Minimally Conscious State Research Articles

Treating Traumatic Brain Injuries with Electroceuticals: Implications for the Neuroanatomy of Consciousness

According to the Centers for Disease Control and Prevention (CDC), traumatic brain injury (TBI) is the leading cause of loss of consciousness, long-term disability, and death in children and young adults (age 1 to 44). Currently, there are no United States Food and Drug Administration (FDA) approved pharmacological treatments for post-TBI regeneration and recovery, particularly related to permanent disability and level of consciousness. In some cases, long-term disorders of consciousness (DoC) exist, including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) characterized by the exhibition of reflexive behaviors only or a minimally conscious state (MCS) with few purposeful movements and reflexive behaviors. Electroceuticals, including non-invasive brain stimulation (NIBS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS) have proved efficacious in some patients with TBI and DoC. In this review, we examine how electroceuticals have improved our understanding of the neuroanatomy of consciousness. However, the level of improvements in general arousal or basic bodily and visual pursuit that constitute clinically meaningful recovery on the Coma Recovery Scale-Revised (CRS-R) remain undefined. Nevertheless, these advancements demonstrate the importance of the vagal nerve, thalamus, reticular activating system, and cortico-striatal-thalamic-cortical loop in the process of consciousness recovery.

Comparison of synchrosqueezing transform to alternative methods for time-frequency analysis of TMS-evoked EEG oscillations

BackgroundTranscranial magnetic stimulation combined with electroencephalography (TMS-EEG) has become a powerful tool to assess cortical properties, such as cortical oscillation. An accurate and robust time–frequency analysis tool with high resolution would facilitate the understanding of TMS-evoked oscillations. MethodsThe synchrosqueezing transform (SST), the Hilbert-Huang transform (HHT) and the Morlet wavelet transform (MWT) were used to analyze TMS-evoked oscillations. Firstly, we generated simulation data, and compared the performance of three methods to analyze the time–frequency characteristics of simulation data; then, we collected TMS-EEG data from normal people (NOR), patients with minimally conscious state (MCS) and vegetative state (VS). SST was used to analysis time–frequency characteristics of TMS-evoked oscillations in different states of consciousness. In addition, relative power (RP) and spectral entropy (SeEn) were calculated based on SST results. ResultsSimulation results showed that SST detected rhythm characteristics of instantaneous signal and background signal more completely. Results of NOR group showed that SST could more accurately detect TMS-evoked oscillations with high frequency resolution than HHT and MWT. The main frequency of TMS-evoked oscillations for DOC patients (MCS: 11.73 ± 1.94 Hz; VS: 2.06 ± 0.25 Hz) was different from that of NOR (22.79 ± 1.42 Hz) based on SST. RP and SeEn further verified the differences of the main frequency of TMS-evoked oscillations between NOR and DOC patients. ConclusionsThe results suggest that SST is a robust analytical method and outperforms HHT and MWT in studying TMS-evoked oscillations. The main frequency of TMS-evoked oscillations of DOC was lower than that of NOR.

Spontaneous transient brain states in EEG source space in disorders of consciousness

Spontaneous transient states were recently identified by functional magnetic resonance imaging and magnetoencephalography in healthy subjects. They organize and coordinate neural activity in brain networks. How spontaneous transient states are altered in abnormal brain conditions is unknown. Here, we conducted a transient state analysis on resting-state electroencephalography (EEG) source space and developed a state transfer analysis to patients with disorders of consciousness (DOC). They uncovered different neural coordination patterns, including spatial power patterns, temporal dynamics, spectral shifts, and connectivity construction varies at potentially very fast (millisecond) time scales, in groups with different consciousness levels: healthy subjects, patients in minimally conscious state (MCS), and patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS). Machine learning based on transient state features reveal high classification accuracy between MCS and VS/UWS. This study developed methodology of transient states analysis on EEG source space and abnormal brain conditions. Findings correlate spontaneous transient states with human consciousness and suggest potential roles of transient states in brain disease assessment.

Estimating the Minimal Number of Repeated Examinations for Random Responsiveness With the Coma Recovery Scale-Revised as an Example.

Objective: The aim of this study was to develop a general method to estimate the minimal number of repeated examinations needed to detect patients with random responsiveness, given a limited rate of missed diagnosis.Methods: Basic statistical theory was applied to develop the method. As an application, 100 patients with disorders of consciousness (DOC) were assessed with the Coma Recovery Scale–Revised (CRS-R). DOC patients were supposed to be examined for 13 times over 20 days, while anyone who was diagnosed as a minimally conscious state (MCS) in a round would no longer be examined in the subsequent rounds. To test the validation of this method, a series of the stochastic simulation was completed by computer software under all the conditions of possible combinations of three kinds of distributions for p, five values of p, and four sizes of the sample and repeated for 100 times.Results: A series of formula was developed to estimate the probability of a positive response to a single examination given by a patient and the minimal number of successive examinations needed based on the numbers of patients detected in the first i (i =1, 2,.) rounds of repeated examinations. As applied to the DOC patients assessed with the CRS-R, with a rate of missed diagnosis < 0.0001, the estimate of the minimal number of examinations was six in traumatic brain injury patients and five in non-traumatic brain injury patients. The outcome of the simulation showed that this method performed well under various conditions possibly occurring in practice.Interpretation: The method developed in this paper holds in theory and works well in application and stochastic simulation. It could be applied to any other kind of examinations for random responsiveness, not limited to CRS-R for detecting MCS; this should be validated in further research.

Disrupted Strength and Stability of Regional Brain Activity in Disorder of Consciousness Patients: A Resting-State Functional Magnetic Resonance Imaging Study

Although the resting-state networks of patients with disorders of consciousness (DOC) have been widely investigated, the underlying neural mechanisms remain unclear. Here we aimed to explore the static and dynamic alterations in the regional brain activity in patients with DOC and detect the diagnostic ability of each index. Nineteen patients in the vegetative state, 19 in the minimally conscious state (MCS), and 41 healthy controls were recruited for this study. The fractional amplitudes of the low-frequency fluctuation (fALFF) and dynamic fALFF (dfALFF) values were computed, and intergroup differences were detected by analysis of variance. Sub-frequency analysis (slow-4 band and slow-5 band) of fALFF was also performed. Machine learning classifiers were established based on these measures to explore the classification accuracies between patients and controls. The fALFF and dfALFF analyses showed significant intergroup differences in the medial prefrontal gyrus, precuneus, left angular gyrus, and right middle cingulate cortex (MCC), whereas only the dfALFF analysis revealed aberrations in the right inferior frontal gyrus (IFG), right angular gyrus, left supramarginal gyrus (SMG), and left middle occipital gyrus (MOG). Sub-frequency analysis suggested a potential frequency dependent alteration in the default mode network (DMN). The fALFF model exhibited a higher classification accuracy (ACC) (90.50%) than the dfALFF model (86.29%). The combination of fALFF and dfALFF did not improve classification performance. The strength and stability of regional brain activities were disrupted in patients with DOC. Our findings demonstrate that dynamic analysis may reveal more pathological regions and provide a better understanding of the pathophysiologic mechanisms of DOC.

Epidemiology and clinical characteristics of patients discharged from the ICU in a vegetative or minimally conscious state.

PurposeA significant percentage of patients are discharged from intensive care units (ICU) with disorders of counciousness (DoC). The aim of this retrospective, case-control study was to compare patients discharged from the ICU in a vegetative state (VS) or minimally conscious state (MCS) and the rest of ICU survivors, and to identify independent predictors of DoC among ICU survivors.MethodsData from 14,368 adult ICU survivors identified in a Silesian Registry of Intensive Care Units (active in the Silesian Region of Poland between October 2010 and December 2019) were analyzed. Patients discharged from the ICU in a VS or MCS were compared to the remaining ICU survivors. Pre-admission and admission variables that independently influence ICU discharge with DoC were identified.ResultsAmong the 14,368 analyzed adult ICU survivors, 1,064 (7.4%) were discharged from the ICU in a VS or MCS. The percentage of patients discharged from the ICU with DoC was similar in all age groups. Compared to non- DoC ICU patients, they had a higher mean APACHE II and SAPS III score at admission. Independent variables affecting ICU discharge with DoC included unconsciousness at ICU admission, cardiac arrest and craniocerebral trauma as primary cause of ICU admission, as well as a history of previous chronic neurological disorders and cerebral stroke (p<0.001).ConclusionDischarge in a VS and MCS was relatively frequent among ICU survivors. Discharge with DoC was more likely among patients who were unconscious at admission and admitted to the ICU due to cardiac arrest or craniocerebral trauma.

Annals of Neurology: Volume 90, Number 1, July 2021

A series of schematic drawings of EEG functional connectivity in the alpha range (upper row) and delta range (lower row) across the brain, with more intense connections in warmer colors, and less intense ones in cooler colors. The two images on the left represent patients in the unresponsive wakefulness syndrome (UWS) and on the right in healthy controls. Patients in the minimally conscious state (MCS) are shown in the third column, and to their left are patients in the MCS* state, who are behaviorally unresponsive but have a better outcome than typical UWS patients. See Thibaut et al., (pp. 89–100, this issue) for details.

The Timecourse of Electrophysiological Brain-Heart Interaction in DoC Patients.

Disorders of Consciousness (DOC) are a spectrum of pathologies affecting one’s ability to interact with the external world. Two possible conditions of patients with DOC are Unresponsive Wakefulness Syndrome/Vegetative State (UWS/VS) and Minimally Conscious State (MCS). Analysis of spontaneous EEG activity and the Heart Rate Variability (HRV) are effective techniques in exploring and evaluating patients with DOC. This study aims to observe fluctuations in EEG and HRV parameters in the morning/afternoon resting-state recording. The study enrolled 13 voluntary Healthy Control (HC) subjects and 12 DOC patients (7 MCS, 5 UWS/VS). EEG and EKG were recorded. PSDalpha, PSDtheta powerband, alpha-blocking, alpha/theta of the EEG, Complexity Index (CI) and SDNN of EKG were analyzed. Higher values of PSDalpha, alpha-blocking, alpha/theta and CI values and lower values of PSD theta characterized HC individuals in the morning with respect to DOC patients. In the afternoon, we detected a significant difference between groups in the CI, PSDalpha, PSDtheta, alpha/theta and SDNN, with lower PSDtheta value for HC. CRS-R scores showed a strong correlation with recorded parameters mainly during evaluations in the morning. Our finding put in evidence the importance of the assessment, as the stimulation of DOC patients in research for behavioural response, in the morning.

Preservation of Brain Activity in Unresponsive Patients Identifies MCS Star.

ObjectiveBrain‐injured patients who are unresponsive at the bedside (ie, vegetative state/unresponsive wakefulness syndrome – VS/UWS) may present brain activity similar to patients in minimally conscious state (MCS). This peculiar condition has been termed “non‐behavioural MCS” or “MCS*”. In the present study we aimed to investigate the proportion and underlying brain characteristics of patients in MCS*.MethodsBrain 18F‐fluorodeoxyglucose Positron Emission Tomography (FDG‐PET) was acquired on 135 brain‐injured patients diagnosed in prolonged VS/UWS (n = 48) or MCS (n = 87). From an existing database, relative metabolic preservation in the fronto‐parietal network (measured with standardized uptake value) was visually inspected by three experts. Patients with hypometabolism of the fronto‐parietal network were labelled “VS/UWS”, while its (partial) preservation either confirmed the behavioural diagnosis of “MCS” or, in absence of behavioural signs of consciousness, suggested a diagnosis of “MCS*”. Clinical outcome at 1‐year follow‐up, functional connectivity, grey matter atrophy, and regional brain metabolic patterns were investigated in the three groups (VS/UWS, MCS* and MCS).Results67% of behavioural VS/UWS presented a partial preservation of brain metabolism (ie, MCS*). Compared to VS/UWS patients, MCS* patients demonstrated a better outcome, global functional connectivity and grey matter preservation more compatible with the diagnosis of MCS. MCS* patients presented lower brain metabolism mostly in the posterior brain regions compared to MCS patients.InterpretationMCS* is a frequent phenomenon that is associated with better outcome and better brain preservation than the diagnosis of VS/UWS. Complementary exams should be provided to all unresponsive patients before taking medical decisions. ANN NEUROL 2021;90:89–100

Pain Perception in Disorder of Consciousness: A Scoping Review on Current Knowledge, Clinical Applications, and Future Perspective.

Pain perception in individuals with prolonged disorders of consciousness (PDOC) is still a matter of debate. Advanced neuroimaging studies suggest some cortical activations even in patients with unresponsive wakefulness syndrome (UWS) compared to those with a minimally conscious state (MCS). Therefore, pain perception has to be considered even in individuals with UWS. However, advanced neuroimaging assessment can be challenging to conduct, and its findings are sometimes difficult to be interpreted. Conversely, multichannel electroencephalography (EEG) and laser-evoked potentials (LEPs) can be carried out quickly and are more adaptable to the clinical needs. In this scoping review, we dealt with the neurophysiological basis underpinning pain in PDOC, pointing out how pain perception assessment in these individuals might help in reducing the misdiagnosis rate. The available literature data suggest that patients with UWS show a more severe functional connectivity breakdown among the pain-related brain areas compared to individuals in MCS, pointing out that pain perception increases with the level of consciousness. However, there are noteworthy exceptions, because some UWS patients show pain-related cortical activations that partially overlap those observed in MCS individuals. This suggests that some patients with UWS may have residual brain functional connectivity supporting the somatosensory, affective, and cognitive aspects of pain processing (i.e., a conscious experience of the unpleasantness of pain), rather than only being able to show autonomic responses to potentially harmful stimuli. Therefore, the significance of the neurophysiological approach to pain perception in PDOC seems to be clear, and despite some methodological caveats (including intensity of stimulation, multimodal paradigms, and active vs. passive stimulation protocols), remain to be solved. To summarize, an accurate clinical and neurophysiological assessment should always be performed for a better understanding of pain perception neurophysiological underpinnings, a more precise differential diagnosis at the level of individual cases as well as group comparisons, and patient-tailored management.

One-Year Demographical and Clinical Indices of Patients with Chronic Disorders of Consciousness.

This work aims to evaluate the prognostic value of the demographical and clinical data on long-term outcomes (up to 12 months) in patients with severe acquired brain injury with vegetative state/unresponsive wakefulness syndrome (VS/UWS/UWS) or a minimally conscious state (MCS). Patients (n = 211) with VS/UWS/UWS (n = 123) and MCS (n = 88) were admitted to the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology after anoxic brain injury (n = 53), vascular lesions (n = 59), traumatic brain injury (n = 93), and other causes (n = 6). At the beginning of the 12-month study, younger age and a higher score by the Coma Recovery Scale-Revised (CRS-R) predicted a survival. However, no reliable markers of significant positive dynamics of consciousness were found. Based on the etiology, anoxic brain injury has the most unfavorable prognosis. For patients with vascular lesions, the first three months after injury have the most important prognostic value. No correlations were found between survival, increased consciousness, and gender. The demographic and clinical characteristics of patients with chronic DOC can be used to predict long-term mortality in patients with chronic disorders of consciousness. Further research should be devoted to finding reliable predictors of recovery of consciousness.

Thinking without speaking: Neuropsychological testing with individuals who have communication impairments

ABSTRACT Purpose Cognitive ability may be masked by communication impairments. This study aimed to assess cognitive functioning using binary choice (i.e., yes/no) neuropsychological tests in patients with communication impairments. Four participants underwent neuropsychological testing. Two participants were in the minimally conscious state (MCS), one participant had locked-in syndrome and was an alternative communication user, and one participant was an augmentative communication user. There was better performance in all cognitive domains for the augmentative and alternative communication (AAC) users (who performed like the non-communication impaired normative data) compared to the MCS participants. However, using established yes/no communication methods, MCS participants performed above chance on a measure of memory and performance on measures of auditory comprehension was variable. Auditory comprehension appeared to be more influenced by working memory demands for the MCS participants than for the AAC users. For emotional functioning, the AAC users endorsed lower mood compared to the MCS participants. The results support the need to assess cognition, communication, as well as capacity in individuals with communication impairments with the consultation of a neuropsychologist and a speech-language pathologist.

Food as Love: Ethical and Moral Dilemmas in Withdrawal of Artificial Nutrition and Hydration in the Minimally Conscious State.

Supportive Palliative Care and Hospice professionals frequently attend to Minimally Conscious State (MCS) patients near the end of life and in so doing, face decisions over maintenance or withdrawal of artificial nutrition and hydration. Although both withholding and withdrawal of artificial nutrition and hydration (ANH) in such circumstances are considered by experts in ethics and law to be acceptable, not all families nor health care professionals agree. This paper will explore basic aspects of serious brain injuries, especially MCS, the psychological role of food in interpersonal relationships, and lessons from clinical ethics that can help in goals of care discussions about withdrawal of ANH.

Volumetric Analysis of Malignant Middle Cerebral Infarction (MMI): Infarction Volume Before Decompressive Hemicraniectomy for MMI is Associated With Poor Consciousness

Objective In patients with malignant middle cerebral infarction (MMI), early decompressive hemicraniectomy (DHC) is well-known to reduce mortality and improve clinical outcome. Nevertheless, its effectiveness in clinical outcomes has only been confirmed by defining outcomes in terms of the modified Rankin scale (mRS), and many studies have already suggested that survival with severe dependency, such as mRS 4 or 5, is not acceptable. However, several other important domains are closely related to quality of life, such as consciousness or cognition, and these are not directly measured in the mRS. Therefore, the present study aimed to identify significant factors associated with poor consciousness, such as minimally conscious state (MCS) or vegetative state (VS) in patients undergoing DHC to treat MMI. Methods Between January 2011 and December 2017, 22 patients who survived from MMI after DHC and had more than 6 months of follow-up were enrolled our study. Clinical outcomes 6 months after DHC were measured, and the patients were divided into two groups based on their level of consciousness. Preserved consciousness was categorized as a favorable outcome, while poor consciousness such as MCS or VS constituted an unfavorable outcome. Clinical and radiological variables using volumetric measurement were analyzed to identify factors that were significantly associated with unfavorable outcome. Results Of the entire cohort, eight patients (36.36%) were placed in the unfavorable outcome (MCS or VS) 6 months after DHC to treat MMI. In univariate and multivariate logistic analysis, only infarction volume in the preoperative CT was a significant independent predictor of unfavorable outcome (odds ratio: 1.021, 95% confidence interval: 1.001–1.042, p = 0.023). Conclusions The present study suggested that defining unfavorable outcome based on level of consciousness to reflect quality of life should be considered. We identified infarction volume as a significant predictor of poor consciousness. Keywords: Decompressive craniectomy; MCA infarction; Outcome; Consciousness; mRS.

Behavioral signs of recovery from unresponsive wakefulness syndrome to emergence of minimally conscious state after severe brain injury.

Precise description of behavioral signs denoting transition from unresponsive wakefulness syndrome/vegetative state (UWS/VS) to minimally conscious state (MCS) or emergence from MCS after severe brain injury is crucial for prognostic purposes. A few studies have attempted this goal but involved either non-standardized instruments, limited temporal accuracy or samples, or focused on (sub)acute patients. The objective of this study was to describe the behavioral signs that led to a change of diagnosis, as well as the factors influencing this transition, in a large sample of patients with chronic disorders of consciousness after severe brain injury. In this retrospective cohort study, 185 patients in UWS/VS or MCS were assessed with the Coma Recovery Scale Revised (CRS-R) five times within the two weeks following their admission to a neurorehabilitation center and then weekly until emergence from MCS, discharge or death. Of these 185 patients, 33 patients in UWS/VS and 45 patients in MCS transitioned to another state. Transition to MCS was mostly denoted by one behavioral sign (72%), predominantly visual fixation (57%), followed by localization to noxious stimulation (27%), visual pursuit (21%) and object manipulation (12%), and could be predicted by etiology, time post-injury and age. Emergence from MCS was characterized by one sign in 64% of patients and by two signs (functional communication and objects use) in the remaining cases, and could be predicted by time post-injury and number of behavioral signs at admission. Clinicians should be therefore advised to pay particular attention to visual and motor subscales of the CRS-R to detect behavioral recovery.

A novel closed-loop EEG-tDCS approach to promote responsiveness of patients in minimally conscious state: A study protocol

Transcranial direct current stimulation (tDCS) applied over the prefrontal cortex has been shown to improve behavioral responsiveness in patients with disorders of consciousness following severe brain injury, especially those in minimally conscious state (MCS). However, one potential barrier of clinical response to tDCS is the timing of stimulation with regard to the fluctuations of vigilance that characterize this population. Indeed, a previous study showed that the vigilance of MCS patients has periodic average cycles of 70 min (range 57−80 min), potentially preventing them to be in an optimal neural state to benefit from tDCS when applied randomly. To tackle this issue, we propose a new protocol to optimize the application of tDCS by selectively stimulating at high and low vigilance states. Electroencephalography (EEG) real-time spectral entropy will be used as a marker of vigilance and to trigger tDCS, in a closed-loop fashion. We will conduct a randomized controlled crossover clinical trial on 16 patients in prolonged MCS who will undergo three EEG-tDCS sessions 5 days apart (1. tDCS applied at high vigilance; 2. tDCS applied at low vigilance; 3. tDCS applied at a random moment). Behavioral effects will be assessed using the Coma Recovery Scale-Revised at baseline and right after the stimulations. EEG will be recorded throughout the session and for 30 min after the end of the stimulation. This unique and novel approach will provide patients’ tailored treatment options, currently lacking in the field of disorders of consciousness.

Communication Abilities of Children with DoC after Severe Brain Injury in ICF Frames.

Introduction: The ability to communicate is one of the fundamental factors underlying human relationships. Severe brain damage and disorders of consciousness may indispose a person to participate in everyday social and family life. In spite of this fact, however, the issue of holistic approach to communication in the context of severe traumatic brain injury is still not well explained and described. The goal of this article is to introduce a profile of nonverbal behavior of children with disorders of consciousness. Materials and methods: The study included 30 children with minimal conscious state after severe brain trauma, aged between 7 and 16 years old. Research was conducted using the Coma Recovery Scale—Revised and the Bykova–Lukyanov Scale of Communication Activity. Results: Significant differences in communication level between investigated groups were demonstrated, both in Body Function (F = 9.184; p < 0.001) and Activity and Participation (F = 13.100; p < 0.001). Conclusions: It is possible to map and classify communication ability of children with minimal conscious state by using International Classification of Functioning, Disability and Health (ICF) protocol and the Bykova–Lukyanov Scale of Communication Activity, with specific consideration of Activities and Participation factors. This approach reveals differences in communication and disability level between children with minimal conscious state plus (MSC+) and minimal conscious state minus (MSC−).

Can Music Influence Patients With Disorders of Consciousness? An Event-Related Potential Study.

BackgroundLong-term disorders of consciousness (DOC) are a huge burden on both patients and their families. Previously, music intervention has been attempted as a potential therapy in DOC, with results indicating an enhancement of arousal and awareness; yet, to date, there are limited studies on music interventions in DOC with electroencephalogram monitoring. Meanwhile, prediction of awareness recovery is a challenge facing clinicians. The predictive value mismatch negativity (MMN), as a classical cognitive component in event-related potential, is still controversial. In this study, we use auditory event-related potential to probe the effect of music in DOC, and investigate whether music may improve the predictive value of MMN in awareness recovery.MethodsFourteen DOC patients were included in the prospective study. Auditory oddball electroencephalogram data were recorded twice with each patient, before and after 5 min of listening to a Chinese symphony that has joyful associations. The outcome was assessed 6 months later.ResultsSignificant differences of MMN amplitude were found between healthy controls and pre-music DOC patients (p < 0.001), but no significant differences were found between healthy controls and post-music DOC patients. The presence of MMN before music was not correlated with favorable outcome, and 50% of patients with MMN did not recover awareness. When MMN was absent, 50% of patients awoke. After listening to music, among the 11 patients who showed MMN, seven patients recovered awareness. When MMN was absent, no one recovered awareness.ConclusionsSome DOC patients, even those in a minimal consciousness state and those with unresponsive wakefulness syndrome (UWS), were affected by music. The MMN amplitude was elevated by the music to some extent. A single test of MMN did not have a good prognostic value of our study; however, retesting of MMN after stimulation with familiar music that has joyful associations might be valuable for observation and detection of possible recovery. The musical processing in DOC patients and the effect of musical therapeutic practices need further investigations.

Therapeutic Use of Transcranial Direct Current Stimulation in the Rehabilitation of Prolonged Disorders of Consciousness.

Patients with Prolonged Disorders of Consciousness (PDOC) have catastrophic disabilities and very complex needs for care. Therapeutic options are very limited, and patients often show little functional improvement over time. Neuroimaging studies have demonstrated that a significant number of PDOC patients retain a high level of cognitive functioning, and in some cases even awareness, and are simply unable to show this with their external behavior - a condition known as cognitive-motor dissociation (CMD). Despite vast implications for diagnosis, the discovery of covert cognition in PDOC patients is not typically associated with a more favorable prognosis, and the majority of patients will remain in a permanent state of low responsiveness. Recently, transcranial direct current stimulation (tDCS) has attracted attention as a potential therapeutic tool in PDOC. Research to date suggests that tDCS can lead to clinical improvements in patients with a minimally conscious state (MCS), especially when administered over multiple sessions. While promising, the outcomes of these studies have been highly inconsistent, partially due to small sample sizes, heterogeneous methodologies (in terms of both tDCS parameters and outcome measures), and limitations related to electrode placement and heterogeneity of brain damage inherent to PDOC. In addition, we argue that neuroimaging and electrophysiological assessments may serve as more sensitive biomarkers to identify changes after tDCS that are not yet apparent behaviorally. Finally, given the evidence that concurrent brain stimulation and physical therapy can enhance motor rehabilitation, we argue that future studies should focus on the integration of tDCS with conventional rehabilitation programmes from the subacute phase of care onwards, to ascertain whether any synergies exist.

Hybrid asynchronous brain–computer interface for yes/no communication in patients with disorders of consciousness

Objective. For patients with disorders of consciousness (DOC), such as vegetative state (VS) and minimally conscious state (MCS), communication is challenging. Currently, the communication methods of DOC patients are limited to behavioral responses. However, patients with DOC cannot provide sufficient behavioral responses due to motor impairments and limited attention. In this study, we proposed a hybrid asynchronous brain–computer interface (BCI) system that provides a new communication channel for patients with DOC. Approach. Seven patients with DOC (3 VS and 4 MCS) and eleven healthy subjects participated in our experiment. Each subject was instructed to focus on the square with the Chinese words ‘Yes’ and ‘No’. Then, the BCI system determined the target square with both P300 and steady-state visual evoked potential (SSVEP) detections. For the healthy group, we tested the performance of the hybrid system and the single-modality BCI system. Main results. All healthy subjects achieved significant accuracy (ranging from 72% to 100%) in both the hybrid system and the single modality system. The hybrid asynchronous BCI system outperformed the P300-only and SSVEP-only systems. Furthermore, we employed the asynchronous approach to dynamically collect the electroencephalography signal. Compared with the synchronous system, there was a 21% reduction in the average required rounds and a reduction of 105 s in the online experiment time. This asynchronous system was applied to detect the ‘yes/no’ communication function of seven patients with DOC, and the results showed that three of the patients (3 MCS) not only showed significant accuracies (67 ± 3%) in the online experiment, and their Coma Recovery Scale-Revised scores were also improved compared with the scores before the experiment. This result demonstrated that 3 of 7 patients were able to communicate using our hybrid asynchronous BCI system. Significance. This hybrid asynchronous BCI system can be used as a useful auxiliary bedside tool for simple communication with DOC patients.