Non-Functional Jaw Muscular Activity in Patients with Disorders of Consciousness Revealed by A Long-Lasting Polygraphy.

The presence of involuntary, non-functional jaw muscle activity (NFJMA) has not yet been assessed in patients with disorders of consciousness (DOC), although the presence of bruxism and other forms of movement disorders involving facial muscles is probably more frequent than believed. In this work, we evaluated twenty-two prolonged or chronic DOC patients with a long-lasting polygraphic recording to verify NFJMA occurrence and assess its neurophysiological patterns in this group of patients. A total of 5 out of 22 patients showed the presence of significant NFJMA with electromyographic patterns similar to what can be observed in non-DOC patients with bruxism, thus suggesting a disinhibition of masticatory motor nuclei from the cortical control. On the other hand, in two DOC patients, electromyographic patterns advised for the presence of myorhythmia, thus suggesting a brainstem/diencephalic involvement. Functional, non-invasive tools such as long-lasting polygraphic recordings should be extended to a larger sample of patients, since they are increasingly important in revealing disorders potentially severe and impacting the quality of life of DOC patients.

Towards a New Assessment Tool for Caregivers of Patients with Disorders of Consciousness: The Social and Family Evaluation Scale (SAFE).

Monitoring the level of responsiveness of patients with Disorders of Consciousness (DoCs) represents an issue in all the settings where there is not the daily presence of clinicians, such as long-term and domestic settings. The involvement of patients' informal caregivers (i.e., patients' family) in such a monitoring process is thus fundamental. However, to date, no standardized tailored-made instruments exist that informal caregivers can use without the presence of clinicians, despite evidence illustrating the good accuracy of caregivers when expressing their opinions about the level of responsiveness of DoC patients. The present work aims to set the foundational knowledge, to create a standardized instrument that is able to assess the level of responsiveness of patients with DoCs by their informal caregivers. After selecting and modifying the items to be included in the new scale from the gold standard to diagnose DoCs (i.e., the Coma Recovery Scale-revised), and following a consensus process, we created the Social and Family Evaluation (SAFE) scale for caregivers of patients with DoCs. Although the SAFE needs a validation process, with the present work we provided its preliminary description along with insights into its clinical utility.

Incidence, prevalence and disability associated with neurological disorders in Italy between 1990 and 2019: an analysis based on the Global Burden of Disease Study 2019.

BACKGROUND: Neurological conditions are highly prevalent and disabling, in particular in the elderly. The Italian population has witnessed sharp ageing and we can thus expect a rising trend in the incidence, prevalence and disability of these conditions. METHODS: We relied on the Global Burden of Disease 2019 study to extract Italian data on incidence, prevalence and years lived with a disability (YLDs) referred to a broad set of neurological disorders including, brain and nervous system cancers, stroke, encephalitis, meningitis, tetanus, traumatic brain injury, and spinal cord injury. We assessed changes between 1990 and 2019 in counts and age-standardized rates. RESULTS: The most prevalent conditions were tension-type headache, migraine, and dementias, whereas the most disabling were migraine, dementias and traumatic brain injury. YLDs associated with neurological conditions increased by 22.5%, but decreased by 2.3% in age-standardized rates. The overall increase in prevalence and YLDs counts was stronger for non-communicable diseases with onset in old age compared to young to adult-age onset ones. The same trends were in the opposite direction when age-standardized rates were taken into account. CONCLUSIONS: The increase in YLDs associated with neurological conditions is mostly due to population ageing and growth: nevertheless, lived disability and, as a consequence, impact on health systems has increased. Actions are needed to improve outcome and mitigate disability associated with neurological conditions, spanning among diagnosis, treatment, care pathways and workplace interventions.

Global survey on disruption and mitigation of neurological services during COVID-19: the perspective of global international neurological patients and scientific associations.

BACKGROUND: The COVID-19 pandemic outbreak has dramatically disrupted healthcare systems. Two rapid WHO pulse surveys studied disruptions in mental health services, but did not particularly focus on neurology. Here, a global survey was conducted and addresses the impact of the pandemic on neurology services. METHODS: A cross-sectional study was carried out in which 34 international neurological associations were asked to distribute the survey to national associations. The responses represented the national situation, in November-December 2020, with regard to the main disrupted neurological services, reasons and the mitigation strategies implemented as well as the disruption on training of residents and on neurological research. A comparison with the situation in February-April 2020, first pandemic wave, was also requested. FINDINGS: 54 completed surveys came from 43 countries covering all the 6 WHO regions. Overall, neurological services disruption was reported as mild by 26%, moderate by 30%, complete by 13% of associations. The most affected services were cross-sectoral neurological services (57%) and neurorehabilitation (56%). The second wave of the pandemic, however, was associated with the improvement of service provision for diagnostics services (44%) and for neurorehabilitation (41%). Governmental directives were the major cause of services' disruption (56%). Mitigation strategies were mostly established through telemedicine (48%). Almost half of respondents reported a significant impact on neurological research (48%) and educational activities (60%). Most associations (67%) were not involved in decision making for neurological patients' issues by their national government. INTERPRETATION: The COVID-19 pandemic affects neurological services and raises the universal need for the development of neurological health care at the policy, systems and services levels. A global national plan on mitigation strategies for disruption of neurological services during pandemic situations should be established and neurological scientific and patients associations should get involved in decision making.

Analyzing the Loss and the Recovery of Consciousness: Functional Connectivity Patterns and Changes in Heart Rate Variability During Propofol-Induced Anesthesia.

The analysis of the central and the autonomic nervous systems (CNS, ANS) activities during general anesthesia (GA) provides fundamental information for the study of neural processes that support alterations of the consciousness level. In the present pilot study, we analyzed EEG signals and the heart rate (HR) variability (HRV) in a sample of 11 patients undergoing spinal surgery to investigate their CNS and ANS activities during GA obtained with propofol administration. Data were analyzed during different stages of GA: baseline, the first period of anesthetic induction, the period before the loss of consciousness, the first period after propofol discontinuation, and the period before the recovery of consciousness (ROC). In EEG spectral analysis, we found a decrease in posterior alpha and beta power in all cortical areas observed, except the occipital ones, and an increase in delta power, mainly during the induction phase. In EEG connectivity analysis, we found a significant increase of local efficiency index in alpha and delta bands between baseline and loss of consciousness as well as between baseline and ROC in delta band only and a significant reduction of the characteristic path length in alpha band between the baseline and ROC. Moreover, connectivity results showed that in the alpha band there was mainly a progressive increase in the number and in the strength of incoming connections in the frontal region, while in the beta band the parietal region showed mainly a significant increase in the number and in the strength of outcoming connections values. The HRV analysis showed that the induction of anesthesia with propofol was associated with a progressive decrease in complexity and a consequent increase in the regularity indexes and that the anesthetic procedure determined bradycardia which was accompanied by an increase in cardiac sympathetic modulation and a decrease in cardiac parasympathetic modulation during the induction. Overall, the results of this pilot study showed as propofol-induced anesthesia caused modifications on EEG signal, leading to a "rebalance" between long and short-range cortical connections, and had a direct effect on the cardiac system. Our data suggest interesting perspectives for the interactions between the central and autonomic nervous systems for the modulation of the consciousness level.

Theoretical Models of Consciousness: A Scoping Review.

The amount of knowledge on human consciousness has created a multitude of viewpoints and it is difficult to compare and synthesize all the recent scientific perspectives. Indeed, there are many definitions of consciousness and multiple approaches to study the neural correlates of consciousness (NCC). Therefore, the main aim of this article is to collect data on the various theories of consciousness published between 2007-2017 and to synthesize them to provide a general overview of this topic. To describe each theory, we developed a thematic grid called the dimensional model, which qualitatively and quantitatively analyzes how each article, related to one specific theory, debates/analyzes a specific issue. Among the 1130 articles assessed, 85 full texts were included in the prefinal step. Finally, this scoping review analyzed 68 articles that described 29 theories of consciousness. We found heterogeneous perspectives in the theories analyzed. Those with the highest grade of variability are as follows: subjectivity, NCC, and the consciousness/cognitive function. Among sub-cortical structures, thalamus, basal ganglia, and the hippocampus were the most indicated, whereas the cingulate, prefrontal, and temporal areas were the most reported for cortical ones also including the thalamo-cortical system. Moreover, we found several definitions of consciousness and 21 new sub-classifications.

Talking with hands: body representation in British Sign Language users.

Body representation (BR) refers to the mental representation of motor, sensory, emotional and semantic information about the physical body. This cognitive representation is used in our everyday life, continuously, even though most of the time we do not appreciate it consciously. In some cases, BR is vital to be able to communicate. A crucial feature of signed languages (SLs), for instance, is that body parts such as hands are used to communicate. Nevertheless, little is known about BR in SL: is the communicative function of the body overwriting the physical constraints? Here, we explored this question by comparing twelve British Sign Language (BSL) learners to seventeen tango dancers (body expertise but not for communication) and fourteen control subjects (no special body expertise). We administered the Body Esteem Scale (BES), the Hand Laterality Task (HLT) and the Mental Motor Chronometry (MMC). To control for visual imagery, we administered ad hoc control tasks. We did not identify parameters able to differentiate between SL users and the other groups, whereas the more implicit parameters distinguished clearly tango dancers from controls. Importantly, neither tasks on visual imagery nor the BES revealed differences. Our findings offer initial evidence that linguistic use of the body not necessarily influences the cognitive components we explored of body representation.

Visual fixation in disorders of consciousness: Development of predictive models to support differential diagnosis.

The visual fixation represents a doubtful behavioral sign to discriminate Vegetative from Minimally Conscious State (MCS). To disentangle its meaning, we fitted univariate and multivariable logistic regression models matching different neurophysiological and neuroimaging data of 54 patients with Disorders of Consciousness to select the best model predicting which visual performance (visual blink or pursuit) was shown by patients and the best predictors set. The best models found highlighted the importance of the structural MRI and the visual evoked potentials data in predicting visual pursuit. Then, a qualitative pilot test was made on four patients showing visual fixation revealing that the obtained models correctly predict whether the patients' visual performance could support/correlate to a cognitively mediated behavior. The present pilot models could help clinicians to evaluate if the visual fixation response can support the MCS diagnosis.

Metric biases in body representation extend to objects.

We typically misestimate the dimensions of our body e.g., we perceive our fingers as shorter, and our torso as more elongated, than they actually are. It stands to reason that those metric biases may also extend to objects that we interact with, to facilitate attunement with the environment. To explore this hypothesis, we compared the metric representations of seven objects and the subjects' own hand using the Line Length Judgment task, in six experiments involving 152 healthy subjects. We evaluated the size estimation errors made for each target (hand or previously observed objects) by asking subjects to compare the vertical or horizontal dimension of a specific target against the length of a vertical or horizontal line. As expected, we showed that the hand is misperceived in its dimensions. Interestingly, we found that metric biases are also present for daily-life objects, such as a mobile phone and a coffee mug, and are not affected by familiarity with the objects. In contrast, objects that are less likely to be manipulated, either because they are potentially harmful or disgusting, were differently represented. Furthermore, the propensity to interact with an object, rated by an independent sample of subjects, best predicted the pattern of metric biases associated with that object. Taken together, these findings support the hypothesis that biases affecting the hand representation extend to objects that elicit action-oriented behavior, highlighting the importance of studying the body as integrated and active in the environment.

Avoiding the Banality of Evil in Times of COVID-19: Thinking Differently with a Biopsychosocial Perspective for Future Health and Social Policies Development.

The COVID-19 pandemic provides the opportunity to re-think health policies and health systems approaches by the adoption of a biopsychosocial perspective, thus acting on environmental factors so as to increase facilitators and diminish barriers. Specifically, vulnerable people should not face discrimination because of their vulnerability in the allocation of care or life-sustaining treatments. Adoption of biopsychosocial model helps to identify key elements where to act to diminish effects of the pandemics. The pandemic showed us that barriers in health care organization affect mostly those that are vulnerable and can suffer discrimination not because of severity of diseases but just because of their vulnerability, be this age or disability and this can be avoided by biopsychosocial planning in health and social policies. It is possible to avoid the banality of evil, intended as lack of thinking on what we do when we do, by using the emergence of the emergency of COVID-19 as a Trojan horse to achieve some of the sustainable development goals such as universal health coverage and equity in access, thus acting on environmental factors is the key for global health improvement.

Autonomic responses to emotional linguistic stimuli and amplitude of low-frequency fluctuations predict outcome after severe brain injury.

An accurate prognosis on the outcome of brain-injured patients with disorders of consciousness (DOC) remains a significant challenge, especially in the acute stage. In this study, we applied a multiple-technique approach to provide accurate predictions on functional outcome after 6 months in 15 acute DOC patients. Electrophysiological correlates of implicit cognitive processing of verbal stimuli and data-driven voxel-wise resting-state fMRI signals, such as the fractional amplitude of low-frequency fluctuations (fALFF), were employed. Event-related electrodermal activity, an index of autonomic activation, was recorded in response to emotional words and pseudo-words at baseline (T0). On the same day, patients also underwent a resting-state fMRI scan. Six months later (T1), patients were classified as outcome-negative and outcome-positive using a standard functional outcome scale. We then revisited the baseline measures to test their predictive power for the functional outcome measured at T1. We found that only outcome-positive patients had an earlier, higher autonomic response for words compared to pseudo-words, a pattern similar to that of healthy awake controls. Furthermore, DOC patients showed reduced fALFF in the posterior cingulate cortex (PCC), a brain region that contributes to autonomic regulation and awareness. The event-related electrodermal marker of residual cognitive functioning was found to have a significant correlation with residual local neuronal activity in the PCC. We propose that a residual autonomic response to cognitively salient stimuli, together with a preserved resting-state activity in the PCC, can provide a useful prognostic index in acute DOC.

Visual behaviors in disorders of consciousness: Disentangling conscious visual processing by a multimodal approach.

One of the major challenges for clinicians who treat patients with Disorders of Consciousness (DoCs) concerns the detection of signs of consciousness that distinguish patients in Vegetative State from those in Minimally Conscious State. Recent studies showed how visual responses to tailored stimuli are one of the first evidence revealing that one patient is changing from one state to another. This study aimed to explore the integrity of the neural structures being part of the visual system in patients with DoCs manifesting a reflexive behavior (visual blink) and in those manifesting a cognitively and cortically mediated behavior (visual pursuit). We collected instrumental data using specialized equipment (EEG following the rules of the International 10-20 system, 3T Magnetic Resonance, and Positron Emission Tomography) in 54 DoC patients. Our results indicated that visual pursuit group showed a better fVEPs response than the visual blink group, because of a greater area under the N2/P2 component of fVEPs (AUC could be seen as an indicator of the residual activity of visual areas). Considering neuroimaging data, the main structural differences between groups were found in the retrochiasmatic areas, specifically in the right optic radiation and visual cortex (V1), areas statistically less impaired in patients able to perform a visual pursuit. FDG-PET analysis confirmed difference between groups at the level of the right calcarine cortex and neighboring right lingual gyrus. In conclusion, although there are methodological and theoretical limitations that should be considered, our study suggests a new perspective to consider for a future diagnostic protocol.

Mental representation of the body in action in Parkinson's disease.

Mixed findings characterize studies in Parkinson's disease (PD): some studies indicate a relationship between physical impairments and the ability to mentally represent the body, while others suggest spared abilities for this cognitive function. To clarify the matter, in the present study we explored the mental representations of the body in action in the same PD patients, taking also into account lateralization of symptoms and visual imagery skills. 10 PD patients with left- (lPD), 10 with right (rPD) lateralized symptoms (lPD), and 20 matched healthy controls have been recruited for the study. All patients were screened for neuropsychological impairments. To explore a more implicit component we used the hand laterality task (HLT), while the mental motor chronometry (MMC) was used to explore a more explicit one. Two control tasks, with objects instead of body parts, were administered to control for visual imagery skills. In the HLT, we detected the effects of biomechanical constraints effects in both controls and PD patients. In the latter group, importantly, this was true independently from lateralization of symptoms. In the MMC, we found the expected positive correlation between executed and imagined movements for both hands in controls only, while all PD patients, again independently form lateralization, only showed this effect for the left hand. In terms of visual imagery, only rPD patients differed from controls when asked to implicitly rotate letters, and in terms of accuracy only. However, this difference is explained by executive functions measured through the neuropsychological assessment rather than by a "pure" visual imagery impairment. In summary, our findings suggest that two different aspects of the mental representations of the body in action, one more implicit and the other more explicit, can be differently affected by PD. These impairments are unlikely explained by a basic visual imagery deficit. When present, impairments concern a higher dimension, related to motor functions and awareness, and not driven by sensory impairments, as shown by the independence of effects from physical laterality of symptoms.

Neuroimaging Studies on Disorders of Consciousness: A Meta-Analytic Evaluation.

Neuroimaging tools could open a window on residual neurofunctional activity in the absence of detectable behavioural responses in patients with disorders of consciousness (DOC). Nevertheless, the literature on this topic is characterised by a large heterogeneity of paradigms and methodological approaches that can undermine the reproducibility of the results. To explicitly test whether task-related functional magnetic resonance imaging (fMRI) can be used to systematically detect neurofunctional differences between different classes of DOC, and whether these differences are related with a specific category of cognitive tasks (either active or passive), we meta-analyzed 22 neuroimaging studies published between 2005 and 2017 using the Activation Likelihood Estimate method. The results showed that: (1) active and passive tasks rely on well-segregated patterns of activations; (2) both unresponsive wakeful syndrome and patients in minimally conscious state activated a large portion of the dorsal-attentional network; (3) shared activations between patients fell mainly in the passive activation map (7492 voxels), while only 48 voxels fell in a subcortical region of the active-map. Our results suggest that DOCs can be described along a continuum-rather than as separated clinical categories-and characterised by a widespread dysfunction of brain networks rather than by the impairment of a well functionally anatomically defined one.

Easy quantitative methodology to assess visual-motor skills.

INTRODUCTION: Visual-motor skills are the basis for a great number of daily activities. To define a correct rehabilitation program for neurological patients who have impairment in these skills, there is a need for simple and cost-effective tools to determine which of the visual-motor system levels of organization are compromised by neurological lesions. In their 1995 book, The Visual Brain in Action (Oxford: Oxford University Press), AD Milner and MA Goodale proposed the existence of two pathways for the processing of visual information, the "ventral stream" and "dorsal stream," that interact in movement planning and programming. Beginning with this model, our study aimed to validate a method to quantify the role of the ventral and dorsal streams in perceptual and visual-motor skills. SUBJECTS AND METHODS: Nineteen right-handed healthy subjects (mean age 22.8 years ± 3.18) with normal or corrected-to-normal vision were recruited. We proposed that a delayed pointing task, a distance reproduction task, and a delayed anti-pointing task could be used to assess the ventral stream, while the dorsal stream could be evaluated with a grasping task and an immediate pointing task. Performance was recorded and processed with the video-analysis software Dartfish ProSuite. RESULTS: Results showed the expected pattern of predominance of attention for the superior left visual field, predominance of the flexor tone in proximal peri-personal space arm movements, tendency toward overestimation of short distances, and underestimation of long distances. CONCLUSION: We believe that our method is advantageous as it is simple and easily transported, but needs further testing in neurologically compromised patients.