Circadian course of the P300 ERP in patients with amyotrophic lateral sclerosis - implications for brain-computer interfaces (BCI).

BACKGROUND: Accidents or neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) can lead to progressing, extensive, and complete paralysis leaving patients aware but unable to communicate (locked-in state). Brain-computer interfaces (BCI) based on electroencephalography represent an important approach to establish communication with these patients. The most common BCI for communication rely on the P300, a positive deflection arising in response to rare events. To foster broader application of BCIs for restoring lost function, also for end-users with impaired vision, we explored whether there were specific time windows during the day in which a P300 driven BCI should be preferably applied. METHODS: The present study investigated the influence of time of the day and modality (visual vs. auditory) on P300 amplitude and latency. A sample of 14 patients (end-users) with ALS and 14 healthy age matched volunteers participated in the study and P300 event-related potentials (ERP) were recorded at four different times (10, 12 am, 2, & 4 pm) during the day. RESULTS: Results indicated no differences in P300 amplitudes or latencies between groups (ALS patients v. healthy participants) or time of measurement. In the auditory condition, latencies were shorter and amplitudes smaller as compared to the visual condition. CONCLUSION: Our findings suggest applicability of EEG/BCI sessions in patients with ALS throughout normal waking hours. Future studies using actual BCI systems are needed to generalize these findings with regard to BCI effectiveness/efficiency and other times of day.

Basic discriminative and semantic processing in patients in the vegetative and minimally conscious state.

Patients who survive injuries to the brain following accidents or diseases often acquire a disorder of consciousness (DOC). Assessment of the state of consciousness in these patients is difficult since they are usually incapable of reproducible motor movements. The application of event-related potentials (ERP) recorded via EEG constitutes one promising approach to complement the assessment of cognitive functions in DOC patients. For these assessments, a hierarchical approach was suggested which means that paradigms aiming at higher order ERPs are only presented if early responses were found. In this study, 19 behaviorally unresponsive or low-responsive DOC patients were presented with three auditory paradigms using passive instructions. The paradigms aimed at eliciting the Mismatch Negativity (MMN) and N400 and were applied at two time points. One oddball paradigm (MMN) and two semantic paradigms (word-pairs: N400 Words; sentences: N400 Sentences) were included. The majority of patients (n=15) did not show any response to the stimulation. In the MMN paradigm, an MMN was identified in two patients, in the N400 Words paradigm, only an N1 was identified in one patient, and in the N400 Sentences paradigm, a late positive complex (LPC) was identified in two patients. These data contradict the hierarchical approach since the LPC was identified in patients who did not exhibit an MMN. They further support the notion that even higher information processing as addressed with the N400 paradigms is preserved in a minority of DOC patients. Thus, in this sample, around 10% of the DOC patients exhibited indicators of preserved consciousness.

Information processing in patients in vegetative and minimally conscious states.

OBJECTIVE: Evaluation of a short two-tone oddball paradigm to discriminate between the vegetative state (VS) and minimal consciousness state (MCS) in a sample of patients with severe disorders of consciousness (DOC). METHOD: EEG was recorded from 45 DOC patients and 14 healthy participants while listening to an auditory oddball paradigm presented in a passive - just listen - and an active - count the odd tones - condition. In patients, the experiment was repeated after a minimum of one week. RESULTS: Prevalence of the P300 was higher in healthy participants (71%) than in patients, but did not discriminate between VS (T1: ∼10%; T2: ∼11%) and MCS (T1: ∼13%; T2: 25%) patients. CONCLUSION: Results cast doubt on whether this simple auditory stimulation paradigm, which requires cognitive action from the listener, is sensitive enough to discriminate between patients with DOC. SIGNIFICANCE: The sensitivity of the P300 ERP obtained in a short two-tone oddball paradigm presented in a passive and an active condition appears to be too low for routine application in a clinical setting aiming at distinguishing between VS and MCS patients.

Task instructions modulate the attentional mode affecting the auditory MMN and the semantic N400.

Event-related potentials (ERPs) have been proven to be a useful tool to complement clinical assessment and to detect residual cognitive functions in patients with disorders of consciousness. These ERPs are often recorded using passive or unspecific instructions. Patient data obtained this way are then compared to data from healthy participants, which are usually recorded using active instructions. The present study investigates the effect of attentive modulations and particularly the effect of active vs. passive instruction on the ERP components mismatch negativity (MMN) and N400. A sample of 18 healthy participants listened to three auditory paradigms: an oddball, a word priming, and a sentence paradigm. Each paradigm was presented three times with different instructions: ignoring auditory stimuli, passive listening, and focused attention on the auditory stimuli. After each task, the participants indicated their subjective effort. The N400 decreased from the focused task to the passive task, and was extinct in the ignore task. The MMN exhibited higher amplitudes in the focused and passive task compared to the ignore task. The data indicate an effect of attention on the supratemporal component of the MMN. Subjective effort was equally high in the passive and focused tasks but reduced in the ignore task. We conclude that passive listening during EEG recording is stressful and attenuates ERPs, which renders the interpretation of the results obtained in such conditions difficult.

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.