Local sleep-like cortical reactivity in the awake brain after focal injury.

The functional consequences of focal brain injury are thought to be contingent on neuronal alterations extending beyond the area of structural damage. This phenomenon, also known as diaschisis, has clinical and metabolic correlates but lacks a clear electrophysiological counterpart, except for the long-standing evidence of a relative EEG slowing over the injured hemisphere. Here, we aim at testing whether this EEG slowing is linked to the pathological intrusion of sleep-like cortical dynamics within an awake brain. We used a combination of transcranial magnetic stimulation and electroencephalography (TMS/EEG) to study cortical reactivity in a cohort of 30 conscious awake patients with chronic focal and multifocal brain injuries of ischaemic, haemorrhagic and traumatic aetiology. We found that different patterns of cortical reactivity typically associated with different brain states (coma, sleep, wakefulness) can coexist within the same brain. Specifically, we detected the occurrence of prominent sleep-like TMS-evoked slow waves and off-periods-reflecting transient suppressions of neuronal activity-in the area surrounding focal cortical injuries. These perilesional sleep-like responses were associated with a local disruption of signal complexity whereas complex responses typical of the awake brain were present when stimulating the contralesional hemisphere. These results shed light on the electrophysiological properties of the tissue surrounding focal brain injuries in humans. Perilesional sleep-like off-periods can disrupt network activity but are potentially reversible, thus representing a principled read-out for the neurophysiological assessment of stroke patients, as well as an interesting target for rehabilitation

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

Cardio-respiratory autonomic responses to nociceptive stimuli in patients with disorders of consciousness.

The autonomic response to pain might discriminate among consciousness disorders. Therefore, aim of this study was to describe differences between minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS) patients in their autonomic response to a nociceptive stimulus. ECG, respiration, finger blood pressure (BP) and total peripheral resistances (TPR) were continuously recorded before, during and after a standardized noxious stimulus in 20 adult brain-injured patients, 14 in UWS and 6 in MCS. Occurrence of fast autonomic responses synchronous with the stimulus was detected by visual inspection of the tracings; short-term (<20 s) and long-term (between 20s and 50 s from the stimulus) responses were evaluated by beat-by-beat quantitative analysis. The noxious stimulus elicited fast responses in both groups, but only MCS patients showed a significant short-term response in TPR and long-term response in HR. Thus, short- and long-term cardiovascular responses to pain might integrate neuro-behavioural assessments to discriminate between MCS and UWS

Evidence of altered pressure pain thresholds in persons with disorders of consciousness as measured by the Nociception Coma Scale-Italian version

Pain assessment in patients with disorders of consciousness (DoC) is a controversial issue for clinicians, who require tools and standardised procedures for testing nociception in non-communicative patients. The aims of the present study were, first, to analyse the psychometric properties of the Italian version of the Nociception Coma Scale and, second, to evaluate pressure pain thresholds in a group of patients with DoC. The authors conducted a multi-centre study on 40 healthy participants and 60 DoC patients enrolled from six hospitals in Italy. For each group an electronic algometer was used to apply all nociceptive pressure stimuli. Our results show that the Italian version of the NCS retains the good psychometric properties of the original version and is therefore suitable for standardised pain assessment in clinical practice. In our study, pressure pain thresholds measured in a group of patients in vegetative and minimally conscious state were relatively lower than pain threshold values found in a group of healthy participants. Such findings motivate additional investigation on possible pain sensitisation in patients with severe brain injury and multiple co-morbidities, and on application of tailored therapeutic approaches useful for pain management in patients unable verbally to communicate their feelings

Stratification of unresponsive patients by an independently validated index of brain complexity

ObjectiveValidating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousnessthe Perturbational Complexity Index (PCI)in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). MethodsThe benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). ResultsWe found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. InterpretationGiven its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718-729Prin "Connage" (Italian Government)European Union (EU)James S. McDonnell Foundation Scholar AwardBelgian National Fund for Scientific ResearchTempleton World Charity FoundationMcDonnell FoundationDistinguished Chair in Consciousness Science at the University of WisconsinUniv Milan, Dept Biomed & Clin Sci L Sacco, Via GB Grassi 74, I-20157 Milan, ItalyFdn Europea Ric Biomed, Milan, ItalyUniv Milano Bicocca, Sch Med & Surg, Dept Hlth Sci, Monza, ItalyUniv Fed Sao Paulo, Inst Sci & Technol, Sao Jose Dos Campos, BrazilFdn Don Gnocchi Onlus, Ist Ricovero & Cura Carattere Sci, Milan, ItalyUniv Wisconsin, Dept Psychiat, Madison, WI 53706 USAUniv Wisconsin, Dept Neurol, Madison, WI 53706 USAUniv Liege, Coma Sci Grp, GIGA, Liege, BelgiumUniv Liege, Dept Neurol, Liege, BelgiumUniv Hosp Liege, Liege, BelgiumGrande Osped Metropolitano Niguarda Ca Granda, Neurocrit Care Unit, Azienda Sociosanit Terr, Dept Neurosci, Milan, ItalyInstitute of Science and Technology, Universidade Federal de São Paulo (UNIFESP), São José dos Campos, BrazilEU: 600806EU: 686764EU: 720270Web of Scienc