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 ...

Stratton VA Medical Center

State University of New York at Albany

Nothing either good or bad but action makes it so.

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. 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.

Why New Spinal Cord Plasticity Does Not Disrupt Old Motor Behaviors.

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.

The negotiated equilibrium model of spinal cord function.

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.

Retraining Reflexes: Clinical Translation of Spinal Reflex Operant Conditioning.

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 ( < 0.05 for both, paired -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.

Effects of Sensorimotor Rhythm Modulation on the Human Flexor Carpi Radialis H-Reflex.

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.

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

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.

H-reflex conditioning during locomotion in people with spinal cord injury.

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.

Brain-computer interfaces: Definitions and principles.

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.

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

Evidence that neurohormones contribute to the contralateral effects of unilateral brain injury challenges a fundamental assumption of basic neuroscience and clinical neurology.

A major new dimension in the problem of brain injury.

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.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.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.This new method has numerous potential clinical, scientific, and industrial applications.

Jonathan R. Wolpaw

National Center for Adaptive Neurotechnologies

Stratton VA Medical Center

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

Jonathan R. Wolpaw

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}National Center for Adaptive Neurotechnologies

Stratton VA Medical Center

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

National Center for Adaptive Neurotechnologies