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International audience; 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

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.

Recent advances in functional neuroimaging have demonstrated novel potential for informingdiagnosisandprognosisin the unresponsive wakeful syndrome and minimally conscious states. However, these technologies come with considerable expense and difficulty, limiting the possibility of wider clinical application in patients. Here, we show that high density electroencephalography, collected from 104 patients measured at rest, can provide valuable information aboutbrainconnectivity that correlates with behaviour and functional neuroimaging. Using graph theory, we visualize and quantify spectral connectivity estimated from electroencephalography as a densebrainnetwork. Our findings demonstrate that key quantitative metrics of thesenetworkscorrelate with the continuum of behavioural recovery in patients, ranging from those diagnosed as unresponsive, through those who have emerged from minimally conscious, to the fully conscious locked-in syndrome. In particular, a network metric indexing the presence of densely interconnected central hubs of connectivity discriminated behaviouralconsciousnesswith accuracy comparable to that achieved by expert assessment with positron emission tomography. We also show that this metric correlates strongly withbrainmetabolism. Further, with classification analysis, wepredictthe behaviouraldiagnosis,brainmetabolismand 1-year clinical outcome of individual patients. Finally, we demonstrate that assessments ofbrainnetworksshow robust connectivity in patients diagnosed as unresponsive by clinical consensus, but later rediagnosed as minimally conscious with the Coma Recovery Scale-Revised. Classification analysis of theirbrainnetwork identified each of these misdiagnosed patients as minimally conscious, corroborating their behavioural diagnoses. If deployed at thebedsidein the clinical context, such network measurements could complement systematic behavioural assessment and help reduce the high misdiagnosis rate reported in these patients. These metrics could also identify patients in whom further assessment is warranted using neuroimaging or conventional clinical evaluation. Finally, by providing objective characterization of states ofconsciousness, repeated assessments of network metrics could help track individual patients longitudinally, and also assess their neural responses to therapeutic and pharmacological interventions.

Patients with prolonged disorders of consciousness (DoC) after severe brain injury may present residual behavioral and cognitive functions. Yet the bedside assessment of these functions is compromised by patients' multiple impairments. Standardized behavioral scales such as the Coma Recovery Scale-Revised (CRS-R) have been developed to diagnose DoC, but there is also a need for neuropsychological measurement in these patients. The Cognitive Assessment by Visual Election (CAVE) was therefore recently created. In this study, we describe five patients in minimally conscious state (MCS) or emerging from the MCS (EMCS). Their cognitive profiles, derived from the CRS-R and CAVE, are presented alongside their neuroimaging results using structural magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET). Scores on the CAVE decreased along with the CRS-R total score, establishing a consistent behavioral/cognitive profile for each patient. Out of these five cases, the one with highest CRS-R and CAVE performance had the least extended cerebral hypometabolism. All patients showed structural and functional brain impairments that were consistent with their behavioral/cognitive profile as based on previous literature. For instance, the presence of visual and motor residual functions was respectively associated with a relative preservation of occipital and motor cortex/cerebellum metabolism. Moreover, residual language comprehension skills were found in the presence of preserved temporal and angular cortex metabolism. Some patients also presented structural impairment of hippocampus, suggesting the presence of memory impairments. Our results suggest that brain-behavior relationships might be observed even in severely brain-injured patients and they highlight the importance of developing new tools to assess residual cognition and language in MCS and EMCS patients. Indeed, a better characterization of their cognitive profile will be helpful in preparation of rehabilitation programs and daily routines.

Detection and interpretation of signs of "covert command following" in patients with disorders of consciousness (DOC) remains a challenge for clinicians. In this study, we used a tactile P3-based BCI in 12 patients without behavioral command following, attempting to establish "covert command following." These results were then confronted to cerebral metabolism preservation as measured with glucose PET (FDG-PET). One patient showed "covert command following" (i.e., above-threshold BCI performance) during the active tactile paradigm. This patient also showed a higher cerebral glucose metabolism within the language network (presumably required for command following) when compared with the other patients without "covert command-following" but having a cerebral glucose metabolism indicative of minimally conscious state. Our results suggest that the P3-based BCI might probe "covert command following" in patients without behavioral response to command and therefore could be a valuable addition in the clinical assessment of patients with DOC

Detection and interpretation of signs of “covert command following” in patients with disorders of consciousness (DOC) remains a challenge for clinicians. In this study, we used a tactile P3-based BCI in 12 patients without behavioral command following, attempting to establish “covert command following.” These results were then confronted to cerebral metabolism preservation as measured with glucose PET (FDG-PET). One patient showed “covert command following” (i.e., above-threshold BCI performance) during the active tactile paradigm. This patient also showed a higher cerebral glucose metabolism within the language network (presumably required for command following) when compared with the other patients without “covert command-following” but having a cerebral glucose metabolism indicative of minimally conscious state. Our results suggest that the P3-based BCI might probe “covert command following” in patients without behavioral response to command and therefore could be a valuable addition in the clinical assessment of patients with DOC.

Proceedings Of The 6Th International Bci Meeting: Bci Past, Present, And Future

Background and Objectives: Persistent post-concussive symptoms (PCS) consist of neurologic and psychological complaints persisting after a mild traumatic brain injury (mTBI). It affects up to 50% of mTBI patients, may cause long-term disability, and reduce patients' quality of life. The aim of this review was to examine the possible use of different neuroimaging modalities in PCS. Methods: Articles from Pubmed database were screened to extract studies that investigated the relationship between any neuroimaging features and symptoms of PCS. Descriptive statistics were applied to report the results. Results: A total of 80 out of 939 papers were included in the final review. Ten examined conventional MRI (30% positive finding), 24 examined diffusion weighted imaging (54.17% positive finding), 23 examined functional MRI (82.61% positive finding), nine examined electro(magneto)encephalography (77.78% positive finding), and 14 examined other techniques (71% positive finding). Conclusion: MRI was the most widely used technique, while functional techniques seem to be the most sensitive tools to evaluate PCS. The common functional patterns associated with symptoms of PCS were a decreased anti-correlation between the default mode network and the task positive network and reduced brain activity in specific areas (most often in the prefrontal cortex). Significance: Our findings highlight the importance to use functional approaches which demonstrated a functional alteration in brain connectivity and activity in most studies assessing PCS.

Charles Bonnet syndrome (CBS) is a rare clinical condition characterized by complex visual hallucinations in people with loss of vision. So far, the neurobiological mechanisms underlying the hallucinations remain elusive. This case-report study aims at investigating electrical activity changes in a CBS patient during visual hallucinations, as compared to a resting-state period (without hallucinations). Prior to the EEG, the patient underwent neuropsychological, ophthalmologic, and neurological examinations. Spectral and connectivity, graph analyses and signal diversity were applied to high-density EEG data. Visual hallucinations (as compared to resting-state) were characterized by a significant reduction of power in the frontal areas, paralleled by an increase in the midline posterior regions in delta and theta bands and by an increase of alpha power in the occipital and midline posterior regions. We next observed a reduction of theta connectivity in the frontal and right posterior areas, which at a network level was complemented by a disruption of small-worldness (lower local and global efficiency) and by an increase of network modularity. Finally, we found a higher signal complexity especially when considering the frontal areas in the alpha band. The emergence of hallucinations may stem from these changes in the visual cortex and in core cortical regions encompassing both the default mode and the fronto-parietal attentional networks.

Transcranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) has induced promising behavioral improvement, both in acute and chronic minimally conscious state (MCS - [ 1 ]) patients [ 2 , 3 ]. We previously defined a tDCS-responder as a patient who demonstrates a new sign of consciousness following stimulation, which was neither present beforehand, nor before or after the sham stimulation [ 2 ]. In a study investigating the metabolic and structural differences between DLPFC-tDCS-responders and non-responders, we have identified that tDCS-responders presented a preservation of brain metabolism and grey matter integrity under the stimulated area, but also in the thalamus and the precuneus, areas involved in consciousness recovery [ 4 ]. Even if these results provided relevant insights into potential biomarkers of responsiveness, the access to such neuroimaging techniques (positron emission tomography - PET - and magnetic resonance imaging - MRI) remains limited. Recently, it has been demonstrated that high-density electroencephalography (hdEEG) network metrics in the alpha band correlates with the level of consciousness [ 5 ]. In addition, a strong correlation between brain metabolism and hdEEG network metrics was reported, making this bedside assessment a robust way to evaluate patients’ brain function.

Persons diagnosed with disorders of consciousness (DOC) typically suffer from motor disablities, and thus assessing their spared cognitive abilities can be difficult. Recent research from several groups has shown that non-invasive brain-computer interface (BCI) technology can provide assessments of these patients' cognitive function that can supplement information provided through conventional behavioral assessment methods. In rare cases, BCIs may provide a binary communication mechanism. Here, we present results from a vibrotactile BCI assessment aiming at detecting command-following and communication in 12 unresponsive wakefulness syndrome (UWS) patients. Two different paradigms were administered at least once for every patient: (i) VT2 with two vibro-tactile stimulators fixed on the patient's left and right wrists and (ii) VT3 with three vibro-tactile stimulators fixed on both wrists and on the back. The patients were instructed to mentally count either the stimuli on the left or right wrist, which may elicit a robust P300 for the target wrist only. The EEG data from - 100 to + 600ms around each stimulus were extracted and sub-divided into 8 data segments. This data was classified with linear discriminant analysis (using a 10 x 10 cross validation) and used to calibrate a BCI to assess command following and YES/NO communication abilities. The grand average VT2 accuracy across all patients was 38.3%, and the VT3 accuracy was 26.3%. Two patients achieved VT3 accuracy >= 80% and went through communication testing. One of these patients answered 4 out of 5 questions correctly in session 1, whereas the other patient answered 6/10 and 7/10 questions correctly in sessions 2 and 4. In 6 other patients, the VT2 or VT3 accuracy was above the significance threshold of 23% for at least one run, while in 4 patients, the accuracy was always below this threshold. The study highlights the importance of repeating EEG assessments to increase the chance of detecting command-following in patients with severe brain injury. Furthermore, the study shows that BCI technology can test command following in chronic UWS patients and can allow some of these patients to answer YES/NO questions.