French Survey on Pain Perception and Management in Patients with Locked-In Syndrome.

peer reviewedPatients with locked-in syndrome (LIS) may suffer from pain, which can significantly affect their daily life and well-being. In this study, we aim to investigate the presence and the management of pain in LIS patients. Fifty-one participants completed a survey collecting socio-demographic information and detailed reports regarding pain perception and management (type and frequency of pain, daily impact of pain, treatments). Almost half of the LIS patients reported experiencing pain (49%) that affected their quality of life, sleep and cognition. The majority of these patients reported that they did not communicate their pain to clinical staff. Out of the 25 patients reporting pain, 18 (72%) received treatment (60% pharmacological, 12% non-pharmacological) and described the treatment efficacy as 'moderate'. In addition, 14 (56%) patients were willing to try other non-pharmacological treatments, such as hypnosis or meditation. This study provides a comprehensive characterization of pain perception in LIS patients and highlights the lack of guidelines for pain detection and its management. This is especially pertinent given that pain affects diagnoses, by either inducing fatigue or by using pharmacological treatments that modulate the levels of wakefulness and concentration of such patients

Associations between regular cannabis use and brain resting-state functional connectivity in adolescents and adults

BACKGROUND/AIM: Cannabis use is highly prevalent in adolescents; however, little is known about its effects on adolescent brain function. METHOD: Resting-state functional magnetic resonance imaging was used in matched groups of regular cannabis users (N = 70, 35 adolescents: 16-17 years old, 35 adults: 26-29 years old) and non-regular-using controls (N = 70, 35 adolescents/35 adults). Pre-registered analyses examined the connectivity of seven major cortical and sub-cortical brain networks (default mode network, executive control network (ECN), salience network, hippocampal network and three striatal networks) using seed-based analysis methods with cross-sectional comparisons between user groups and age groups. RESULTS: The regular cannabis use group (across both age groups), relative to controls, showed localised increases in connectivity only in the ECN analysis. All networks showed localised connectivity differences based on age group, with the adolescents generally showing weaker connectivity than adults, consistent with the developmental effects. Mean connectivity across entire network regions of interest (ROIs) was also significantly decreased in the ECN in adolescents. However, there were no significant interactions found between age group and user group in any of the seed-based or ROI analyses. There were also no associations found between cannabis use frequency and any of the derived connectivity measures. CONCLUSION: Regular cannabis use is associated with changes in connectivity of the ECN, which may reflect allostatic or compensatory changes in response to regular cannabis intoxication. However, these associations were not significantly different in adolescents compared to adults

Identification and neuromodulation of brain states to promote recovery of consciousness

Experimental and clinical studies of consciousness identify brain states (i.e., transient, relevant features of the brain associated with the state of consciousness) in a non-systematic manner and largely independent from the research into the induction of state changes. In this narrative review with a focus on patients with a disorder of consciousness (DoC), we synthesize advances on the identification of brain states associated with consciousness in animal models and physiological (sleep), pharmacological (anesthesia) and pathological (DoC) states of altered consciousness in human. We show that in reduced consciousness the frequencies in which the brain operates are slowed down and that the pattern of functional communication in the brain is sparser, less efficient, and less complex. The results also highlight damaged resting state networks, in particular the default mode network, decreased connectivity in long-range connections and in the thalamocortical loops. Next, we show that therapeutic approaches to treat DoC, through pharmacology (e.g., amantadine, zolpidem), and (non-)invasive brain stimulation (e.g., transcranial current stimulation, deep brain stimulation) have shown some effectiveness to promote consciousness recovery. It seems that these deteriorated features of conscious brain states may improve in response to these neuromodulation approaches, yet, targeting often remains non-specific and does not always lead to (behavioral) improvements. Furthermore, in silico model-based approaches allow the development of personalized assessment of the effect of treatment on brain-wide dynamics. Although still in infancy, the fields of brain state identification and neuromodulation of brain states in relation to consciousness are showing fascinating developments that, when united, might propel the development of new and better targeted techniques for DoC. For example, brain states could be identified in a predictive setting, and the theoretical and empirical testing (i.e., in animals, under anesthesia and patients with a DoC) of neuromodulation techniques to promote consciousness could be investigated. This review further helps to identify where challenges and opportunities lay for the maturation of brain state research in the context of states of consciousness. Finally, it aids in recognizing possibilities and obstacles for the clinical translation of these diagnostic techniques and neuromodulation treatment options across both the multi-modal and multi-species approaches outlined throughout the review. This paper presents interactive figures, supported by the Live Paper initiative of the Human Brain Project, enabling the interaction with data and figures illustrating the concepts in the paper through EBRAINS (go to https://wiki.ebrains.eu/bin/view/Collabs/live-paper-states-altered-consciousness and get started with an EBRAINS account).NA is research fellow, OG is Research Associate, and SL is research director at FRS-FNRS. JA is postdoctoral fellow at the FWO. The study was further supported by the University and University Hospital of Liège, the BIAL Foundation, the Belgian National Funds for Scientific Research (FRS-FNRS), the European Union's Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3), the FNRS PDR project (T.0134.21), the ERA-Net FLAG-ERA JTC2021 project ModelDXConsciousness (Human Brain Project Partnering Project), the fund Generet, the King Baudouin Foundation, the Télévie Foundation, the European Space Agency (ESA) and the Belgian Federal Science Policy Office (BELSPO) in the framework of the PRODEX Programme, the Public Utility Foundation 'Université Européenne du Travail', "Fondazione Europea di Ricerca Biomedica", the BIAL Foundation, the Mind Science Foundation, the European Commission, the Fondation Leon Fredericq, the Mind-Care foundation, the DOCMA project (EU-H2020-MSCA–RISE–778234), the National Natural Science Foundation of China (Joint Research Project 81471100) and the European Foundation of Biomedical Research FERB Onlus

Neuroimaging and neurophysiological diagnosis and prognosis in paediatric disorders of consciousness

peer reviewe

Pharmacological treatments

editorial reviewedThis chapter reviews the current state of knowledge about pharmacological treatments acting on the recovery of consciousness in patients with severe brain injury. Potential pharmacological agents (amantadine, apomorphine, levodopa, methylphenidate, bromocriptine, modafinil, selegiline, zolpidem, and baclofen) and their underlying mechanisms are examined. Clinical considerations, off-label use of specific medication, limitations of current research, and future directions are also outlined. Finally, we discuss the potential of whole-brain computational modelling to test treatments in-silico whilst also driving forward the understanding of the mechanisms of consciousness

The current and future contribution of neuroimaging to the understanding of disorders of consciousness.

peer reviewedPatients with disorders of consciousness (DoC) represent a group of severely brain-injured patients with varying capacities for consciousness in terms of both wakefulness and awareness. The current state-of-the-art for assessing these patients is through standardised behavioural examinations, but inaccuracies are commonplace. Neuroimaging and electrophysiological techniques have revealed vast insights into the relationships between neural alterations, andcognitive and behavioural features of consciousness in patients with DoC. This has led to the establishment of neuroimaging paradigms for the clinical assessment of DoC patients. Here, we review selected neuroimaging findings on the DoC population, outlining key findings of the dysfunction underlying DoC and presenting the current clinical utility of neuroimaging tools. We discuss that whilst individual brain areas play instrumental roles in generating and supporting consciousness, activation of these areas alone is not sufficient for conscious experience. Instead, for consciousness to arise, we need preserved thalamo-cortical circuits, in addition to sufficient connectivity between distinctly differentiated brain networks, underlined by connectivity both within, and between such brain networks. Finally, we present recent advances and future perspectives in computational methodologies applied to DoC, supporting the notion that progress in the science of DoC will be driven by a symbiosis of these data-driven analyses, and theory-driven research. Both perspectives will work in tandem to provide mechanistic insights contextualised within theoretical frameworks which ultimately inform the practice of clinical neurology

The nature of consciousness in anaesthesia

Neuroscientists agree on the value of locating the source of consciousness within the brain. Anaesthesiologists are no exception, and have their own operational definition of consciousness based on phenomenological observations during anaesthesia. The full functional correlates of consciousness are yet to be precisely identified, however rapidly evolving progress in this scientific domain has yielded several theories that attempt to model the generation of consciousness. They have received variable support from experimental observations, including those involving anaesthesia and its ability to reversibly modulate different aspects of consciousness. Aside from the interest in a better understanding of the mechanisms of consciousness, exploring the functional tenets of the phenomenological consciousness states of general anaesthesia has the potential to ultimately improve patient management. It could facilitate the design of specific monitoring devices and approaches, aiming at reliably detecting each of the possible states of consciousness during an anaesthetic procedure, including total absence of mental content (unconsciousness), and internal awareness (sensation of self and internal thoughts) with or without conscious perception of the environment (connected or disconnected consciousness, respectively). Indeed, it must be noted that unresponsiveness is not sufficient to infer absence of connectedness or even absence of consciousness. This narrative review presents the current knowledge in this field from a system-level, underlining the contribution of anaesthesia studies in supporting theories of consciousness, and proposing directions for future research