Central olfactory processing in patients with disorders of consciousness.

The management of patients suffering from chronic disorders of consciousness (DOC) inevitably raises important ethical questions about the end of life decisions. Some ethical positions claim respect of human life sacredness and the use of good medical practices require allowing DOC patients to live as long as possible, since no one can arbitrarily end either his/her or others’ life. On the other hand, some currents of thought claim respect of human life dignity, patients’ wishes, and the right of free choice entail allowing the withdrawal of life sustaining therapy. This could happen when patients (or surrogates) believe their own life to be not worth living, or if therapy is not very beneficial, excessively burdensome, or even futile. Indeed, the decision to withdraw therapies in a DOC patient should be guided by reliable information about DOC diagnosis and prognosis and on how the patient would wish to be treated in such a condition. Taking into account such issues, it would be possible to make the decision that more adequately fits a DOC patient’s best interest. This review aims to overview the range of ethical issues referring to end-of-life decisions in DOC patients, with regard to the thorny debate on the sacredness and dignity of human life.

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.

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

Repetitive transcranial magnetic stimulation (rTMS) has been applied for the treatment of patients with disorders of consciousness (DOC). Timely and accurate assessments of its modulation effects are very useful. This study evaluated rTMS modulation effects on electroencephalography (EEG) oscillation in patients with chronic DOC. Eighteen patients with a diagnosis of DOC lasting more than 3 months were recruited. All patients received one session of 10-Hz rTMS at the left dorsolateral prefrontal cortex and then 12 of them received consecutive rTMS treatment everyday for 20 consecutive days. Resting-state EEGs were recorded before the experiment (T0) after one session of rTMS (T1) and after the entire treatment (T2). The JFK Coma Recovery Scale-Revised scale scores were also recorded at the time points. Our data showed that application of 10-Hz rTMS to the left dorsolateral prefrontal cortex decreased low-frequency band power and increased high-frequency band power in DOC patients, especially in minimal conscious state patients. Considering the correlation of the EEG spectrum with the consciousness level of patients with DOC, quantitative EEG might be useful for assessment of the effect of rTMS in DOC patients.

The evaluation of the level of consciousness in patients with disorders of consciousness (DOC) is primarily based on behavioural assessments. Patients with unresponsive wakefulness syndrome (UWS) do not show any sign of awareness of their environment, while minimally conscious state (MCS) patients show reproducible but fluctuating signs of awareness. Some patients, although with remaining cognitive abilities, are not able to exhibit overt voluntary responses at the bedside and may be misdiagnosed as UWS. Several studies investigated functional neuroimaging and neurophysiology as an additional tool to evaluate the level of consciousness and to detect covert command following in DOC. Most of these studies are based on auditory stimulation, neglecting patients suffering from decreased or absent hearing abilities. In the present study, we aim to assess the response to a P3-based paradigm in 40 patients with DOC and 12 healthy participants using auditory (AEP) and vibrotactile (VTP) stimulation. To this end, an EEG-based brain-computer interface was used at DOC patient’s bedside. We compared the significance of the P3 performance (i.e., the interpretation of significance of the evoked P3 response) as obtained by ‘direct processing’ (i.e., theoretical-based significance threshold) and ‘offline processing’ (i.e., permutation-based single subject level threshold). We evaluated whether the P3 performances were dependent on clinical variables such as diagnosis (UWS and MCS), aetiology and time since injury. Last we tested the dependency of AEP and VTP performances at the single subject level. Direct processing tends to overestimate P3 performance. We did not find any difference in the presence of a P3 performance according to the level of consciousness (UWS vs. MCS) or the aetiology (traumatic vs. non-traumatic brain injury). The performance achieved at the AEP paradigm was independent from what was achieved at the VTP paradigm, indicating that some patients performed better on the AEP task while others performed better on the VTP task. Our results support the importance of using multimodal approaches in the assessment of DOC patients in order to optimise the evaluation of patient’s abilities.

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.

Disorders of consciousness include coma (cannot be aroused, eye remain closed), vegetative state-VS (can appear to be awake, but unable to purposefully interact) and minimally conscious state-MCS (minimal but definite awareness). The objective of this study is to assess the impact of the SARS-CoV-2 infection on the Disorder of Consciousness (DOC) Rehabilitation Unit. This is a retrospective, longitudinal, descriptive, observational, pilot study. We consecutively enrolled 18 patients (age range: 40-72 years, 9 females and 9 males), from three to five months after a brain injury. They were grouped into VS (n = 8) and MCS (n = 10). A confirmed case of COVID-19 was defined as a positive result on high-throughput sequencing or real-time reverse-transcription polymerase chain reaction analysis of throat swab specimens. We collected data of lung Computed Tomography (CT) and laboratory exams. DOC patients who were positive for SARS-CoV-2 were classified into severe and no severe infected group, according to the American Thoracic Society guidelines. A total of 18 hospitalized patients with (16) and without confirmed (2) SARS-CoV-2 infection were included in the analysis. After one month, a follow-up clinical evaluation reported that one patient died, one patient was transferred from Covid Unit to Emergency Unit and 3 patients were resulted negative to double swab and they returned to Rehabilitative Unit. Significant differences were reported about hypertension, cardiac disease and respiratory problems between the patients with severe infection and patients without severe infection (P< 0.001). The laboratory findings, such as blood cell counts (P < 0.001), C-reactive protein, D-dimer, potassium and vitamin D levels, seemed to be considered as useful prognostic predictors. To our knowledge, this is the first longitudinal study on a sample of chronic DOC patients affected by SARS-CoV-2. This study may offer important new clinical information on COVID-19 for management of DOC patients. Our findings showed that for the subjects with severe infection due to COVID-19, rapid clinical deterioration or worsening could be associated with clinical and laboratory findings, which could contribute to high mortality rate. During the COVID-19 epidemic period, the clinicians should consider all the reported risk factors to avoid delayed diagnosis or misdiagnosis and to prevent the infection transmission in DOC Rehabilitation Unit.

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.

Diagnosis and prognosis of patients with disorders of consciousness (DOC) is a challenge for neuroscience and clinical practice. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) is an effective tool to measure the level of consciousness. However, a scientific and accurate method to quantify TMS-evoked activity is still lacking. This study applied fast perturbational complexity index (PCIst) to the diagnosis and prognosis of DOC patients. TMS-EEG data of 30 normal healthy participants (NOR) and 181 DOC patients were collected. The PCIst was used to assess the time-space complexity of TMS-evoked potentials (TEP). We selected parameters of PCIst in terms of data length, data delay, sampling rate and frequency band. In addition, we collected Coma Recovery Scale-Revised (CRS-R) values for 114 DOC patients after one year. Finally, we trained the classification and regression model. 1) PCIst shows the differences among NOR, minimally consciousness state (MCS) and unresponsive wakefulness syndrome (UWS) and has low computational cost. 2) Optimal parameters of data length and delay after TMS are 300 ms and 101-300 ms. Significant differences of PCIst at 5-8 Hz and 9-12 Hz bands are found among NOR, MCS and UWS groups. PCIst still works when TEP is down-sampled to 250 Hz. 3) PCIst at 9-12 Hz shows the highest performance in diagnosis and prognosis of DOC. This study confirms that PCIst can quantify the level of consciousness. PCIst is a potential measure for the diagnosis and prognosis of DOC patients.

Spasticity Management in Persons with Disorders of Consciousness.

Neuroimaging biomarkers for the diagnosis and prognosis of patients with disorders of consciousness

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.

Neuroscientific and clinical studies on auditory perception often use headphones to limit sound interference. In these conditions, sounds are perceived as internalized because they lack the sound-attributes that normally occur with a sound produced from a point in space around the listener. Without the spatial attention mechanisms that occur with localized sounds, auditory functional assessments could thus be underestimated. We hypothesize that adding virtually externalization and localization cues to sounds through headphones enhance sound discrimination in both healthy participants and patients with a disorder of consciousness (DOC). Hd-EEG was analyzed in 14 healthy participants and 18 patients while they listened to self-relevant and irrelevant stimuli in two forms: diotic (classic sound presentation with an “internalized” feeling) and convolved with a binaural room impulse response (to create an “externalized” feeling). Convolution enhanced the brains’ discriminative response as well as the processing of irrelevant sounds itself, in both healthy participants and DOC patients. For the healthy participants, these effects could be associated with enhanced activation of both the dorsal (where/how) and ventral (what) auditory streams, suggesting that spatial attributes support speech discrimination. Thus, virtually spatialized sounds might “call attention to the outside world” and improve the sensitivity of assessment of brain function in 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.

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