The independence and predictivity of resting pain-free slow alpha frequency as a biomarker of pain: A reply to Mazaheri et al.

In response to Mazaheri et al.'s critique, we revisited our study (Valentini et al., 2022) on the relationship between peak alpha frequency (PAF) and pain. Their commentary prompted us to reassess our data to address the independence between slow and slowing alpha brain oscillations, as well as the predictivity of slow alpha oscillations in pain perception. Bayesian correlation analyses revealed mixed support for independence. Investigating predictivity, we found inconsistent associations between pre-PAF and unpleasantness ratings. We critically reflected on methodological and theoretical issues on the path to PAF validation as a pain biomarker. We emphasized the need for diversified methodology and analytical approaches as well as robust findings across research groups.

Validation of Cross-Individual Pain Assessment with Individual Recognition Model from Electroencephalogram.

Cross-individual pain assessment models based on electroencephalography (EEG) allow pain assessment in individuals who cannot report pain (e.g., unresponsive patients). The main obstacle to the generalisation of pain assessment models is the individual variation of brain responses to pain. Hence, we took the individual variation into account in cross-individual model development. We developed two convolutional neural networks (CNN) sharing an encoder architecture. One CNN predicts pain, while the other predicts the identity of an individual. We performed a leave-one-out (LOO) test with the exclusion of each subject and applied evidence accumulation to it for validating the pain prediction model's performance, where the binary classifier involves the states of pain (Hot) and resting state (Eyes-open). The mean accuracy produced by the LOO tests was 57.81% (max: 73.33%), and the mean accuracy of evidence accumulation achieved 69.75% (max: 100.00%). The individual recognition model achieved an accuracy of 99.63%. Nevertheless, when we acquired the most similar subject to a novel subject using the individual recognition model, where the most similar subject was used to train a subject-wise pain prediction model. The accuracy of predicting the pain-related conditions of the novel subject by the subject-wise model was only 53.73% (max: 79.50%). Therefore, the approach to utilising the features related to individual variation extracted by the CNN model needs more investigation for improving cross-individual pain assessment.Clinical relevance- This model can be applied to assess pain from EEG signals at the bedside with future improvement, which can help caretakers of unresponsive patients.

Classification of Tonic Pain Experience based on Phase Connectivity in the Alpha Frequency Band of the Electroencephalogram using Convolutional Neural Networks.

The complexity of brain activity involved in the generation of the experience of pain makes it hard to identify neural markers able to predict pain states. The within and between subjects variability of pain hinders the predictive potential of machine learning models trained across participants. This challenge can be tackled by implementing deep learning classifiers based on convolutional neural networks (CNNs). We targeted phase-based connectivity in the alpha band recorded with electroencephalography (EEG) during resting states and sensory conditions (eyes open [O] and closed [C] as resting states, and warm [W] and hot [H] water as sensory conditions). Connectivity features were extracted and re-organized as square matrices, because CNNs are effective in detecting the patterns from 2D data. To assess the classifier performance we implemented two complementary approaches: we 1) trained and tested the classifier with data from all participants, and 2) using a leave-one-out approach, that is excluding one participant at a time during training while using their data as a test set. The accuracy of binary classification between pain condition (H) and eyes open resting state (O) was 94.16% with the first approach, and 61.01 % with the leave-one-out approach. Clinical relevance-Further validation of the CNN classifier may help caregivers track the rehabilitation of chronic pain patients and dynamically modify the therapy. Further refinement of the model may allow its application in critical care setting with unresponsive patients to identify pain-like states otherwise incommunicable to medical personnel.

Assessing the specificity of the relationship between brain alpha oscillations and tonic pain.

Recent research proposed that the slowing of individual alpha frequency (IAF) could be an objective marker of pain. However, it is unclear whether this research can fully address the requirements of specificity and sensitivity of IAF to the pain experience. Here, we sought to develop a robust methodology for assessing the specificity of the relationship between alpha oscillations and acute tonic pain in healthy individuals. We recorded electroencephalography (EEG) of 36 volunteers during consecutive 5-minute sessions of painful hot water immersion, innocuous warm water immersion and aversive, non-painful auditory stimulus, matched by unpleasantness to the painful condition. Participants rated stimulus unpleasantness throughout each condition. We isolated two regions of the scalp displaying peak alpha activity across participants: centro-parietal (CP) and parieto-occipital (PO) ROI. In line with previous research our findings revealed decreased IAF during hot compared with warm stimulation, however the effect was not specific for pain as we found no difference between hot and sound in the CP ROI (compared to baseline). In contrast, the PO ROI reported the same pattern of differences, but their direction was opposite to the CP in that this ROI revealed faster frequency during hot condition than controls. Finally, we show that IAF in both ROIs did not mediate the relationship between the experimental manipulation and the affective experience. Altogether, these findings emphasize the importance of a robust methodological and analytical design to disclose the functional role of alpha oscillations during affective processing. Likewise, they suggest the absence of a causal role of IAF in the generation of acute pain experience in healthy individuals.

Workshops of the Eighth International Brain-Computer Interface Meeting: BCIs: The Next Frontier.

The Eighth International Brain-Computer Interface (BCI) Meeting was held June 7-9th, 2021 in a virtual format. The conference continued the BCI Meeting series' interactive nature with 21 workshops covering topics in BCI (also called brain-machine interface) research. As in the past, workshops covered the breadth of topics in BCI. Some workshops provided detailed examinations of specific methods, hardware, or processes. Others focused on specific BCI applications or user groups. Several workshops continued consensus building efforts designed to create BCI standards and increase the ease of comparisons between studies and the potential for meta-analysis and large multi-site clinical trials. Ethical and translational considerations were both the primary topic for some workshops or an important secondary consideration for others. The range of BCI applications continues to expand, with more workshops focusing on approaches that can extend beyond the needs of those with physical impairments. This paper summarizes each workshop, provides background information and references for further study, presents an overview of the discussion topics, and describes the conclusion, challenges, or initiatives that resulted from the interactions and discussion at the workshop.

Changes in measures of consciousness during anaesthesia of one hemisphere (Wada test).

BACKGROUND: In the Wada test, one hemisphere is selectively anaesthetised by unilateral intracarotid injection of a fast-acting anaesthetic agent. This gives a unique opportunity to observe the functions and physiological activity of one hemisphere while anaesthetising the other, allowing direct comparisons between brain states and hemispheres that are not possible in any other setting. AIM: To test whether potential measures of consciousness would be affected by selective anaesthesia of one hemisphere, and reliably distinguish the states of the anesthetised and non-anesthetised hemispheres. METHODS: We analysed EEG data from 7 patients undergoing Wada-tests in preparation for neurosurgery and computed several measures reported to correlate with the state of consciousness: power spectral density, functional connectivity, and measures of signal diversity. These measures were compared between conditions (normal rest vs. unilateral anaesthesia) and hemispheres (injected vs. non-injected), and used with a support vector machine to classify the state and site of injection objectively from individual patient's recordings. RESULTS: Although brain function, assessed behaviourally, appeared to be substantially altered only on the injected side, we found large bilateral changes in power spectral density for all frequency bands tested, and functional connectivity changed significantly both between and within both hemispheres. Surprisingly, we found no statistically significant differences in the measures of signal diversity between hemispheres or states, for the group of 7 patients, although 4 of the individual patients showed a significant decrease in signal diversity on the injected side. Nevertheless, including signal diversity measures improved the classification results, indicating that these measures carry at least some non-redundant information about the condition and injection site. We propose that several of these results may be explained by conduction of activity, via the corpus callosum, from the injected to the contralateral hemisphere and vice versa, without substantially affecting the function of the receiving hemisphere, thus reflecting what we call "cross-state unreceptiveness".

Neural mechanisms of training an auditory event-related potential task in a brain-computer interface context.

Effective use of brain-computer interfaces (BCIs) typically requires training. Improved understanding of the neural mechanisms underlying BCI training will facilitate optimisation of BCIs. The current study examined the neural mechanisms related to training for electroencephalography (EEG)-based communication with an auditory event-related potential (ERP) BCI. Neural mechanisms of training in 10 healthy volunteers were assessed with functional magnetic resonance imaging (fMRI) during an auditory ERP-based BCI task before (t1) and after (t5) three ERP-BCI training sessions outside the fMRI scanner (t2, t3, and t4). Attended stimuli were contrasted with ignored stimuli in the first-level fMRI data analysis (t1 and t5); the training effect was verified using the EEG data (t2-t4); and brain activation was contrasted before and after training in the second-level fMRI data analysis (t1 vs. t5). Training increased the communication speed from 2.9 bits/min (t2) to 4 bits/min (t4). Strong activation was found in the putamen, supplementary motor area (SMA), and superior temporal gyrus (STG) associated with attention to the stimuli. Training led to decreased activation in the superior frontal gyrus and stronger haemodynamic rebound in the STG and supramarginal gyrus. The neural mechanisms of ERP-BCI training indicate improved stimulus perception and reduced mental workload. The ERP task used in the current study showed overlapping activations with a motor imagery based BCI task from a previous study on the neural mechanisms of BCI training in the SMA and putamen. This suggests commonalities between the neural mechanisms of training for both BCI paradigms.

Psychological Predictors of Visual and Auditory P300 Brain-Computer Interface Performance.

Brain-Computer Interfaces (BCIs) provide communication channels independent from muscular control. In the current study we used two versions of the P300-BCI: one based on visual the other on auditory stimulation. Up to now, data on the impact of psychological variables on P300-BCI control are scarce. Hence, our goal was to identify new predictors with a comprehensive psychological test-battery. A total of N = 40 healthy BCI novices took part in a visual and an auditory BCI session. Psychological variables were measured with an electronic test-battery including clinical, personality, and performance tests. The personality factor "emotional stability" was negatively correlated (Spearman's rho = -0.416; p < 0.01) and an output variable of the non-verbal learning test (NVLT), which can be interpreted as ability to learn, correlated positively (Spearman's rho = 0.412; p < 0.01) with visual P300-BCI performance. In a linear regression analysis both independent variables explained 24% of the variance. "Emotional stability" was also negatively related to auditory P300-BCI performance (Spearman's rho = -0.377; p < 0.05), but failed significance in the regression analysis. Psychological parameters seem to play a moderate role in visual P300-BCI performance. "Emotional stability" was identified as a new predictor, indicating that BCI users who characterize themselves as calm and rational showed worse BCI performance. The positive relation of the ability to learn and BCI performance corroborates the notion that also for P300 based BCIs learning may constitute an important factor. Further studies are needed to consolidate or reject the presented predictors.

Comparison of Four Control Methods for a Five-Choice Assistive Technology.

Severe motor impairments can affect the ability to communicate. The ability to see has a decisive influence on the augmentative and alternative communication (AAC) systems available to the user. To better understand the initial impressions users have of AAC systems we asked naïve healthy participants to compare two visual (a visual P300 brain-computer interface (BCI) and an eye-tracker) and two non-visual systems (an auditory and a tactile P300 BCI). Eleven healthy participants performed 20 selections in a five choice task with each system. The visual P300 BCI used face stimuli, the auditory P300 BCI used Japanese Hiragana syllables and the tactile P300 BCI used a stimulator on the small left finger, middle left finger, right thumb, middle right finger and small right finger. The eye-tracker required a dwell time of 3 s on the target for selection. We calculated accuracies and information-transfer rates (ITRs) for each control method using the selection time that yielded the highest ITR and an accuracy above 70% for each system. Accuracies of 88% were achieved with the visual P300 BCI (4.8 s selection time, 20.9 bits/min), of 70% with the auditory BCI (19.9 s, 3.3 bits/min), of 71% with the tactile BCI (18 s, 3.4 bits/min) and of 100% with the eye-tracker (5.1 s, 28.2 bits/min). Performance between eye-tracker and visual BCI correlated strongly, correlation between tactile and auditory BCI performance was lower. Our data showed no advantage for either non-visual system in terms of ITR but a lower correlation of performance which suggests that choosing the system which suits a particular user is of higher importance for non-visual systems than visual systems.

A Multifunctional Brain-Computer Interface Intended for Home Use: An Evaluation with Healthy Participants and Potential End Users with Dry and Gel-Based Electrodes.

Current brain-computer interface (BCIs) software is often tailored to the needs of scientists and technicians and therefore complex to allow for versatile use. To facilitate home use of BCIs a multifunctional P300 BCI with a graphical user interface intended for non-expert set-up and control was designed and implemented. The system includes applications for spelling, web access, entertainment, artistic expression and environmental control. In addition to new software, it also includes new hardware for the recording of electroencephalogram (EEG) signals. The EEG system consists of a small and wireless amplifier attached to a cap that can be equipped with gel-based or dry contact electrodes. The system was systematically evaluated with a healthy sample, and targeted end users of BCI technology, i.e., people with a varying degree of motor impairment tested the BCI in a series of individual case studies. Usability was assessed in terms of effectiveness, efficiency and satisfaction. Feedback of users was gathered with structured questionnaires. Two groups of healthy participants completed an experimental protocol with the gel-based and the dry contact electrodes (N = 10 each). The results demonstrated that all healthy participants gained control over the system and achieved satisfactory to high accuracies with both gel-based and dry electrodes (average error rates of 6 and 13%). Average satisfaction ratings were high, but certain aspects of the system such as the wearing comfort of the dry electrodes and design of the cap, and speed (in both groups) were criticized by some participants. Six potential end users tested the system during supervised sessions. The achieved accuracies varied greatly from no control to high control with accuracies comparable to that of healthy volunteers. Satisfaction ratings of the two end-users that gained control of the system were lower as compared to healthy participants. The advantages and disadvantages of the BCI and its applications are discussed and suggestions are presented for improvements to pave the way for user friendly BCIs intended to be used as assistive technology by persons with severe paralysis.

An Evaluation of Training with an Auditory P300 Brain-Computer Interface for the Japanese Hiragana Syllabary.

Gaze-independent brain-computer interfaces (BCIs) are a possible communication channel for persons with paralysis. We investigated if it is possible to use auditory stimuli to create a BCI for the Japanese Hiragana syllabary, which has 46 Hiragana characters. Additionally, we investigated if training has an effect on accuracy despite the high amount of different stimuli involved. Able-bodied participants (N = 6) were asked to select 25 syllables (out of fifty possible choices) using a two step procedure: First the consonant (ten choices) and then the vowel (five choices). This was repeated on 3 separate days. Additionally, a person with spinal cord injury (SCI) participated in the experiment. Four out of six healthy participants reached Hiragana syllable accuracies above 70% and the information transfer rate increased from 1.7 bits/min in the first session to 3.2 bits/min in the third session. The accuracy of the participant with SCI increased from 12% (0.2 bits/min) to 56% (2 bits/min) in session three. Reliable selections from a 10 × 5 matrix using auditory stimuli were possible and performance is increased by training. We were able to show that auditory P300 BCIs can be used for communication with up to fifty symbols. This enables the use of the technology of auditory P300 BCIs with a variety of applications.

Comparison of eye tracking, electrooculography and an auditory brain-computer interface for binary communication: a case study with a participant in the locked-in state.

BACKGROUND: In this study, we evaluated electrooculography (EOG), an eye tracker and an auditory brain-computer interface (BCI) as access methods to augmentative and alternative communication (AAC). The participant of the study has been in the locked-in state (LIS) for 6 years due to amyotrophic lateral sclerosis. He was able to communicate with slow residual eye movements, but had no means of partner independent communication. We discuss the usability of all tested access methods and the prospects of using BCIs as an assistive technology. METHODS: Within four days, we tested whether EOG, eye tracking and a BCI would allow the participant in LIS to make simple selections. We optimized the parameters in an iterative procedure for all systems. RESULTS: The participant was able to gain control over all three systems. Nonetheless, due to the level of proficiency previously achieved with his low-tech AAC method, he did not consider using any of the tested systems as an additional communication channel. However, he would consider using the BCI once control over his eye muscles would no longer be possible. He rated the ease of use of the BCI as the highest among the tested systems, because no precise eye movements were required; but also as the most tiring, due to the high level of attention needed to operate the BCI. CONCLUSIONS: In this case study, the partner based communication was possible due to the good care provided and the proficiency achieved by the interlocutors. To ease the transition from a low-tech AAC method to a BCI once control over all muscles is lost, it must be simple to operate. For persons, who rely on AAC and are affected by a progressive neuromuscular disease, we argue that a complementary approach, combining BCIs and standard assistive technology, can prove valuable to achieve partner independent communication and ease the transition to a purely BCI based approach. Finally, we provide further evidence for the importance of a user-centered approach in the design of new assistive devices.

Brain Computer Interface on Track to Home.

The novel BackHome system offers individuals with disabilities a range of useful services available via brain-computer interfaces (BCIs), to help restore their independence. This is the time such technology is ready to be deployed in the real world, that is, at the target end users' home. This has been achieved by the development of practical electrodes, easy to use software, and delivering telemonitoring and home support capabilities which have been conceived, implemented, and tested within a user-centred design approach. The final BackHome system is the result of a 3-year long process involving extensive user engagement to maximize effectiveness, reliability, robustness, and ease of use of a home based BCI system. The system is comprised of ergonomic and hassle-free BCI equipment; one-click software services for Smart Home control, cognitive stimulation, and web browsing; and remote telemonitoring and home support tools to enable independent home use for nonexpert caregivers and users. BackHome aims to successfully bring BCIs to the home of people with limited mobility to restore their independence and ultimately improve their quality of life.

Rapid P300 brain-computer interface communication with a head-mounted display.

Visual ERP (P300) based brain-computer interfaces (BCIs) allow for fast and reliable spelling and are intended as a muscle-independent communication channel for people with severe paralysis. However, they require the presentation of visual stimuli in the field of view of the user. A head-mounted display could allow convenient presentation of visual stimuli in situations, where mounting a conventional monitor might be difficult or not feasible (e.g., at a patient's bedside). To explore if similar accuracies can be achieved with a virtual reality (VR) headset compared to a conventional flat screen monitor, we conducted an experiment with 18 healthy participants. We also evaluated it with a person in the locked-in state (LIS) to verify that usage of the headset is possible for a severely paralyzed person. Healthy participants performed online spelling with three different display methods. In one condition a 5 × 5 letter matrix was presented on a conventional 22 inch TFT monitor. Two configurations of the VR headset were tested. In the first (glasses A), the same 5 × 5 matrix filled the field of view of the user. In the second (glasses B), single letters of the matrix filled the field of view of the user. The participant in the LIS tested the VR headset on three different occasions (glasses A condition only). For healthy participants, average online spelling accuracies were 94% (15.5 bits/min) using three flash sequences for spelling with the monitor and glasses A and 96% (16.2 bits/min) with glasses B. In one session, the participant in the LIS reached an online spelling accuracy of 100% (10 bits/min) using the glasses A condition. We also demonstrated that spelling with one flash sequence is possible with the VR headset for healthy users (mean: 32.1 bits/min, maximum reached by one user: 71.89 bits/min at 100% accuracy). We conclude that the VR headset allows for rapid P300 BCI communication in healthy users and may be a suitable display option for severely paralyzed persons.

Usability and Workload of Access Technology for People With Severe Motor Impairment: A Comparison of Brain-Computer Interfacing and Eye Tracking.

BACKGROUND: Eye trackers are widely used among people with amyotrophic lateral sclerosis, and their benefits to quality of life have been previously shown. On the contrary, Brain-computer interfaces (BCIs) are still quite a novel technology, which also serves as an access technology for people with severe motor impairment. OBJECTIVE: To compare a visual P300-based BCI and an eye tracker in terms of information transfer rate (ITR), usability, and cognitive workload in users with motor impairments. METHODS: Each participant performed 3 spelling tasks, over 4 total sessions, using an Internet browser, which was controlled by a spelling interface that was suitable for use with either the BCI or the eye tracker. At the end of each session, participants evaluated usability and cognitive workload of the system. RESULTS: ITR and System Usability Scale (SUS) score were higher for the eye tracker (Wilcoxon signed-rank test: ITR T = 9, P = .016; SUS T = 12.50, P = .035). Cognitive workload was higher for the BCI (T = 4; P = .003). CONCLUSIONS: Although BCIs could be potentially useful for people with severe physical disabilities, we showed that the usability of BCIs based on the visual P300 remains inferior to eye tracking. We suggest that future research on visual BCIs should use eye tracking-based control as a comparison to evaluate performance or focus on nonvisual paradigms for persons who have lost gaze control.

Control or non-control state: that is the question! An asynchronous visual P300-based BCI approach.

OBJECTIVE: Brain-computer interfaces (BCI) based on event-related potentials (ERP) were proven to be a reliable synchronous communication method. For everyday life situations, however, this synchronous mode is impractical because the system will deliver a selection even if the user is not paying attention to the stimulation. So far, research into attention-aware visual ERP-BCIs (i.e., asynchronous ERP-BCIs) has led to variable success. In this study, we investigate new approaches for detection of user engagement. APPROACH: Classifier output and frequency-domain features of electroencephalogram signals as well as the hybridization of them were used to detect the user's state. We tested their capabilities for state detection in different control scenarios on offline data from 21 healthy volunteers. MAIN RESULTS: The hybridization of classifier output and frequency-domain features outperformed the results of the single methods, and allowed building an asynchronous P300-based BCI with an average correct state detection accuracy of more than 95%. SIGNIFICANCE: Our results show that all introduced approaches for state detection in an asynchronous P300-based BCI can effectively avoid involuntary selections, and that the hybrid method is the most effective approach.

Brain-controlled applications using dynamic P300 speller matrices.

OBJECTIVES: Access to the world wide web and multimedia content is an important aspect of life. We present a web browser and a multimedia user interface adapted for control with a brain-computer interface (BCI) which can be used by severely motor impaired persons. METHODS: The web browser dynamically determines the most efficient P300 BCI matrix size to select the links on the current website. This enables control of the web browser with fewer commands and smaller matrices. The multimedia player was based on an existing software. Both applications were evaluated with a sample of ten healthy participants and three end-users. All participants used a visual P300 BCI with face-stimuli for control. RESULTS: The healthy participants completed the multimedia player task with 90% accuracy and the web browsing task with 85% accuracy. The end-users completed the tasks with 62% and 58% accuracy. All healthy participants and two out of three end-users reported that they felt to be in control of the system. CONCLUSIONS: In this study we presented a multimedia application and an efficient web browser implemented for control with a BCI. SIGNIFICANCE: Both applications provide access to important areas of modern information retrieval and entertainment.

Epidural electrocorticography for monitoring of arousal in locked-in state.

Electroencephalography (EEG) often fails to assess both the level (i.e., arousal) and the content (i.e., awareness) of pathologically altered consciousness in patients without motor responsiveness. This might be related to a decline of awareness, to episodes of low arousal and disturbed sleep patterns, and/or to distorting and attenuating effects of the skull and intermediate tissue on the recorded brain signals. Novel approaches are required to overcome these limitations. We introduced epidural electrocorticography (ECoG) for monitoring of cortical physiology in a late-stage amytrophic lateral sclerosis patient in completely locked-in state (CLIS). Despite long-term application for a period of six months, no implant-related complications occurred. Recordings from the left frontal cortex were sufficient to identify three arousal states. Spectral analysis of the intrinsic oscillatory activity enabled us to extract state-dependent dominant frequencies at <4, ~7 and ~20 Hz, representing sleep-like periods, and phases of low and elevated arousal, respectively. In the absence of other biomarkers, ECoG proved to be a reliable tool for monitoring circadian rhythmicity, i.e., avoiding interference with the patient when he was sleeping and exploiting time windows of responsiveness. Moreover, the effects of interventions addressing the patient's arousal, e.g., amantadine medication, could be evaluated objectively on the basis of physiological markers, even in the absence of behavioral parameters. Epidural ECoG constitutes a feasible trade-off between surgical risk and quality of recorded brain signals to gain information on the patient's present level of arousal. This approach enables us to optimize the timing of interactions and medical interventions, all of which should take place when the patient is in a phase of high arousal. Furthermore, avoiding low-responsiveness periods will facilitate measures to implement alternative communication pathways involving brain-computer interfaces (BCI).

Effects of mental workload and fatigue on the P300, alpha and theta band power during operation of an ERP (P300) brain-computer interface.

The study aimed at revealing electrophysiological indicators of mental workload and fatigue during prolonged usage of a P300 brain-computer interface (BCI). Mental workload was experimentally manipulated with dichotic listening tasks. Medium and high workload conditions alternated. Behavioral measures confirmed that the manipulation of mental workload was successful. Reduced P300 amplitude was found for the high workload condition. Along with lower performance and an increase in the subjective level of fatigue, an increase of power in the alpha band was found for the last as compared to the first run of both conditions. The study confirms that a combination of signals derived from the time and frequency domain of the electroencephalogram is promising for the online detection of workload and fatigue. It also demonstrates that satisfactory accuracies can be achieved by healthy participants with the P300 speller, despite constant distraction and when pursuing the task for a long time.

Assessing attention and cognitive function in completely locked-in state with event-related brain potentials and epidural electrocorticography.

OBJECTIVE: Patients in the completely locked-in state (CLIS), due to, for example, amyotrophic lateral sclerosis (ALS), no longer possess voluntary muscle control. Assessing attention and cognitive function in these patients during the course of the disease is a challenging but essential task for both nursing staff and physicians. APPROACH: An electrophysiological cognition test battery, including auditory and semantic stimuli, was applied in a late-stage ALS patient at four different time points during a six-month epidural electrocorticography (ECoG) recording period. Event-related cortical potentials (ERP), together with changes in the ECoG signal spectrum, were recorded via 128 channels that partially covered the left frontal, temporal and parietal cortex. MAIN RESULTS: Auditory but not semantic stimuli induced significant and reproducible ERP projecting to specific temporal and parietal cortical areas. N1/P2 responses could be detected throughout the whole study period. The highest P3 ERP was measured immediately after the patient's last communication through voluntary muscle control, which was paralleled by low theta and high gamma spectral power. Three months after the patient's last communication, i.e., in the CLIS, P3 responses could no longer be detected. At the same time, increased activity in low-frequency bands and a sharp drop of gamma spectral power were recorded. SIGNIFICANCE: Cortical electrophysiological measures indicate at least partially intact attention and cognitive function during sparse volitional motor control for communication. Although the P3 ERP and frequency-specific changes in the ECoG spectrum may serve as indicators for CLIS, a close-meshed monitoring will be required to define the exact time point of the transition.