Neurophysiological aspects of the completely locked-in syndrome in patients with advanced amyotrophic lateral sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) patients in completely locked-in syndrome (CLIS) are incapable of expressing themselves, and their state of consciousness and awareness is difficult to evaluate. Due to the complete paralysis included paralysis of eye muscles, any assessment of the perceptual and psychophysiological state can only be implemented in passive experimental paradigms with neurophysiological recordings. METHODS: Four patients in CLIS were investigated in several experiments including resting state, visual stimulation (eyes open vs eyes closed), auditory stimulation (modified local-global paradigm), somatosensory stimulation (electrical stimulation of the median nerve), and during sleep. RESULTS: All patients showed altered neurophysiological metrics, but a unique and common pattern could not be found between patients. However, slowing of the electroencephalography (EEG) and attenuation or absence of alpha wave activity was common in all patients. In two of the four patients, a slow dominant frequency emerged at 4 Hz with synchronized EEG at all channels. In the other two patients slowing of EEG appears less synchronized. EEGs between eyes open and eyes closed were significantly different in all patients. The dominant slow frequency during the day changes during slow-wave sleep (supposedly sleep stage 3) to even slower frequencies below 2 Hz. Somatosensory evoked potentials (SEPs) were absent or significantly altered in comparison to healthy subjects, similarly for auditory evoked potentials (AEPs). CONCLUSIONS: The heterogeneity of the results underscores the fact that no single neurophysiological index is available to assess psychophysiological states in unresponsive ALS patients in CLIS. This caveat may also be valid for the assessment of cognitive processes; a functioning BCI can be the solution. SIGNIFICANCE: Most of the studies of the neurophysiology of ALS patients focused on the early stage of the disease, and there are very few studies on the late stage when patients are completely paralyzed with no means of communication (i.e., CLIS). This study provides quantitative metrics of different neurophysiological aspects of these patients.

Dorsolateral prefrontal cortex-based control with an implanted brain-computer interface.

The objective of this study was to test the feasibility of using the dorsolateral prefrontal cortex as a signal source for brain-computer interface control in people with severe motor impairment. We implanted two individuals with locked-in syndrome with a chronic brain-computer interface designed to restore independent communication. The implanted system (Utrecht NeuroProsthesis) included electrode strips placed subdurally over the dorsolateral prefrontal cortex. In both participants, counting backwards activated the dorsolateral prefrontal cortex consistently over the course of 47 and 22 months, respectively. Moreover, both participants were able to use this signal to control a cursor in one dimension, with average accuracy scores of 78 ± 9% (standard deviation) and 71 ± 11% (chance level: 50%), respectively. Brain-computer interface control based on dorsolateral prefrontal cortex activity is feasible in people with locked-in syndrome and may become of relevance for those unable to use sensorimotor signals for control.

Dramatic Response to Pramipexole in Delayed-Onset Parkinsonism from Osmotic Demyelinating Syndrome.

Background: Delayed parkinsonism and dystonia are recognized phenomena in osmotic demyelinating syndrome (ODS). Dopamine receptor agonists and levodopa have been reported to benefit select patients. Case report: We report a patient with ODS with severe pseudobulbar deficits, parkinsonism and dystonia, poorly responsive to levodopa, who experienced a remarkable improvement with pramipexole. Discussion: A marked response to pramipexole with lack of response to levodopa suggests a pre-synaptic source for his deficits coupled with injuries to non-nigral compensatory structures. Highlights: This case highlights a dramatic response of osmotic demyelination-induced parkinsonism/dystonia to pramipexole. A lack of response to levodopa suggests deficits in the pre-synaptic nigral as well as non-nigral compensatory structures.

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.

Sleep in the completely locked-in state (CLIS) in amyotrophic lateral sclerosis.

Persons in the completely locked-in state (CLIS) suffering from amyotrophic lateral sclerosis (ALS) are deprived of many zeitgebers of the circadian rhythm: While cognitively intact, they are completely paralyzed, eyes mostly closed, with artificial ventilation and artificial nutrition, and social communication extremely restricted or absent. Polysomnographic recordings in eight patients in CLIS, however, revealed the presence of regular episodes of deep sleep during night time in all patients. It was also possible to distinguish an alpha-like state and a wake-like state. Classification of rapid eye movement (REM) sleep is difficult because of absent eye movements and absent muscular activity. Four out of eight patients did not show any sleep spindles. Those who have spindles also show K-complexes and thus regular phases of sleep stage 2. Thus, despite some irregularities, we found a surprisingly healthy sleep pattern in these patients.

Diffusion tensor imaging reveals diffuse white matter injuries in locked-in syndrome patients.

Locked-in syndrome (LIS) is a state of quadriplegia and anarthria with preserved consciousness, which is generally triggered by a disruption of specific white matter fiber tracts, following a lesion in the ventral part of the pons. However, the impact of focal lesions on the whole brain white matter microstructure and structural connectivity pathways remains unknown. We used diffusion tensor magnetic resonance imaging (DT-MRI) and tract-based statistics to characterise the whole white matter tracts in seven consecutive LIS patients, with ventral pontine injuries but no significant supratentorial lesions detected with morphological MRI. The imaging was performed in the acute phase of the disease (26 ± 13 days after the accident). DT-MRI-derived metrics were used to quantitatively assess global white matter alterations. All diffusion coefficient Z-scores were decreased for almost all fiber tracts in all LIS patients, with diffuse white matter alterations in both infratentorial and supratentorial areas. A mixture model of two multidimensional Gaussian distributions was fitted to cluster the white matter fiber tracts studied in two groups: the least (group 1) and most injured white matter fiber tracts (group 2). The greatest injuries were revealed along pathways crossing the lesion responsible for the LIS: left and right medial lemniscus (98.4% and 97.9% probability of belonging to group 2, respectively), left and right superior cerebellar peduncles (69.3% and 45.7% probability) and left and right corticospinal tract (20.6% and 46.5% probability). This approach demonstrated globally compromised white matter tracts in the acute phase of LIS, potentially underlying cognitive deficits.

Electroencephalography-based endogenous brain-computer interface for online communication with a completely locked-in patient.

BACKGROUND: Brain-computer interfaces (BCIs) have demonstrated the potential to provide paralyzed individuals with new means of communication, but an electroencephalography (EEG)-based endogenous BCI has never been successfully used for communication with a patient in a completely locked-in state (CLIS). METHODS: In this study, we investigated the possibility of using an EEG-based endogenous BCI paradigm for online binary communication by a patient in CLIS. A female patient in CLIS participated in this study. She had not communicated even with her family for more than one year with complete loss of motor function. Offline and online experiments were conducted to validate the feasibility of the proposed BCI system. In the offline experiment, we determined the best combination of mental tasks and the optimal classification strategy leading to the best performance. In the online experiment, we investigated whether our BCI system could be potentially used for real-time communication with the patient. RESULTS: An online classification accuracy of 87.5% was achieved when Riemannian geometry-based classification was applied to real-time EEG data recorded while the patient was performing one of two mental-imagery tasks for 5 s. CONCLUSIONS: Our results suggest that an EEG-based endogenous BCI has the potential to be used for online communication with a patient in CLIS.

Comprehensive, technology-based, team approach for a patient with locked-in syndrome: A case report of improved function & quality of life.

One of the most severe types of stroke is locked-in syndrome (LIS) due to the loss of almost all voluntary motor functions and a high mortality rate. The majority of the literature regarding LIS is based on case reports that utilized multidisciplinary interventions focused on improving functional communication and respiratory care with minimal focus on motor retraining. These reports were neither dynamic nor multi-sensory, and the only technology utilized was in the form of augmentative communication. There are additional types of technology frequently used in the general stroke population that can address similar motor deficits that occur in the LIS population. This case report explains an interdisciplinary approach using motor and communication interventions that are multisensory, progressive, multi-modal, and technology- based. The length of stay was 153 days in acute rehabilitation, after which the patient returned home making significant gains in overall function. In this patient, the FIM changes in motor (+42), cognitive (+29) and total change score of (+71) surpassed what was determined to be a minimal clinically important difference. These results suggest that this treatment program and approach may be a key reason why this patient was able to achieve significant functional gains and report improved quality of life.

Wandering thoughts about consciousness, the brain, and the commentary system of Larry Weiskrantz.

Larry Weiskrantz has always pursued a keen interest in consciousness in humans and other animals by performing clever experiments and proposing clever ideas. In this rather idiosyncratic essay I selectively review some old and new evidence on real and apparent losses of consciousness in humans, new means that allow the human brain to expose its conscious awareness directly, and experiments on animals that may bridge their consciousness with that of humans.