Electrophysiological investigations of brain function in coma, vegetative and minimally conscious patients.

Electroencephalographic activity in the context of disorders of consciousness is a swiss knife like tool that can evaluate different aspects of cognitive residual function, detect consciousness and provide a mean to communicate with the outside world without using muscular channels. Standard recordings in the neurological department offer a first global view of the electrogenesis of a patient and can spot abnormal epileptiform activity and therefore guide treatment. Although visual patterns have a prognosis value, they are not sufficient to provide a diagnosis between vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS) patients. Quantitative electroencephalography (qEEG) processes the data and retrieves features, not visible on the raw traces, which can then be classified. Current results using qEEG show that MCS can be differentiated from VS/UWS patients at the group level. Event Related Potentials (ERP) are triggered by varying stimuli and reflect the time course of information processing related to the stimuli from low-level peripheral receptive structures to high-order associative cortices. It is hence possible to assess auditory, visual, or emotive pathways. Different stimuli elicit positive or negative components with different time signatures. The presence of these components when observed in passive paradigms is usually a sign of good prognosis but it cannot differentiate VS/UWS and MCS patients. Recently, researchers have developed active paradigms showing that the amplitude of the component is modulated when the subject's attention is focused on a task during stimulus presentation. Hence significant differences between ERPs of a patient in a passive compared to an active paradigm can be a proof of consciousness. An EEG-based brain-computer interface (BCI) can then be tested to provide the patient with a communication tool. BCIs have considerably improved the past two decades. However they are not easily adaptable to comatose patients as they can have visual or auditory impairments or different lesions affecting their EEG signal. Future progress will require large databases of resting state-EEG and ERPs experiment of patients of different etiologies. This will allow the identification of specific patterns related to the diagnostic of consciousness. Standardized procedures in the use of BCIs will also be needed to find the most suited technique for each individual patient.Peer reviewe

Decoding Mental States after Severe Brain Injury

Some patients with disorders of consciousness retain sensory and cognitive abilities that are not apparent from their outward behaviour. It is crucial to identify and characterise these covert abilities for diagnosis, prognosis, and medical ethics. This thesis uses neuroimaging techniques to investigate cognitive preservation and awareness in patients who are behaviourally non-responsive due to acquired brain injuries. In the first chapter, a large sample of healthy volunteers, including experienced athletes and musicians, imagined actions of varying complexity and familiarity. Motor imagery involving certain complex, familiar actions correlated with a more robust sensorimotor rhythm. In the second chapter, several patients with disorders of consciousness participated in multiple experiments based on neural responses to mental imagery, including one task featuring complex, familiar imagined actions. Although the patients did not generate enhanced sensorimotor rhythms for the complex, familiar motor imagery, the detection of covert cognition was more sensitive owing to the multi-modal nature of the assessment. In the final empirical chapter, a sample of healthy volunteers and a heterogeneous cohort of patients with disorders of consciousness completed a novel oddball task based on tactile stimulation. Critically, this task delineated an attentional hierarchy in the patient sample, and patients with the ability to follow commands were differentiated from those unable to do so by event-related potential evidence of attentional orienting. Due to the heterogeneity of aetiology and pathology in the disorders of consciousness, these patients vary in their suitability for neuroimaging, the preservation of neural structures, and the cognitive resources available to them. Assessments of several perceptual and cognitive abilities supported by spatially-distinct brain regions and indexed by multiple neural signatures are therefore required to accurately characterise a patient’s abilities and probable subjective experience

Functional Magnetic Resonance Imaging as an Assessment Tool in Critically Ill Patients

Little is known about whether residual cognitive function occurs in the earliest stages of brain injury. The overarching goal of the work presented in this dissertation was to elucidate the role of functional neuroimaging in assessing brain activity in critically ill patients. The overall objective was addressed in the following four empirical chapters: In Chapter 2, three versions of a hierarchically-designed auditory task were developed and their ability to detect various levels of auditory language processing was assessed in individual healthy participants. The same procedure was then applied in two acutely comatose patients. In Chapter 3, a hierarchical auditory task was employed in a heterogeneous cohort of acutely comatose patients. The results revealed that the level of auditory processing in coma may be predictive of subsequent functional recovery. In Chapter 4, two mental imagery paradigms were utilized to assess covert command-following in coma. The findings demonstrate, for the first time, preserved awareness in an acutely comatose patient. In Chapter 5, functional neuroimaging techniques were used for covert communication with two completely locked-in, critically ill patients. The results suggest that this methodology could be used as an augmentative communication tool to allow patients to be involved in their own medical decision-making. Taken together, the proceeding chapters of this work demonstrate that functional neuroimaging can detect preserved cognitive functions in some acutely comatose patients, which has both diagnostic and prognostic relevance. Moreover, these techniques may be extended even further to be used as a communication tool in critically ill patients

Manipulating Paradigm and Attention via a Mindfulness Meditation Training Program Improves P300-Based BCI.

To date, only one study has situationally bolstered attentional resources in an effort to improve P300-BCI performance. The current study implements a 4-week Mindfulness Meditation Training Program (MMTP) as a nonmedicinal means to increase concentrative attention and to reduce lapses of attention; MMTP is expected to improve P300-BCI performance by enhancing attentional resources and reducing distractibility. A second aim is to test the efficacy of the checkerboard paradigm (CBP) against the standard row-column paradigm (RCP). Online results show that MMTP had greater accuracies than CTRL and that CBP outperformed the RCP. MMTP participants provided greater amplitude positive target responses, but these differences were not statistically significant. CBP had greater positive amplitude peaks and negative peaks than RCP. The discussion focuses on potential benefits of MMTP for P300-based BCIs, provides further support for the construct validity of mindfulness, and addresses future directions of the translational applicability of MMTP to in-home settings

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

Brain-Computer Interfaces and its Place in the Management of Disorders of Consciousness

editorial reviewedBrain-computer interfaces (BCI) constitute a growing and constantly evolving field of study showing promising applications that span a multitude of potential disciplines. In this chapter, we will introduce BCIs and the roles that different technologies and paradigms play specifically for the management of patients with a disorder of consciousness (DoC). We will provide an overview of the state of the art concerning BCI research in the field of DoC by highlighting some of the most paramount works in the current literature. Contrasting the advances in research with current recommendations and applications in clinical practice exposes the severe lack of recognition that BCI usage receives in routine care for patients with a DoC. To conclude, we mention some potentially interesting future perspectives to further develop this domain

Detection of response to command using voluntary control of breathing in disorders of consciousness

Background:: Detecting signs of consciousness in patients in a vegetative state/unresponsive wakefulness syndrome (UWS/VS) or minimally conscious state (MCS) is known to be very challenging. Plotkin et al. (2010) recently showed the possibility of using a breathing-controlled communication device in patients with locked in syndrome. We here aim to test a breathing-based “sniff controller” that could be used as an alternative diagnostic tool to evaluate response to command in severely brain damaged patients with chronic disorders of consciousness (DOC). Methods:: Twenty-five DOC patients were included. Patients’ resting breathing-amplitude was measured during a 5 min resting condition. Next, they were instructed to end the presentation of a music sequence by sniffing vigorously. An automated detection of changes in breathing amplitude (i.e., >1.5 SD of resting) ended the music and hence provided positive feedback to the patient. Results:: None of the 11 UWS/VS patients showed a sniff-based response to command. One out of 14 patients with MCS was able to willfully modulate his breathing pattern to answer the command on 16/19 trials (accuracy 84%). Interestingly, this patient failed to show any other motor response to command. Discussion: We here illustrate the possible interest of using breathing-dependent response to command in the detection of residual cognition in patients with DOC after severe brain injury

The Potential Role of fNIRS in Evaluating Levels of Consciousness

Over the last few decades, neuroimaging techniques have transformed our understanding of the brain and the effect of neurological conditions on brain function. More recently, light-based modalities such as functional near-infrared spectroscopy have gained popularity as tools to study brain function at the bedside. A recent application is to assess residual awareness in patients with disorders of consciousness, as some patients retain awareness albeit lacking all behavioural response to commands. Functional near-infrared spectroscopy can play a vital role in identifying these patients by assessing command-driven brain activity. The goal of this review is to summarise the studies reported on this topic, to discuss the technical and ethical challenges of working with patients with disorders of consciousness, and to outline promising future directions in this field

Electroencephalogram Signal Processing For Hybrid Brain Computer Interface Systems

The goal of this research was to evaluate and compare three types of brain computer interface (BCI) systems, P300, steady state visually evoked potentials (SSVEP) and Hybrid as virtual spelling paradigms. Hybrid BCI is an innovative approach to combine the P300 and SSVEP. However, it is challenging to process the resulting hybrid signals to extract both information simultaneously and effectively. The major step executed toward the advancement to modern BCI system was to move the BCI techniques from traditional LED system to electronic LCD monitor. Such a transition allows not only to develop the graphics of interest but also to generate objects flickering at different frequencies. There were pilot experiments performed for designing and tuning the parameters of the spelling paradigms including peak detection for different range of frequencies of SSVEP BCI, placement of objects on LCD monitor, design of the spelling keyboard, and window time for the SSVEP peak detection processing. All the experiments were devised to evaluate the performance in terms of the spelling accuracy, region error, and adjacency error among all of the paradigms: P300, SSVEP and Hybrid. Due to the different nature of P300 and SSVEP, designing a hybrid P300-SSVEP signal processing scheme demands significant amount of research work in this area. Eventually, two critical questions in hybrid BCl are: (1) which signal processing strategy can best measure the user\u27s intent and (2) what a suitable paradigm is to fuse these two techniques in a simple but effective way. In order to answer these questions, this project focused mainly on developing signal processing and classification technique for hybrid BCI. Hybrid BCI was implemented by extracting the specific information from brain signals, selecting optimum features which contain maximum discrimination information about the speller characters of our interest and by efficiently classifying the hybrid signals. The designed spellers were developed with the aim to improve quality of life of patients with disability by utilizing visually controlled BCI paradigms. The paradigms consist of electrodes to record electroencephalogram signal (EEG) during stimulation, a software to analyze the collected data, and a computing device where the subject’s EEG is the input to estimate the spelled character. Signal processing phase included preliminary tasks as preprocessing, feature extraction, and feature selection. Captured EEG data are usually a superposition of the signals of interest with other unwanted signals from muscles, and from non-biological artifacts. The accuracy of each trial and average accuracy for subjects were computed. Overall, the average accuracy of the P300 and SSVEP spelling paradigm was 84% and 68.5 %. P300 spelling paradigms have better accuracy than both the SSVEP and hybrid paradigm. Hybrid paradigm has the average accuracy of 79 %. However, hybrid system is faster in time and more soothing to look than other paradigms. This work is significant because it has great potential for improving the BCI research in design and application of clinically suitable speller paradigm

Enhancing Nervous System Recovery through Neurobiologics, Neural Interface Training, and Neurorehabilitation.

After an initial period of recovery, human neurological injury has long been thought to be static. In order to improve quality of life for those suffering from stroke, spinal cord injury, or traumatic brain injury, researchers have been working to restore the nervous system and reduce neurological deficits through a number of mechanisms. For example, neurobiologists have been identifying and manipulating components of the intra- and extracellular milieu to alter the regenerative potential of neurons, neuro-engineers have been producing brain-machine and neural interfaces that circumvent lesions to restore functionality, and neurorehabilitation experts have been developing new ways to revitalize the nervous system even in chronic disease. While each of these areas holds promise, their individual paths to clinical relevance remain difficult. Nonetheless, these methods are now able to synergistically enhance recovery of native motor function to levels which were previously believed to be impossible. Furthermore, such recovery can even persist after training, and for the first time there is evidence of functional axonal regrowth and rewiring in the central nervous system of animal models. To attain this type of regeneration, rehabilitation paradigms that pair cortically-based intent with activation of affected circuits and positive neurofeedback appear to be required-a phenomenon which raises new and far reaching questions about the underlying relationship between conscious action and neural repair. For this reason, we argue that multi-modal therapy will be necessary to facilitate a truly robust recovery, and that the success of investigational microscopic techniques may depend on their integration into macroscopic frameworks that include task-based neurorehabilitation. We further identify critical components of future neural repair strategies and explore the most updated knowledge, progress, and challenges in the fields of cellular neuronal repair, neural interfacing, and neurorehabilitation, all with the goal of better understanding neurological injury and how to improve recovery