The Evoked Potential Operant Conditioning System (EPOCS): A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders.

The Evoked Potential Operant Conditioning System (EPOCS) is a software tool that implements protocols for operantly conditioning stimulus-triggered muscle responses in people with neuromuscular disorders, which in turn can improve sensorimotor function when applied appropriately. EPOCS monitors the state of specific target muscles-e.g., from surface electromyography (EMG) while standing, or from gait cycle measurements while walking on a treadmill-and automatically triggers calibrated stimulation when pre-defined conditions are met. It provides two forms of feedback that enable a person to learn to modulate the targeted pathway's excitability. First, it continuously monitors ongoing EMG activity in the target muscle, guiding the person to produce a consistent level of activity suitable for conditioning. Second, it provides immediate feedback of the response size following each stimulation and indicates whether it has reached the target value. To illustrate its use, this article describes a protocol through which a person can learn to decrease the size of the Hoffmann reflex-the electrically-elicited analog of the spinal stretch reflex-in the soleus muscle. Down-conditioning this pathway's excitability can improve walking in people with spastic gait due to incomplete spinal cord injury. The article demonstrates how to set up the equipment; how to place stimulating and recording electrodes; and how to use the free software to optimize electrode placement, measure the recruitment curve of direct motor and reflex responses, measure the response without operant conditioning, condition the reflex, and analyze the resulting data. It illustrates how the reflex changes over multiple sessions and how walking improves. It also discusses how the system can be applied to other kinds of evoked responses and to other kinds of stimulation, e.g., motor evoked potentials to transcranial magnetic stimulation; how it can address various clinical problems; and how it can support research studies of sensorimotor function in health and disease.

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.

Brain-computer interface-based assessment of color vision.

Objective.Present methods for assessing color vision require the person's active participation. Here we describe a brain-computer interface-based method for assessing color vision that does not require the person's participation.Approach.This method uses steady-state visual evoked potentials to identify metamers-two light sources that have different spectral distributions but appear to the person to be the same color.Main results.We demonstrate that: minimization of the visual evoked potential elicited by two flickering light sources identifies the metamer; this approach can distinguish people with color-vision deficits from those with normal color vision; and this metamer-identification process can be automated.Significance.This new method has numerous potential clinical, scientific, and industrial applications.

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.

Breathable, large-area epidermal electronic systems for recording electromyographic activity during operant conditioning of H-reflex.

Operant conditioning of Hoffmann's reflex (H-reflex) is a non-invasive and targeted therapeutic intervention for patients with movement disorders following spinal cord injury. The reflex-conditioning protocol uses electromyography (EMG) to measure reflexes from specific muscles elicited using transcutaneous electrical stimulation. Despite recent advances in wearable electronics, existing EMG systems that measure muscle activity for operant conditioning of spinal reflexes still use rigid metal electrodes with conductive gels and aggressive adhesives, while requiring precise positioning to ensure reliability of data across experimental sessions. Here, we present the first large-area epidermal electronic system (L-EES) and demonstrate its use in every step of the reflex-conditioning protocol. The L-EES is a stretchable and breathable composite of nanomembrane electrodes (16 electrodes in a four by four array), elastomer, and fabric. The nanomembrane electrode array enables EMG recording from a large surface area on the skin and the breathable elastomer with fabric is biocompatible and comfortable for patients. We show that L-EES can record direct muscle responses (M-waves) and H-reflexes, both of which are comparable to those recorded using conventional EMG recording systems. In addition, L-EES may improve the reflex-conditioning protocol; it has potential to automatically optimize EMG electrode positioning, which may reduce setup time and error across experimental sessions.

Acquisition, Maintenance, and Therapeutic Use of a Simple Motor Skill.

Operant conditioning of the spinal stretch reflex (SSR) or its electrical analog, the H-reflex, is a valuable experimental paradigm for studying the acquisition and maintenance of a simple motor skill. The CNS substrate of this skill consists of brain and spinal cord plasticity that operates as a hierarchy-the learning experience induces plasticity in the brain that guides and maintains plasticity in the spinal cord. This is apparent in the two components of the skill acquisition: task-dependent adaptation, reflecting brain plasticity; and long-term change, reflecting gradual development of spinal plasticity. The inferior olive, cerebellum, sensorimotor cortex, and corticospinal tract (CST) are essential components of this hierarchy. The neuronal and synaptic mechanisms of the spinal plasticity are under study. Because acquisition of this skill changes the spinal cord, it can affect other skills, such as locomotion. Thus, it enables investigation of how the highly plastic spinal cord supports the acquisition and maintenance of a broad repertoire of motor skills throughout life. These studies have resulted in the negotiated equilibrium model of spinal cord function, which reconciles the spinal cord's long-recognized reliability as the final common pathway for behaviors with its recently recognized ongoing plasticity. In accord with this model, appropriate H-reflex conditioning in a person with spasticity due to an incomplete spinal cord injury can trigger wider beneficial plasticity that markedly improves walking. H-reflex operant conditioning appears to provide a valuable new method for enhancing functional recovery in people with spinal cord injury and possibly other disorders as well.

Retraining Reflexes: Clinical Translation of Spinal Reflex Operant Conditioning.

Neurological disorders, such as spinal cord injury, stroke, traumatic brain injury, cerebral palsy, and multiple sclerosis cause motor impairments that are a huge burden at the individual, family, and societal levels. Spinal reflex abnormalities contribute to these impairments. Spinal reflex measurements play important roles in characterizing and monitoring neurological disorders and their associated motor impairments, such as spasticity, which affects nearly half of those with neurological disorders. Spinal reflexes can also serve as therapeutic targets themselves. Operant conditioning protocols can target beneficial plasticity to key reflex pathways; they can thereby trigger wider plasticity that improves impaired motor skills, such as locomotion. These protocols may complement standard therapies such as locomotor training and enhance functional recovery. This paper reviews the value of spinal reflexes and the therapeutic promise of spinal reflex operant conditioning protocols; it also considers the complex process of translating this promise into clinical reality.

The performance of 9-11-year-old children using an SSVEP-based BCI for target selection.

OBJECTIVE: In this paper, we report the performance of 9-11-year-old children using a steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) and provide control data collected from adults for comparison. Children in our study achieved a much higher performance (79% accuracy; average age 9.64 years old) than the only previous investigation of children using an SSVEP-based BCI (∼50% accuracy; average age 9.86 years old). APPROACH: Experiments were conducted in two phases, a short calibration phase and a longer experimental phase. An offline analysis of the data collected during the calibration phase was used to set two parameters for a classifier and to screen participants who did not achieve a minimum accuracy of 85%. MAIN RESULTS: Eleven of the 14 children and all 11 of the adults who completed the calibration phase met the minimum accuracy requirement. During the experimental phase, children selected targets with a similar accuracy (79% for children versus 78% for adults), latency (2.1 s for children versus 1.9 s for adults), and bitrate (0.50 bits s-1 for children and 0.56 bits s-1 for adults) as adults. SIGNIFICANCE: This study shows that children can use an SSVEP-based BCI with higher performance than previously believed and is the first to report the performance of children using an SSVEP-based BCI in terms of latency and bitrate. The results of this study imply that children with severe motor disabilities (such as locked-in syndrome) may use an SSVEP-based BCI to restore/replace the ability to communicate.

Alpha and theta band dynamics related to sentential constraint and word expectancy.

Despite strong evidence for prediction during language comprehension, the underlying mechanisms, and the extent to which they are specific to language, remain unclear. Re-analyzing an ERP study, we examined responses in the time-frequency domain to expected and unexpected (but plausible) words in strongly and weakly constraining sentences, and found results similar to those reported in nonverbal domains. Relative to expected words, unexpected words elicited an increase in the theta band (4-7 Hz) in strongly constraining contexts, suggesting the involvement of control processes to deal with the consequences of having a prediction disconfirmed. Prior to critical word onset, strongly constraining sentences exhibited a decrease in the alpha band (8-12 Hz) relative to weakly constraining sentences, suggesting that comprehenders can take advantage of predictive sentence contexts to prepare for the input. The results suggest that the brain recruits domain-general preparation and control mechanisms when making and assessing predictions during sentence comprehension.

Soft, conformal bioelectronics for a wireless human-wheelchair interface.

There are more than 3 million people in the world whose mobility relies on wheelchairs. Recent advancement on engineering technology enables more intuitive, easy-to-use rehabilitation systems. A human-machine interface that uses non-invasive, electrophysiological signals can allow a systematic interaction between human and devices; for example, eye movement-based wheelchair control. However, the existing machine-interface platforms are obtrusive, uncomfortable, and often cause skin irritations as they require a metal electrode affixed to the skin with a gel and acrylic pad. Here, we introduce a bioelectronic system that makes dry, conformal contact to the skin. The mechanically comfortable sensor records high-fidelity electrooculograms, comparable to the conventional gel electrode. Quantitative signal analysis and infrared thermographs show the advantages of the soft biosensor for an ergonomic human-machine interface. A classification algorithm with an optimized set of features shows the accuracy of 94% with five eye movements. A Bluetooth-enabled system incorporating the soft bioelectronics demonstrates a precise, hands-free control of a robotic wheelchair via electrooculograms.

The elicitation of steady-state visual evoked potentials during sleep.

This study confirmed the hypothesis that it is possible to elicit SSVEPs through closed eyelids during NREM sleep. To test this hypothesis, SSVEP amplitudes were measured in eight subjects across two conditions of stimulation (stimulation on and stimulation off) and three brain states (waking, light sleep, and deep sleep). Results showed a significant interaction between stimulation and brain state. In particular, EEG activity at the frequency of stimulation was higher during both light sleep and deep sleep in the stimulation on condition than in the stimulation off condition. The fact that it is possible to elicit SSVEPs during sleep may provide a new way to study how SSVEPs are generated in the brain-one that might help resolve open questions such as identifying the SSVEP activation sequence or deciding if SSVEPs derive from evoked or oscillatory neural processes.

Epidermal mechano-acoustic sensing electronics for cardiovascular diagnostics and human-machine interfaces.

Physiological mechano-acoustic signals, often with frequencies and intensities that are beyond those associated with the audible range, provide information of great clinical utility. Stethoscopes and digital accelerometers in conventional packages can capture some relevant data, but neither is suitable for use in a continuous, wearable mode, and both have shortcomings associated with mechanical transduction of signals through the skin. We report a soft, conformal class of device configured specifically for mechano-acoustic recording from the skin, capable of being used on nearly any part of the body, in forms that maximize detectable signals and allow for multimodal operation, such as electrophysiological recording. Experimental and computational studies highlight the key roles of low effective modulus and low areal mass density for effective operation in this type of measurement mode on the skin. Demonstrations involving seismocardiography and heart murmur detection in a series of cardiac patients illustrate utility in advanced clinical diagnostics. Monitoring of pump thrombosis in ventricular assist devices provides an example in characterization of mechanical implants. Speech recognition and human-machine interfaces represent additional demonstrated applications. These and other possibilities suggest broad-ranging uses for soft, skin-integrated digital technologies that can capture human body acoustics.

Soft, curved electrode systems capable of integration on the auricle as a persistent brain-computer interface.

Recent advances in electrodes for noninvasive recording of electroencephalograms expand opportunities collecting such data for diagnosis of neurological disorders and brain-computer interfaces. Existing technologies, however, cannot be used effectively in continuous, uninterrupted modes for more than a few days due to irritation and irreversible degradation in the electrical and mechanical properties of the skin interface. Here we introduce a soft, foldable collection of electrodes in open, fractal mesh geometries that can mount directly and chronically on the complex surface topology of the auricle and the mastoid, to provide high-fidelity and long-term capture of electroencephalograms in ways that avoid any significant thermal, electrical, or mechanical loading of the skin. Experimental and computational studies establish the fundamental aspects of the bending and stretching mechanics that enable this type of intimate integration on the highly irregular and textured surfaces of the auricle. Cell level tests and thermal imaging studies establish the biocompatibility and wearability of such systems, with examples of high-quality measurements over periods of 2 wk with devices that remain mounted throughout daily activities including vigorous exercise, swimming, sleeping, and bathing. Demonstrations include a text speller with a steady-state visually evoked potential-based brain-computer interface and elicitation of an event-related potential (P300 wave).

An SSVEP-Based Brain-Computer Interface for Text Spelling With Adaptive Queries That Maximize Information Gain Rates.

This paper presents a brain-computer interface for text entry using steady-state visually evoked potentials (SSVEP). Like other SSVEP-based spellers, ours identifies the desired input character by posing questions (or queries) to users through a visual interface. Each query defines a mapping from possible characters to steady-state stimuli. The user responds by attending to one of these stimuli. Unlike other SSVEP-based spellers, ours chooses from a much larger pool of possible queries-on the order of ten thousand instead of ten. The larger query pool allows our speller to adapt more effectively to the inherent structure of what is being typed and to the input performance of the user, both of which make certain queries provide more information than others. In particular, our speller chooses queries from this pool that maximize the amount of information to be received per unit of time, a measure of mutual information that we call information gain rate. To validate our interface, we compared it with two other state-of-the-art SSVEP-based spellers, which were re-implemented to use the same input mechanism. Results showed that our interface, with the larger query pool, allowed users to spell multiple-word texts nearly twice as fast as they could with the compared spellers.

Playing checkers with your mind: an interactive multiplayer hardware game platform for brain-computer interfaces.

In this paper we describe a multiplayer brain-computer interface (BCI) based on the classic game of checkers using steady-state visually evoked potentials (SSVEPs). Previous research in BCI gaming focuses mainly on the production of software-based games using a computer screen--few hardware-based BCI games using a physical board have been developed. Hardware-based games can present a unique set of challenges when compared to software-based games. Depending on where the user is sitting, some stimuli might be farther away from the player, at a steeper viewing angle, conflated with competing stimuli, or occluded by physical barriers. In our game, we light squares on a checkerboard with flickering LEDs to elicit SSVEP responses in the subjects. When a subject attends to a particular square, the resulting SSVEPs are classified and a robot arm moves the selected piece. In a set of pilot experiments we investigated the ability of two subjects to use the SSVEP-based hardware game platform, and assessed how interstimulus distance, interstimulus angle, distance between target stimulus and subject, number of competing stimuli, and visual occlusions of the stimuli influence classification accuracy.

Materials and optimized designs for human-machine interfaces via epidermal electronics.

Thin, soft, and elastic electronics with physical properties well matched to the epidermis can be conformally and robustly integrated with the skin. Materials and optimized designs for such devices are presented for surface electromyography (sEMG). The findings enable sEMG from wide ranging areas of the body. The measurements have quality sufficient for advanced forms of human-machine interface.

Sequential selection of window length for improved SSVEP-based BCI classification.

Brain-computer interfaces (BCI) utilizing steady-state visually evoked potentials (SSVEP) recorded by electroencephalography (EEG) have exciting potential to enable new systems for disabled individuals and novel controls for robotic and computer systems. To interact with SSVEP-based BCIs, users attend to visual stimuli modulated at predetermined frequencies. A key problem for SSVEP-based BCIs is to classify which modulation frequency the user is attending, for which there is an inherent trade-off between speed and accuracy. As SSVEP signals vary with time and stimulation frequency, a fixed-length data window does not necessarily optimize this trade-off. We propose a strategy, developed from sequential analysis, to vary the window-length used for classification. Our proposed technique adapts to the data, continuing to collect data until it is confident enough to make a classification decision. Our strategy was compared to a fixed window-length method using a simple experiment involving five frequencies presented individually to three participants. Using a canonical correlation analysis classifier to compare the proposed variable-length scheme to a standard fixed-length scheme, the variable-length approach improved the classifier information transfer rate by an average of 43%.