Die ereigniskorrelierten Potentiale Mismatch Negativity, P300, und N400: Effekte von Aufmerksamkeitsmodulation und Anwendung in Patienten mit Störungen des Bewusstseins

The present work comprises four studies dealing with the investigation of the auditory event-related potentials (ERP) Mismatch Negativity (MMN), P300, and N400 under different attentional instructions, and with their application in patients with disorders of consciousness (DOC) to assess residual cognitive functioning. In guided interviews (study 1), practitioners working with DOC patients stated their general interest in and an objective need for the complementation of current diagnostic procedures by reliable and valid ERP-based methods. Subsequently, in study 2, simple oddball and semantic paradigms were applied to 19 behaviorally non-responsive DOC patients revealing the presence of at least one ERP in eight patients investigated. In the third and fourth study, specific attentional effects on ERPs were investigated in healthy participants to define optimal instructions and stimulus parameters. In study 3, MMN and N400 amplitudes were assessed in 18 participants, and in study 4, MMN and P300 amplitudes were assessed in 32 participants. Both studies included an ignore task (attention on simultaneous visual stimuli), a passive task, and a focused task and revealed distinct attentional effects on P300 and N400 with largest amplitudes in the focused task, smaller ones in the passive task and no ERP in the ignore task. An MMN was elicited in all tasks, but still, amplitudes differed as a function of task. In addition, study 4 included oddball paradigms comprising several deviants in different dimensions. Higher amplitudes were found in this multifeature paradigm compared to traditional oddball paradigms and larger amplitudes were elicited by deviants highly different from standards. It is concluded that ERPs represent a promising tool to complement clinical assessment of DOC patients. Application of ERP paradigms should include focused instructions, especially when using semantic material. Furthermore, multifeature paradigms have been proven especially useful eliciting large amplitudes and allowing for the investigation of several dimensions of deviants at the same time.Die vorliegende Arbeit beinhaltet vier Studien, die die auditorischen ereigniskorrelierten Potentiale (EKP) Mismatch Negativität (MMN), P300, und N400 unter verschiedenen Instruktionen untersuchen, und deren Anwendung bei Patienten mit Bewusstseinsstörungen darstellen. In Studie 1 äußerten neurologische Fachärzte in Leitfadeninterviews ein generelles Interesse und eine objektive Notwendigkeit der Ergänzung bisheriger diagnostischer Vorgehensweisen durch EKP-basierte Methoden. In Studie 2 wurden 19 motorisch nicht-responsiven Patienten verschiedene Stimuli in Form einfacher Oddball-Paradigmen und semantischen Materials dargeboten und es konnte in acht Patienten mindestens ein EKP nachgewiesen wer-den. Studie 3 und 4 dienten der Untersuchung spezifischer Aufmerksamkeitseffekte auf EKPs in Gesunden, um optimale Instruktionen und Stimulusparameter zu definieren. Es wurden jeweils MMN und N400 in 18 Teilnehmern und MMN und P300 in 32 Teilnehmern untersucht. Beide Studien enthielten eine Ablenkungsaufgabe (simultane visuelle Reize), eine passive und eine fokussierte Aufgabe und zeigten deutliche Aufgabeneffekte auf P300 und N400. Die höchsten Amplituden wurden in der fokussierten Aufgabe ausgelöst, kleinere in der passiven und kein EKP in der Ablenkungsaufgabe. Eine MMN wurde in allen Aufgaben ausgelöst, aber auch hier unterschieden sich die Amplituden in Abhängigkeit der Aufgabe. Studie 4 ent-hielt außerdem ein Oddball mit mehreren abweichenden Tönen in vier Dimensionen. Dieses erzielte höhere Amplituden als das klassische Oddball mit nur einem abweichenden Ton. Hö-here Amplituden wurden von abweichenden Tönen ausgelöst, welche sich stark vom Standardton unterschieden. EKPs stellen ein vielversprechendes Instrument zur Ergänzung klini-scher Diagnosen bewusstseinsgestörter Patienten dar. Es sollte auf eindeutig zu differenzierende abweichende Reize und bei semantischen Material auf fokussierte Instruktionen zurückgegriffen werden. Paradigmen mit verschiedenen abweichenden Tönen können aufgrund höherer Amplituden und eines umfassenden Reizverarbeitungsprofils besonders nützlich sein

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 of ten 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 activevs. passive instruction on the ERP components mismatch negativity (MMN) and N400. A sample of 18 healthy participants listened to three auditory paradigms: anoddball, aword 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

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

Brain-computer interfaces for assessment and communication in disorders of consciousness

Many patients with Disorders of Consciousness (DOC) are misdiagnosed for a variety of reasons. These patients typically cannot communicate. Because such patients are not provided with the needed tools, one of their basic human needs remains unsatisfied, leaving them truly locked in to their bodies. This chapter first reviews current methods and problems of diagnoses and assistive technology for communication, supporting the view that advances in both respects are needed for patients with DOC. The authors also discuss possible solutions to these problems and introduce emerging developments based on EEG (Electroencephalography), fMRI (Functional Magnetic Resonance Imaging), and fNIRS (Functional Near-Infrared Spectroscopy) that have been validated with patients and healthy volunteers

The auditory P300-based single-switch brain–computer interface:Paradigm transition from healthy subjects to minimally consciouspatients

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 appearingdeviant tones at random positions were used as stimuli. This paradigm was evaluated in 10 healthysubjects 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 usedto 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 thanrandom. In 8 of the 10 subjects, focused attention on at least one of the tone streams could be detectedon a single-trial basis. By averaging 10 data segments, classification accuracies up to 90.6 % could bereached. However, for MCS patients only a small number of classification results were above chance leveland none of the results were sufficient for communication purposes. Nevertheless, signs of consciousnesswere detected in 9 of the 12 patients, not on a single-trial basis, but after averaging of all correspondingdata segments and computing significant differences. These significant results, however, strongly variedacross sessions and conditions.Conclusion: This work shows the transition of a paradigm from healthy subjects to MCS patients. Promisingresults with healthy subjects are, however, no guarantee of good results with patients. Therefore, moreinvestigations are required before any definite conclusions about the usability of this paradigm for MCSpatients can be drawn. Nevertheless, this paradigm might offer an opportunity to support bedside clinicalassessment of MCS patients and eventually, to provide them with a means of communication