Cognitive Motor Dissociation Research Articles

A Focus on Subtle Signs and Motor Behavior to Unveil Awareness in Unresponsive Brain-Impaired Patients: The Importance of Being Clinical.

Brain-injured patients in a state of cognitive motor dissociation (CMD) exhibit a lack of command following using conventional neurobehavioral examination tools but a high level of awareness and language processing when assessed using advanced imaging and electrophysiology techniques. Because of their behavioral unresponsiveness, patients with CMD may seem clinically indistinguishable from those with a true disorder of consciousness that affects awareness on a substantial level (coma, vegetative state/unresponsive wakefulness state, or minimally conscious state minus). Yet, by expanding the range of motor testing across limb, facial, and ocular motricity, we may detect subtle, purposeful movements even in the subset of patients classified as vegetative state/unresponsive wakefulness state. We propose the term of clinical CMD to describe patients showing these slight but determined motor responses and exhibiting a characteristic akinetic motor behavior as opposed to a pyramidal motor system behavior. These patients may harbor hidden cognitive capabilities and significant potential for a good long-term outcome. Indeed, we envision CMD as ranging from complete (no motor response) to partial (subtle clinical motor response) forms, falling within a spectrum of progressively better motor output in patients with considerable cognitive capabilities. In addition to providing a decisional flowchart, we present this novel approach to classification as a graphical model that illustrates the range of clinical manifestations and recovery trajectories fundamentally differentiating true disorders of consciousness from the spectrum of CMD.

Locked-in syndrome revisited

The locked-in syndrome (LiS) is characterized by quadriplegia with preserved vertical eye and eyelid movements and retained cognitive abilities. Subcategorization, aetiologies and the anatomical foundation of LiS are discussed. The damage of different structures in the pons, mesencephalon and thalamus are attributed to symptoms of classical, complete and incomplete LiS and the locked-in plus syndrome, which is characterized by additional impairments of consciousness, making the clinical distinction to other chronic disorders of consciousness at times difficult. Other differential diagnoses are cognitive motor dissociation (CMD) and akinetic mutism. Treatment options are reviewed and an early, interdisciplinary and aggressive approach, including the provision of psychological support and coping strategies is favoured. The establishment of communication is a main goal of rehabilitation. Finally, the quality of life of LiS patients and ethical implications are considered. While patients with LiS report a high quality of life and well-being, medical professionals and caregivers have largely pessimistic perceptions. The negative view on life with LiS must be overthought and the autonomy and dignity of LiS patients prioritized. Knowledge has to be disseminated, diagnostics accelerated and technical support system development promoted. More well-designed research but also more awareness of the needs of LiS patients and their perception as individual persons is needed to enable a life with LiS that is worth living.

542: AWAKENING AFTER EXTRACORPOREAL LIFE SUPPORT: ASSESSING AWARENESS IN UNRESPONSIVE WAKEFULNESS

Introduction: Emergence from coma have many stages. Patients enter unresponsive wakefulness (UW) from coma when they open eyes with only reflexive motor responses. The development of voluntary responses to stimuli indicates a minimally conscious state (MCS). The addition of functional communication or object use signifies emergence from MCS. Cognitive motor dissociation has been reported in unresponsive patients with evidence of appropriate brain activation. We present a pediatric case where we detected awareness with bedside electroencephalogram (EEG) and the patient showed eventual emergence from UW. Description: A depressed teenage girl was admitted after suicidal attempt with fluoxetine and lamotrigine ingestion with subsequent cardiopulmonary arrest. After prolonged cardiopulmonary resuscitation, she was cannulated on veno-arterial extracorporeal membrane oxygenation. Initial head computed tomography showed preserved gray-white differentiation. On post-arrest day 5, she was successfully decannulated but remained in an unresponsive wakefulness state. Brain magnetic resonance imaging showed diffuse cerebral microhemorrhages. To assess preserved awareness, we performed protocolized stimulation with EEG. Consistent reactivity with increased frequency and amplitude were observed after both nociceptive and auditory stimulation, with greater response to stimuli from her parent. After slow improvement she emerged from UW on post-arrest day 35 and showed consistent appropriate responses. She was discharged to inpatient rehabilitation on post-arrest day 50. Discussion: Analysis of quantitative EEG data often requires advanced machine learning algorithms that were not readily available to bedside providers. Assessing EEG reactivity with protocolized stimulation is an effective alternative to assess preserved awareness. Our case adds to limited pediatric literature on emergence from coma and detection of preserved awareness early after brain injury. Clinically she was unresponsive to external stimuli but demonstrated signs of arousal to nociceptive and auditory stimuli on EEG, especially when from her parents. Our case demonstrates the feasibility of assessing preserved awareness at bedside via protocolized stimulation with EEG, which may assist in prognosis.

Understanding, detecting, and stimulating consciousness recovery in the ICU.

Coma is a medical and socioeconomic emergency. Although underfunded, research on coma and disorders of consciousness has made impressive progress. Lesion-network-mapping studies have delineated the precise brainstem regions that consistently produce coma when damaged. Functional neuroimaging has revealed how mechanisms like "communication through coherence" and "inhibition by gating" work in synergy to enable cortico-cortical processing and how this information transfer is disrupted in brain injury. On the cellular level, break-down of intracellular communication between the layer 5 pyramidal cell soma and the apical dendritic part impairs dendritic information integration, with up-stream effects on microcircuits in local neuronal populations and on large-scale fronto-parietal networks, which correlates with loss of consciousness. A breakthrough in clinical concepts occurred when fMRI, and later EEG, studies revealed that 15% of clinically unresponsive patients in acute and chronic settings are in fact awake and aware, as shown by their command following abilities revealed by brain activation during motor and locomotion imagery tasks. This condition is now termed "cognitive motor dissociation." Furthermore, epidemiological data on coma were literally non-existent until recently because of difficulties related to case ascertainment with traditional methods, but crowdsourcing of family observations enabled the first estimates of how frequent coma is in the general population (pooled annual incidence of 201 coma cases per 100,000 population in the UK and the USA). Diagnostic guidelines on coma and disorders of consciousness by the American Academy of Neurology and the European Academy of Neurology provide ambitious clinical frameworks to accommodate these achievements. As for therapy, a broad range of medical and non-medical treatment options is now being tested in increasingly larger trials; in particular, amantadine and transcranial direct current stimulation appear promising in this regard. Major international initiatives like the Curing Coma Campaign aim to raise awareness for coma and disorders of consciousness in the public, with the ultimate goal to make more brain-injured patients recover consciousness after a coma. To highlight all these accomplishments, this paper provides a comprehensive overview of recent progress and future challenges related to understanding, detecting, and stimulating consciousness recovery in the ICU.

Infraclinical detection of voluntary attention in coma and post-coma patients using electrophysiology

ObjectiveEarly functional evaluation and prognosis of patients with disorders of consciousness is a major challenge that clinical assessments alone cannot solve. Objective measures of brain activity could help resolve this uncertainty. We used electroencephalogram at bedside to detect voluntary attention with a paradigm previously validated in healthy subjects. MethodsUsing auditory-oddball sequences, our approach rests on detecting known attentional modulations of Event Related Potentials that reflect compliance with verbal instructions. Sixty-eight unresponsive patients were tested in their first year after coma onset (37 coma and 31 first year post-coma patients). Their evolution 6 months after the test was considered. ResultsFourteen of the 68 patients, showed a positive response. Nine were in a coma and 5 in a minimally conscious state (MCS). Except for one who died early, all responders evolved to exit-MCS within 6 months (93%), while 35 (65%) among non-responders only. ConclusionsAmong those patients for whom the outcome is highly uncertain, 21% responded positively to this simple but cognitively demanding test. Strikingly, some coma patients were among responders. SignificanceThe proposed paradigm revealed cognitive-motor dissociation in some coma patients. This ability to sustain attention on demand predicted awakening within 6 months and represents an immediately useful information for relatives and caregivers.

Objective Neurophysiologic Markers of Cognition After Pediatric Brain Injury.

Following brain injury, clinical assessments of residual and emerging cognitive function are difficult and fraught with errors. In adults, recent American Academy of Neurology (AAN) practice guidelines recommend objective neuroimaging and neurophysiologic measures to support diagnosis. Equivalent measures are lacking in pediatrics-an especially great challenge due to the combined heterogeneity of both brain injury and pediatric development. Therefore, we aim to establish quantitative, clinically practicable measures of cognitive function following pediatric brain injury. Participants with and without brain injury were aged 8-18 years, clinically classified according to cognitive recovery state: N = 8 in disorders of consciousness (DoC), N = 7 in confusional state, N = 19 cognitively impaired, and N = 13 typically developing uninjured controls. We prospectively measured electroencephalographic markers of sensory processing and attention in an auditory oddball paradigm, and of covert movement attempts in a command-following paradigm. In 3 participants with DoC, EEG markers of active attempted command following revealed cognitive function that clinical assessment had failed to detect. These same 3 individuals could also be distinguished from the rest of their group by 2 event-related potentials that correlate with sensory processing and orienting attention in the oddball paradigm. Considered across the whole participant group, magnitudes of these 2 ERP markers significantly increased as cognitive recovery progressed (ANOVA: each p < 0.001); viewed jointly, the 2 ERP markers cleanly delineated the 4 cognitive states. Despite heterogeneity of brain injuries and brain development, our objective EEG markers reflected cognitive recovery independent of motor function. Two of these markers required no active participation. Together, they allowed us to identify 3 individuals who meet the criteria for cognitive-motor dissociation. To diagnose, prognose, and track cognitive recovery accurately, such markers should be used in pediatrics.

Cognitive-motor dissociation and time to functional recovery in patients with acute brain injury in the USA: a prospective observational cohort study

Recovery trajectories of clinically unresponsive patients with acute brain injury are largely uncertain. Brain activation in the absence of a behavioural response to spoken motor commands can be detected by EEG, also known as cognitive-motor dissociation. We aimed to explore the role of cognitive-motor dissociation in predicting time to recovery in patients with acute brain injury. In this observational cohort study, we prospectively studied two independent cohorts of clinically unresponsive patients (aged ≥18 years) with acute brain injury. Machine learning was applied to EEG recordings to diagnose cognitive-motor dissociation by detecting brain activation in response to verbal commands. Survival statistics and shift analyses were applied to the data to identify an association between cognitive-motor dissociation and time to and magnitude of recovery. The prediction accuracy of the model that was built using the derivation cohort was assessed using the validation cohort. Functional outcomes of all patients were assessed with the Glasgow Outcome Scale-Extended (GOS-E) at hospital discharge and at 3, 6, and 12 months after injury. Patients who underwent withdrawal of life-sustaining therapies were censored, and death was treated as a competing risk. Between July 1, 2014, and Sept 30, 2021, we screened 598 patients with acute brain injury and included 193 (32%) patients, of whom 100 were in the derivation cohort and 93 were in the validation cohort. At 12 months, 28 (15%) of 193 unresponsive patients had a GOS-E score of 4 or above. Cognitive-motor dissociation was seen in 27 (14%) patients and was an independent predictor of shorter time to good recovery (hazard ratio 5·6 [95% CI 2·5-12·5]), as was underlying traumatic brain injury or subdural haematoma (4·4 [1·4-14·0]), a Glasgow Coma Scale score on admission of greater than or equal to 8 (2·2 [1·0-4·7]), and younger age (1·0 [1·0-1·1]). Among patients discharged home or to a rehabilitation setting, those diagnosed with cognitive-motor dissociation consistently had higher scores on GOS-E indicating better functional recovery compared with those without cognitive-motor dissociation, which was seen as early as 3 months after the injury (odds ratio 4·5 [95% CI 2·0-33·6]). Recovery trajectories of clinically unresponsive patients diagnosed with cognitive-motor dissociation early after brain injury are distinctly different from those without cognitive-motor dissociation. A diagnosis of cognitive-motor dissociation could inform the counselling of families of clinically unresponsive patients, and it could help clinicians to identify patients who will benefit from rehabilitation. US National Institutes of Health.

Classifying Disorders of Consciousness: Past, Present, and Future.

With the advent of advanced analytical methods applied to functional neuroimaging and neurophysiological data, cerebral conditions have been defined that challenge the established classification of disorders of consciousness. A subset of brain-damaged patients has been identified who cannot carry out motor commands, but who exhibit patterns of cerebral activation during mental imagery tasks that are indistinguishable from those in healthy controls. This condition, termed "cognitive motor dissociation," has overturned many assumptions regarding the detection, diagnosis, prognosis, and care of patients with brain injury. Three factors are likely to influence efforts to improve the classification of disorders of consciousness in the near future: the types of data that will become available to characterize brain states, the modeling paradigms utilized for data analysis, and the ability to implement classification schemes in the clinical setting. Here we review past achievements, present states, and future projections for the classification of impaired consciousness and responsiveness.

Brain-Computer Interfaces for Awareness Detection, Auxiliary Diagnosis, Prognosis, and Rehabilitation in Patients with Disorders of Consciousness.

In recent years, neuroimaging studies have remarkably demonstrated the presence of cognitive motor dissociation in patients with disorders of consciousness (DoC). These findings accelerated the development of brain-computer interfaces (BCIs) as clinical tools for behaviorally unresponsive patients. This article reviews the recent progress of BCIs in patients with DoC and discusses the open challenges. In view of the practical application of BCIs in patients with DoC, four aspects of the relevant literature are introduced: consciousness detection, auxiliary diagnosis, prognosis, and rehabilitation. For each aspect, the paradigm design, brain signal processing methods, and experimental results of representative BCI systems are analyzed. Furthermore, this article provides guidance for BCI design for patients with DoC and discusses practical challenges for future research.

Cognitive-Motor Dissociation Following Pediatric Brain Injury: What About the Children?

Background and ObjectivesFollowing severe brain injury, up to 16% of adults showing no clinical signs of cognitive function nonetheless have preserved cognitive capacities detectable via neuroimaging and neurophysiology; this has been designated cognitive-motor dissociation (CMD). Pediatric medicine lacks both practice guidelines for identifying covert cognition and epidemiologic data regarding CMD prevalence.MethodsWe applied a diverse battery of neuroimaging and neurophysiologic tests to evaluate 2 adolescents (aged 15 and 18 years) who had shown no clinical evidence of preserved cognitive function following brain injury at age 9 and 13 years, respectively. Clinical evaluations were consistent with minimally conscious state (minus) and vegetative state, respectively.ResultsBoth participants' EEG, and 1 participant's fMRI, provided evidence that they could understand commands and make consistent voluntary decisions to follow them. Both participants' EEG demonstrated larger-than-expected responses to auditory stimuli and intact semantic processing of words in context.DiscussionThese converging lines of evidence lead us to conclude that both participants had preserved cognitive function dissociated from their motor output. Throughout the 5+ years since injury, communication attempts and therapy had remained uninformed by such objective evidence of their cognitive abilities. Proper diagnosis of CMD is an ethical imperative. Children with covert cognition reflect a vulnerable and isolated population; the methods outlined here provide a first step in identifying such persons to advance efforts to alleviate their condition.

Ethical Considerations in Clinical Trials for Disorders of Consciousness.

As the clinical trial landscape for patients with disorders of consciousness (DoC) expands, consideration of associated ethical challenges and opportunities is of ever-increasing importance. Responsible conduct of research in the vulnerable population of persons with DoC, including those with coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), covert cortical processing (CCP), and cognitive motor dissociation (CMD), demands proactive deliberation of unique ethical issues that may arise and the adoption of robust protections to safeguard patients, surrogates, and other key stakeholders. Here we identify and critically evaluate four central categories of ethical considerations in clinical trials involving participants with DoC: (1) autonomy, respect for persons and informed consent of individuals with liminal consciousness; (2) balancing unknown benefits and risks, especially considering the epistemological gap between behavior and consciousness that complicates ordinary ascription of subjective states; (3) disclosure to surrogates and clinical teams of investigational results pertaining to consciousness; and (4) justice considerations, including equitable access to clinical trial enrollment across communities and geographies. We outline guiding principles and research opportunities for clinicians, neuroethicists, and researchers engaged in DoC clinical trials to advance ethical study design and deployment in this complex yet crucial area of investigation.

Case of cognitive motor dissociation diagnosed in patient with traumatic brain injury and hypoxia

Cognitive Motor Dissociation (CMD) is a subtype of disorders of consciousness which can be characterized as a detection of command following in clinically unresponsive patients. CMD detection requires usage of sophisticated diagnostical tools, such as functional magnetic resonance imaging to evaluate activation of following brain zones due to audial commands. Differential diagnosis between CMD and unresponsive wakefulness syndrome (UWS) or minimally consciousness state minus (MCS-) is crucial due to different prognosis for all these categories of patients. Patients with diagnosed CMD demonstrate regaining of consciousness more often than UWS patients. Here we described case of CMD, diagnosed in clinically unresponsive patient after severe traumatic brain injury complicated with hypoxia.

Big Data/AI in Neurocritical Care: Maybe/Summary.

Big data (BD) and artificial intelligence (AI) have increasingly been used in neurocritical care. "BD" can be operationally defined as extremely large datasets that are so large and complex that they cannot be analyzed by using traditional statistical modeling. "AI" means the ability of machines to perform tasks similar to those performed by human intelligence. We present a brief overview of the most commonly applied AI techniques to perform BD analytics and discuss some of the recent promising examples in the field of neurocritical care. The latter include the following: cognitive motor dissociation in disorders of consciousness, hypoxic-ischemic injury following cardiac arrest, delayed cerebral ischemia and vasospasm after subarachnoid hemorrhage, and monitoring of intracranial pressure. It is imperative that we develop multicenter collaborations to tackle BD. These collaborations will allow us to share data, combine predictive algorithms, and analyze multiple and cumulative sources of data retrospectively and prospectively. Once AI algorithms are validated at multiple centers, they should be tested in randomized controlled trials investigating their impact on clinical outcome. The neurocritical care community must work to ensure that AI incorporates standards to ensure fairness and health equity rather than reflect our biases present in our collective conscience.

Development of paradigms for the diagnosis of "covert cognition" and cognitive motor dissociation in patients with chronic disorders of consciousness

The detection of signs of consciousness in patients with chronic disorders of consciousness is a complex clinical task. In recent decades, instrumental methods have been used to improve the accuracy of diagnostics. The phenomenon of covert cognition and cognitive motor dissociation have been demonstrated in a small proportion of patients in studies using instrumental methods in combination with different paradigms. This article describes the main features of the diagnostic paradigms used for such purposes. Currently, the development of its own complex of paradigms is held at the Research Center of Neurology collaboratively with group of neuropsychologists from Lomonosov Moscow State University. The general characteristics of this complex of paradigms are indicated. The practical significance of detecting the phenomenon of covert cognition and cognitive motor dissociation in patients with chronic disorders of consciousness is discussed.

Residual Cognitive Capacities in Patients With Cognitive Motor Dissociation, and Their Implications for Well-Being.

Patients with severe disorders of consciousness are thought to be unaware of themselves or their environment. However, research suggests that a minority of patients diagnosed as having a disorder of consciousness remain aware. These patients, designated as having “cognitive motor dissociation” (CMD), can demonstrate awareness by imagining specific tasks, which generates brain activity detectable via functional neuroimaging. The discovery of consciousness in these patients raises difficult questions about their well-being, and it has been argued that it would be better for these patients if they were allowed to die. Conversely, I argue that CMD patients may have a much higher level of well-being than is generally acknowledged. It is far from clear that their lives are not worth living, because there are still significant gaps in our understanding of how these patients experience the world. I attempt to fill these gaps, by analyzing the neuroscientific research that has taken place with these patients to date. Having generated as comprehensive a picture as possible of the capacities of CMD patients, I examine this picture through the lens of traditional philosophical theories of well-being. I conclude that the presumption that CMD patients do not have lives worth living is not adequately supported.

Cognitive motor dissociation in patients with chronic disorders of consciousness: a literature review

Chronic disorders of consciousness include several conditions that differ significantly in both clinical and neurophysiological features. As medical technology continues to develop, the differential diagnosis of disorders of consciousness extends beyond purely clinical work. Nevertheless, all types of consciousness disorders are united by varying degrees of dissociation between wakefulness, cognitive and motor activity. The external similarity and minimal differences in clinical symptoms in unresponsive patients may hide different morphofunctional variants of this condition. In particular, use of electroencephalography and functional magnetic re- sonance imaging techniques allows us to detect covert consciousness in some clinically unresponsive patients. Based on various estimates, this phenomenon occurs in 515% of all cases. A special instance of covert consciousness is cognitive motor dissociation (CMD), defined as activation of cortical motor centers, recorded using neurophysiological techniques, in response to a corresponding instruction to perform a movement without its visible performance. Some researchers believe that detection of CMD indicates a more favourable prognosis for the subsequent restoration of consciousness, rather than its absence. The aim of this review is to examine CMD and its potential significance for outcomes in patients with chronic disorders of consciousness.

Evoked and Event-Related Potentials as Biomarkers of Consciousness State and Recovery.

Summary:The definition of consciousness has been the subject of great interest for many scientists and philosophers. To better understand how evoked potentials may be identified as biomarkers of consciousness and recovery, the different theoretical models sustaining neural correlates of consciousness are reviewed. A multimodal approach can help to better predict clinical outcome in patients presenting with disorders of consciousness. Evoked potentials are inexpensive and easy-to-implement bedside examination techniques. Evoked potentials are an integral part of prognostic evaluation, particularly in cases of cognitive motor dissociation. Prognostic criteria are well established in postanoxic disorders of consciousness, especially postcardiac arrest but are less well determined in other etiologies. In the early examination, bilateral absence of N20 in disorder of consciousness patients is strongly associated with unfavorable outcome (i.e., death or unresponsive wakefulness syndrome) especially in postanoxic etiologies. This predictive value is lower in other etiologies and probably also in children. Both N20 and mismatch negativity are proven outcome predictors for acute coma. Many studies have shown that mismatch negativity and P3a are characterized by a high prognostic value for awakening, but some patients presenting unresponsive wakefulness syndrome also process a P3a. The presence of long-latency event-related potential components in response to stimuli is indicative of a better recovery. All neurophysiological data must be integrated within a multimodal approach combining repeated clinical evaluation, neuroimaging, functional imaging, biology, and neurophysiology combining passive and active paradigms.

A Precision Medicine Framework for Classifying Patients with Disorders of Consciousness: Advanced Classification of Consciousness Endotypes (ACCESS).

Consciousness in patients with brain injury is traditionally assessed based on semiological evaluation at the bedside. This classification is limited because of low granularity, ill-defined and rigid nomenclatures incompatible with the highly fluctuating nature of consciousness, failure to identify specific brain states like cognitive motor dissociation, and neglect for underlying biological mechanisms. Here, the authors present a pragmatic framework based on consciousness endotypes that combines clinical phenomenology with all essential physiological and biological data, emphasizing recovery trajectories, therapeutic potentials and clinical feasibility. The Neurocritical Care Society's Curing Coma Campaign identified an international group of experts who convened in a series of online meetings between May and November 2020 to discuss and propose a novel framework for classifying consciousness. The expert group proposes Advanced Classification of Consciousness Endotypes (ACCESS), a tiered multidimensional framework reflecting increasing complexity and an aspiration to consider emerging and future approaches. Tier 1 is based on clinical phenotypes and structural imaging. Tier 2 adds functional measures including EEG, PET and functional MRI, that can be summarized using the Arousal, Volition, Cognition and Mechanisms (AVCM) score (where "Volition" signifies volitional motor responses). Finally, Tier 3 reflects dynamic changes over time with a (theoretically infinite) number of physiologically distinct states to outline consciousness recovery and identify opportunities for therapeutic interventions. Whereas Tiers 1 and 2 propose an approach for low-resource settings and state-of-the-art expertise at leading academic centers, respectively, Tier 3 is a visionary multidimensional consciousness paradigm driven by continuous incorporation of new knowledge while addressing the Curing Coma Campaign's aspirational goals.

Therapeutic Use of Transcranial Direct Current Stimulation in the Rehabilitation of Prolonged Disorders of Consciousness.

Patients with Prolonged Disorders of Consciousness (PDOC) have catastrophic disabilities and very complex needs for care. Therapeutic options are very limited, and patients often show little functional improvement over time. Neuroimaging studies have demonstrated that a significant number of PDOC patients retain a high level of cognitive functioning, and in some cases even awareness, and are simply unable to show this with their external behavior - a condition known as cognitive-motor dissociation (CMD). Despite vast implications for diagnosis, the discovery of covert cognition in PDOC patients is not typically associated with a more favorable prognosis, and the majority of patients will remain in a permanent state of low responsiveness. Recently, transcranial direct current stimulation (tDCS) has attracted attention as a potential therapeutic tool in PDOC. Research to date suggests that tDCS can lead to clinical improvements in patients with a minimally conscious state (MCS), especially when administered over multiple sessions. While promising, the outcomes of these studies have been highly inconsistent, partially due to small sample sizes, heterogeneous methodologies (in terms of both tDCS parameters and outcome measures), and limitations related to electrode placement and heterogeneity of brain damage inherent to PDOC. In addition, we argue that neuroimaging and electrophysiological assessments may serve as more sensitive biomarkers to identify changes after tDCS that are not yet apparent behaviorally. Finally, given the evidence that concurrent brain stimulation and physical therapy can enhance motor rehabilitation, we argue that future studies should focus on the integration of tDCS with conventional rehabilitation programmes from the subacute phase of care onwards, to ascertain whether any synergies exist.

Prolonged disorders of consciousness: a critical evaluation of the new UK guidelines.

In March 2020, the Royal College of Physicians in the UK published national guidelines on the management of patients with prolonged disorders of consciousness, updating their 2013 guidance 'particularly in relation to recent developments in assessment and management and … changes in the law governing … the withdrawal of clinically assisted nutrition and hydration'. The report's primary focus is on patients who could live for many years with treatment and care. This update, by a neurologist, an imaging neuroscientist, and a lawyer-ethicist, questions the document's rejection of any significant role for neuroimaging techniques including functional MRI and/or bedside EEG to detect covert consciousness in such patients. We find the reasons for this rejection unconvincing, given (i) the significant advances made in the use of this technology in recent years; and (ii) the wider scope for its use envisaged by the earlier (2018) guidelines issued by the American Academy of Neurology. We suggest that, since around one in five patients diagnosed with prolonged disorders of consciousness are in fact conscious enough to follow commands in a neuroimaging context (i.e. those who are 'covertly conscious' or those with 'cognitive motor dissociation'), and given the clinical, ethical and legal importance of determining whether patients with prolonged disorders of consciousness are legally competent or at least able to express their views and feelings, the guidance from the Royal College of Physicians requires urgent review.