How brain-computer interface technology may improve the diagnosis of the disorders of consciousness: A comparative study

Visual pursuit assessment is extensively applied in the behavioral scale-based clinical examination of patients with disorders of consciousness (DOC). However, this assessment is challenging because it relies on behavioral markers, and these patients severely lack behavioral responses. Brain-computer interfaces (BCIs) may provide a potential solution to detect brain responses to external stimuli without requiring behavioral expressions. A BCI system was designed to simulate visual pursuit detection in the coma recovery scale-revised (CRS-R). The graphical user interface included four buttons, one that moved on the screen and three that did not. These buttons flashed in a random order. The patients were prompted to follow the moving button. Based on the collected electroencephalography data, the algorithm determined whether the patient focused on the moving target. Among the 14 DOC patients who participated in the assessments based on the BCI system and the CRS-R, four patients exhibited visual pursuit, and three were nonresponsive in both assessments. More importantly, seven patients who did not exhibit visual pursuit in CRS-R were detected to be responsive to the moving target stimuli in the BCI assessment. Furthermore, five out of seven recovered consciousness to some degree and showed visual pursuit in the second CRS-R assessment. The proposed BCI system is better able to detect visual pursuit than the behavioral scale-based assessment and thus can assist in clinically evaluating the challenging population of DOC patients.

Brain-computer interface (BCI) has been emerging as an assessment tool for patients with disorder of consciousness (DOC). With the advantages of high time resolution, low cost and portable design, EEG based BCI systems are especially suitable for bedside measurement. Recent studies showed the successful application of an EEG based BCI on DOC assessment and communication. However, the effect of repeated BCI measurement on this patient group is not clear. In this study, a tactile BCI paradigm was repeated 12 runs for 10 consecutive days on 5 DOC patients. Although the BCI performance varied among runs and days, every patient reached at least once the accuracy above 60%. Moreover, the Coma Recovery Scale Revised improved on two out of the five patients. This study addressed the significance of repeating a tactile BCI on DOC patients, and indicates a promising recovery effect of a tactile BCI on DOC patients.

With the continuous advancement of neuroimaging technologies, clinical research has discovered the phenomenon of cognitive-motor dissociation in patients with disorders of consciousness (DoC). This groundbreaking finding has provided new impetus for the development and application of brain-computer interface (BCI) in clinic. Currently, BCI has been widely applied in DoC patients as an important tool for assessing and assisting behaviorally unresponsive individuals. This paper reviews the current applications of BCI in DoC patients, focusing four main aspects including consciousness detection, auxiliary diagnosis, prognosis assessment, and rehabilitation treatment. It also provides an in-depth analysis of representative key techniques and experimental outcomes in each aspect, which include BCI paradigm designs, brain signal decoding method, and feedback mechanisms. Furthermore, the paper offers recommendations for BCI design tailored to DoC patients and discusses future directions for research and clinical practice in this field.

Making an appropriate diagnosis and effective treatment for hydrocephalus in patients with severe disorders of consciousness (DOC) remains controversial and difficult. Given that the typical symptoms are usually concealed by the limited behavioral responsiveness of patients with severe DOC, hydrocephalus diagnosis is likely to be missed in the clinic. Even if not, the presence of hydrocephalus may reduce the likelihood of DOC recovery, posing a conundrum for clinicians. From December 2013 to January 2023, the clinical data and therapeutic schedule of hydrocephalus in patients with severe DOC at Huashan Hospital's Neurosurgical Emergency Center were studied retrospectively. Sixty-eight patients [mean age (± SD) 52.53 ± 17.03 years, 35 males and 33 females] with severe DOC had been included. The hydrocephalus was discovered after computerized tomography (CT) or magnetic resonance imaging (MRI) revealed enlarged ventricles in the patients. During the hospitalization, the patient underwent a surgical treatment that included a ventriculoperitoneal (V-P) shunt and/or cranioplasty (CP) implantation. Following the surgery, an individualized V-P pressure was established based on the patient's ventricle size and neurological function variation. To account for the improvement in consciousness in patients with severe DOC, the Glasgow Coma Scale (GCS) and the Coma Recovery Scale-Revised (CRS-R) assessments were performed before and after hydrocephalus treatment. All severe DOC patients have varying degrees of ventricular enlargement, deformation, and poor brain compliance. Approximately 60.3% (41/68) of them had low- or negative-pressure hydrocephalus (LPH or NegPH). 45.5% (31/68) of the patients had a one-stage V-P shunt and CP operation performed concurrently, while the remaining 37 patients had a single V-P shunt operation performed independently. Beside of two DOC patients developed surgical complications, 92.4% (61/66) of the survivors showed an improvement in consciousness after hydrocephalus treatment. In patients with severe DOC, LPH or NegPH was common. Secondary hydrocephalus in DOC patients had been largely ignored, hampering their neurological rehabilitation. Even months or years after the onset of severe DOC, active treatment of hydrocephalus can significantly improve patients' consciousness and neurological function. Meanwhile, this study summarized several evidence-based treatment experiences of hydrocephalus in patients with DOC.

BackgroundOccasionally, patients show dramatic recovery from disorders of consciousness (DOC) under intrathecal baclofen (ITB), an established treatment option for severe supraspinal spasticity. Anecdotal explanations for ITB‐related recovery of cognition include modulation of afferent impulses at the spinal level, thereby reducing spasticity‐related proprioceptive information overload within cortico–thalamo–cortical connections.ObjectiveIn this retrospective patient chart analysis, we assessed whether a reduction in spasticity would be associated with an increase in Coma Recovery Scale revised (CRS‐R) scores in a larger sample of patients than previously published.MethodsFrom a hospital‐based ITB treatment register, we extracted data from 26 patients with DOC and severe supraspinal spasticity who improved by >2 points on the Coma Recovery Scale revised (CRS‐R) within 6 months after ITB treatment initiation. We assessed Modified Ashworth scale (MAS) scores and CRS‐R scores on admission (PRE) and 3 and 6 months after initiation of ITB treatment (3M, 6M). We performed correlation analysis of the scores and their respective changes (PRE to 3M, 3M to 6M). We also correlated the time from acute event until ITB initiation to CRS‐R scores at 3M and 6M.ResultsITB led to significant improvement in spasticity based on MAS scores, which did not correlate to the improvements seen in CRS‐R total and subscale scores. Daily ITB dose did neither correlate to MAS scores nor to CRS‐total scores in the whole patient group, but after 3 months, ITB dose correlated to some CRS‐R subscale scores in some patient subgroups. Time until ITB treatment did not correlate to CRS‐R scores later on.ConclusionsOur data confirm that ITB may exert beneficial effects in selected DOC patients with respect to improved cognitive functions, which, however, do not correlate to its antispastic effect. The lack of correlation between time to ITB and CRS‐R outcome, but significant CRS‐R improvements following pump implantation, renders spontaneous remissions unlikely and leaves room for alternative pharmacological mechanisms.

The proper assessment of cognitive functioning is the subject of numerous scientific studies. Current behavioral methods essentially preclude this assessment in patients with disorders of consciousness (DOC). However, the development of eye-tracking technology (ETT) and the establishment of contact via this channel have created an opportunity to diagnose the cognitive function (CF) of DOC patients. The purpose of this study was to assess the level of CF of DOC patients for whom vision is the only channel of communication to introduce the CF assessment tool for DOC patients for whom vision remains the only channel for communication. The clinical multicenter study involved 31 DOC patients, whose attention, language functions, visual-spatial functions, personal orientation, memory, and abstract thinking were assessed three times (T1-T3) using the Cognitive Functions Assessment (CFA) scale, installed on the C-EYE X system. The collected data were compared with the CF assessment results obtained with the Coma Recovery Scale-Revised (CRS-R), and then statistically analyzed. There were no statistically significant differences between different time points. Patients scoring higher on the CRS-R receive higher values on the CFA. Statistically significant and moderate correlations were found between the total CFA and CRS-R scores. The results of the study indicate that the diagnosis of CF made with the use of the CFA allows for an accurate assessment of a wide spectrum of CF as well as makes their assessment independent of the experience of the examiner and the cooperation of the patient. The use of ETT, without reducing the quality of the examination, may reduce the workload of qualified personnel. The study was registered on the ClinicalTrials.gov clinical trials platform ID NCT05536921.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-27996-6.

Over the last 30 years, there has been a growing trend in clinical trials towards assessing novel interventions not only against the benchmark of statistical significance, but also with respect to whether they lead to clinically meaningful changes for patients. In the context of Disorders of Consciousness (DOC), despite a growing landscape of experimental interventions, there is no agreed standard as to what counts as a minimal clinically important difference (MCID). In part, this issue springs from the fact that, by definition, DOC patients are either unresponsive (i.e., in a Vegetative State; VS) or non-communicative (i.e., in a Minimally Conscious State; MCS), which renders it impossible to assess any subjective perception of benefit, one of the two core aspects of MCIDs. Here, we develop a novel approach that leverages published, international diagnostic guidelines to establish a probability-based minimal clinically important difference (pMCID), and we apply it to the most validated and frequently used scale in DOC: the Coma Recovery Scale–Revised (CRS-R). This novel method is objective (i.e., based on published criteria for patient diagnosis) and easy to recalculate as the field refines its agreed-upon criteria for diagnosis. We believe this new approach can help clinicians determine whether observed changes in patients’ behavior are clinically important, even when patients cannot communicate their experiences, and can align the landscape of clinical trials in DOC with the practices in other medical fields.

Electroencephalography quadratic phase self-coupling correlates with consciousness states and restoration in patients with disorders of consciousness

Neurological disorders such as Parkinson's disease, stroke, and spinal cord injury can pose significant threats to human mortality, morbidity, and functional independence. Brain-Computer Interface (BCI) technology, which facilitates direct communication between the brain and external devices, emerges as an innovative key to unlocking neurological conditions, demonstrating significant promise in this context. This comprehensive review uniquely synthesizes the latest advancements in BCI research across multiple neurological disorders, offering an interdisciplinary perspective on both clinical applications and emerging technologies. We explore the progress in BCI research and its applications in addressing various neurological conditions, with a particular focus on recent clinical studies and prospective developments. Initially, the review provides an up-to-date overview of BCI technology, encompassing its classification, operational principles, and prevalent paradigms. It then critically examines specific BCI applications in movement disorders, disorders of consciousness, cognitive and mental disorders, as well as sensory disorders, highlighting novel approaches and their potential impact on patient care. This review reveals emerging trends in BCI applications, such as the integration of artificial intelligence and the development of closed-loop systems, which represent significant advancements over previous technologies. The review concludes by discussing the prospects and directions of BCI technology, underscoring the need for interdisciplinary collaboration and ethical considerations. It emphasizes the importance of prioritizing bidirectional and high-performance BCIs, areas that have been underexplored in previous reviews. Additionally, we identify crucial gaps in current research, particularly in long-term clinical efficacy and the need for standardized protocols. The role of neurosurgery in spearheading the clinical translation of BCI research is highlighted. Our comprehensive analysis presents BCI technology as an innovative key to unlocking neurological disorders, offering a transformative approach to diagnosing, treating, and rehabilitating neurological conditions, with substantial potential to enhance patients' quality of life and advance the field of neurotechnology.

INTRODUCTION: Patients with disorders of consciousness (DoC) represent a complex patient cohort requiring a multidisciplinary approach. Despite the availability of modern national clinical guidelines (2023), real-world clinical practice in Russia continues to be challenged by the use of outdated terminology, insufficient implementation of validated diagnostic scales, and a lack of standardized management approaches, including pain assessment and management. This study was prompted by the need to assess the current situation and identify key issues to improve the quality of care for patients with DoC in Russia. OBJECTIVE: To assess the current practices, awareness, and key challenges faced by Russian healthcare professionals in the diagnosis, treatment, and management of patients with chronic DoC. MATERIALS AND METHODS: In 2024, an anonymous online survey of 204 medical and paramedical professionals (anesthesiologists, neurologists, rehabilitation specialists, psychologists, nursing staff) from various regions of Russia was conducted. The 47-item questionnaire covered demographic data, terminology used, diagnostic scales, treatment and rehabilitation methods, as well as approaches to pain assessment and management. RESULTS: Despite modern clinical guidelines, outdated terminology persists in practice: apallic syndrome (13.3 %), vegetative state. Only 62.9 % of respondents use the validated Coma Recovery Scale-Revised (CRS-R) for DoC diagnosis, while 77.1 % still use non-relevant scales (Glasgow Coma Scale, Full Outline of UnResponsiveness — FOUR). 30 % of respondents, including physicians responsible for diagnosis, use exclusively these non-relevant tools. Significant differences in approaches were identified among specialists of different profiles (intensivists, neurologists, rehabilitation specialists). The majority of respondents (83 %) acknowledge that DoC patients experience pain; however, the assessment methods (autonomic signs, grimacing) are not standardized and can be non-specific. CONCLUSIONS: The study results indicate insufficient awareness and fragmented implementation of modern standards for the diagnosis and management of patients with DoC in Russia. The findings highlight the necessity of developing and implementing educational programs for healthcare professionals aimed at standardizing terminology, promoting the use of validated diagnostic scales (CRS-R), and harmonizing approaches to pain management.

The Coma Recovery Scale-Revised (CRS-R) is the most recommended clinical tool to examine the neurobehavioral condition of individuals with disorders of consciousness (DOCs). Different studies have investigated the prognostic value of the information provided by the conventional administration of the scale, while other measures derived from the scale have been proposed to improve the prognosis of DOCs. However, the heterogeneity of the data used in the different studies prevents a reliable comparison of the identified predictors and measures. This study investigates which information derived from the CRS-R provides the most reliable prediction of both the clinical diagnosis and recovery of consciousness at the discharge of a long-term neurorehabilitation program. Retrospective observational multisite study. The enrollment was performed in three neurorehabilitation facilities of the same hospital network. A total of 171 individuals with DOCs admitted to an inpatient neurorehabilitation program for a minimum of 3 months were enrolled. Machine learning classifiers were trained to predict the clinical diagnosis and recovery of consciousness at discharge using clinical confounders and different metrics extracted from the CRS-R scale. Results showed that the neurobehavioral state at discharge was predicted with acceptable and comparable predictive value with all the indices and measures derived from the CRS-R, but for the clinical diagnosis and the Consciousness Domain Index, and the recovery of consciousness was predicted with higher accuracy and similarly by all the investigated measures, with the exception of initial clinical diagnosis. Interestingly, the total score in the CRS-R and, especially, the total score in its subscales provided the best overall results, in contrast to the clinical diagnosis, which could indicate that a comprehensive measure of the clinical diagnosis rather than the condition of the individuals could provide a more reliable prediction of the neurobehavioral progress of individuals with prolonged DOC. The results of this work have important implications in clinical practice, offering a more accurate prognosis of patients and thus giving the possibility to personalize and optimize the rehabilitation plan of patients with DoC using low-cost and easily collectable information.

Precise detection of awareness in disorders of consciousness using deep learning framework

Role of transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) in disorders of consciousness (DOC)

Deep brain stimulation (DBS) has been proposed as a promising therapeutic intervention for patients with disorders of consciousness (DoC). DBS is hypothesized to modulate brain activity in local and widespread functional networks by delivering electrical impulses to deep brain nuclei, thereby promoting arousal. This individual patient data meta-analysis aimed to evaluate the therapeutic impact of DBS on improving conscious awareness in patients with DoC and to identify potential predictors of treatment responsiveness. Nine studies comprising 81 patients with DoC who underwent DBS were included. The primary outcome measure across all studies was the Coma Recovery Scale-Revised (CRS-R). Subgroup analyses were performed based on age, duration of DoC, etiology, and DBS target. Study-level data were pooled using random-effects meta-analytic models. The pooled mean CRS-R improvement post-DBS was 2.15 (95% CI: 1.06-3.23), indicating a modest treatment effect. Only 39.5% of patients achieved the minimum clinically important difference of ≥three CRS-R points, and 30.9% transitioned to a higher DoC category. Younger patients with shorter DoC durations tended to show greater improvements. Etiology was largely nonpredictive, although patients with hypoxic-ischemic encephalopathy exhibited marginally better responses. Considerable heterogeneity was observed across studies (I2 = 76.5%). Adverse effects, including infections and seizures, were reported. DBS may confer modest improvements in conscious awareness for selected patients with DoC, but therapeutic benefits remain limited and risks substantial. Rigorous patient selection frameworks and standardized protocols are essential to guide clinical decision-making and future trials.

Primary objective This study aimed to verify the reliability and validity of the Japanese version of the Coma Recovery Scale-Revised (CRS-R). Methods Subjects included 59 patients with disorders of consciousness (DOC) due to acquired brain injury. To validate test-retest reliability, Evaluator A assessed the CRS-R twice on the same day (A1, A2). To examine inter-rater reliability, Evaluators A (A2) and B (B) assessed the CRS-R without a time interval. To test concurrent validity, Evaluator A (A1) assessed the CRS-R, Japan Coma Scale (JCS), and the Glasgow Coma Scale (GCS) consecutively. To validate diagnostic accuracy, we evaluated the degree of agreement between A1 and A2 and between A2 and B in their diagnosis of DOC by CRS-R. Results The test-retest (ρ = 0.92) and inter- (ρ = 0.98) reliability of CRS-R were excellent” and Concurrent validity of CRS-R with JCS (ρ = −0.82) and GCS (ρ = 0.92) were high. Results of DOC diagnosis were consistent for 48/59 cases (κ = 0.82) for A1 and A2 and for 54/59 cases (κ = 0.92) for A2 and B. Conlcusion The Japanese version of the CRS-R may be as reliable and valid as the original English and other language versions.