Toward an Attention-Based Diagnostic Tool for Patients With Locked-in Syndrome.

Electroencephalography (EEG) has been proposed as a supplemental tool for reducing clinical misdiagnosis in severely brain-injured populations helping to distinguish conscious from unconscious patients. We studied the use of spectral entropy as a measure of focal attention in order to develop a motor-independent, portable, and objective diagnostic tool for patients with locked-in syndrome (LIS), answering the issues of accuracy and training requirement. Data from 20 healthy volunteers, 6 LIS patients, and 10 patients with a vegetative state/unresponsive wakefulness syndrome (VS/UWS) were included. Spectral entropy was computed during a gaze-independent 2-class (attention vs rest) paradigm, and compared with EEG rhythms (delta, theta, alpha, and beta) classification. Spectral entropy classification during the attention-rest paradigm showed 93% and 91% accuracy in healthy volunteers and LIS patients respectively. VS/UWS patients were at chance level. EEG rhythms classification reached a lower accuracy than spectral entropy. Resting-state EEG spectral entropy could not distinguish individual VS/UWS patients from LIS patients. The present study provides evidence that an EEG-based measure of attention could detect command-following in patients with severe motor disabilities. The entropy system could detect a response to command in all healthy subjects and LIS patients, while none of the VS/UWS patients showed a response to command using this system.

Electromyographic decoding of response to command in disorders of consciousness.

OBJECTIVE: To propose a new methodology based on single-trial analysis for detecting residual response to command with EMG in patients with disorders of consciousness (DOC), overcoming the issue of trial dependency and decreasing the influence of a patient's fluctuation of vigilance or arousal over time on diagnostic accuracy. METHODS: Forty-five patients with DOC (18 with vegetative/unresponsive wakefulness syndrome [VS/UWS], 22 in a minimally conscious state [MCS], 3 who emerged from MCS [EMCS], and 2 with locked-in syndrome [LIS]) and 20 healthy controls were included in the study. Patients were randomly instructed to either move their left or right hand or listen to a control command ("It is a sunny day") while EMG activity was recorded on both arms. RESULTS: Differential EMG activity was detected in all MCS cases displaying reproducible response to command at bedside on multiple assessments, even though only 6 of the 14 individuals presented a behavioral response to command on the day of the EMG assessment. An EMG response was also detected in all EMCS and LIS patients, and 2 MCS patients showing nonreflexive movements without command following at the bedside. None of the VS/UWS presented a response to command with this method. CONCLUSIONS: This method allowed us to reliably distinguish between different levels of consciousness and could potentially help decrease diagnostic errors in patients with motor impairment but presenting residual motor activity.

Preserved covert cognition in noncommunicative patients with severe brain injury?

BACKGROUND: Despite recent evidence suggesting that some severely brain-injured patients retain some capacity for top-down processing (covert cognition), the degree of sparing is unknown. OBJECTIVE: Top-down attentional processing was assessed in patients in minimally conscious (MCS) and vegetative states (VS) using an active event-related potential (ERP) paradigm. METHODS: A total of 26 patients were included (38 ± 12 years old, 9 traumatic, 21 patients >1 year postonset): 8 MCS+, 8 MCS-, and 10 VS patients. There were 14 healthy controls (30 ± 8 years old). The ERP paradigm included (1) a passive condition and (2) an active condition, wherein the participant was instructed to voluntarily focus attention on his/her own name. In each condition, the participant's own name was presented 100 times (ie, 4 blocks of 25 stimuli). RESULTS: In 5 MCS+ patients as well as in 3 MCS- patients and 1 VS patient, an enhanced P3 amplitude was observed in the active versus passive condition. Relative to controls, patients showed a response that was (1) widely distributed over frontoparietal areas and (2) not present in all blocks (3 of 4). In patients with covert cognition, the amplitude of the response was lower in frontocentral electrodes compared with controls but did not differ from that in the MCS+ group. CONCLUSION: The results indicate that volitional top-down attention is impaired in patients with covert cognition. Further investigation is crucially needed to better understand top-down cognitive functioning in this population because this may help refine brain-computer interface-based communication strategies.

Detection of visual pursuit in patients in minimally conscious state: a matter of stimuli and visual plane?

OBJECTIVES: The aim of this study was to determine whether the assessment of pursuit eye movements in patients in minimally conscious state (MCS) is influenced by the choice of the visual stimulus (study 1) and by the moving plane (study 2). METHODS: Patients with MCS (MCS- and MCS+) in the acute (<1 month post-injury) or chronic (>1 month) setting were assessed. The Coma Recovery Scale-Revised (CRS-R) procedure was used to test visual pursuit of a moving mirror, object and person (study 1, n = 88) and to test vertical and horizontal visual tracking (study 2, n = 94). RESULTS: Study 1: Patients with visual pursuit tracked preferentially the moving mirror over the moving person or object. Study 2: Patients displaying visual pursuit, especially in MCS- and in chronic setting, preferentially tracked on the horizontal rather than the vertical plane. CONCLUSION: The findings confirm the importance of using a mirror to assess visual pursuit in patients in MCS and of initiating testing using the horizontal plane, specifically in patients in MCS- and those in chronic setting. Assessment should then be done on the vertical plane if visual pursuit is not detected on the horizontal plane.

Volitional electromyographic responses in disorders of consciousness.

OBJECTIVE: The aim of the study was to validate the use of electromyography (EMG) for detecting responses to command in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS). METHODS: Thirty-eight patients were included in the study (23 traumatic, 25 patients >1 year post-onset), 10 diagnosed as being in VS/UWS, eight in MCS- (no response to command) and 20 in MCS+ (response to command). Eighteen age-matched controls participated in the experiment. The paradigm consisted of three commands (i.e. 'Move your hands', 'Move your legs' and 'Clench your teeth') and one control sentence (i.e. 'It is a sunny day') presented in random order. Each auditory stimulus was repeated 4 times within one block with a stimulus-onset asynchrony of 30 seconds. RESULTS: Post-hoc analyses with Bonferroni correction revealed that EMG activity was higher solely for the target command in one patient in permanent VS/UWS and in three patients in MCS+. CONCLUSION: The use of EMG could help clinicians to detect conscious patients who do not show any volitional response during standard behavioural assessments. However, further investigations should determine the sensitivity of EMG as compared to neuroimaging and electrophysiological assessments.

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.

Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study.

Zolpidem has been reported as an "awakening drug" in some patients with disorders of consciousness (DOC). We here present the results of a prospective openlabel study in chronic DOC patients. Sixty patients (35±15 years; 18 females; mean time since insult ± SD: 4±5.5 years; 31 with traumatic etiology) with a diagnosis of vegetative state/unresponsive wakefulness syndrome (n=28) or minimally conscious state (n=32) were behaviorally assessed using the Coma Recovery Scale-Revised (CRS-R) before and one hour after administration of 10 mg of zolpidem. At the group level, the diagnosis did not change after intake of zolpidem (p=0.10) and CRS-R total scores decreased (p=0.01). Twelve patients (20%) showed improved behaviors and/or CRS-R total scores after zolpidem administration but in only one patient was the diagnosis after zolpidem intake found to show a significant improvement (functional object use), which suggested a change of diagnosis. However, in this patient, a double-blind placebo-controlled trial was performed in order to better specify the effects of zolpidem, but the patient, on this trial, failed to show any clinical improvements. The present open-label study therefore failed to show any clinically significant improvement (i.e., change of Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study diagnosis) in any of the 60 studied chronic DOC patients.