Mental imagery for brain-computer interface control and communication in non-responsive individuals.

BACKGROUND: People who survive severe brain damage may eventually develop a prolonged consciousness disorder. Others can regain full consciousness but remain unable to speak or move because of the severity of the lesions, as for those with locked-in syndrome (LIS). Brain-computer interface techniques can be useful to disentangle these states by detecting neurophysiological correlates of conscious processing of information to enable communication with these individuals after the diagnosis. OBJECTIVE: The goal of our study was to evaluate with a user-centered design approach the usability of a mental imagery task to detect signs of voluntary information processing and enabling communication in a group of severely disabled individuals. METHODS: Five individuals with LIS participated in the study. Participants were instructed to imagine hand, arm or feet movements during electroencephalography (EEG) to detect patterns of event-related synchronization/desynchronization associated with each task. After the user-centered design, usability was evaluated (i.e., efficiency, effectiveness and satisfaction). RESULTS: Two participants achieved significant levels of accuracy in 2 different tasks. The associated workload and levels of satisfaction perceived by the users were moderate and were mainly related to the time demand of the task. CONCLUSION: Results showed lack of effectiveness of the task to detect voluntary brain activity and thus detect consciousness or communicate with non-responsive individuals. The application must be modified to be sufficiently satisfying for the intended end-users and suggestions are made in this regard.

Hypnosis modulates behavioural measures and subjective ratings about external and internal awareness.

In altered subjective states, the behavioural quantification of external and internal awareness remains challenging due to the need for reports on the subjects' behalf. With the aim to characterize the behavioural counterpart of external and internal awareness in a modified subjective condition, we used hypnosis during which subjects remain fully responsive. Eleven right-handed subjects reached a satisfactory level of hypnotisability as evidenced by subjective reports on arousal, absorption and dissociation. Compared to normal wakefulness, in hypnosis (a) participants' self-ratings for internal awareness increased and self-ratings for external awareness decreased, (b) the two awareness components tended to anticorrelate less and the switches between external and internal awareness self-ratings were less frequent, and (c) participants' reaction times were higher and lapses in key presses were more frequent. The identified imbalance between the two components of awareness is considered as of functional relevance to subjective (meta)cognition, possibly mediated by allocated attentional properties brought about by hypnosis. Our results highlight the presence of a cognitive counterpart in resting state, indicate that the modified contents of awareness are measurable behaviourally, and provide leverage for investigations of more challenging altered conscious states, such as anaesthesia, sleep and disorders of consciousness.

Biased binomial assessment of cross-validated estimation of classification accuracies illustrated in diagnosis predictions.

Multivariate classification is used in neuroimaging studies to infer brain activation or in medical applications to infer diagnosis. Their results are often assessed through either a binomial or a permutation test. Here, we simulated classification results of generated random data to assess the influence of the cross-validation scheme on the significance of results. Distributions built from classification of random data with cross-validation did not follow the binomial distribution. The binomial test is therefore not adapted. On the contrary, the permutation test was unaffected by the cross-validation scheme. The influence of the cross-validation was further illustrated on real-data from a brain-computer interface experiment in patients with disorders of consciousness and from an fMRI study on patients with Parkinson disease. Three out of 16 patients with disorders of consciousness had significant accuracy on binomial testing, but only one showed significant accuracy using permutation testing. In the fMRI experiment, the mental imagery of gait could discriminate significantly between idiopathic Parkinson's disease patients and healthy subjects according to the permutation test but not according to the binomial test. Hence, binomial testing could lead to biased estimation of significance and false positive or negative results. In our view, permutation testing is thus recommended for clinical application of classification with cross-validation.

The auditory P300-based single-switch brain-computer interface: paradigm transition from healthy subjects to minimally conscious patients.

OBJECTIVE: Within this work an auditory P300 brain-computer interface based on tone stream segregation, which allows for binary decisions, was developed and evaluated. METHODS AND MATERIALS: Two tone streams consisting of short beep tones with infrequently appearing deviant tones at random positions were used as stimuli. This paradigm was evaluated in 10 healthy subjects and applied to 12 patients in a minimally conscious state (MCS) at clinics in Graz, Würzburg, Rome, and Liège. A stepwise linear discriminant analysis classifier with 10×10 cross-validation was used to detect the presence of any P300 and to investigate attentional modulation of the P300 amplitude. RESULTS: The results for healthy subjects were promising and most classification results were better than random. In 8 of the 10 subjects, focused attention on at least one of the tone streams could be detected on a single-trial basis. By averaging 10 data segments, classification accuracies up to 90.6% could be reached. However, for MCS patients only a small number of classification results were above chance level and none of the results were sufficient for communication purposes. Nevertheless, signs of consciousness were detected in 9 of the 12 patients, not on a single-trial basis, but after averaging of all corresponding data segments and computing significant differences. These significant results, however, strongly varied across sessions and conditions. CONCLUSION: This work shows the transition of a paradigm from healthy subjects to MCS patients. Promising results with healthy subjects are, however, no guarantee of good results with patients. Therefore, more investigations are required before any definite conclusions about the usability of this paradigm for MCS patients can be drawn. Nevertheless, this paradigm might offer an opportunity to support bedside clinical assessment of MCS patients and eventually, to provide them with a means of communication.

Changes in effective connectivity by propofol sedation.

Mechanisms of propofol-induced loss of consciousness remain poorly understood. Recent fMRI studies have shown decreases in functional connectivity during unconsciousness induced by this anesthetic agent. Functional connectivity does not provide information of directional changes in the dynamics observed during unconsciousness. The aim of the present study was to investigate, in healthy humans during an auditory task, the changes in effective connectivity resulting from propofol induced loss of consciousness. We used Dynamic Causal Modeling for fMRI (fMRI-DCM) to assess how causal connectivity is influenced by the anesthetic agent in the auditory system. Our results suggest that the dynamic observed in the auditory system during unconsciousness induced by propofol, can result in a mixture of two effects: a local inhibitory connectivity increase and a decrease in the effective connectivity in sensory cortices.

Thalamus, brainstem and salience network connectivity changes during propofol-induced sedation and unconsciousness.

In this functional magnetic resonance imaging study, we examined the effect of mild propofol sedation and propofol-induced unconsciousness on resting state brain connectivity, using graph analysis based on independent component analysis and a classical seed-based analysis. Contrary to previous propofol research, which mainly emphasized the importance of connectivity in the default mode network (DMN) and external control network (ECN), we focused on the salience network, thalamus, and brainstem. The importance of these brain regions in brain arousal and organization merits a more detailed examination of their connectivity response to propofol. We found that the salience network disintegrated during propofol-induced unconsciousness. The thalamus decreased connectivity with the DMN, ECN, and salience network, while increasing connectivity with sensorimotor and auditory/insular cortices. Brainstem regions disconnected from the DMN with unconsciousness, while the pontine tegmental area increased connectivity with the insulae during mild sedation. These findings illustrate that loss of consciousness is associated with a wide variety of decreases and increases of both cortical and subcortical connectivity. It furthermore stresses the necessity of also examining resting state connectivity in networks representing arousal, not only those associated with awareness.

Connectivity changes underlying spectral EEG changes during propofol-induced loss of consciousness.

The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast rhythms (from beta to gamma range), slow activity (from delta to alpha range) rises selectively during loss of consciousness. Dynamic causal modeling was used to investigate the neural mechanisms mediating these changes in spectral power in humans. We analyzed source-reconstructed data from frontal and parietal cortices during normal wakefulness, propofol-induced mild sedation, and loss of consciousness. Bayesian model selection revealed that the best model for explaining spectral changes across the three states involved changes in corticothalamic interactions. Compared with wakefulness, mild sedation was accounted for by an increase in thalamic excitability, which did not further increase during loss of consciousness. In contrast, loss of consciousness per se was accompanied by a decrease in backward corticocortical connectivity from frontal to parietal cortices, while thalamocortical connectivity remained unchanged. These results emphasize the importance of recurrent corticocortical communication in the maintenance of consciousness and suggest a direct effect of propofol on cortical dynamics.

Reaching across the abyss: recent advances in functional magnetic resonance imaging and their potential relevance to disorders of consciousness.

Disorders of consciousness (DOC) raise profound scientific, clinical, ethical, and philosophical issues. Growing knowledge on fundamental principles of brain organization in healthy individuals offers new opportunities for a better understanding of residual brain function in DOCs. We here discuss new perspectives derived from a recently proposed scheme of brain organization underlying consciousness in healthy individuals. In this scheme, thalamo-cortical networks can be divided into two, often antagonistic, global systems: (i) a system of externally oriented, sensory-motor networks (the "extrinsic" system); and (ii) a system of inward-oriented networks (the "intrinsic" or default system). According to this framework, four distinct mental states would be possible that could be relevant for understanding DOCs. In normal healthy volunteers and locked-in syndrome patients, a state of high functionality of both the extrinsic and intrinsic or default systems is expected--associated with full awareness of environment and self. In this case, mental imagery tasks combined with fMRI can be used to detect covert awareness in patients that are unable to communicate. According to the framework, two complementary states of system imbalance are also possible, in which one system is in a hyperfunctional state, while the other is hypoactive. Extrinsic system hyperfunction is expected to lead to a state of total sensory-motor "absorption" or "lost self." In contrast, intrinsic or default system hyperfunction is expected to lead to a state of complete detachment from the external world. A state where both extrinsic and intrinsic systems are hypofunctional is predicted to lead to markedly impaired consciousness as seen in DOCs. Finally, we review the potential use of ultra-slow fluctuations in BOLD signal as a tool for assessing the functional integrity of extrinsic and intrinsic systems during "resting state" fMRI acquisitions. In particular, we discuss the potential provided by assessment of these slow spontaneous BOLD fluctuations as a novel tool in assessing the cognitive state and chances of recovery from brain pathologies underlying DOCs.