(Photo Credit: University of Illinois Urbana-Champaign)
NIH R01
Abstract
The emergence of abnormal movement synergies following a stroke presents a major limitation to the recovery of independent function by constraining voluntary movements to stereotypical muscle coactivation patterns. The resulting expression of the flexion synergy limits arm/hand function, like reaching and hand opening; and has also been reported to be linked to hyperactive stretch reflexes or spasticity. Previous studies found that flexion synergy and spasticity are associated with the recruitment of contralesional descending cortico- bulbospinal pathways. However, how the somatosensory system adapts to this change in the use of motor pathways and the role of adaptive sensory feedback to the abnormal motor control of the paretic arm remain largely unknown. The ascending sensory pathways that convey somatosensation from the paretic arm project contralaterally to the primary sensory cortex in the lesioned hemisphere. Our preliminary data, however, suggests that, in individuals that express the flexion synergy and spasticity, this sensory information is subsequently transferred to the contralesional hemisphere, a process that may support the manifestation of the abnormal movement patterns in hemiparetic stroke. The overall goal of the proposed research is to examine the pathophysiology of this maladaptive hemispheric somatosensory “shift” and its relationship to the upper limb motor impairments following a hemiparetic stroke. The results will lead to a greater understanding of abnormal limb synergies and spasticity by closing the sensorimotor loop, which should provide a novel means by which to therapeutically prevent and mitigate the emergence and expression of upper limb motor impairments, following a stroke. The proposed research aims to test the following key hypotheses in our specific aims: Following a unilateral motor stroke, a hemispheric shift in somatosensory processing provides sensory feedback to support the maladaptive hemispheric shift in the motor system. This adaptive sensory shift likely not only supports the adaptive contralesional control of volitional movement that is associated with the expression of the flexion synergy (Aim 1), but also affects the transcortical loop of the stretch reflex that is related to the hyperactive stretch reflexes (or spasticity) and the increased onset delay of the long-latency stretch reflex (Aim 2). Furthermore, the hemispheric sensory shift, as a result of neuroplasticity in an injured brain, can occur in the absence of motor output; and this sensory shift can indicate the extent of motor deficits (Aim 3). By testing these hypotheses, the proposed research will improve our understanding of the role of sensory feedback in post-stroke motor impairments. This should allow for the determination of motor deficits from a new sensory perspective for more impaired individuals who have difficulty performing motor tasks. Furthermore, the knowledge gained in this study will facilitate the future development of targeted, hypothesis-driven therapeutical interventions that aim at reducing maladaptive cross-hemispheric sensory-motor connectivity during recovery thus, facilitating motor recovery in more impaired individuals.
NSF Career
Abstract
The goal of this project is to advance the scientific study of brain functional changes after a stroke and pioneer a tailored rehabilitation strategy that fits each individual’s needs. Movement impairments following a stroke are a major cause of adult disability in this country. The routine treatment is not yet optimal for every individual due to a lack of sufficient understanding of brain functional changes to inform clinical practice. This project seeks to combine different imaging methods to guide electrical stimulation to the brain that improves the recovery of movement. The outcomes of this project have the potential to advance stroke or brain injury research broadly to help over half a million people who undergo rehabilitation each year. This will reduce the healthcare and nursing costs for long-term disability caused by stroke and other similar brain injuries. Through education activities in this project, a multi-disciplinary research-education eco-system will be built to connect engineering students, clinician trainees, and STEM educators to promote the education of next-generation rehabilitation pioneers.
Despite numerous efforts to develop new technologies for movement rehabilitation post-brain injuries, from brain imaging to neuromodulation approaches, optimal recovery is still limited due to a lack of imaging guidance and real-time neurofeedback to tailor rehabilitation strategies for each individual. This project will address this limitation and establish a unique rehabilitation engineering research paradigm based on a novel multi-modal brain imaging approach and a closed-loop high-definition transcranial direct current stimulation (HD-tDCS) platform. This new approach will precisely assess the changes to motor control in an injured brain and identify the key network to target for more precise HD-tDCS stimulation. The investigator will take integrated experimental and computational approaches to: 1) Identify and characterize individualized brain networks for movement control in injured brains; 2) Model and evaluate the dynamic effect of HD-tDCS on a live brain to enable targeted, precision stimulation of brain networks; and 3) Develop closed-loop imaging and neurofeedback guided HD-tDCS to improve brain function and behavior outcomes. This interdisciplinary project will be integrated with education and outreach activities to promote awareness of interdependencies between engineering and rehabilitation sciences and promote interdisciplinary education and training for next-generation rehabilitation engineers, with three educational objectives: 1) Promote the engagement of engineering and physical therapy students via summer research training, 2) Translate rehabilitation engineering knowledge to grade-appropriate STEM education via training high school teachers, and 3) Increase public awareness of engineering’s contributions to rehabilitation via museum events.
This project is jointly funded by the Disability and Rehabilitation Engineering Program and the Established Program to Stimulate Competitive Research (EPSCoR).
This award reflects NSF’s statutory mission and has been deemed worthy of support through evaluation using the Foundation’s intellectual merit and broader impact review criteria.
AHA Career
Abstract
Significant motor impairments occur in 80% of individuals after moderate to severe stroke, and impact the body side to the lesioned hemisphere. Typical motor impairments involve loss of dexterity with highly-prevalent upper limb flexion synergy. Flexion synergy interacts with weakness and abnormal joint postures, resulting in functional limitations, such as inability to reach, open the hand and manipulate objects. Advances in treating flexion synergy impairments have been hampered by a lack of precision rehabilitation. Previous studies suggest and support the role of cortico-reticulospinal tract (CRST) hyperexcitability in post-stroke flexion synergy. CRST hyperexcitability is often caused by damage to the corticospinal tract (CST). The PI hypothesizes that: 1) inhibiting the contralesional dorsal premotor cortex (cPMd) will directly reduce the CRST hyperexcitability and thus, reduce the expression of the flexion synergy; 2) facilitating the ipsilesional primary motor cortex (iM1) will improve the excitability of the damaged CST, therefore reducing the CRST hyperexcitability and the flexion synergy. Recent studies demonstrated that tDCS could be a promising and safe approach to modulate cortical excitability. However, the effect of conventional tDCS is limited as it uses large size “sponge” electrodes, making it difficult to target a specific region of interest in the brain for testing the hypothesis. To address the limitation of conventional tDCS that non-specifically activates many brain areas, the PI proposes to use a novel targeted high-definition tDCS (THD-tDCS) to specifically modulate the targeted cortical regions for testing his hypothesis, via the following aims: Aim 1. Evaluate the effect of cathodal THD-tDCS over the cPMd on reducing the CRST hyperexcitability and the expression of flexion synergy. Aim 2. Evaluate the effect of anodal THD-tDCS over the iM1 on improving the excitability of the CST, and determine whether this, thus, also reduces the CRST hyperexcitability and the flexion synergy. Aim 3. Evaluate the confluence effect of bilateral THD-tDCS, i.e., simultaneous cathodal stimulation over the cPMd and anodal over the iM1. The proposed work will facilitate the development of targeted interventions to enhance the recovery of the injured motor system after stroke. PI’s effort follows the AHA mission and if successful, will ultimately result in beneficial reductions in motor impairments for hemiparetic stroke survivors.
NIH R21
Abstract
Motor impairments post-stroke, such as the upper limb flexion synergy and abnormal stretch reflexes, greatly affect an individual’s ability to implement activities of daily living. Despite the development of various clinical interventions for motor recovery after stroke, rehabilitation treatments, especially in more impaired individuals, are only minimally effective. This is due to: 1) many remaining gaps in our understanding of specific mechanisms underlying motor impairments post stroke that inform clinical practice, and 2) lack of sensitive biomarkers to determine the neuroplasticity resulting from interruptions of neural pathways caused by the stroke and during recovery. Our long-term goal is to develop a sensitive way to quantitatively assess the lesion-induced utilization of remaining motor pathways post stroke, which would allow better examination of stroke recovery and evaluation of rehabilitation interventions. Our previous studies indicate that motor impairments post hemiparetic stroke are likely caused by an increased reliance on contralesional indirect motor pathways via the brainstem, following stroke-induced losses of ipsilesional corticospinal projections. Thus, the objective of this proposal is to quantitatively determine the usage of indirect motor pathways and its link to the expression of the flexion synergy and abnormal stretch reflexes, by examining changes in neural connectivity of motor pathways as a function of shoulder abduction (SABD) load. In contrast to the direct corticospinal tract, these indirect pathways contain more synapses, which thus may cause an enhanced nonlinear neural connectivity via the motor pathways due to the nonlinear sigmoid shape of synaptic behavior and its cumulative effect across synapses. Thus, our central hypotheses are that: 1) an increased usage of indirect motor pathways while lifting the paretic arm, requiring SABD and causing the flexion synergy, will lead to enhanced nonlinear connectivity between brain and muscle activity; 2) the recruitment of indirect motor pathways will also affect the stretch reflex, in particular, its transcortical reflex component, resulting in increased nonlinear connectivity between stretch perturbations and muscle activity. Finally, these indirect pathways may prolong the neural transmission delay in the transcortical reflex loop, resulting in an increased time lag between perturbations and muscle activity. Using our recently developed nonlinear connectivity method and mechanically well-controlled experimental paradigms, we aim to test these hypotheses by: 1) comparing linear vs. nonlinear connectivity between brain and muscle activity during the generation of different levels of SABD torque in individuals post hemiparetic stroke; 2) quantifying changes of nonlinear connectivity and time delay of the stretch reflex post-stroke as a function of SABD torque level. As such, this project will provide new sensitive biomarkers that determine the recruitment of indirect motor pathways resulting in functional disability of upper extremity post hemiparetic stroke. This will also lead to a better understanding of neural mechanisms underlying stroke-induced motor impairments that inform clinical practice to combat the flexion synergy and associated hyperactive stretch reflexes following a unilateral brain injury.
https://reporter.nih.gov/search/eZomA6_O60-HPXwWe78vTw/project-details/9978864