Electromagnetic Brain Stimulation in Patients With Disorders of Consciousness

Severe brain injury is a common cause of coma. In some cases, despite vigilance improvement, disorders of consciousness (DoC) persist. Several states of impaired consciousness have been defined, according to whether the patient exhibits only reflexive behaviors as in the vegetative state/unresponsive wakefulness syndrome (VS/UWS) or purposeful behaviors distinct from reflexes as in the minimally conscious state (MCS). Recently, this clinical distinction has been enriched by electrophysiological and neuroimaging data resulting from a better understanding of the physiopathology of DoC. However, therapeutic options, especially pharmacological ones, remain very limited. In this context, electroceuticals, a new category of therapeutic agents which act by targeting the neural circuits with electromagnetic stimulations, started to develop in the field of DoC. We performed a systematic review of the studies evaluating therapeutics relying on the direct or indirect electro-magnetic stimulation of the brain in DoC patients. Current evidence seems to support the efficacy of deep brain stimulation (DBS) and non-invasive brain stimulation (NIBS) on consciousness in some of these patients. However, while the latter is non-invasive and well tolerated, the former is associated with potential major side effects. We propose that all chronic DoC patients should be given the possibility to benefit from NIBS, and that transcranial direct current stimulation (tDCS) should be preferred over repetitive transcranial magnetic stimulation (rTMS), based on the literature and its simple use. Surgical techniques less invasive than DBS, such as vagus nerve stimulation (VNS) might represent a good compromise between efficacy and invasiveness but still need to be further investigated

Clinical review: Prognostic value of magnetic resonance imaging in acute brain injury and coma

Progress in management of critically ill neurological patients has led to improved survival rates. However, severe residual neurological impairment, such as persistent coma, occurs in some survivors. This raises concerns about whether it is ethically appropriate to apply aggressive care routinely, which is also associated with burdensome long-term management costs. Adapting the management approach based on long-term neurological prognosis represents a major challenge to intensive care. Magnetic resonance imaging (MRI) can show brain lesions that are not visible by computed tomography, including early cytotoxic oedema after ischaemic stroke, diffuse axonal injury after traumatic brain injury and cortical laminar necrosis after cardiac arrest. Thus, MRI increases the accuracy of neurological diagnosis in critically ill patients. In addition, there is some evidence that MRI may have potential in terms of predicting outcome. Following a brief description of the sequences used, this review focuses on the prognostic value of MRI in patients with traumatic brain injury, anoxic/hypoxic encephalopathy and stroke. Finally, the roles played by the main anatomical structures involved in arousal and awareness are discussed and avenues for future research suggested

Two Distinct Dynamic Modes Subtend the Detection of Unexpected Sounds

International audienceThe brain response to auditory novelty comprises two main EEG components: an early mismatch negativity and a late P300. Whereas the former has been proposed to reflect a prediction error, the latter is often associated with working memory updating. Interestingly, these two proposals predict fundamentally different dynamics: prediction errors are thought to propagate serially through several distinct brain areas, while working memory supposes that activity is sustained over time within a stable set of brain areas. Here we test this temporal dissociation by showing how the generalization of brain activity patterns across time can characterize the dynamics of the underlying neural processes. This method is applied to magnetoencephalography (MEG) recordings acquired from healthy participants who were presented with two types of auditory novelty. Following our predictions, the results show that the mismatch evoked by a local novelty leads to the sequential recruitment of distinct and short-lived patterns of brain activity. In sharp contrast, the global novelty evoked by an unexpected sequence of five sounds elicits a sustained state of brain activity that lasts for several hundreds of milliseconds. The present results highlight how MEG combined with multivariate pattern analyses can characterize the dynamics of human cortical processes

Event related potentials elicited by violations of auditory regularities in patients with impaired consciousness.

International audienceImproving our ability to detect conscious processing in non communicating patients remains a major goal of clinical cognitive neurosciences. In this perspective, several functional brain imaging tools are currently under development. Bedside cognitive event-related potentials (ERPs) derived from the EEG signal are a good candidate to explore consciousness in these patients because: (1) they have an optimal time resolution within the millisecond range able to monitor the stream of consciousness, (2) they are fully non-invasive and relatively cheap, (3) they can be recorded continuously on dedicated individual systems to monitor consciousness and to communicate with patients, (4) and they can be used to enrich patients' autonomy through brain-computer interfaces. We recently designed an original auditory rule extraction ERP test that evaluates cerebral responses to violations of temporal regularities that are either local in time or global across several seconds. Local violations led to an early response in auditory cortex, independent of attention or the presence of a concurrent visual task, while global violations led to a late and spatially distributed response that was only present when subjects were attentive and aware of the violations. In the present work, we report the results of this test in 65 successive recordings obtained at bedside from 49 non-communicating patients affected with various acute or chronic neurological disorders. At the individual level, we confirm the high specificity of the 'global effect': only conscious patients presented this proposed neural signature of conscious processing. Here, we also describe in details the respective neural responses elicited by violations of local and global auditory regularities, and we report two additional ERP effects related to stimuli expectancy and to task learning, and we discuss their relations to consciousness

Converging Intracranial Markers of Conscious Access

We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram (iEEG) in ten patients. Nonconscious processing of masked words was observed in multiple cortical areas, mostly within an early time window (<300 ms), accompanied by induced gamma-band activity, but without coherent long-distance neural activity, suggesting a quickly dissipating feedforward wave. In contrast, conscious processing of unmasked words was characterized by the convergence of four distinct neurophysiological markers: sustained voltage changes, particularly in prefrontal cortex, large increases in spectral power in the gamma band, increases in long-distance phase synchrony in the beta range, and increases in long-range Granger causality. We argue that all of those measures provide distinct windows into the same distributed state of conscious processing. These results have a direct impact on current theoretical discussions concerning the neural correlates of conscious access

Survival and consciousness recovery are better in the minimally conscious state than in the vegetative state

BACKGROUND The prognosis value of early clinical diagnosis of consciousness impairment is documented by an extremely limited number of studies, whereas it may convey important information to guide medical decisions. OBJECTIVE We aimed at determining if patients diagnosed at an early stage (<90 days after brain injury) as being in the minimally conscious state (MCS) have a better prognosis than patients in the vegetative state/Unresponsive Wakefulness syndrome (VS/UWS), independent of care limitations or withdrawal decisions. METHODS Patients hospitalized in ICUs of the Pitié-Salpêtrière Hospital (Paris, France) from November 2008 to January 2011 were included and evaluated behaviourally with standardized assessment and with the Coma Recovery Scale-Revised as being either in the VS/UWS or in the MCS. They were then prospectively followed until 1July 2011 to evaluate their outcome with the GOSE. We compared survival function and outcomes of these two groups. RESULTS Both survival function and outcomes, including consciousness recovery, were significantly better in the MCS group. This difference of outcome still holds when considering only patients still alive at the end of the study. CONCLUSIONS Early accurate clinical diagnosis of VS/UWS or MCS conveys a strong prognostic value of survival and of consciousness recovery

Unifying turbulent dynamics framework distinguishes different brain states.

peer reviewedSignificant advances have been made by identifying the levels of synchrony of the underlying dynamics of a given brain state. This research has demonstrated that non-conscious dynamics tend to be more synchronous than in conscious states, which are more asynchronous. Here we go beyond this dichotomy to demonstrate that different brain states are underpinned by dissociable spatiotemporal dynamics. We investigated human neuroimaging data from different brain states (resting state, meditation, deep sleep and disorders of consciousness after coma). The model-free approach was based on Kuramoto's turbulence framework using coupled oscillators. This was extended by a measure of the information cascade across spatial scales. Complementarily, the model-based approach used exhaustive in silico perturbations of whole-brain models fitted to these measures. This allowed studying of the information encoding capabilities in given brain states. Overall, this framework demonstrates that elements from turbulence theory provide excellent tools for describing and differentiating between brain states