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ObjectiveBrain-computer interface (BCI) technology is attracting increasing interest as a tool for enhancing recovery of motor function after stroke, yet the optimal way to apply this technology is unknown. Here, we studied the immediate and therapeutic effects of BCI-based training to control pre-movement sensorimotor rhythm (SMR) amplitude on robot-assisted finger extension in people with stroke.ApproachEight people with moderate to severe hand impairment due to chronic stroke completed a four-week three-phase protocol during which they practiced finger extension with assistance from the FINGER robotic exoskeleton. In Phase 1, we identified spatiospectral SMR features for each person that correlated with the intent to extend the index and/or middle finger(s). In Phase 2, the participants learned to increase or decrease SMR features given visual feedback, without movement. In Phase 3, the participants were cued to increase or decrease their SMR features, and when successful, were then cued to immediately attempt to extend the finger(s) with robot assistance.Main resultsOf the four participants that achieved SMR control in Phase 2, three initiated finger extensions with a reduced reaction time after decreasing (versus increasing) pre-movement SMR amplitude during Phase 3. Two also extended at least one of their fingers more forcefully after decreasing pre-movement SMR amplitude. Hand function, measured by the box and block test (BBT), improved by 7.3  ±  7.5 blocks versus 3.5  ±  3.1 blocks in those with and without SMR control, respectively. Higher BBT scores at baseline correlated with a larger change in BBT score.SignificanceThese results suggest that learning to control person-specific pre-movement SMR features associated with finger extension can improve finger extension ability after stroke for some individuals. These results merit further investigation in a rehabilitation context.

Humans can acquire and maintain motor skills throughout their lives through motor learning. Motor learning and skill acquisition are essential for rehabilitation following neurological disease or injury. Adaptation, the initial stage of motor learning, involves short-term changes in motor performance in response to a new demand in the person's environment. Repeated adaptation can improve skill performance and result in long-term skill retention. Locomotor adaptation is extensively studied using split-belt treadmill paradigms. In this study we explored whether bidirectional walking (BDW) on a split-belt treadmill can induce short-term gait adaptations. Twelve healthy volunteers participated in our single session, starting with 2 minutes of normal walking (NW), followed by four 5-minute blocks of BDW with a 1-minute passive rest in between blocks, and ending with another 2-minute of NW. We recorded body kinematics and ground reaction forces throughout the experiment. Participants quickly adapted to BDW with both legs showing decreased step lengths. However, only the backward-walking leg exhibited aftereffects upon returning to NW, indicating short-term adaptation. Notable kinematic changes were observed, particularly in hip extension and pelvis tilt, though these varied among participants. Our findings suggest that BDW induces unilateral adaptations despite bilateral changes in gait, offering new insights into locomotor control and spinal CPG organization., Competing Interests: Competing Interests The authors have no competing interests to declare.

We are studying the mechanisms of H-reflex operant conditioning, a simple form of learning. Modelling studies in the literature and our previous data suggested that changes in the axon initial segment (AIS) might contribute. To explore this, we used blinded quantitative histological and immunohistochemical methods to study in adult rats the impact of H-reflex conditioning on the AIS of the spinal motoneuron that produces the reflex. Successful, but not unsuccessful, H-reflex up-conditioning was associated with greater AIS length and distance from soma; greater length correlated with greater H-reflex increase. Modelling studies in the literature suggest that these increases may increase motoneuron excitability, supporting the hypothesis that they may contribute to H-reflex increase. Up-conditioning did not affect AIS ankyrin G (AnkG) immunoreactivity (IR), p-p38 protein kinase IR, or GABAergic terminals. Successful, but not unsuccessful, H-reflex down-conditioning was associated with more GABAergic terminals on the AIS, weaker AnkG-IR, and stronger p-p38-IR. More GABAergic terminals and weaker AnkG-IR correlated with greater H-reflex decrease. These changes might potentially contribute to the positive shift in motoneuron firing threshold underlying H-reflex decrease; they are consistent with modelling suggesting that sodium channel change may be responsible. H-reflex down-conditioning did not affect AIS dimensions. This evidence that AIS plasticity is associated with and might contribute to H-reflex conditioning adds to evidence that motor learning involves both spinal and brain plasticity, and both neuronal and synaptic plasticity. AIS properties of spinal motoneurons are likely to reflect the combined influence of all the motor skills that share these motoneurons. KEY POINTS: Neuronal action potentials normally begin in the axon initial segment (AIS). AIS plasticity affects neuronal excitability in development and disease. Whether it does so in learning is unknown. Operant conditioning of a spinal reflex, a simple learning model, changes the rat spinal motoneuron AIS. Successful, but not unsuccessful, H-reflex up-conditioning is associated with greater AIS length and distance from soma. Successful, but not unsuccessful, down-conditioning is associated with more AIS GABAergic terminals, less ankyrin G, and more p-p38 protein kinase. The associations between AIS plasticity and successful H-reflex conditioning are consistent with those between AIS plasticity and functional changes in development and disease, and with those predicted by modelling studies in the literature. Motor learning changes neurons and synapses in spinal cord and brain. Because spinal motoneurons are the final common pathway for behaviour, their AIS properties probably reflect the combined impact of all the behaviours that use these motoneurons., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Computer-controlled treadmills are common in many gait labs and offer great potential for conducting perturbation-based postural studies. However, the time-course of these disturbances can be too brief to be controlled manually through product software. Here we present a system that combines a Bertec® split-belt treadmill with custom hardware and software to deliver postural disturbances during standing and record data from multiple sources simultaneously. We used this system to administer to 15 healthy participants an 8-session perturbation-based training protocol in which they learned to respond without stepping to progressively larger perturbations. Kinematic, electromyographic, and force data were collected throughout. Motion capture was used to characterize the accuracy and repeatability of the treadmill-delivered perturbations with respect to duration, displacement, and peak velocity. These (observed) data were compared to that expected based on software commands and the known constraints of the treadmill (i.e., 10 Hz operating speed). We found perturbation durations to be as expected. Peak velocities and displacements were slightly higher than expected (average increases were 0.59 cm/s and 1.76 cm, respectively). Because this increase in magnitude was consistent, it did not impede training or affect data analysis. Treadmill behavior was repeatable across 95 % of trials., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier Ltd.)

Neurorehabilitation is now one of the most exciting areas in neuroscience. Recognition that the central nervous system (CNS) remains plastic through life, new understanding of skilled behaviors (skills), and novel methods for engaging and guiding beneficial plasticity combine to provide unprecedented opportunities for restoring skills impaired by CNS injury or disease. The substrate of a skill is a distributed network of neurons and synapses that changes continually through life to ensure that skill performance remains satisfactory as new skills are acquired, and as growth, aging, and other life events occur. This substrate can extend from cortex to spinal cord. It has recently been given the name "heksor." In this new context, the primary goal of rehabilitation is to enable damaged heksors to repair themselves so that their skills are once again performed well. Skill-specific practice, the mainstay of standard therapy, often fails to optimally engage the many sites and kinds of plasticity available in the damaged CNS. New noninvasive technology-based interventions can target beneficial plasticity to critical sites in damaged heksors; these interventions may thereby enable much wider beneficial plasticity that enhances skill recovery. Targeted-plasticity interventions include operant conditioning of a spinal reflex or corticospinal motor evoked potential (MEP), paired-pulse facilitation of corticospinal connections, and brain-computer interface (BCI)-based training of electroencephalographic (EEG) sensorimotor rhythms. Initial studies in people with spinal cord injury, stroke, or multiple sclerosis show that these interventions can enhance skill recovery beyond that achieved by skill-specific practice alone. After treatment ends, the repaired heksors maintain the benefits., Competing Interests: The authors are inventors on several patents relevant to the subject of this review., (© 2023 Wolpaw and Thompson.)

Weak transcranial direct current stimulation (tDCS) is known to affect corticospinal excitability and enhance motor skill acquisition, whereas its effects on spinal reflexes in actively contracting muscles are yet to be established. Thus, in this study, we examined the acute effects of Active and Sham tDCS on the soleus H-reflex during standing. In fourteen adults without known neurological conditions, the soleus H-reflex was repeatedly elicited at just above M-wave threshold throughout 30 min of Active (N = 7) or Sham (N = 7) 2-mA tDCS over the primary motor cortex in standing. The maximum H-reflex (H max ) and M-wave (M max ) were also measured before and immediately after 30 min of tDCS. The soleus H-reflex amplitudes became significantly larger (by 6%) ≈1 min into Active or Sham tDCS and gradually returned toward the pre-tDCS values, on average, within 15 min. With Active tDCS, the amplitude reduction from the initial increase appeared to occur more swiftly than with Sham tDCS. An acute temporary increase in the soleus H-reflex amplitude within the first minute of Active and Sham tDCS found in this study indicates a previously unreported effect of tDCS on the H-reflex excitability. The present study suggests that neurophysiological characterization of Sham tDCS effects is just as important as investigating Active tDCS effects in understanding and defining acute effects of tDCS on the excitability of spinal reflex pathways., (© 2023. The Author(s).)

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., (© 2022. The Author(s).)

After a neurological injury, people develop abnormal patterns of neural activity that limit motor recovery. Traditional rehabilitation, which concentrates on practicing impaired skills, is seldom fully effective. New targeted neuroplasticity protocols interact with the central nervous system to induce beneficial plasticity in key sites and thereby enable wider beneficial plasticity. They can complement traditional therapy and enhance recovery. However, their development and validation is difficult because many different targeted neuroplasticity protocols are conceivable, and evaluating even one of them is lengthy, laborious, and expensive. Computational models can address this problem by triaging numerous candidate protocols rapidly and effectively. Animal and human empirical testing can then concentrate on the most promising ones. Here, we simulate a neural network of corticospinal neurons that control motoneurons eliciting unilateral finger extension. We use this network to (i) study the mechanisms and patterns of cortical reorganization after a stroke; and (ii) identify and parameterize a targeted neuroplasticity protocol that improves recovery of extension torque. After a simulated stroke, standard training produced abnormal bilateral cortical activation and suboptimal torque recovery. To enhance recovery, we interdigitated standard training with trials in which the network was given feedback only from a targeted population of sub-optimized neurons. Targeting neurons in secondary motor areas on ∼20% of the total trials restored lateralized cortical activation and improved recovery of extension torque. The results illuminate mechanisms underlying suboptimal cortical activity post-stroke; they enable the identification and parameterization of the most promising targeted neuroplasticity protocols. By providing initial guidance, computational models could facilitate and accelerate the realization of new therapies that improve motor recovery., (Published by Oxford University Press on behalf of the Guarantors of Brain 2022.)

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.

Over the past half-century, the largely hardwired central nervous system (CNS) of 1970 has become the ubiquitously plastic CNS of today, in which change is the rule not the exception. This transformation complicates a central question in neuroscience: how are adaptive behaviours - behaviours that serve the needs of the individual - acquired and maintained through life? It poses a more basic question: how do many adaptive behaviours share the ubiquitously plastic CNS? This question compels neuroscience to adopt a new paradigm. The core of this paradigm is a CNS entity with unique properties, here given the name heksor from the Greek hexis. A heksor is a distributed network of neurons and synapses that changes itself as needed to maintain the key features of an adaptive behaviour, the features that make the behaviour satisfactory. Through their concurrent changes, the numerous heksors that share the CNS negotiate the properties of the neurons and synapses that they all use. Heksors keep the CNS in a state of negotiated equilibrium that enables each heksor to maintain the key features of its behaviour. The new paradigm based on heksors and the negotiated equilibrium they create is supported by animal and human studies of interactions among new and old adaptive behaviours, explains otherwise inexplicable results, and underlies promising new approaches to restoring behaviours impaired by injury or disease. Furthermore, the paradigm offers new and potentially important answers to extant questions, such as the generation and function of spontaneous neuronal activity, the aetiology of muscle synergies, and the control of homeostatic plasticity., (© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

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., (© 2021 IOP Publishing Ltd.)

Evidence that neurohormones contribute to the contralateral effects of unilateral brain injury challenges a fundamental assumption of basic neuroscience and clinical neurology., Competing Interests: JW, JC No competing interests declared, (© 2021, Wolpaw and Carp.)

Key Points: In people or animals with incomplete spinal cord injury (SCI), changing a spinal reflex through an operant conditioning protocol can improve locomotion. All previous studies conditioned the reflex during steady-state maintenance of a specific posture. By contrast, the present study down-conditioned the reflex during the swing-phase of locomotion in people with hyperreflexia as a result of chronic incomplete SCI. The aim was to modify the functioning of the reflex in a specific phase of a dynamic movement. This novel swing-phase conditioning protocol decreased the reflex much faster and farther than did the steady-state protocol in people or animals with or without SCI, and it also improved locomotion. The reflex decrease persisted for at least 6 months after conditioning ended. The results suggest that conditioning reflex function in a specific phase of a dynamic movement offers a new approach to enhancing and/or accelerating recovery after SCI or in other disorders., Abstract: In animals and people with incomplete spinal cord injury, appropriate operant conditioning of a spinal reflex can improve impaired locomotion. In all previous conditioning studies, the reflex was conditioned during steady-state maintenance of a stable posture; this steady-state protocol aimed to change the excitability of the targeted reflex pathway; reflex size gradually changed over 8-10 weeks. The present study introduces a new protocol, comprising a dynamic protocol that aims to change the functioning of the reflex pathway during a specific phase of a complex movement. Specifically, we down-conditioned the soleus H-reflex during the swing-phase of locomotion in people with hyperreflexia as a result of chronic incomplete SCI. The swing-phase H-reflex, which is absent or very small in neurologically normal individuals, is abnormally large in this patient population. The results were clear. With swing-phase down-conditioning, the H-reflex decreased much faster and farther than did the H-reflex in all previous animal or human studies with the steady-state protocol, and the decrease persisted for at least 6 months after conditioning ended. The H-reflex decrease was accompanied by improvements in walking speed and in the modulation of locomotor electromyograph activity in proximal and distal muscles of both legs. These results provide new insight into the factors controlling spinal reflex conditioning; they suggest that the conditioning protocols targeting reflex function in a specific movement phase provide a promising new opportunity to enhance functional recovery after SCI or in other disorders., (© 2019 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Throughout life, the central nervous system (CNS) interacts with the world and with the body by activating muscles and excreting hormones. In contrast, brain-computer interfaces (BCIs) quantify CNS activity and translate it into new artificial outputs that replace, restore, enhance, supplement, or improve the natural CNS outputs. BCIs thereby modify the interactions between the CNS and the environment. Unlike the natural CNS outputs that come from spinal and brainstem motoneurons, BCI outputs come from brain signals that represent activity in other CNS areas, such as the sensorimotor cortex. If BCIs are to be useful for important communication and control tasks in real life, the CNS must control these brain signals nearly as reliably and accurately as it controls spinal motoneurons. To do this, they might, for example, need to incorporate software that mimics the function of the subcortical and spinal mechanisms that participate in normal movement control. The realization of high reliability and accuracy is perhaps the most difficult and critical challenge now facing BCI research and development. The ongoing adaptive modifications that maintain effective natural CNS outputs take place primarily in the CNS. The adaptive modifications that maintain effective BCI outputs can also take place in the BCI. This means that the BCI operation depends on the effective collaboration of two adaptive controllers, the CNS and the BCI. Realization of this second adaptive controller, the BCI, and management of its interactions with concurrent adaptations in the CNS comprise another complex and critical challenge for BCI development. BCIs can use different kinds of brain signals recorded in different ways from different brain areas. Decisions about which signals recorded in which ways from which brain areas should be selected for which applications are empirical questions that can only be properly answered by experiments. BCIs, like other communication and control technologies, often face artifacts that contaminate or imitate their chosen signals. Noninvasive BCIs (e.g., EEG- or fNIRS-based) need to take special care to avoid interpreting nonbrain signals (e.g., cranial EMG) as brain signals. This typically requires comprehensive topographical and spectral evaluations. In theory, the outputs of BCIs can select a goal or control a process. In the future, the most effective BCIs will probably be those that combine goal selection and process control so as to distribute control between the BCI and the application in a fashion suited to the current action. Through such distribution, BCIs may most effectively imitate natural CNS operation. The primary measure of BCI development is the extent to which BCI systems benefit people with neuromuscular disorders. Thus, BCI clinical evaluation, validation, and dissemination is a key step. It is at the same time a complex and difficult process that depends on multidisciplinary collaboration and management of the demanding requirements of clinical studies. Twenty-five years ago, BCI research was an esoteric endeavor pursued in only a few isolated laboratories. It is now a steadily growing field that engages many hundreds of scientists, engineers, and clinicians throughout the world in an increasingly interconnected community that is addressing the key issues and pursuing the high potential of BCI technology., (© 2020 Elsevier B.V. All rights reserved.)

Objective: Brain-computer interface (BCI) technology enables people to use direct measures of brain activity for communication and control. The National Center for Adaptive Neurotechnologies and Helen Hayes Hospital are studying long-term independent home use of P300-based BCIs by people with amyotrophic lateral sclerosis (ALS). This BCI use takes place without technical oversight, and users can encounter substantial variation in their day-to-day BCI performance. The purpose of this study is to identify and evaluate features in the electroencephalogram (EEG) that correlate with successful BCI performance during home use with the goal of improving BCI for people with neuromuscular disorders., Approach: Nine people with ALS used a P300-based BCI at home over several months for communication and computer control. Sessions from a routine calibration task were categorized as successful ([Formula: see text]70%) or unsuccessful (<70%) BCI performance. The correlation of temporal and spectral EEG features with BCI performance was then evaluated., Main Results: BCI performance was positively correlated with an increase in alpha-band (8-14 Hz) activity at locations PO8, P3, Pz, and P4; and beta-band (15-30 Hz) activity at occipital locations. In addition, performance was significantly positively correlated with a positive deflection in EEG amplitude around 220 ms at frontal mid-line locations (i.e. Fz and Cz). BCI performance was negatively correlated with delta-band (1-3 Hz) activity recorded from occipital locations., Significance: These results highlight the variability found in the EEG and describe EEG features that correlate with successful BCI performance during day-to-day use of a P300-based BCI by people with ALS. These results should inform studies focused on improved BCI reliability for people with neuromuscular disorders.

The belief that the spinal cord is hardwired is no longer tenable. Like the rest of the CNS, the spinal cord changes during growth and ageing, when new motor behaviours are acquired, and in response to trauma and disease. This paper describes a new model of spinal cord function that reconciles its recently appreciated plasticity with its long-recognized reliability as the final common pathway for behaviour. According to this model, the substrate of each motor behaviour comprises brain and spinal plasticity: the plasticity in the brain induces and maintains the plasticity in the spinal cord. Each time a behaviour occurs, the spinal cord provides the brain with performance information that guides changes in the substrate of the behaviour. All the behaviours in the repertoire undergo this process concurrently; each repeatedly induces plasticity to preserve its key features despite the plasticity induced by other behaviours. The aggregate process is a negotiation among the behaviours: they negotiate the properties of the spinal neurons and synapses that they all use. The ongoing negotiation maintains the spinal cord in an equilibrium - a negotiated equilibrium - that serves all the behaviours. This new model of spinal cord function is supported by laboratory and clinical data, makes predictions borne out by experiment, and underlies a new approach to restoring function to people with neuromuscular disorders. Further studies are needed to test its generality, to determine whether it may apply to other CNS areas such as the cerebral cortex, and to develop its therapeutic implications., (© 2018 Wadsworth Center. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

People can learn over training sessions to increase or decrease sensorimotor rhythms (SMRs) in the electroencephalogram (EEG). Activity-dependent brain plasticity is thought to guide spinal plasticity during motor skill learning; thus, SMR training may affect spinal reflexes and thereby influence motor control. To test this hypothesis, we investigated the effects of learned mu (8-13 Hz) SMR modulation on the flexor carpi radialis (FCR) H-reflex in 6 subjects with no known neurological conditions and 2 subjects with chronic incomplete spinal cord injury (SCI). All subjects had learned and practiced over more than 10 < 30-min training sessions to increase (SMR-up trials) and decrease (SMR-down trials) mu-rhythm amplitude over the hand/arm area of left sensorimotor cortex with ≥80% accuracy. Right FCR H-reflexes were elicited at random times during SMR-up and SMR-down trials, and in between trials. SMR modulation affected H-reflex size. In all the neurologically normal subjects, the H-reflex was significantly larger [116% ± 6 (mean ± SE)] during SMR-up trials than between trials, and significantly smaller (92% ± 1) during SMR-down trials than between trials ( p < 0.05 for both, paired t -test). One subject with SCI showed similar H-reflex size dependence (high for SMR-up trials, low for SMR-down trials): the other subject with SCI showed no dependence. These results support the hypothesis that SMR modulation has predictable effects on spinal reflex excitability in people who are neurologically normal; they also suggest that it might be used to enhance therapies that seek to improve functional recovery in some individuals with SCI or other CNS disorders.

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., (© 2018 American Academy of Neurology.)

A brain-computer interface (BCI) is a computer-based system that acquires, analyzes, and translates brain signals into output commands in real time. Perdikis and colleagues demonstrate superior performance in a Cybathlon BCI race using a system based on "three pillars": machine learning, user training, and application. These results highlight the fact that BCI use is a learned skill and not simply a matter of "mind reading.", Competing Interests: The authors have declared that no competing interests exist.

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.

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.

Brain-Computer Interfaces (BCIs) are real-time computer-based systems that translate brain signals into useful commands. To date most applications have been demonstrations of proof-of-principle; widespread use by people who could benefit from this technology requires further development. Improvements in current EEG recording technology are needed. Better sensors would be easier to apply, more confortable for the user, and produce higher quality and more stable signals. Although considerable effort has been devoted to evaluating classifiers using public datasets, more attention to real-time signal processing issues and to optimizing the mutually adaptive interaction between the brain and the BCI are essential for improving BCI performance. Further development of applications is also needed, particularly applications of BCI technology to rehabilitation. The design of rehabilitation applications hinges on the nature of BCI control and how it might be used to induce and guide beneficial plasticity in the brain.

The rat is a commonly used model for the study of lower urinary tract function before and after spinal cord injury. We have previously reported that in unanesthetized freely moving rats, although phasic external urethral sphincter (EUS) activity (bursting) is most common during micturition, productive voiding can occur in the absence of bursting, which differs from results seen in anesthetized or unanesthetized restrained animals. The purpose of the present study was to characterize EUS behavior in unanesthetized, freely moving rats before and after mid-thoracic (T8) or thoraco-lumbar (T13-L1) spinal transection to determine how EUS behavior after spinal cord injury differs from that seen in anesthetized or unanesthetized restrained rats. Several abnormalities became evident that were comparable after transection at either level, including the following: repetitive non-voiding EUS contractions; increased prevalence, intensity, and duration of EUS bursting; decreased rate of urine evacuation during bursting; increased void size and decreased number of daily voids; shorter inter-burst silent period and increased frequency of bursting; and loss of the direct linear relationships that are evident in intact animals between void size and bursting silent period. These data suggest that transection-induced delayed initiation of EUS bursting allows co-contraction of the bladder and the EUS that prevents or limits urine evacuation, resulting in a detrusor-sphincter dyssynergia-like phenomenon. In addition, the higher-than-normal frequency at which EUS bursting occurs after transection is associated with shorter silent periods during which urine typically flows, which interferes with voiding by slowing the rate of urine evacuation. That results were comparable after either transection suggests that the central pattern generator responsible for EUS bursting is located caudal to the L1 spinal segment.

When new motor learning changes the spinal cord, old behaviors are not impaired; their key features are preserved by additional compensatory plasticity. To explore the mechanisms responsible for this compensatory plasticity, we transected the spinal dorsal ascending tract before or after female rats acquired a new behavior-operantly conditioned increase or decrease in the right soleus H-reflex-and examined an old behavior-locomotion. Neither spinal dorsal ascending tract transection nor H-reflex conditioning alone impaired locomotion. Nevertheless, when spinal dorsal ascending tract transection and H-reflex conditioning were combined, the rats developed a limp and a tilted posture that correlated in direction and magnitude with the H-reflex change. When the right H-reflex was increased by conditioning, the right step lasted longer than the left and the right hip was higher than the left; when the right H-reflex was decreased by conditioning, the opposite occurred. These results indicate that ascending sensory input guides the compensatory plasticity that normally prevents the plasticity underlying H-reflex change from impairing locomotion. They support the concept of the state of the spinal cord as a negotiated equilibrium that reflects the concurrent influences of all the behaviors in an individual's repertoire; and they support the new therapeutic strategies this concept introduces. SIGNIFICANCE STATEMENT The spinal cord provides a reliable final common pathway for motor behaviors throughout life. Until recently, its reliability was explained by the assumption that it is hardwired; but it is now clear that the spinal cord changes continually as new behaviors are acquired. Nevertheless, old behaviors are preserved. This study shows that their preservation depends on sensory feedback from the spinal cord to the brain: if feedback is removed, the acquisition of a new behavior may disrupt an old behavior. In sum, when a new behavior changes the spinal cord, sensory feedback to the brain guides further change that preserves old behaviors. This finding contributes to a new understanding of spinal cord function and to development of new rehabilitation therapies., (Copyright © 2017 the authors 0270-6474/17/378198-09$15.00/0.)

Objective: Emotion dysregulation is an important aspect of many psychiatric disorders. Brain-computer interface (BCI) technology could be a powerful new approach to facilitating therapeutic self-regulation of emotions. One possible BCI method would be to provide stimulus-specific feedback based on subject-specific electroencephalographic (EEG) responses to emotion-eliciting stimuli., Approach: To assess the feasibility of this approach, we studied the relationships between emotional valence/arousal and three EEG features: amplitude of alpha activity over frontal cortex; amplitude of theta activity over frontal midline cortex; and the late positive potential over central and posterior mid-line areas. For each feature, we evaluated its ability to predict emotional valence/arousal on both an individual and a group basis. Twenty healthy participants (9 men, 11 women; ages 22-68) rated each of 192 pictures from the IAPS collection in terms of valence and arousal twice (96 pictures on each of 4 d over 2 weeks). EEG was collected simultaneously and used to develop models based on canonical correlation to predict subject-specific single-trial ratings. Separate models were evaluated for the three EEG features: frontal alpha activity; frontal midline theta; and the late positive potential. In each case, these features were used to simultaneously predict both the normed ratings and the subject-specific ratings., Main Results: Models using each of the three EEG features with data from individual subjects were generally successful at predicting subjective ratings on training data, but generalization to test data was less successful. Sparse models performed better than models without regularization., Significance: The results suggest that the frontal midline theta is a better candidate than frontal alpha activity or the late positive potential for use in a BCI-based paradigm designed to modify emotional reactions.

The inferior olive (IO) is essential for operant down-conditioning of the rat soleus H-reflex, a simple motor skill. To evaluate the role of the IO in long-term maintenance of this skill, the H-reflex was down-conditioned over 50 days, the IO was chemically ablated, and down-conditioning continued for up to 102 more days. H-reflex size just before IO ablation averaged 62(±2 SE)% of its initial value (P < 0.001 vs. initial). After IO ablation, H-reflex size rose to 75-80% over ∼10 days, remained there for ∼30 days, rose over 10 days to above its initial value, and averaged 140(±14)% for the final 10 days of study (P < 0.01 vs. initial). This two-stage loss of down-conditioning maintenance correlated with IO neuronal loss (r = 0.75, P < 0.01) and was similar to the loss of down-conditioning that follows ablation of the cerebellar output nuclei dentate and interpositus. In control (i.e., unconditioned) rats, IO ablation has no long-term effect on H-reflex size. These results indicate that the IO is essential for long-term maintenance of a down-conditioned H-reflex. With previous data, they support the hypothesis that IO and cortical inputs to cerebellum combine to produce cerebellar plasticity that produces sensorimotor cortex plasticity that produces spinal cord plasticity that produces the smaller H-reflex. H-reflex down-conditioning appears to depend on a hierarchy of plasticity that may be guided by the IO and begin in the cerebellum. Similar hierarchies may underlie other motor learning.

Aims: In anesthetized rats, voiding is typically associated with phasic activation (bursting) of the external urethral sphincter (EUS). During spontaneous voiding in unanesthetized, unrestrained rats, EUS bursting is the most common form of EUS activity exhibited, but it is not necessary for productive voiding to occur. The aim of the present study was to determine which aspects of EUS activity contributed to void size during bursting and non-bursting voiding in conscious, freely moving rats., Methods: Female rats were implanted with electrodes adjacent to the EUS for recording electromyographic activity (EMG). EUS EMG recordings were performed during 24-hr sessions in a metabolic cage while voided urine was continuously collected and weighed., Results: Void size was positively correlated with the duration of the intra-burst silent and active periods and variables reflecting the overall intensity and duration of bursting, particularly at lower frequencies within the 3-10 Hz range of EUS bursting. In addition, void size was inversely related to the frequency of bursting and to the average EMG amplitude during voiding, both in voids with and without bursting., Conclusions: EUS bursting contributes to productive voiding when bursting is present. Lower bursting frequencies elicit more productive voiding than do higher frequencies. In the absence of bursting, the association of increased void size with smaller average EUS EMG amplitude suggests that conscious rats can perform synergic voiding (i.e., bladder contraction with EUS relaxation) that is comparable to that seen in humans and other typically non-bursting species. Neurourol. Urodynam. 35:696-702, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

We evaluated the role of the inferior olive (IO) in acquisition of the spinal cord plasticity that underlies H-reflex down-conditioning, a simple motor skill. The IO was chemically ablated before a 50-day exposure to an operant conditioning protocol that rewarded a smaller soleus H-reflex. In normal rats, down-conditioning succeeds (i.e., H-reflex size decreases at least 20%) in 80% of animals. Down-conditioning failed in every IO-ablated rat (P< 0.001 vs. normal rats). IO ablation itself had no long-term effect on H-reflex size. These results indicate that the IO is essential for acquisition of a down-conditioned H-reflex. With previous data, they support the hypothesis that IO and cortical inputs to cerebellum enable the cerebellum to guide sensorimotor cortex plasticity that produces and maintains the spinal cord plasticity that underlies the down-conditioned H-reflex. They help to further define H-reflex conditioning as a model for understanding motor learning and as a new approach to enhancing functional recovery after trauma or disease.

Objective: Brain-computer interface (BCI) technology might contribute to rehabilitation of motor function. This speculation is based on the premise that modifying the electroencephalographic (EEG) activity will modify behavior, a proposition for which there is limited empirical data. The present study asked whether learned modulation of pre-movement sensorimotor rhythm (SMR) activity can affect motor performance in normal human subjects., Approach: Eight individuals first performed a joystick-based cursor-movement task with variable warning periods. Targets appeared randomly on a video monitor and subjects moved the cursor to the target and pressed a select button within 2 s. SMR features in the pre-movement EEG that correlated with performance speed and accuracy were identified. The subjects then learned to increase or decrease these features to control a two-target BCI task. Following successful BCI training, they were asked to increase or decrease SMR amplitude in order to initiate the joystick task., Main Results: After BCI training, pre-movement SMR amplitude was correlated with performance in subjects with initial poor performance: lower amplitude was associated with faster and more accurate movement. The beneficial effect on performance of lower SMR amplitude was greater in subjects with lower initial performance levels., Significance: These results indicate that BCI-based SMR training can affect a standard motor behavior. They provide a rationale for studies that integrate such training into rehabilitation protocols and examine its capacity to enhance restoration of useful motor function.

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., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Sensorimotor cortex exerts both short-term and long-term control over the spinal reflex pathways that serve motor behaviors. Better understanding of this control could offer new possibilities for restoring function after central nervous system trauma or disease. We examined the impact of ongoing sensorimotor cortex (SMC) activity on the largely monosynaptic pathway of the H-reflex, the electrical analog of the spinal stretch reflex. In 41 awake adult rats, we measured soleus electromyographic (EMG) activity, the soleus H-reflex, and electrocorticographic activity over the contralateral SMC while rats were producing steady-state soleus EMG activity. Principal component analysis of electrocorticographic frequency spectra before H-reflex elicitation consistently revealed three frequency bands: μβ (5-30 Hz), low γ (γ1; 40-85 Hz), and high γ (γ2; 100-200 Hz). Ongoing (i.e., background) soleus EMG amplitude correlated negatively with μβ power and positively with γ1 power. In contrast, H-reflex size correlated positively with μβ power and negatively with γ1 power, but only when background soleus EMG amplitude was included in the linear model. These results support the hypothesis that increased SMC activation (indicated by decrease in μβ power and/or increase in γ1 power) simultaneously potentiates the H-reflex by exciting spinal motoneurons and suppresses it by decreasing the efficacy of the afferent input. They may help guide the development of new rehabilitation methods and of brain-computer interfaces that use SMC activity as a substitute for lost or impaired motor outputs., (Copyright © 2015 the American Physiological Society.)

People with incomplete spinal cord injury (SCI) frequently suffer motor disabilities due to spasticity and poor muscle control, even after conventional therapy. Abnormal spinal reflex activity often contributes to these problems. Operant conditioning of spinal reflexes, which can target plasticity to specific reflex pathways, can enhance recovery. In rats in which a right lateral column lesion had weakened right stance and produced an asymmetrical gait, up-conditioning of the right soleus H-reflex, which increased muscle spindle afferent excitation of soleus, strengthened right stance and eliminated the asymmetry. In people with hyperreflexia due to incomplete SCI, down-conditioning of the soleus H-reflex improved walking speed and symmetry. Furthermore, modulation of electromyographic activity during walking improved bilaterally, indicating that a protocol that targets plasticity to a specific pathway can trigger widespread plasticity that improves recovery far beyond that attributable to the change in the targeted pathway. These improvements were apparent to people in their daily lives. They reported walking faster and farther, and noted less spasticity and better balance. Operant conditioning protocols could be developed to modify other spinal reflexes or corticospinal connections; and could be combined with other therapies to enhance recovery in people with SCI or other neuromuscular disorders., (© The Author(s) 2014.)

An operant-conditioning protocol that bases reward on the electromyographic response produced by a specific CNS pathway can change that pathway. For example, in both animals and people, an operant-conditioning protocol can increase or decrease the spinal stretch reflex or its electrical analog, the H-reflex. Reflex change is associated with plasticity in the pathway of the reflex as well as elsewhere in the spinal cord and brain. Because these pathways serve many different behaviors, the plasticity produced by this conditioning can change other behaviors. Thus, in animals or people with partial spinal cord injuries, appropriate reflex conditioning can improve locomotion. Furthermore, in people with spinal cord injuries, appropriate reflex conditioning can trigger widespread beneficial plasticity. This wider plasticity appears to reflect an iterative process through which the multiple behaviors in the individual's repertoire negotiate the properties of the spinal neurons and synapses that they all use. Operant-conditioning protocols are a promising new therapeutic method that could complement other rehabilitation methods and enhance functional recovery. Their successful use requires strict adherence to appropriately designed procedures, as well as close attention to accommodating and engaging the individual subject in the conditioning process., (© 2015 Elsevier B.V. All rights reserved.)

Operant conditioning of a spinal cord reflex can improve locomotion in rats and humans with incomplete spinal cord injury. This study examined the persistence of its beneficial effects. In rats in which a right lateral column contusion injury had produced asymmetric locomotion, up-conditioning of the right soleus H-reflex eliminated the asymmetry while down-conditioning had no effect. After the 50-day conditioning period ended, the H-reflex was monitored for 100 [±9 (SD)] (range 79-108) more days and locomotion was then reevaluated. After conditioning ended in up-conditioned rats, the H-reflex continued to increase, and locomotion continued to improve. In down-conditioned rats, the H-reflex decrease gradually disappeared after conditioning ended, and locomotion at the end of data collection remained as impaired as it had been before and immediately after down-conditioning. The persistence (and further progression) of H-reflex increase but not H-reflex decrease in these spinal cord-injured rats is consistent with the fact that up-conditioning improved their locomotion while down-conditioning did not. That is, even after up-conditioning ended, the up-conditioned H-reflex pathway remained adaptive because it improved locomotion. The persistence and further enhancement of the locomotor improvement indicates that spinal reflex conditioning protocols might supplement current therapies and enhance neurorehabilitation. They may be especially useful when significant spinal cord regeneration becomes possible and precise methods for retraining the regenerated spinal cord are needed., (Copyright © 2014 the American Physiological Society.)

In normal animals, operant conditioning of the spinal stretch reflex or the H-reflex has lesser effects on synergist muscle reflexes. In rats and people with incomplete spinal cord injury (SCI), soleus H-reflex operant conditioning can improve locomotion. We studied in normal humans the impact of soleus H-reflex down-conditioning on medial (MG) and lateral gastrocnemius (LG) H-reflexes and on locomotion. Subjects completed 6 baseline and 30 conditioning sessions. During conditioning trials, the subject was encouraged to decrease soleus H-reflex size with the aid of visual feedback. Every sixth session, MG and LG H-reflexes were measured. Locomotion was assessed before and after conditioning. In successfully conditioned subjects, the soleus H-reflex decreased 27.2%. This was the sum of within-session (task dependent) adaptation (13.2%) and across-session (long term) change (14%). The MG H-reflex decreased 14.5%, due mainly to task-dependent adaptation (13.4%). The LG H-reflex showed no task-dependent adaptation or long-term change. No consistent changes were detected across subjects in locomotor H-reflexes, EMG activity, joint angles, or step symmetry. Thus, in normal humans, soleus H-reflex down-conditioning does not induce long-term changes in MG/LG H-reflexes and does not change locomotion. In these subjects, task-dependent adaptation of the soleus H-reflex is greater than it is in people with SCI, whereas long-term change is less. This difference from results in people with SCI is consistent with the fact that long-term change is beneficial in people with SCI, since it improves locomotion. In contrast, in normal subjects, long-term change is not beneficial and may necessitate compensatory plasticity to preserve satisfactory locomotion., (Copyright © 2014 the American Physiological Society.)

The external urethral sphincter muscle (EUS) plays an important role in urinary function and often contributes to urinary dysfunction. EUS study would benefit from methodology for longitudinal recording of electromyographic activity (EMG) in unanesthetized animals, but this muscle is a poor substrate for chronic intramuscular electrodes, and thus the required methodology has not been available. We describe a method for long-term recording of EUS EMG by implantation of fine wires adjacent to the EUS that are secured to the pubic bone. Wires pass subcutaneously to a skull-mounted plug and connect to the recording apparatus by a flexible cable attached to a commutator. A force transducer-mounted cup under a metabolic cage collected urine, allowing recording of EUS EMG and voided urine weight without anesthesia or restraint. Implant durability permitted EUS EMG recording during repeated (up to 3 times weekly) 24-h sessions for more than 8 wk. EMG and voiding properties were stable over weeks 2-8. The degree of EUS phasic activity (bursting) during voiding was highly variable, with an average of 25% of voids not exhibiting bursting. Electrode implantation adjacent to the EUS yielded stable EMG recordings over extended periods and eliminated the confounding effects of anesthesia, physical restraint, and the potential for dislodgment of the chronically implanted intramuscular electrodes. These results show that micturition in unanesthetized, unrestrained rats is usually, but not always, associated with EUS bursting. This methodology is applicable to studying EUS behavior during progression of gradually evolving disease and injury models and in response to therapeutic interventions., (Copyright © 2014 the American Physiological Society.)

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.

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.

Operant conditioning protocols can change spinal reflexes gradually, which are the simplest behaviors. This article summarizes the evidence supporting two propositions: that these protocols provide excellent models for defining the substrates of learning and that they can induce and guide plasticity to help restore skills, such as locomotion, that have been impaired by spinal cord injury or other disorders.

New appreciation of the adaptive capabilities of the nervous system, recent recognition that most spinal cord injuries are incomplete, and progress in enabling regeneration are generating growing interest in novel rehabilitation therapies. Here we review the 35-year evolution of one promising new approach, operant conditioning of spinal reflexes. This work began in the late 1970's as basic science; its purpose was to develop and exploit a uniquely accessible model for studying the acquisition and maintenance of a simple behavior in the mammalian central nervous system (CNS). The model was developed first in monkeys and then in rats, mice, and humans. Studies with it showed that the ostensibly simple behavior (i.e., a larger or smaller reflex) rests on a complex hierarchy of brain and spinal cord plasticity; and current investigations are delineating this plasticity and its interactions with the plasticity that supports other behaviors. In the last decade, the possible therapeutic uses of reflex conditioning have come under study, first in rats and then in humans. The initial results are very exciting, and they are spurring further studies. At the same time, the original basic science purpose and the new clinical purpose are enabling and illuminating each other in unexpected ways. The long course and current state of this work illustrate the practical importance of basic research and the valuable synergy that can develop between basic science questions and clinical needs.

When new motor learning changes neurons and synapses in the spinal cord, it may affect previously learned behaviors that depend on the same spinal neurons and synapses. To explore these effects, we used operant conditioning to strengthen or weaken the right soleus H-reflex pathway in rats in which a right spinal cord contusion had impaired locomotion. When up-conditioning increased the H-reflex, locomotion improved. Steps became longer, and step-cycle asymmetry (i.e., limping) disappeared. In contrast, when down-conditioning decreased the H-reflex, locomotion did not worsen. Steps did not become shorter, and asymmetry did not increase. Electromyographic and kinematic analyses explained how H-reflex increase improved locomotion and why H-reflex decrease did not further impair it. Although the impact of up-conditioning or down-conditioning on the H-reflex pathway was still present during locomotion, only up-conditioning affected the soleus locomotor burst. Additionally, compensatory plasticity apparently prevented the weaker H-reflex pathway caused by down-conditioning from weakening the locomotor burst and further impairing locomotion. The results support the hypothesis that the state of the spinal cord is a "negotiated equilibrium" that serves all the behaviors that depend on it. When new learning changes the spinal cord, old behaviors undergo concurrent relearning that preserves or improves their key features. Thus, if an old behavior has been impaired by trauma or disease, spinal reflex conditioning, by changing a specific pathway and triggering a new negotiation, may enable recovery beyond that achieved simply by practicing the old behavior. Spinal reflex conditioning protocols might complement other neurorehabilitation methods and enhance recovery.

Introduction: Operant conditioning can gradually change the human soleus H-reflex. The protocol conditions the reflex near M-wave threshold. In this study we examine its impact on the reflexes at other stimulus strengths., Methods: H-reflex recruitment curves were obtained before and after a 24-session exposure to an up-conditioning (HRup) or a down-conditioning (HRdown) protocol and were compared., Results: In both HRup and HRdown subjects, conditioning affected the entire H-reflex recruitment curve. In 5 of 6 HRup and 3 of 6 HRdown subjects, conditioning elevated (HRup) or depressed (HRdown), respectively, the entire curve. In the other HRup subject or the other 3 HRdown subjects, the curve was shifted to the left or to the right, respectively., Conclusions: H-reflex conditioning does not simply change the H-reflex to a stimulus of particular strength; it also changes the H-reflexes to stimuli of different strengths. Thus, it is likely to affect many actions in which this pathway participates., (Copyright © 2012 Wiley Periodicals, Inc.)