NCAN’s Ten Most Distinctive and Important Achievements

1. A New Conceptual Paradigm for Skill Acquisition and Maintenance. Recent recognition that the CNS changes continually through life complicates a key question in neuroscience: how are adaptive behaviors (i.e., skills) acquired and maintained? To answer it, NCAN developed the heksor/negotiated equilibrium paradigm summarized above (Wolpaw, 2010, 2018a; Wolpaw and Kamesar, 2022). It is supported by animal and human studies, explains otherwise inexplicable results, and offers new answers to questions such as the origin and function of spontaneous neuronal activity, the etiology of muscle synergies, and the control of homeostatic plasticity.


2. Triple-Strategy Therapeutic Framework. NCAN’s new paradigm clarifies the goal of rehabilitation and defines new therapeutic strategies. When CNS damage disrupts skills, the primary goal is to enable damaged heksors to repair themselves. The standard strategy, skill-specific practice, is often inadequate. As described above and in Figure 3, two new strategies enhance practice. Together, the strategies produce recovery far superior to that produced by practice alone (e.g., Thompson et al., 2013b; Jo and Perez, 2020; Chen et al., 2024, in review).


3. BCI2000 is a general-purpose, open-source, brain-computer interface software platform that acquires and analyzes physiological and other signals from >50 devices, interfaces with many presentation packages and stimulators, enables prototyping of lab and clinical studies, has >11,000 users, and has supported the studies in 2,500 papers. NCAN assists labs in using it for their needs and as infrastructure for multicenter research.


4. Therapeutic Use of Operant Conditioning of H-Reflexes and Other Evoked Potentials. NCAN staff were the first to demonstrate H-reflex operant conditioning and show its therapeutic value in animals and humans (Wolpaw, 1987; Chen et al., 2006e; Thompson et al., 2013b). We recently reported operant conditioning of the corticospinal motor evoked potential (MEP) and cutaneous reflexes, and their efficacy in people with stroke or multiple sclerosis (Thompson et al., 2022, 2018b). We found that conditioning in a specific locomotor phase produces faster and greater H-reflex change (Thompson and Wolpaw, 2021). Through courses, hands-on workshops, and visits to NCAN, we have enabled others to master and apply these new therapies.


5. An Operant Conditioning System for Clinical Use. Our CP with BioCircuit Tech translated our lab operant conditioning system into a compact, automated system for clinical research and practice suitable for commercialization. (Hill et al., 2022; McKinnon et al., 2023). We plan to extend this system to support in-home conditioning, thereby reducing clinical visits and costs, and potentially increasing therapeutic efficacy.


6. A system for 24/7 monitoring & stimulation in rats. The BCI2000-based Elizan system supports long-term (>1 yr) 24/7 monitoring (EMG, EEG, ECoG) and stimulation (e.g., operant conditioning) in chronically-implanted freely moving animals. It supported the work leading to the new paradigm described above and the therapies based on it (e.g., Chen et al., 2006e; Wang et al., 2024). We help others to use Elizan for their own work.


7. A resource center for electrophysiological studies in patients. NCAN helps other groups implement BCI2000- based studies in clinical settings. NCAN also connects investigators using BCI2000 in specific patient populations or animal models to form consortia and develop joint projects. In the past year alone, these groups applied for >$50 million in NIH funding. They have received $13.5 million to date.


8. A rapid safe tool for mapping cortical function. NCAN created BCI2000-based software to map cortical function from ECoG/sEEG signals at bedside or in the operating room (Brunner et al., 2009; de Pesters et al., 2016; Taplin et al., 2016). Its results equal those of electrical stimulation mapping, in much less time and without seizure risk. We licensed it to a company that developed it into a product that passed FDA 510k review in 2020.


9. Mapping language under general anesthesia. NCAN technology for mapping expressive and receptive language function under general anesthesia is now undergoing clinical validation (de Pesters et al., 2016; Nourmohammadi et al., 2023). Once validated, it should enhance patient monitoring for many surgical procedures.


10. Comprehensive course in Adaptive Neurotechnologies. It covers: neuroscience and engineering principles; theory and applications of these technologies; translation (clinical, ethical, legal, regulatory, intellectual property, reimbursement, commercialization issues); hands-on training in designing and using these technologies; and case studies of specific technologies. Participant feedback has been outstanding. The 42 lectures (92 hrs) are on the NCAN website. This core curriculum serves our many topic-specific workshops and symposia.


References

Brunner, P., Ritaccio, A. L., Lynch, T. M., Emrich, J. F., Wilson, J. A., Williams, J. C., Aarnoutse, E. J., Ramsey, N. F., Leuthardt, E. C., Bischof, H., and Schalk, G., (2009). A practical procedure for real-time functional mapping of eloquent cortex using electrocorticographic signals in humans. Epilepsy Behav 15(3):278–286. PMCID: PMC2754703.
Chen, Y., Chen, X. Y., Jakeman, L. B., Chen, L., Stokes, B. T., and Wolpaw, J. R., (2006e). Operant conditioning of H-reflex can correct a locomotor abnormality after spinal cord injury in rats. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 26(48):12537–12543. ISSN 1529-2401. PMCID: PMC6674902.
de Pesters, A., Taplin, A. M., Adamo, M. A., Ritaccio, A. L., and Schalk, G., (2016). Electrocorticographic mapping of expressive language function without requiring the patient to speak: A report of three cases. Epilepsy & Behavior Case Reports 6:13–18. ISSN 2213-3232. PMCID: PMC4925928.
Hill, N. J., Gupta, D., Eftekhar, A., Brangaccio, J. A., Norton, J. J. S., McLeod, M., Fake, T., Wolpaw, J. R., and Thompson, A. K., (2022). The Evoked Potential Operant Conditioning System (EPOCS): A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders. Journal of Visualized Experiments (186):63736. ISSN 1940-087X.
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McKinnon, M. L., Hill, N. J., Carp, J. S., Dellenbach, B., and Thompson, A. K., (2023). Methods for automated delineation and assessment of EMG responses evoked by peripheral nerve stimulation in diagnostic and closed-loop therapeutic applications. Journal of Neural Engineering 20(4). ISSN 1741-2552. PMCID: PMC10445400.
Nourmohammadi, A., Swift, J. R., de Pesters, A., Guay, C. S., Adamo, M. A., Dalfino, J. C., Ritaccio, A. L., Schalk, G., and Brunner, P., (2023). Passive functional mapping of receptive language cortex during general anesthesia using electrocorticography. Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology 147:31–44. ISSN 1872-8952. PMCID: PMC10267852.
Taplin, A. M., de Pesters, A., Brunner, P., Hermes, D., Dalfino, J. C., Adamo, M. A., Ritaccio, A. L., and Schalk, G., (2016). Intraoperative mapping of expressive language cortex using passive real-time electrocorticography. Epilepsy & Behavior Case Reports 5:46–51. ISSN 2213-3232. PMCID: PMC4922734.
Thompson, A. K. and Wolpaw, J. R., (2021). H-reflex conditioning during locomotion in people with spinal cord injury. The Journal of Physiology 599(9):2453–2469. ISSN 1469-7793. PMCID: PMC7241089.
Thompson, A. K., Pomerantz, F. R., and Wolpaw, J. R., (2013b). Operant Conditioning of a Spinal Reflex Can Improve Locomotion after Spinal Cord Injury in Humans. The Journal of Neuroscience 33(6):2365–2375. ISSN 0270-6474, 1529-2401. PMCID: PMC3579496.
Thompson, A. K., Favale, B. M., Velez, J., and Falivena, P., (2018b). Operant Up-Conditioning of the Tibialis Anterior Motor-Evoked Potential in Multiple Sclerosis: Feasibility Case Studies. Neural Plasticity 2018:1–10. ISSN 2090-5904, 1687-5443. PMCID: PMC6079394.
Thompson, A. K., Gill, C. R., Feng, W., and Segal, R. L., (2022). Operant down-conditioning of the soleus H-reflex in people after stroke. Frontiers in Rehabilitation Sciences 3:859724. ISSN 2673-6861. PMCID: PMC9397863.
Wang, Y., Chen, Y., Chen, L., Herron, B. J., Chen, X. Y., and Wolpaw, J. R., (2024). Motor learning changes the axon initial segment of the spinal motoneuron. The Journal of Physiology 602(9):2107–2126. ISSN 1469-7793. PMCID: PMC11196014.
Wolpaw, J. R. and Kamesar, A., (2022). Heksor: The central nervous system substrate of an adaptive behaviour. The Journal of Physiology 600(15):3423–3452. ISSN 1469-7793. PMCID: PMC9545119.
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Wolpaw, J. R., (2018a). The negotiated equilibrium model of spinal cord function. The Journal of Physiology 596(16):3469–3491. ISSN 1469-7793. PMCID: PMC6092289.