NCAN continues a 45-year research program that exemplifies and has helped to drive recognition that the CNS is plastic through life. NCAN has produced what is, to our knowledge, the first conceptual paradigm that explains how skills are acquired and maintained in a ubiquitously plastic CNS. This paradigm clarifies the goal of neurorehabilitation and provides a comprehensive strategic framework for maximizing recovery.
NCAN includes technology development, basic/preclinical animal studies, and basic/ translational human studies. These elements comprise a highly iterative and synergistic program in which they complement and benefit each other. An investigator, postdoc, or student often participates in several elements and thereby gains perspective and experience that generates new ideas and drives further progress. Animal research guides clinical translation and clinical results lead to new animal research, all within the same research program.
The NCAN staff has deep understanding and broad experience in basic neuroscience, signal analysis, software engineering, and clinical research. Our collaborators further augment these attributes. All our endeavors combine close attention to CNS anatomy and physiology with realistic engagement of engineering principles and methods. In the new multidisciplinary field of neurotechnology, such a well-integrated multidisciplinary team facilitates advances that would otherwise be extremely difficult or simply not achievable.
NCAN creates methods, protocols, and systems that are robust, applicable to scientific problems and clinical needs, and accessible to other researchers. We focus on quantitative measures that directly reflect CNS functions, and on creating systems that are reliable across days, months, and years. These systems have provided unprecedented insights into CNS plasticity, and they support initial testing of new therapies. We provide system software, along with hardware specifications and associated training, to other researchers.
NCAN Research Comprises Three Technology Research & Development Projects (TRDs)
TRD1: Noninvasive Combined-Therapy Protocols in Humans
TRD1 has two aims. Aim 1 is to develop and validate a new BCI2000-based combined-therapy platform for humans that can parameterize and synchronize several generalized and/or targeted plasticity therapies with each other and with skill-specific practice. Aim 2 is to use this new platform to evaluate the efficacy of combined therapies. It will begin by combining clinically successful, mechanistically-defined, noninvasive targeted-plasticity therapies developed by NCAN staff members – H-reflex operant conditioning (HROC), motor-evoked potential (MEP) operant conditioning, and paired associative stimulation (PAS) (Wolpaw, 1987; Chen et al., 2006e; Thompson et al., 2013b; Ingram et al., 2017; Jo and Perez, 2020). We will test combinations that simultaneously target beneficial plasticity to two critical sites in a heksor damaged by spinal cord injury, thereby producing synergy between them. We expect the result to be clinical benefit exceeding that of either alone or both applied separately. We will also assess the extra benefits of synchronizing combined therapy with skill-specific practice (e.g., Thompson and Wolpaw, 2021). We will also try to further enhance efficacy by adding a generalized-plasticity therapy (i.e., 4-aminopyridine), which we have already shown to increase the beneficial effects of PAS alone (Chen et al., 2024, in review). With our CPs, we will assess the clinical range of these combined protocols and develop the new combined-therapy platform into a robust system suitable for clinical dissemination.
TRD2: Creating and Exploring Combined-Therapy Protocols in Animals
TRDs 1&2 continues the iterative interaction of animal and human research that has proved so productive over the past 20 years. TRD2 evaluates in rats with defined CNS lesions the effects of promising combined therapies. In parallel with TRD1 Aim 1, TRD2 Aim 1 is to create a BCI2000-based combined-therapy platform for freely-moving chronically-implanted rats. It will parameterize and synchronize several therapies with each other and with skill-specific practice. Development will start from Elizan, the 24/7 animal platform that we used for 30 years to study H-reflex conditioning (HROC) and show its therapeutic value (e.g., Wang et al., 2024; Chen et al., 2014c). We recently used it to establish paired-associative stimulation (PAS) in a rat model (Gaikwad et al., 2024, in review) TRD2 Aim 2 is to test combined therapies that produce beneficial plasticity at several sites and/or by several mechanisms in a heksor damaged by spinal cord injury, thus creating synergies that enhance benefits. It will explore the physiological, anatomical, and molecular biological mechanisms, and identify combined protocols for human testing. With our CPs, we will assess in humans those that have proved successful in animals.
TRD3: ECoG/SEEG-based Combined-Therapy Protocols for Cognitive/Behavioral Disorders
Like sensorimotor disorders, cognitive/behavioral disorders may result from an unsatisfactory negotiated equilibrium in the underlying neural circuitry. Post-traumatic stress disorder (PTSD), can be understood as the product of a pathological heksor that interferes with other behaviors by creating an unsatisfactory equilibrium. Appropriate direct electrical stimulation (DES) could target beneficial plasticity in the circuitry comprising the PTSD heksor and thereby enable wider beneficial plasticity that restores a more satisfactory negotiated equilibrium. Beneficial DES-based plasticity requires the ability to define appropriate DES parameters. This has been hampered by the long delay between DES and its behavioral effect (e.g., fear reduction). In the past decade, TRD3 has built technology for solving this problem by studying patients with temporary ECoG/sEEG implants prior to surgery. We used local field potentials to define the relevant circuitry and appropriate parameters. We will now incorporate these new methods in a BCI2000-based clinical system that interacts with the CNS to change circuitry in real-time. With the new ability to parameterize DES, TRD3 will relate DES behavioral/physiological effects to later benefits. This will produce a set of amygdala-mediated measures that we will validate in ECoG/sEEG monitored patients and use to assess and address amygdala-circuitry imbalances underlying a range of disorders. The results should enhance understanding of amygdala-mediated functions; and the new clinical system should enable scientists and clinicians to develop and apply new neuromodulatory therapies for devastating chronic disorders such as PTSD.
These three Research Projects involve a wide range of different approaches that can be grouped into six Research Areas based on how they use adaptive neurotechnologies to help people. You can learn more about these six Research Areas by clicking here.
In addition to its NCAN-based endeavors, each TRD has several Collaborative Projects with funded investigators elsewhere and a number of simpler Service Projects. You can learn more about Collaborative and Service Projects and how to apply to engage in one of these Projects by clicking here. You can learn more about our current Collaborative Projects by clicking here.
