02512nas a2200193   4500008004100000022001400041245009200055210006900147260001600216300002200232520181300254100002402067700002202091700002102113700002202134700001902156700002502175856011802200       2026                        eng d  a1552-684400aNeurorehabilitation in the 21st Century: New Science, New Strategies, New Expectations.0 aNeurorehabilitation in the 21st Century New Science New Strategi  c2026 Feb 16  a154596832514123093 a<p>Background: Neurorehabilitation is among the most vibrant areas of biomedical research. Its main strategy has been skill-specific practice, which often fails to produce adequate recovery. Now, new recognition of central nervous system (CNS) plasticity, new understanding of skills, and new technologies provide new strategies that enhance the efficacy of practice. Objectives: The substrate of a skill is a network of neurons and synapses that extends from cortex to spinal cord and is now called a heksor. A heksor changes continually to maintain the key features of its skill, the attributes that make the skill satisfactory. Muscle activity and kinematics may change; key features are maintained. Heksors share neurons and synapses. Through their concurrent changes, they keep the CNS in a negotiated equilibrium that enables each to maintain its skill. When CNS damage occurs, the goal is to enable damaged heksors to repair themselves. Results: Two new strategies enhance the efficacy of skill-specific practice. One increases plasticity. A damaged heksor shapes the additional plasticity through practice. The other targets beneficial plasticity to a critical site in a damaged heksor. This improves practice, enabling the heksor to achieve wider beneficial plasticity. In animals and humans, protocols that combine these strategies with practice enhance lasting recovery. Conclusions: The challenge is to develop, optimize, and validate these combined protocols. Computational modeling can accelerate the process. Controlled trials and comprehensive outcome assessments are essential. Pre-morbid factors and physiological measures may identify biomarkers that can predict efficacy or guide patient-specific protocol design. Many combined protocols will be noninvasive and suitable for home use.</p>1 aWolpaw, Jonathan, R1 aThompson, Aiko, K1 aPerez, Monica, A1 aNorman, Sumner, L1 aOudega, Martin1 aWinstein, Carolee, J  uhttps://www.neurotechcenter.org/publications/2026/neurorehabilitation-21st-century-new-science-new-strategies-new02320nas a2200157   4500008004100000245006500041210006500106300001600171490000800187520175900195100002501954700002101979700002302000700002402023856011502047       2025                        eng d00aBidirectional locomotion induces asymmetric limb adaptations0 aBidirectional locomotion induces asymmetric limb adaptations  a1774–17840 v1343 aHumans can acquire and maintain motor skills throughout their lives through motor learning. Motor learning and skill acquisition are essential for rehabilitation after 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 has been extensively studied with 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 min of forward walking (FW), followed by four 5-min blocks of BDW with a 1-min passive rest in between blocks, and ending with another 2-min block of FW. We recorded body kinematics and ground reaction forces throughout the experiment. Participants modified both temporal (interlimb phasing, double stance duration) and spatial (step length) aspects of gait to meet the mechanical demands of backward dual walking (BDW). Adaptation occurred rapidly, with bilateral reductions in step length, adjustments in stance and swing phase timing, alterations in interlimb phasing, and decreased double stance duration in the limb walking backward. Notably, only the backward-walking limb (right) exhibited persistent aftereffects upon return to FW. These results demonstrate that BDW elicits adaptations in both spatial and temporal gait parameters, with transient aftereffects consistent with short-term motor learning. To our knowledge, this is the first report characterizing such spatiotemporal adaptations during BDW.1 aHardesty, Russell, L1 aMojtabavi, Helia1 aGemoets, Darren, E1 aWolpaw, Jonathan, R  uhttps://www.neurotechcenter.org/publications/2025/bidirectional-locomotion-induces-asymmetric-limb-adaptations02933nas a2200181   4500008004100000245013500041210006900176300001100245490000700256520224100263100001702504700002102521700002102542700002202563700002402585700001702609856012502626       2025                        eng d00aFrequency dependence of cortical somatosensory evoked response to peripheral nerve stimulation with controlled afferent excitation0 aFrequency dependence of cortical somatosensory evoked response t  a0260350 v223 aObjective: H-reflex targeted neuroplasticity (HrTNP) protocols comprise a promising rehabilitation approach to improve motor function after brain or spinal injury. In this operant conditioning protocol, concurrent measurement of cortical responses, such as somatosensory evoked potentials (SEPs), would be useful for examining supraspinal involvement and neuroplasticity mechanisms. To date, this potential has not been exploited. However, the stimulation parameters used in the HrTNP protocol deviate from the classically recommended settings for SEP measurements. Most notably, it demands a much longer pulse width, higher stimulation intensity, and lower frequency than traditional SEP settings. In this paper, we report SEP measurements performed within the HrTNP stimulation parameter constraints, specifically characterizing the effect of stimulation frequency.
Approach: SEPs were acquired for tibial nerve stimulation at three stimulation frequencies (0.2, 1, and 2 Hz) in 13 subjects while maintaining the afferent volley by controlling the direct soleus muscle response via the Evoked Potential Operant Conditioning System. The amplitude and latency of the short-latency P40 and mid-latency N70 SEP components were measured at the central scalp region using non-invasive electroencephalography.
Main results: As frequency rose from 0.2 Hz, P40 amplitude and latency did not change. In contrast, N70 amplitude decreased significantly (39% decrease at 1 Hz, and 57% decrease at 2 Hz), presumably due to gating effects. N70 latency was not affected. Across all three frequencies, N70 amplitude increased significantly with stimulation intensity and correlated with M-wave amplitude.
Significance: We assess SEPs within an HrTNP protocol, focusing on P40 and N70, elicited with controlled afferent excitation at three stimulation frequencies. HrTNP conditioning protocols show promise for enhancing motor function after brain and spinal injuries. While SEPs offer valuable insights into supraspinal involvement, the stimulation parameters in HrTNP often differ from standard SEP measurement protocols. We address these deviations and provide recommendations for effectively integrating SEP assessments into HrTNP studies.


1 aGupta, Disha1 aBrangaccio, Jodi1 aMojtabavi, Helia1 aCarp, Jonathan, S1 aWolpaw, Jonathan, R1 aHill, Jeremy  uhttps://www.neurotechcenter.org/publications/2025/frequency-dependence-cortical-somatosensory-evoked-response-peripheral00572nas a2200157   4500008004100000022001400041245007100055210006900126260001600195300001200211490000800223100002500231700002100256700002400277856011300301       2025                        eng d  a1522-159800aSpinal reflexes: a potential target for treating hemiparetic gait.0 aSpinal reflexes a potential target for treating hemiparetic gait  c2025 Jul 01  a290-2910 v1341 aHardesty, Russell, L1 aMojtabavi, Helia1 aWolpaw, Jonathan, R  uhttps://www.neurotechcenter.org/publications/2025/spinal-reflexes-potential-target-treating-hemiparetic-gait02058nas a2200157   4500008004100000022001400041245006600055210006500121260001600186520149000202100002501692700002101717700002301738700002401761856011501785       2024                        eng d  a2692-820500aBidirectional locomotion induces unilateral limb adaptations.0 aBidirectional locomotion induces unilateral limb adaptations  c2024 Aug 233 a<p>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.</p>1 aHardesty, Russell, L1 aMotjabavi, Helia1 aGemoets, Darren, E1 aWolpaw, Jonathan, R  uhttps://www.neurotechcenter.org/publications/2024/bidirectional-locomotion-induces-unilateral-limb-adaptations03911nas a2200361   4500008004100000022001400041245007800055210006900133260001300202300001400215490000800229520287700237653001203114653001303126653002503139653001003164653002603174653001303200653001303213653000903226653001803235653002403253653000903277653002503286653001603311100001303327700001303340700001303353700002103366700002203387700002403409856011603433       2024                        eng d  a1469-779300aMotor learning changes the axon initial segment of the spinal motoneuron.0 aMotor learning changes the axon initial segment of the spinal mo  c2024 May  a2107-21260 v6023 a<p>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.</p>10aAnimals10aAnkyrins10aAxon Initial Segment10aAxons10aConditioning, Operant10aH-Reflex10aLearning10aMale10aMotor Neurons10aNeuronal Plasticity10aRats10aRats, Sprague-Dawley10aSpinal Cord1 aWang, Yu1 aChen, Yi1 aChen, Lu1 aHerron, Bruce, J1 aChen, Xiang, Yang1 aWolpaw, Jonathan, R  uhttps://www.neurotechcenter.org/publications/2024/motor-learning-changes-axon-initial-segment-spinal-motoneuron02285nas a2200253   4500008004100000022001400041245007600055210006900131260001200200300001400212490000800226520146600234653001001700653002901710653001301739653001101752653002101763653002201784653004401806100002001850700002401870700002201894856011501916       2023                        eng d  a1432-110600aEffects of active and sham tDCS on the soleus H-reflex during standing.0 aEffects of active and sham tDCS on the soleus Hreflex during sta  c06/2023  a1611-16220 v2413 a<p>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) and M-wave (M) 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.</p>10aAdult10aEvoked Potentials, Motor10aH-Reflex10aHumans10aMuscle, Skeletal10aStanding Position10aTranscranial Direct Current Stimulation1 aMcCane, Lynn, M1 aWolpaw, Jonathan, R1 aThompson, Aiko, K  uhttps://www.neurotechcenter.org/publications/2023/effects-active-and-sham-tdcs-soleus-h-reflex-during-standing02579nas a2200289   4500008004100000022001400041245014200055210006900197260001200266300001400278490000800292520157400300653003401874653003001908653002701938653001101965653002201976653001101998100002802009700001602037700002502053700002102078700002102099700002402120700002402144856012102168       2023                        eng d  a1432-145900aTowards clinical application of implantable brain-computer interfaces for people with late-stage ALS: medical and ethical considerations.0 aTowards clinical application of implantable braincomputer interf  c03/2023  a1323-13360 v2703 a<p>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.</p>10aAmyotrophic Lateral Sclerosis10abrain-computer interfaces10aElectroencephalography10aHumans10aSelf-Help Devices10aSpeech1 aVansteensel, Mariska, J1 aKlein, Eran1 avan Thiel, Ghislaine1 aGaytant, Michael1 aSimmons, Zachary1 aWolpaw, Jonathan, R1 aVaughan, Theresa, M  uhttps://www.neurotechcenter.org/publications/2023/towards-clinical-application-implantable-brain-computer-interfaces03130nas a2200313   4500008004100000022001400041245013900055210006900194260001500263520206900278653002002347653002602367653002102393653002202414653001302436653001102449653002702460653002502487100001702512700001702529700001902546700002402565700002302589700002102612700001402633700002402647700002202671856012302693       2022                        eng d  a1940-087X00aThe Evoked Potential Operant Conditioning System (EPOCS): A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders.0 aEvoked Potential Operant Conditioning System EPOCS A Research To  c2022 08 253 a<p>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.</p>10aChronic Disease10aConditioning, Operant10aElectromyography10aEvoked Potentials10aH-Reflex10aHumans10aNeuromuscular Diseases10aSpinal Cord Injuries1 aHill, Jeremy1 aGupta, Disha1 aEftekhar, Amir1 aBrangaccio, Jodi, A1 aNorton, James, J S1 aMcLeod, Michelle1 aFake, Tim1 aWolpaw, Jonathan, R1 aThompson, Aiko, K  uhttps://www.neurotechcenter.org/publications/2022/evoked-potential-operant-conditioning-system-epocs-research-tool-and02437nas a2200241   4500008004100000022001400041245007500055210006900130260001200199300001400211490000800225520167700233653003001910653001201940653002701952653001101979653002401990653001302014653001302027100002402040700001802064856011302082       2022                        eng d  a1469-779300aHeksor: the central nervous system substrate of an adaptive behaviour.0 aHeksor the central nervous system substrate of an adaptive behav  c08/2022  a3423-34520 v6003 a<p>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.</p>10aAdaptation, Psychological10aAnimals10acentral nervous system10aHumans10aNeuronal Plasticity10aPlastics10aSynapses1 aWolpaw, Jonathan, R1 aKamesar, Adam  uhttps://www.neurotechcenter.org/publications/2022/heksor-central-nervous-system-substrate-adaptive-behaviour01696nas a2200289   4500008004100000022001400041245006300055210006000118260001600178490000700194520079100201653003000992653001701022653002701039653003001066653001101096653001001107653002301117653002001140100002301160700002201183700002201205700002201227700002401249700002401273856010901297       2021                        eng d  a1741-255200aBrain-computer interface-based assessment of color vision.0 aBraincomputer interfacebased assessment of color vision  c2021 Nov 260 v183 a<p>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.</p>10abrain-computer interfaces10aColor Vision10aElectroencephalography10aEvoked Potentials, Visual10aHumans10aLight10aPhotic Stimulation10aResearch Design1 aNorton, James, J S1 aDiRisio, Grace, F1 aCarp, Jonathan, S1 aNorton, Amanda, E1 aKochan, Nicholas, S1 aWolpaw, Jonathan, R  uhttps://www.neurotechcenter.org/publications/2021/brain-computer-interface-based-assessment-color-vision02570nas a2200325   4500008004100000022001400041245013800055210006900193260001200262300001100274490000800285520150800293653002601801653002601827653001601853653001301869653001101882653003101893100002001924700002301944700002001967700002001987700001802007700002302025700001902048700001902067700002402086700001902110856011502129       2020                        eng d  a1873-423500aBreathable, large-area epidermal electronic systems for recording electromyographic activity during operant conditioning of H-reflex.0 aBreathable largearea epidermal electronic systems for recording   c10/2020  a1124040 v1653 a<p>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.</p>10aBiosensing Techniques10aConditioning, Operant10aElectronics10aH-Reflex10aHumans10aReproducibility of Results1 aKwon, Young-Tae1 aNorton, James, J S1 aCutrone, Andrew1 aLim, Hyo-Ryoung1 aKwon, Shinjae1 aChoi, Jeongmoon, J1 aKim, Hee, Seok1 aJang, Young, C1 aWolpaw, Jonathan, R1 aYeo, Woon-Hong  uhttps://www.neurotechcenter.org/publications/2020/breathable-large-area-epidermal-electronic-systems-recording