Advances in Disorders of Consciousness

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuropharmacology and Neuropathology".

Deadline for manuscript submissions: closed (5 April 2021) | Viewed by 32757

Special Issue Editors

AOU Policlinico G. Martino, UOSD Stroke Unit, 98100 Messina, Italy
Interests: disorders of consciousness; non-invasive brain stimulation; robotic rehabilitation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Consciousness is a multifaceted concept that has two major components: awareness of the environment of self (i.e., the content of consciousness) and wakefulness (i.e., the level of consciousness). Whereas the level of arousal reflects the overall state of activity in the brain, conscious awareness is a more dynamic and complex process involving various cerebral networks, including the cortico-thalamo-cortical loop. Disorders of consciousness (DOC) is a broad category that encompasses a spectrum of cognitive dysfunction, including unresponsive wakefulness syndrome (UWS; absence of responsiveness and awareness) and minimally conscious state (MCS; inconsistent but clearly discernible behavioral evidence of consciousness). DOC diagnosis, prognosis, and ethical and legal elements should be carefully and thoughtfully considered in order to provide the optimal treatment for patients. In the last 10 years, evidence has shown the importance of neuroimaging, including fMRI, DTI, fiber tracking, and PET, in the management of DOC patients. However, considering that neuroimaging tasks involve the active collaboration of patients, which still leads to high misdiagnosis rates, novel neurophysiological techniques that are able to unmask residual covert connectivity patterns are needed.   

Original research articles advancing our understanding of the pathophysiology and treatment of DOCs are solicited for this Special Issue. Reviews providing an analytical perspective on the existing literature are also welcome.

Dr. Rocco Salvatore Calabrò
Dr. Antonino Naro
Guest Editors

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Published Papers (10 papers)

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Research

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11 pages, 1021 KiB  
Article
The Timecourse of Electrophysiological Brain–Heart Interaction in DoC Patients
Brain Sci. 2021, 11(6), 750; https://doi.org/10.3390/brainsci11060750 - 05 Jun 2021
Cited by 5 | Viewed by 2239
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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16 pages, 1677 KiB  
Article
Disruptions in Effective Connectivity within and between Default Mode Network and Anterior Forebrain Mesocircuit in Prolonged Disorders of Consciousness
Brain Sci. 2021, 11(6), 749; https://doi.org/10.3390/brainsci11060749 - 04 Jun 2021
Cited by 12 | Viewed by 2960
Abstract
Recent research indicates prolonged disorders of consciousness (PDOC) result from structural and functional impairments to key cortical and subcortical networks, including the default mode network (DMN) and the anterior forebrain mesocircuit (AFM). However, the specific mechanisms which underpin such impairments remain unknown. It [...] Read more.
Recent research indicates prolonged disorders of consciousness (PDOC) result from structural and functional impairments to key cortical and subcortical networks, including the default mode network (DMN) and the anterior forebrain mesocircuit (AFM). However, the specific mechanisms which underpin such impairments remain unknown. It is known that disruptions in the striatal-pallidal pathway can result in the over inhibition of the thalamus and lack of excitation to the cortex that characterizes PDOC. Here, we used spectral dynamic causal modelling and parametric empirical Bayes on rs-fMRI data to assess whether DMN changes in PDOC are caused by disruptions in the AFM. PDOC patients displayed overall reduced coupling within the AFM, and specifically, decreased self-inhibition of the striatum, paired with reduced coupling from striatum to thalamus. This led to loss of inhibition from AFM to DMN, mostly driven by posterior areas including the precuneus and inferior parietal cortex. In turn, the DMN showed disruptions in self-inhibition of the precuneus and medial prefrontal cortex. Our results provide support for the anterior mesocircuit model at the subcortical level but highlight an inhibitory role for the AFM over the DMN, which is disrupted in PDOC. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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12 pages, 579 KiB  
Article
One-Year Demographical and Clinical Indices of Patients with Chronic Disorders of Consciousness
Brain Sci. 2021, 11(5), 651; https://doi.org/10.3390/brainsci11050651 - 16 May 2021
Cited by 8 | Viewed by 2196
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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9 pages, 906 KiB  
Article
Effect of Retinohypothalamic Tract Dysfunction on Melatonin Level in Patients with Chronic Disorders of Consciousness
Brain Sci. 2021, 11(5), 559; https://doi.org/10.3390/brainsci11050559 - 28 Apr 2021
Cited by 3 | Viewed by 1701
Abstract
Objective: The aim of this study is to compare the secretion level of nocturnal melatonin and the characteristics of the peripheral part of the visual analyzer in patients with chronic disorders of consciousness (DOC). Materials and Methods: We studied the level of melatonin [...] Read more.
Objective: The aim of this study is to compare the secretion level of nocturnal melatonin and the characteristics of the peripheral part of the visual analyzer in patients with chronic disorders of consciousness (DOC). Materials and Methods: We studied the level of melatonin in 22 patients with chronic DOC and in 11 healthy volunteers. The fundus condition was assessed using the ophthalmoscopic method. Results: The average level of nocturnal melatonin in patients with DOC differed by 80% from the level of indole in healthy volunteers. This reveals a direct relationship between etiology, the level of consciousness, gaze fixation, coma recovery scale-revised score and the level of melatonin secretion. Examination by an ophthalmologist revealed a decrease in the macular reflex in a significant number of DOC patients, which in turn correlates negatively with the time from brain injury and positively with low values of nocturnal melatonin. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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20 pages, 858 KiB  
Article
Towards New Diagnostic Approaches in Disorders of Consciousness: A Proof of Concept Study on the Promising Use of Imagery Visuomotor Task
Brain Sci. 2020, 10(10), 746; https://doi.org/10.3390/brainsci10100746 - 17 Oct 2020
Cited by 6 | Viewed by 2193
Abstract
Background: advanced paraclinical approaches using functional neuroimaging and electroencephalography (EEG) allow identifying patients who are covertly aware despite being diagnosed as unresponsive wakefulness syndrome (UWS). Bedside detection of covert awareness employing motor imagery tasks (MI), which is a universally accepted clinical indicator of [...] Read more.
Background: advanced paraclinical approaches using functional neuroimaging and electroencephalography (EEG) allow identifying patients who are covertly aware despite being diagnosed as unresponsive wakefulness syndrome (UWS). Bedside detection of covert awareness employing motor imagery tasks (MI), which is a universally accepted clinical indicator of awareness in the absence of overt behavior, may miss some of these patients, as they could still have a certain level of awareness. We aimed at assessing covert awareness in patients with UWS using a visuomotor-guided motor imagery task (VMI) during EEG recording. Methods: nine patients in a minimally conscious state (MCS), 11 patients in a UWS, and 15 healthy individuals (control group—CG) were provided with an VMI (imagine dancing while watching a group dance video to command), a simple-MI (imagine squeezing their right hand to command), and an advanced-MI (imagine dancing without watching a group dance video to command) to detect command-following. We analyzed the command-specific EEG responses (event-related synchronization/desynchronization—ERS/ERD) of each patient, assessing whether these responses were appropriate, consistent, and statistically similar to those elicited in the CG, as reliable markers of motor imagery. Results: All patients in MCS, all healthy individuals and one patient in UWS repeatedly and reliably generated appropriate EEG responses to distinct commands of motor imagery with a classification accuracy of 60–80%. Conclusions: VMI outperformed significantly MI tasks. Therefore, patients in UWS may be still misdiagnosed despite a rigorous clinical assessment and an appropriate MI assessment. It is thus possible to suggest that motor imagery tasks should be delivered to patients with chronic disorders of consciousness in visuomotor-aided modality (also in the rehabilitation setting) to greatly entrain patient’s participation. In this regard, the EEG approach we described has the clear advantage of being cheap, portable, widely available, and objective. It may be thus considered as, at least, a screening tool to identify the patients who deserve further, advanced paraclinical approaches. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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14 pages, 1614 KiB  
Article
Stimulation of the Angular Gyrus Improves the Level of Consciousness
Brain Sci. 2019, 9(5), 103; https://doi.org/10.3390/brainsci9050103 - 06 May 2019
Cited by 24 | Viewed by 5102
Abstract
Background: Navigated repetitive transcranial magnetic stimulation (rTMS) is a promising tool for neuromodulation. In previous studies it has been shown that the activity of the default mode network (DMN) areas, particularly of its key region—the angular gyrus—is positively correlated with the level of [...] Read more.
Background: Navigated repetitive transcranial magnetic stimulation (rTMS) is a promising tool for neuromodulation. In previous studies it has been shown that the activity of the default mode network (DMN) areas, particularly of its key region—the angular gyrus—is positively correlated with the level of consciousness. Our study aimed to explore the effect of rTMS of the angular gyrus as a new approach for disorders of consciousness (DOC) treatment; Methods: A 10-session 2-week high-frequency rTMS protocol was delivered over the left angular gyrus in 38 DOC patients with repeated neurobehavioral assessments obtained at baseline and in 2 days after the stimulation course was complete; Results: 20 Hz-rTMS over left angular gyrus improved the coma recovery scale revised (CRS-R) total score in minimally conscious state (MCS) patients. We observed no effects in vegetative state (VS) patients; and Conclusions: The left angular gyrus is likely to be effective target for rTMS in patients with present signs of consciousness. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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Review

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27 pages, 2880 KiB  
Review
A Recent Investigation on Detection and Classification of Epileptic Seizure Techniques Using EEG Signal
Brain Sci. 2021, 11(5), 668; https://doi.org/10.3390/brainsci11050668 - 20 May 2021
Cited by 45 | Viewed by 4880
Abstract
The benefits of early detection and classification of epileptic seizures in analysis, monitoring and diagnosis for the realization and actualization of computer-aided devices and recent internet of medical things (IoMT) devices can never be overemphasized. The success of these applications largely depends on [...] Read more.
The benefits of early detection and classification of epileptic seizures in analysis, monitoring and diagnosis for the realization and actualization of computer-aided devices and recent internet of medical things (IoMT) devices can never be overemphasized. The success of these applications largely depends on the accuracy of the detection and classification techniques employed. Several methods have been investigated, proposed and developed over the years. This paper investigates various seizure detection algorithms and classifications in the last decade, including conventional techniques and recent deep learning algorithms. It also discusses epileptiform detection as one of the steps towards advanced diagnoses of disorders of consciousness (DOCs) and their understanding. A performance comparison was carried out on the different algorithms investigated, and their advantages and disadvantages were explored. From our survey, much attention has recently been paid to exploring the efficacy of deep learning algorithms in seizure detection and classification, which are employed in other areas such as image processing and classification. Hybrid deep learning has also been explored, with CNN-RNN being the most popular. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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19 pages, 738 KiB  
Review
Pain Perception in Disorder of Consciousness: A Scoping Review on Current Knowledge, Clinical Applications, and Future Perspective
Brain Sci. 2021, 11(5), 665; https://doi.org/10.3390/brainsci11050665 - 20 May 2021
Cited by 5 | Viewed by 3147
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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16 pages, 3346 KiB  
Review
Virtual Reality Based Cognitive Rehabilitation in Minimally Conscious State: A Case Report with EEG Findings and Systematic Literature Review
Brain Sci. 2020, 10(7), 414; https://doi.org/10.3390/brainsci10070414 - 01 Jul 2020
Cited by 16 | Viewed by 4076
Abstract
Chronic disorders of consciousness cause a total or partial and fluctuating unawareness of the surrounding environment. Virtual reality (VR) can be useful as a diagnostic and/or a neurorehabilitation tool, and its effects can be monitored by means of both clinical and electroencephalography (EEG) [...] Read more.
Chronic disorders of consciousness cause a total or partial and fluctuating unawareness of the surrounding environment. Virtual reality (VR) can be useful as a diagnostic and/or a neurorehabilitation tool, and its effects can be monitored by means of both clinical and electroencephalography (EEG) data recording of brain activity. We reported on the case of a 17-year-old patient with a disorder of consciousness (DoC) who was provided with VR training to improve her cognitive-behavioral outcomes, which were assessed using clinical scales (the Coma Recovery Scale-Revised, the Disability Rating Scale, and the Rancho Los Amigos Levels of Cognitive Functioning), as well as EEG recording, during VR training sessions. At the end of the training, significant improvements in both clinical and neurophysiological outcomes were achieved. Then, we carried out a systematic review of the literature to investigate the role of EEG and VR in the management of patients with DoC. A search on PubMed, Web of Science, Scopus, and Google Scholar databases was performed, using the keywords: “disorders of consciousness” and “virtual reality”, or “EEG”. The results of the literature review suggest that neurophysiological data in combination with VR could be useful in evaluating the reactions induced by different paradigms in DoC patients, helping in the differential diagnosis. In conclusion, the EEG plus VR approach used with our patient could be promising to define the most appropriate stimulation protocol, so as to promote a better personalization of the rehabilitation program. However, further clinical trials, as well as meta-analysis of the literature, are needed to be affirmative on the role of VR in patients with DoC. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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Other

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19 pages, 366 KiB  
Perspective
Toward Improving Diagnostic Strategies in Chronic Disorders of Consciousness: An Overview on the (Re-)Emergent Role of Neurophysiology
Brain Sci. 2020, 10(1), 42; https://doi.org/10.3390/brainsci10010042 - 10 Jan 2020
Cited by 9 | Viewed by 3124
Abstract
The differential diagnosis of patients with Disorder of Consciousness (DoC), in particular in the chronic phase, is significantly difficult. Actually, about 40% of patients with unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS) are misdiagnosed. Indeed, only advanced paraclinical approaches, including [...] Read more.
The differential diagnosis of patients with Disorder of Consciousness (DoC), in particular in the chronic phase, is significantly difficult. Actually, about 40% of patients with unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS) are misdiagnosed. Indeed, only advanced paraclinical approaches, including advanced EEG analyses, can allow achieving a more reliable diagnosis, that is, discovering residual traces of awareness in patients with UWS (namely, functional Locked-In Syndrome (fLIS)). These approaches aim at capturing the residual brain network models, at rest or that may be activated in response to relevant stimuli, which may be appropriate for awareness to emerge (despite their insufficiency to generate purposeful motor behaviors). For this, different brain network models have been studied in patients with DoC by using sensory stimuli (i.e., passive tasks), probing response to commands (i.e., active tasks), and during resting-state. Since it can be difficult for patients with DoC to perform even simple active tasks, this scoping review aims at summarizing the current, innovative neurophysiological examination methods in resting state/passive modality to differentiate and prognosticate patients with DoC. We conclude that the electrophysiologically-based diagnostic procedures represent an important resource for diagnosis, prognosis, and, therefore, management of patients with DoC, using advance passive and resting state paradigm analyses for the patients who lie in the “greyzones” between MCS, UWS, and fLIS. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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