influences in determining these outcomes. Methods: Thirty-two patients with DoC [17 with vegetative state/unresponsive wakefulness syndrome (VS/UWS) and 15 with minimally conscious state (MCS)], alongside 16 healthy controls (HCs), were recruited for this study. Neural activities in the frontal-parietal network were recorded using scalp electroencephalography (EEG) during baseline (BL), RM and PM. Cerebral-acoustic coherence (CACoh) was explored to investigate participants' abilitiy to track music, meanwhile, the phase-amplitude coupling (PAC) was utilized to evaluate the cross-modal influences of music. Three months post-intervention, the outcomes of patients with DoC were followed up using the Coma Recovery Scale-Revised (CRS-R). Results: HCs and patients with MCS showed higher CACoh compared to VS/UWS patients within musical pulse frequency (p = 0.016, p = 0.045; p < 0.001, p = 0.048, for RM and PM, respectively, following Bonferroni correction). Only theta-gamma PAC demonstrated a significant interaction effect between groups and music conditions (F (2,44) = 2.685, p = 0.036). For HCs, the theta-gamma PAC in the frontal-parietal network was stronger in the PM condition compared to the RM (p = 0.016) and BL condition (p < 0.001). For patients with MCS, the theta-gamma PAC was stronger in the PM than in the BL (p = 0.040), while no difference was observed among the three music conditions in patients with VS/UWS. Additionally, we found that MCS patients who showed improved outcomes after 3 months exhibited evident neural responses to preferred music (p = 0.019). Furthermore, the ratio of theta-gamma coupling changes in PM relative to BL could predict clinical outcomes in MCS patients (r = 0.992, p < 0.001). Conclusion: Individualized music may serve as a potential therapeutic method for patients with DoC through cross-modal influences, which rely on enhanced theta-gamma PAC within the consciousness-related network.

Content-state dimensions characterize different types of neuronal markers of consciousness.

Identifying the neuronal markers of consciousness is key to supporting the different scientific theories of consciousness. Neuronal markers of consciousness can be defined to reflect either the brain signatures underlying specific conscious content or those supporting different states of consciousness, two aspects traditionally studied separately. In this paper, we introduce a framework to characterize markers according to their dynamics in both the "state" and "content" dimensions. The 2D space is defined by the marker's capacity to distinguish the conscious states from non-conscious states (on the x-axis) and the content (e.g. perceived versus unperceived or different levels of cognitive processing on the y-axis). According to the sign of the x- and y-axis, markers are separated into four quadrants in terms of how they distinguish the state and content dimensions. We implement the framework using three types of electroencephalography markers: markers of connectivity, markers of complexity, and spectral summaries. The neuronal markers of state are represented by the level of consciousness in (i) healthy participants during a nap and (ii) patients with disorders of consciousness. On the other hand, the neuronal markers of content are represented by (i) the conscious content in healthy participants' perception task using a visual awareness paradigm and (ii) conscious processing of hierarchical regularities using an auditory local-global paradigm. In both cases, we see separate clusters of markers with correlated and anticorrelated dynamics, shedding light on the complex relationship between the state and content of consciousness and emphasizing the importance of considering them simultaneously. This work presents an innovative framework for studying consciousness by examining neuronal markers in a 2D space, providing a valuable resource for future research, with potential applications using diverse experimental paradigms, neural recording techniques, and modeling investigations.

Factors influencing recovery in a pediatric sample with disorders of consciousness: insights from an observational study.

OBJECTIVE: To estimate rates and time to reach emergence of consciousness from vegetative state/unresponsive wakefulness syndrome (VS/UWS), and explore factors associated with improved recovery in children and adolescents with disorders of consciousness (DoC) following severe traumatic and non-traumatic brain injury. METHODS: Analytical, retrospective, cohort study. Clinical records of consecutively referred patients admitted in VS/UWS to a neurological rehabilitation institute in Argentina, between 2005 and 2021 were reviewed. Seventy children and adolescents were included in the analysis. A specialized 12-week rehabilitation program was administered, and emergence was defined by scores ≥44 points on the Western Neuro Sensory Stimulation Profile (WNSSP), sustained for at least 3 weeks on consecutive weekly evaluations. RESULTS: Emergence from VS/UWS to consciousness occurred within 5.4 (SD 2.6) weeks in almost one-third of patients. Multivariate Cox regression analysis showed emergence was significantly lower in patients with hypoxic ischemic encephalopathy compared to patients with other non-traumatic etiologies [HRadj 0.23 (95% CI 0.06-0.89); p = 0.03)]. CONCLUSIONS: Our findings reinforce growing evidence on the impact of etiology on DoC recovery in pediatric populations, ultimately influencing treatment and family-related decisions in child neurorehabilitation.

A synergistic workspace for human consciousness revealed by Integrated Information Decomposition.

How is the information-processing architecture of the human brain organised, and how does its organisation support consciousness? Here, we combine network science and a rigorous information-theoretic notion of synergy to delineate a 'synergistic global workspace', comprising gateway regions that gather synergistic information from specialised modules across the human brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the human brain's default mode network, whereas broadcasters coincide with the executive control network. We find that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.

The human brain consists of billions of neurons which process sensory inputs, such as sight and sound, and combines them with information already stored in the brain. This integration of information guides our decisions, thoughts, and movements, and is hypothesized to be integral to consciousness. However, it is poorly understood how the brain regions responsible for processing this integration are organized in the brain. To investigate this question, Luppi et al. employed a mathematical framework called Partial Information Decomposition (PID) which can distinguish different types of information: redundancy (available from many regions) and synergy (which reflects genuine integration). The team applied the PID framework to the brain scans of 100 individuals. This allowed them to identify which brain regions combine information from across the brain (known as gateways), and which ones transmit it back to the rest of the brain (known as broadcasters). Next, Luppi et al. set out to find how these regions compared in unconscious and conscious individuals. To do this, they studied 15 healthy volunteers whose brains were scanned (using a technique called functional MRI) before, during, and after anaesthesia. This revealed that the brain integrated less information when unconscious, and that this reduction happens predominantly in gateway rather than broadcaster regions. The same effect was also observed in the brains of individuals who were permanently unconscious due to brain injuries. These findings provide a way of understanding how information is organised in the brain. They also suggest that loss of consciousness due to brain injuries and anaesthesia involve similar brain circuits. This means it may be possible to gain insights about disorders of consciousness from studying how people emerge from anaesthesia.

Assessment of impaired consciousness using EEG-based connectivity features and convolutional neural networks.

Growing electroencephalogram (EEG) studies have linked the abnormities of functional brain networks with disorders of consciousness (DOC). However, due to network data's high-dimensional and non-Euclidean properties, it is difficult to exploit the brain connectivity information that can effectively detect the consciousness levels of DOC patients via deep learning. To take maximum advantage of network information in assessing impaired consciousness, we utilized the functional connectivity with convolutional neural network (CNN) and employed three rearrangement schemes to improve the evaluation performance of brain networks. In addition, the gradient-weighted class activation mapping (Grad-CAM) was adopted to visualize the classification contributions of connections among different areas. We demonstrated that the classification performance was significantly enhanced by applying network rearrangement techniques compared to those obtained by the original connectivity matrix (with an accuracy of 75.0%). The highest classification accuracy (87.2%) was achieved by rearranging the alpha network based on the anatomical regions. The inter-region connections (i.e., frontal-parietal and frontal-occipital connectivity) played dominant roles in the classification of patients with different consciousness states. The effectiveness of functional connectivity in revealing individual differences in brain activity was further validated by the correlation between behavioral performance and connections among specific regions. These findings suggest that our proposed assessment model could detect the residual consciousness of patients.

EEG connectivity and network analyses predict outcome in patients with disorders of consciousness - A systematic review and meta-analysis.

Outcome prediction in prolonged disorders of consciousness (DOC) remains challenging. This can result in either inappropriate withdrawal of treatment or unnecessary prolongation of treatment. Electroencephalography (EEG) is a cheap, portable, and non-invasive device with various opportunities for complex signal analysis. Computational EEG measures, such as EEG connectivity and network metrics, might be ideal candidates for the investigation of DOC, but their capacity in prognostication is still undisclosed. We conducted a meta-analysis aiming to compare the prognostic power of the widely used clinical scale, Coma Recovery Scale-Revised - CRS-R and EEG connectivity and network metrics. We found that the prognostic power of the CRS-R scale was moderate (AUC: 0.67 (0.60-0.75)), but EEG connectivity and network metrics predicted outcome with significantly (p = 0.0071) higher accuracy (AUC:0.78 (0.70-0.86)). We also estimated the prognostic capacity of EEG spectral power, which was not significantly (p = 0.3943) inferior to that of the EEG connectivity and graph-theory measures (AUC:0.75 (0.70-0.80)). Multivariate automated outcome prediction tools seemed to outperform clinical and EEG markers.

Modelling developments in consciousness within a multidimensional framework.

A recent advancement in consciousness science has been the introduction of a multidimensional framework of consciousness. This framework has been applied to global states of consciousness, including psychedelic states and disorders of consciousness, and the consciousness of non-human animals. The multidimensional framework enables a finer parsing of both various states of consciousness and forms of animal consciousness, paving the way for new scientific investigations into consciousness. In this paper, the multidimensional model is expanded by constructing temporal profiles. This expansion allows for the modelling of changes in consciousness across the life cycles of organisms and the progression over time of disorders of consciousness. The result of this expansion is 2-fold: (i) it enables new modes of comparison, both across stages of development and across species; (ii) it proposes that more attention be given to the various types of fluctuations that occur in patients who are suffering from disorders of consciousness.

Arterial Spin Labeling Magnetic Resonance Imaging for Acute Disorders of Consciousness in the Intensive Care Unit.

BACKGROUND: To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC. We hypothesized that ASL-MRI would show compromised CBF in coma and unresponsive wakefulness states (UWS) but relatively preserved CBF in minimally conscious states (MCS) or better. METHODS: We consecutively enrolled ICU patients with acute DoC and categorized them as being clinically unresponsive (i.e., coma or UWS [≤ UWS]) or low responsive (i.e., MCS or better [≥ MCS]). ASL-MRI was then acquired on 1.5 T or 3 T. Healthy controls were investigated with both 1.5 T and 3 T ASL-MRI. RESULTS: We obtained 84 ASL-MRI scans from 59 participants, comprising 36 scans from 35 patients (11 women [31.4%]; median age 56 years, range 18-82 years; 24 ≤ UWS patients, 12 ≥ MCS patients; 32 nontraumatic brain injuries) and 48 scans from 24 healthy controls (12 women [50%]; median age 50 years, range 21-77 years). In linear mixed-effects models of whole-brain cortical CBF, patients had 16.2 mL/100 g/min lower CBF than healthy controls (p = 0.0041). However, ASL-MRI was unable to discriminate between ≤ UWS and ≥ MCS patients (whole-brain cortical CBF: p = 0.33; best hemisphere cortical CBF: p = 0.41). Numerical differences of regional CBF in the thalamus, amygdala, and brainstem in the two patient groups were statistically nonsignificant. CONCLUSIONS: CBF measurement in ICU patients using ASL-MRI is feasible but cannot distinguish between the lower and the upper ends of the acute DoC spectrum. We suggest that pilot testing of diagnostic interventions at the extremes of this spectrum is a time-efficient approach in the continued quest to develop DoC neuroimaging markers in the ICU.

Short-term outcomes of early intensive neurorehabilitation for prolonged disorders of consciousness: A prospective cohort study.

BACKGROUND: Advances in medical care have increased survival in people with severe brain injuries and with that the number of survivors with prolonged disorders of consciousness (PDOC) has increased. In the literature, early intensive neurorehabilitation (EIN) for people with PDOC is recommended to achieve the best possible outcomes. OBJECTIVES: To evaluate the frequency and extent of recovery of consciousness, mortality, complications, pain and discomfort, and medication during a nationwide EIN programme in people with PDOC after acquired brain injury. We hypothesized that level of consciousness would improve in half of people with PDOC. METHODS: Prospective cohort study. People with PDOC aged 16 years and older admitted to the EIN department centralized in a single rehabilitation centre in the Netherlands (Libra Rehabilitation & Audiology) were included. The EIN delivers a subacute medical level of care and rehabilitation for a maximum duration of 14 weeks. The outcome measures were level of consciousness (CRS-R), mortality, number of complications, medication and pain/discomfort (NCS-R). RESULTS: Of the 104 people included, 68 % emerged to a minimal conscious state with command-following or higher during EIN and 44 % regained consciousness. Mortality during EIN was 6 %, and 50 % of deaths followed a non-treatment decision or withdrawal of life-sustaining treatment. Almost all participants had at least 1 medical complication, leading to hospital readmission for 30 %. 73 % showed no pain or discomfort. During EIN, cardiovascular medication and analgesics were reduced by 15 %. CONCLUSIONS: During the EIN programme, a large percentage of people with PDOC regained at least a minimal conscious state or even consciousness. These outcomes and the frequent medical complications in these people suggest that intensive specialized care should be offered to all people with PDOC. The outcomes of this study might help health professionals to better inform the families of people with PDOC about the short-term prognosis of PDOC. PROTOCOL REGISTRATION NUMBER: The Dutch Trial Register, NL 8138.

Psychedelics and disorders of consciousness: the current landscape and the path forward.

Modern medicine has been shaken by the surge of psychedelic science that proposes a new approach to mitigate mental disorders, such as depression and post-traumatic stress disorder. Clinical trials to investigate whether psychedelic substances can treat psychiatric conditions are now underway, yet less discussion gravitates around their use in neurological disorders due to brain injury. One suggested implementation of brain-complexity enhancing psychedelics is to treat people with post-comatose disorders of consciousness (DoC). In this article, we discuss the rationale of this endeavour, examining possible outcomes of such experiments by postulating the existence of an optimal level of complexity. We consider the possible counterintuitive effects of both psychedelics and DoC on the functional connectivity of the default mode network and its possible impact on selfhood. We also elaborate on the role of computational modelling in providing complementary information to experimental studies, both contributing to our understanding of the treatment mechanisms and providing a path towards personalized medicine. Finally, we update the discourse surrounding the ethical considerations, encompassing clinical and scientific values.

The efficacy and safety of bilateral synchronous transcutaneous auricular vagus nerve stimulation for prolonged disorders of consciousness: a multicenter, double-blind, stratified, randomized controlled trial protocol.

Background: Treatment of disorders of consciousness (DOC) poses a huge challenge for clinical medicine. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation method, which shows potential in improving recovery of DOC. However, the evidence came from single-center, small-sample randomized controlled trial, which is insufficient to form a conclusion. Thereby, we propose a prospective, multicenter, double-blind, stratified, two-arm randomized controlled trial protocol to investigate the efficacy and safety of bilateral synchronous taVNS for treatment of DOC. Methods: We aim to recruit 382 patients with prolonged DOC, and divide them into an active stimulation group and a sham stimulation group. The patients in the active stimulation group will receive bilateral synchronous taVNS with a 200 µs pulse width, 20 Hz frequency, and personal adjusted intensity. The sham stimulation group will wear the same stimulator but without current output. Both groups will receive treatment for 30 min per session, twice per day, 6 days per week lasting for 4 weeks. The clinical assessment including Coma Recovery Scale-Revised (CRS-R), Full Outline of Unresponsiveness (FOUR), Glasgow Coma Scale (GCS), and Extended Glasgow Outcome Scale (GOS-E) will be conducted to evaluate its efficacy. Heart rate variability (HRV), blood pressure, and adverse events will be recorded to evaluate its safety. Discussion: These results will enable us to investigate the efficacy and safety of taVNS for DOC. This protocol will provide multicenter, large-sample, high-quality Class II evidence to support bilateral synchronous taVNS for DOC, and will advance the field of treatment options for DOC.Clinical trial registration:https://www.chictr.org.cn/showproj.html?proj=221851, ChiCTR2400081978.

Whole-brain glucose metabolic pattern differentiates minimally conscious state from unresponsive wakefulness syndrome.

AIMS: 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. CONCLUSION: 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.

Equity in Clinical Care and Research Involving Persons with Disorders of Consciousness.

People with disorders of consciousness (DoC) are characteristically unable to synchronously participate in decision-making about clinical care or research. The inability to self-advocate exacerbates preexisting socioeconomic and geographic disparities, which include the wide variability observed across individuals, hospitals, and countries in access to acute care, expertise, and sophisticated diagnostic, prognostic, and therapeutic interventions. Concerns about equity for people with DoC are particularly notable when they lack a surrogate decision-maker (legally referred to as "unrepresented" or "unbefriended"). Decisions about both short-term and long-term life-sustaining treatment typically rely on neuroprognostication and individual patient preferences that carry additional ethical considerations for people with DoC, as even individuals with well thought out advance directives cannot anticipate every possible situation to guide such decisions. Further challenges exist with the inclusion of people with DoC in research because consent must be completed (in most circumstances) through a surrogate, which excludes those who are unrepresented and may discourage investigators from exploring questions related to this population. In this article, the Curing Coma Campaign Ethics Working Group reviews equity considerations in clinical care and research involving persons with DoC in the following domains: (1) access to acute care and expertise, (2) access to diagnostics and therapeutics, (3) neuroprognostication, (4) medical decision-making for unrepresented people, (5) end-of-life decision-making, (6) access to postacute rehabilitative care, (7) access to research, (8) inclusion of unrepresented people in research, and (9) remuneration and reciprocity for research participation. The goal of this discussion is to advance equitable, harmonized, guideline-directed, and goal-concordant care for people with DoC of all backgrounds worldwide, prioritizing the ethical standards of respect for autonomy, beneficence, and justice. Although the focus of this evaluation is on people with DoC, much of the discussion can be extrapolated to other critically ill persons worldwide.

A neurophysiological profiling of the heartbeat-evoked potential in severe acquired brain injuries: A focus on unconsciousness.

Unconsciousness in severe acquired brain injury (sABI) patients occurs with different cognitive and neural profiles. Perturbational approaches, which enable the estimation of proxies for brain reorganization, have added a new avenue for investigating the non-behavioural diagnosis of consciousness. In this prospective observational study, we conducted a comparative analysis of the topological patterns of heartbeat-evoked potentials (HEP) between patients experiencing a prolonged disorder of consciousness (pDoC) and patients emerging from a minimally consciousness state (eMCS). A total of 219 sABI patients were enrolled, each undergoing a synchronous EEG-ECG resting-state recording, together with a standardized consciousness diagnosis. A number of graph metrics were computed before/after the HEP (Before/After) using the R-peak on the ECG signal. The peak value of the global field power of the HEP was found to be significantly higher in eMCS patients with no difference in latency. Power spectrum was not able to discriminate consciousness neither Before nor After. Node assortativity and global efficiency were found to vary with different trends at unconsciousness. Lastly, the Perturbational Complexity Index of the HEP was found to be significantly higher in eMCS patients compared with pDoC. Given that cortical elaboration of peripheral inputs may serve as a non-behavioural determinant of consciousness, we have devised a low-cost and translatable technique capable of estimating causal proxies of brain functionality with an endogenous, non-invasive stimulus. Thus, we present an effective means to enhance consciousness assessment by incorporating the interaction between the autonomic nervous system (ANS) and central nervous system (CNS) into the loop.

Effects of parietal repetitive transcranial magnetic stimulation in prolonged disorders of consciousness: A pilot study.

Objective: Although the parietal cortex is related to consciousness, the dorsolateral prefrontal and primary motor cortices are the usual targets for repetitive transcranial magnetic stimulation (rTMS) for prolonged disorders of consciousness (pDoC). Herein, we applied parietal rTMS to patients with pDoC, to verify its neurobehavioral effects and explore a new potential rTMS target. Materials and methods: Twenty-six patients with pDoC were assigned to a rTMS or sham group. The rTMS group received 10 sessions of parietal rTMS; the sham group received 10 sessions of sham stimulation. The Coma Recovery Scale-Revised (CRS-R) and event-related potential (ERP) were collected before and after the 10 sessions or sham sessions. Results: After the 10 sessions, the rTMS group showed: a significant CRS-R score increase; ERP appearance of a P300 waveform and significantly increased Fz amplitudes; increased potentials on topographic mapping, especially in the left prefrontal cortex; and an increase in delta and theta band powers at Fz, Cz, and Pz. The sham group did not show such changes in CRS-R score or ERP results statistically. Conclusion: Parietal rTMS shows promise as a novel intervention in the recovery of consciousness in pDoC. It showed neurobehavioral enhancement of residual brain function and may promote frontal activity by enhancing frontal-parietal connections. The parietal cortex may thus be an alternative for rTMS therapy protocols.

The ECG abnormalities in persons with chronic disorders of consciousness.

We aimed to investigate the electrocardiogram (ECG) features in persons with chronic disorders of consciousness (DOC, ≥ 29 days since injury, DSI) resulted from the most severe brain damages. The ECG data from 30 patients with chronic DOC and 18 healthy controls (HCs) were recorded during resting wakefulness state for about five minutes. The patients were classified into vegetative state (VS) and minimally conscious state (MCS). Eight ECG metrics were extracted for comparisons between the subject subgroups, and regression analysis of the metrics were conducted on the DSI (29-593 days). The DOC patients exhibit a significantly higher heart rate (HR, p = 0.009) and lower values for SDNN (p = 0.001), CVRR (p = 0.009), and T-wave amplitude (p < 0.001) compared to the HCs. However, there're no significant differences in QRS, QT, QTc, or ST amplitude between the two groups (p > 0.05). Three ECG metrics of the DOC patients-HR, SDNN, and CVRR-are significantly correlated with the DSI. The ECG abnormalities persist in chronic DOC patients. The abnormalities are mainly manifested in the rhythm features HR, SDNN and CVRR, but not the waveform features such as QRS width, QT, QTc, ST and T-wave amplitudes.