Towards clinical application of implantable brain-computer interfaces for people with late-stage ALS: medical and ethical considerations.

Individuals with amyotrophic lateral sclerosis (ALS) frequently develop speech and communication problems in the course of their disease. Currently available augmentative and alternative communication technologies do not present a solution for many people with advanced ALS, because these devices depend on residual and reliable motor activity. Brain-computer interfaces (BCIs) use neural signals for computer control and may allow people with late-stage ALS to communicate even when conventional technology falls short. Recent years have witnessed fast progression in the development and validation of implanted BCIs, which place neural signal recording electrodes in or on the cortex. Eventual widespread clinical application of implanted BCIs as an assistive communication technology for people with ALS will have significant consequences for their daily life, as well as for the clinical management of the disease, among others because of the potential interaction between the BCI and other procedures people with ALS undergo, such as tracheostomy. This article aims to facilitate responsible real-world implementation of implanted BCIs. We review the state of the art of research on implanted BCIs for communication, as well as the medical and ethical implications of the clinical application of this technology. We conclude that the contribution of all BCI stakeholders, including clinicians of the various ALS-related disciplines, will be needed to develop procedures for, and shape the process of, the responsible clinical application of implanted BCIs.

A Voting-Enhanced Dynamic-Window-Length Classifier for SSVEP-Based BCIs.

We present a dynamic window-length classifier for steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) that does not require the user to choose a feature extraction method or channel set. Instead, the classifier uses multiple feature extraction methods and channel selections to infer the SSVEP and relies on majority voting to pick the most likely target. The classifier extends the window length dynamically if no target obtains the majority of votes. Compared with existing solutions, our classifier: (i) does not assume that any single feature extraction method will consistently outperform the others; (ii) adapts the channel selection to individual users or tasks; (iii) uses dynamic window lengths; (iv) is unsupervised (i.e., does not need training). Collectively, these characteristics make the classifier easy-to-use, especially for caregivers and others with limited technical expertise. We evaluated the performance of our classifier on a publicly available benchmark dataset from 35 healthy participants. We compared the information transfer rate (ITR) of this new classifier to those of the minimum energy combination (MEC), maximum synchronization index (MSI), and filter bank canonical correlation analysis (FBCCA). The new classifier increases average ITR to 123.5 bits-per-minute (bpm), 47.5, 51.2, and 19.5 bpm greater than the MEC, MSI, and FBCCA classifiers, respectively.

Brain-computer interfaces for people with amyotrophic lateral sclerosis.

A brain-computer interface (BCI) records and extracts features from brain signals, and translates these features into commands that can replace, restore, enhance, supplement, or improve natural CNS outputs. As demonstrated in the other chapters of this book, the focus of the work of the last three decades of BCI research has been the replacement, restoration, or improvement of diminished or lost function in people with CNS disease or injury including those with amyotrophic lateral sclerosis (ALS). Due in part to the desire to conduct controlled studies, and, in part, to the complexity of BCI technology, most of this work has been carried out in laboratories with healthy controls or with limited numbers of potential consumers with a variety of diagnoses under supervised conditions. The intention of this chapter is to describe the growing body of BCI research that has included people with amyotrophic lateral sclerosis (ALS). People in the late stages of ALS can lose all voluntary control, including the ability to communicate; and while recent research has provided new insights into underlying mechanisms, ALS remains a disease with no cure. As a result, people with ALS and their families, caregivers, and advocates have an active interest in both the current and potential capabilities of BCI technology. The focus of BCI research for people with ALS is on communication, and this topic is well covered elsewhere in this volume. This chapter focuses on the efforts dedicated to make BCI technology useful to people with ALS in their daily lives with a discussion of how researchers, clinicians, and patients must become partners in that process.

Independent home use of a brain-computer interface by people with amyotrophic lateral sclerosis.

OBJECTIVE: To assess the reliability and usefulness of an EEG-based brain-computer interface (BCI) for patients with advanced amyotrophic lateral sclerosis (ALS) who used it independently at home for up to 18 months. METHODS: Of 42 patients consented, 39 (93%) met the study criteria, and 37 (88%) were assessed for use of the Wadsworth BCI. Nine (21%) could not use the BCI. Of the other 28, 27 (men, age 28-79 years) (64%) had the BCI placed in their homes, and they and their caregivers were trained to use it. Use data were collected by Internet. Periodic visits evaluated BCI benefit and burden and quality of life. RESULTS: Over subsequent months, 12 (29% of the original 42) left the study because of death or rapid disease progression and 6 (14%) left because of decreased interest. Fourteen (33%) completed training and used the BCI independently, mainly for communication. Technical problems were rare. Patient and caregiver ratings indicated that BCI benefit exceeded burden. Quality of life remained stable. Of those not lost to the disease, half completed the study; all but 1 patient kept the BCI for further use. CONCLUSION: The Wadsworth BCI home system can function reliably and usefully when operated by patients in their homes. BCIs that support communication are at present most suitable for people who are severely disabled but are otherwise in stable health. Improvements in BCI convenience and performance, including some now underway, should increase the number of people who find them useful and the extent to which they are used.

Toward independent home use of brain-computer interfaces: a decision algorithm for selection of potential end-users.

Noninvasive brain-computer interfaces (BCIs) use scalp-recorded electrical activity from the brain to control an application. Over the past 20 years, research demonstrating that BCIs can provide communication and control to individuals with severe motor impairment has increased almost exponentially. Although considerable effort has been dedicated to offline analysis for improving signal detection and translation, far less effort has been made to conduct online studies with target populations. Thus, there remains a great need for both long-term and translational BCI studies that include individuals with disabilities in their own homes. Completing these studies is the only sure means to answer questions about BCI utility and reliability. Here we suggest an algorithm for candidate selection for electroencephalographic (EEG)-based BCI home studies. This algorithm takes into account BCI end-users and their environment and should assist in study design and substantially improve subject retention rates, thereby improving the overall efficacy of BCI home studies. It is the result of a workshop at the Fifth International BCI Meeting that allowed us to leverage the expertise of multiple research laboratories and people from multiple backgrounds in BCI research.

P300-based brain-computer interface (BCI) event-related potentials (ERPs): People with amyotrophic lateral sclerosis (ALS) vs. age-matched controls.

OBJECTIVE: Brain-computer interfaces (BCIs) aimed at restoring communication to people with severe neuromuscular disabilities often use event-related potentials (ERPs) in scalp-recorded EEG activity. Up to the present, most research and development in this area has been done in the laboratory with young healthy control subjects. In order to facilitate the development of BCI most useful to people with disabilities, the present study set out to: (1) determine whether people with amyotrophic lateral sclerosis (ALS) and healthy, age-matched volunteers (HVs) differ in the speed and accuracy of their ERP-based BCI use; (2) compare the ERP characteristics of these two groups; and (3) identify ERP-related factors that might enable improvement in BCI performance for people with disabilities. METHODS: Sixteen EEG channels were recorded while people with ALS or healthy age-matched volunteers (HVs) used a P300-based BCI. The subjects with ALS had little or no remaining useful motor control (mean ALS Functional Rating Scale-Revised 9.4 (±9.5SD) (range 0-25)). Each subject attended to a target item as the items in a 6×6 visual matrix flashed. The BCI used a stepwise linear discriminant function (SWLDA) to determine the item the user wished to select (i.e., the target item). Offline analyses assessed the latencies, amplitudes, and locations of ERPs to the target and non-target items for people with ALS and age-matched control subjects. RESULTS: BCI accuracy and communication rate did not differ significantly between ALS users and HVs. Although ERP morphology was similar for the two groups, their target ERPs differed significantly in the location and amplitude of the late positivity (P300), the amplitude of the early negativity (N200), and the latency of the late negativity (LN). CONCLUSIONS: The differences in target ERP components between people with ALS and age-matched HVs are consistent with the growing recognition that ALS may affect cortical function. The development of BCIs for use by this population may begin with studies in HVs but also needs to include studies in people with ALS. Their differences in ERP components may affect the selection of electrode montages, and might also affect the selection of presentation parameters (e.g., matrix design, stimulation rate). SIGNIFICANCE: P300-based BCI performance in people severely disabled by ALS is similar to that of age-matched control subjects. At the same time, their ERP components differ to some degree from those of controls. Attention to these differences could contribute to the development of BCIs useful to those with ALS and possibly to others with severe neuromuscular disabilities.

A practical, intuitive brain-computer interface for communicating 'yes' or 'no' by listening.

OBJECTIVE: Previous work has shown that it is possible to build an EEG-based binary brain-computer interface system (BCI) driven purely by shifts of attention to auditory stimuli. However, previous studies used abrupt, abstract stimuli that are often perceived as harsh and unpleasant, and whose lack of inherent meaning may make the interface unintuitive and difficult for beginners. We aimed to establish whether we could transition to a system based on more natural, intuitive stimuli (spoken words 'yes' and 'no') without loss of performance, and whether the system could be used by people in the locked-in state. APPROACH: We performed a counterbalanced, interleaved within-subject comparison between an auditory streaming BCI that used beep stimuli, and one that used word stimuli. Fourteen healthy volunteers performed two sessions each, on separate days. We also collected preliminary data from two subjects with advanced amyotrophic lateral sclerosis (ALS), who used the word-based system to answer a set of simple yes-no questions. MAIN RESULTS: The N1, N2 and P3 event-related potentials elicited by words varied more between subjects than those elicited by beeps. However, the difference between responses to attended and unattended stimuli was more consistent with words than beeps. Healthy subjects' performance with word stimuli (mean 77% ± 3.3 s.e.) was slightly but not significantly better than their performance with beep stimuli (mean 73% ± 2.8 s.e.). The two subjects with ALS used the word-based BCI to answer questions with a level of accuracy similar to that of the healthy subjects. SIGNIFICANCE: Since performance using word stimuli was at least as good as performance using beeps, we recommend that auditory streaming BCI systems be built with word stimuli to make the system more pleasant and intuitive. Our preliminary data show that word-based streaming BCI is a promising tool for communication by people who are locked in.

Brain-computer interface (BCI) evaluation in people with amyotrophic lateral sclerosis.

Brain-computer interfaces (BCIs) might restore communication to people severely disabled by amyotrophic lateral sclerosis (ALS) or other disorders. We sought to: 1) define a protocol for determining whether a person with ALS can use a visual P300-based BCI; 2) determine what proportion of this population can use the BCI; and 3) identify factors affecting BCI performance. Twenty-five individuals with ALS completed an evaluation protocol using a standard 6 × 6 matrix and parameters selected by stepwise linear discrimination. With an 8-channel EEG montage, the subjects fell into two groups in BCI accuracy (chance accuracy 3%). Seventeen averaged 92 (± 3)% (range 71-100%), which is adequate for communication (G70 group). Eight averaged 12 (± 6)% (range 0-36%), inadequate for communication (L40 subject group). Performance did not correlate with disability: 11/17 (65%) of G70 subjects were severely disabled (i.e. ALSFRS-R < 5). All L40 subjects had visual impairments (e.g. nystagmus, diplopia, ptosis). P300 was larger and more anterior in G70 subjects. A 16-channel montage did not significantly improve accuracy. In conclusion, most people severely disabled by ALS could use a visual P300-based BCI for communication. In those who could not, visual impairment was the principal obstacle. For these individuals, auditory P300-based BCIs might be effective.

EEG correlates of P300-based brain-computer interface (BCI) performance in people with amyotrophic lateral sclerosis.

The purpose of this study was to identify electroencephalography (EEG) features that correlate with P300-based brain-computer interface (P300 BCI) performance in people with amyotrophic lateral sclerosis (ALS). Twenty people with ALS used a P300 BCI spelling application in copy-spelling mode. Three types of EEG features were found to be good predictors of P300 BCI performance: (1) the root-mean-square amplitude and (2) the negative peak amplitude of the event-related potential to target stimuli (target ERP) at Fz, Cz, P3, Pz, and P4; and (3) EEG theta frequency (4.5-8 Hz) power at Fz, Cz, P3, Pz, P4, PO7, PO8 and Oz. A statistical prediction model that used a subset of these features accounted for >60% of the variance in copy-spelling performance (p < 0.001, mean R(2) = 0.6175). The correlations reflected between-subject, rather than within-subject, effects. The results enhance understanding of performance differences among P300 BCI users. The predictors found in this study might help in: (1) identifying suitable candidates for long-term P300 BCI operation; (2) assessing performance online. Further work on within-subject effects needs to be done to establish whether P300 BCI user performance could be improved by optimizing one or more of these EEG features.

A brain-computer interface for long-term independent home use.

Our objective was to develop and validate a new brain-computer interface (BCI) system suitable for long-term independent home use by people with severe motor disabilities. The BCI was used by a 51-year-old male with ALS who could no longer use conventional assistive devices. Caregivers learned to place the electrode cap, add electrode gel, and turn on the BCI. After calibration, the system allowed the user to communicate via EEG. Re-calibration was performed remotely (via the internet), and BCI accuracy assessed in periodic tests. Reports of BCI usefulness by the user and the family were also recorded. Results showed that BCI accuracy remained at 83% (r = -.07, n.s.) for over 2.5 years (1.4% expected by chance). The BCI user and his family state that the BCI had restored his independence in social interactions and at work. He uses the BCI to run his NIH-funded research laboratory and to communicate via e-mail with family, friends, and colleagues. In addition to this first user, several other similarly disabled people are now using the BCI in their daily lives. In conclusion, long-term independent home use of this BCI system is practical for severely disabled people, and can contribute significantly to quality of life and productivity.

A scanning protocol for a sensorimotor rhythm-based brain-computer interface.

The scanning protocol is a novel brain-computer interface (BCI) implementation that can be controlled with sensorimotor rhythms (SMRs) of the electroencephalogram (EEG). The user views a screen that shows four choices in a linear array with one marked as target. The four choices are successively highlighted for 2.5s each. When a target is highlighted, the user can select it by modulating the SMR. An advantage of this method is the capacity to choose among multiple choices with just one learned SMR modulation. Each of 10 naive users trained for ten 30 min sessions over 5 weeks. User performance improved significantly (p<0.001) over the sessions and ranged from 30 to 80% mean accuracy of the last three sessions (chance accuracy=25%). The incidence of correct selections depended on the target position. These results suggest that, with further improvements, a scanning protocol can be effective. The ultimate goal is to expand it to a large matrix of selections.

A comparison of classification techniques for the P300 Speller.

This study assesses the relative performance characteristics of five established classification techniques on data collected using the P300 Speller paradigm, originally described by Farwell and Donchin (1988 Electroenceph. Clin. Neurophysiol. 70 510). Four linear methods: Pearson's correlation method (PCM), Fisher's linear discriminant (FLD), stepwise linear discriminant analysis (SWLDA) and a linear support vector machine (LSVM); and one nonlinear method: Gaussian kernel support vector machine (GSVM), are compared for classifying offline data from eight users. The relative performance of the classifiers is evaluated, along with the practical concerns regarding the implementation of the respective methods. The results indicate that while all methods attained acceptable performance levels, SWLDA and FLD provide the best overall performance and implementation characteristics for practical classification of P300 Speller data.

A P300 event-related potential brain-computer interface (BCI): the effects of matrix size and inter stimulus interval on performance.

We describe a study designed to assess properties of a P300 brain-computer interface (BCI). The BCI presents the user with a matrix containing letters and numbers. The user attends to a character to be communicated and the rows and columns of the matrix briefly intensify. Each time the attended character is intensified it serves as a rare event in an oddball sequence and it elicits a P300 response. The BCI works by detecting which character elicited a P300 response. We manipulated the size of the character matrix (either 3 x 3 or 6 x 6) and the duration of the inter stimulus interval (ISI) between intensifications (either 175 or 350 ms). Online accuracy was highest for the 3 x 3 matrix 175-ms ISI condition, while bit rate was highest for the 6 x 6 matrix 175-ms ISI condition. Average accuracy in the best condition for each subject was 88%. P300 amplitude was significantly greater for the attended stimulus and for the 6 x 6 matrix. This work demonstrates that matrix size and ISI are important variables to consider when optimizing a BCI system for individual users and that a P300-BCI can be used for effective communication.

The Third International Meeting on Brain-Computer Interface Technology: making a difference.

This special issue of the IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING provides a representative and comprehensive bird's-eye view of the most recent developments in brain-computer interface (BCI) technology from laboratories around the world. The 30 research communications and papers are the direct outcome of the Third International Meeting on Brain-Computer Interface Technology held at the Rensselaerville Institute, Rensselaerville, NY, in June 2005. Fifty-three research groups from North and South America, Europe, and Asia, representing the majority of all the existing BCI laboratories around the world, participated in this highly focused meeting sponsored by the National Institutes of Health and organized by the BCI Laboratory of the Wadsworth Center of the New York State Department of Health. As demonstrated by the papers in this special issue, the rapid advances in BCI research and development make this technology capable of providing communication and control to people severely disabled by amyotrophic lateral sclerosis (ALS), brainstem stroke, cerebral palsy, and other neuromuscular disorders. Future work is expected to improve the performance and utility of BCIs, and to focus increasingly on making them a viable, practical, and affordable communication alternative for many thousands of severely disabled people worldwide.

The Wadsworth BCI Research and Development Program: at home with BCI.

The ultimate goal of brain-computer interface (BCI) technology is to provide communication and control capacities to people with severe motor disabilities. BCI research at the Wadsworth Center focuses primarily on noninvasive, electroencephalography (EEG)-based BCI methods. We have shown that people, including those with severe motor disabilities, can learn to use sensorimotor rhythms (SMRs) to move a cursor rapidly and accurately in one or two dimensions. We have also improved P300-based BCI operation. We are now translating this laboratory-proven BCI technology into a system that can be used by severely disabled people in their homes with minimal ongoing technical oversight. To accomplish this, we have: improved our general-purpose BCI software (BCI2000); improved online adaptation and feature translation for SMR-based BCI operation; improved the accuracy and bandwidth of P300-based BCI operation; reduced the complexity of system hardware and software and begun to evaluate home system use in appropriate users. These developments have resulted in prototype systems for every day use in people's homes.

Brain-computer interface (BCI) operation: signal and noise during early training sessions.

OBJECTIVE: People can learn to control mu (8-12 Hz) or beta (18-25 Hz) rhythm amplitude in the electroencephalogram (EEG) recorded over sensorimotor cortex and use it to move a cursor to a target on a video screen. The recorded signal may also contain electromyogram (EMG) and other non-EEG artifacts. This study examines the presence and characteristics of EMG contamination during new users' initial brain-computer interface (BCI) training sessions, as they first attempt to acquire control over mu or beta rhythm amplitude and to use that control to move a cursor to a target. METHODS: In the standard one-dimensional format, a target appears along the right edge of the screen and 1s later the cursor appears in the middle of the left edge and moves across the screen at a fixed rate with its vertical movement controlled by a linear function of mu or beta rhythm amplitude. In the basic two-choice version, the target occupies the upper or lower half of the right edge. The user's task is to move the cursor vertically so that it hits the target when it reaches the right edge. The present data comprise the first 10 sessions of BCI training from each of 7 users. Their data were selected to illustrate the variations seen in EMG contamination across users. RESULTS: Five of the 7 users learned to change rhythm amplitude appropriately, so that the cursor hit the target. Three of these 5 showed no evidence of EMG contamination. In the other two of these 5, EMG was prominent in early sessions, and tended to be associated with errors rather than with hits. As EEG control improved over the 10 sessions, this EMG contamination disappeared. In the remaining two users, who never acquired actual EEG control, EMG was prominent in initial sessions and tended to move the cursor to the target. This EMG contamination was still detectable by Session 10. CONCLUSIONS: EMG contamination arising from cranial muscles is often present early in BCI training and gradually wanes. In those users who eventually acquire EEG control, early target-related EMG contamination may be most prominent for unsuccessful trials, and may reflect user frustration. In those users who never acquire EEG control, EMG may initially serve to move the cursor toward the target. Careful and comprehensive topographical and spectral analyses throughout user training are essential for detecting EMG contamination and differentiating between cursor control provided by EEG control and cursor control provided by EMG contamination. SIGNIFICANCE: Artifacts such as EMG are common in EEG recordings. Comprehensive spectral and topographical analyses are necessary to detect them and ensure that they do not masquerade as, or interfere with acquisition of, actual EEG-based cursor control.

The BCI Competition 2003: progress and perspectives in detection and discrimination of EEG single trials.

Interest in developing a new method of man-to-machine communication--a brain-computer interface (BCI)--has grown steadily over the past few decades. BCIs create a new communication channel between the brain and an output device by bypassing conventional motor output pathways of nerves and muscles. These systems use signals recorded from the scalp, the surface of the cortex, or from inside the brain to enable users to control a variety of applications including simple word-processing software and orthotics. BCI technology could therefore provide a new communication and control option for individuals who cannot otherwise express their wishes to the outside world. Signal processing and classification methods are essential tools in the development of improved BCI technology. We organized the BCI Competition 2003 to evaluate the current state of the art of these tools. Four laboratories well versed in EEG-based BCI research provided six data sets in a documented format. We made these data sets (i.e., labeled training sets and unlabeled test sets) and their descriptions available on the Internet. The goal in the competition was to maximize the performance measure for the test labels. Researchers worldwide tested their algorithms and competed for the best classification results. This paper describes the six data sets and the results and function of the most successful algorithms.

Brain-computer interface technology: a review of the Second International Meeting.

This paper summarizes the Brain-Computer Interfaces for Communication and Control, The Second International Meeting, held in Rensselaerville, NY, in June 2002. Sponsored by the National Institutes of Health and organized by the Wadsworth Center of the New York State Department of Health, the meeting addressed current work and future plans in brain-computer interface (BCI) research. Ninety-two researchers representing 38 different research groups from the United States, Canada, Europe, and China participated. The BCIs discussed at the meeting use electroencephalographic activity recorded from the scalp or single-neuron activity recorded within cortex to control cursor movement, select letters or icons, or operate neuroprostheses. The central element in each BCI is a translation algorithm that converts electrophysiological input from the user into output that controls external devices. BCI operation depends on effective interaction between two adaptive controllers, the user who encodes his or her commands in the electrophysiological input provided to the BCI, and the BCI that recognizes the commands contained in the input and expresses them in device control. Current BCIs have maximum information transfer rates of up to 25 b/min. Achievement of greater speed and accuracy requires improvements in signal acquisition and processing, in translation algorithms, and in user training. These improvements depend on interdisciplinary cooperation among neuroscientists, engineers, computer programmers, psychologists, and rehabilitation specialists, and on adoption and widespread application of objective criteria for evaluating alternative methods. The practical use of BCI technology will be determined by the development of appropriate applications and identification of appropriate user groups, and will require careful attention to the needs and desires of individual users.

The Wadsworth Center brain-computer interface (BCI) research and development program.

Brain-computer interface (BCI) research at the Wadsworth Center has focused primarily on using electroencephalogram (EEG) rhythms recorded from the scalp over sensorimotor cortex to control cursor movement in one or two dimensions. Recent and current studies seek to improve the speed and accuracy of this control by improving the selection of signal features and their translation into device commands, by incorporating additional signal features, and by optimizing the adaptive interaction between the user and system. In addition, to facilitate the evaluation, comparison, and combination of alternative BCI methods, we have developed a general-purpose BCI system called BCI-2000 and have made it available to other research groups. Finally, in collaboration with several other groups, we are developing simple BCI applications and are testing their practicality and long-term value for people with severe motor disabilities.