Minoru Shinohara, PhD - US grants

[unreadable] DESCRIPTION (provided by applicant): The general aim of this research is to examine whether enhanced activity of the sympathetic nervous system impairs the ability of individuals to perform fine motor skills. The proposed research represents a novel study that will investigate an unexplored functional connection between the autonomic nervous system and the motor system in humans. Manual dexterity is compromised in individuals with cardiac disease or with advanced age, who often have high levels of basal muscle sympathetic nerve activity (MSNA). This impaired manual dexterity may lead to a decrease in quality of life and capability for independent living. Independent research studies indicate that mental stress increases MSNA and force fluctuations during steady low-level contractions of hand muscles in humans. However, there are no studies that directly link enhanced MSNA with force fluctuations. Furthermore, there is evidence that suggests an increase in sensitivity of the la afferent circuit due to heightened SNA, and associations between the sensitivity of the la afferent circuit and force fluctuations in humans. Hence, we hypothesize that enhanced activity of the sympathetic nervous system impairs the ability of individuals to perform fine motor skills by altering the sensitivity of the la afferent circuit. The specific aims of this proposal are to determine whether increased MSNA increases force fluctuations (Aim 1), and to examine whether increased MSNA alters the sensitivity of the la afferent circuit (Aim 2) during low-force contractions of a hand muscle. To achieve these aims, MSNA, force fluctuations, single motor unit activity, stretch reflex, and H-reflex during steady contractions of a hand muscle will be measured when MSNA is experimentally manipulated by applying negative pressure to the lower body (LBNP). The findings of this study will constitute new information about the physiological mechanisms that impair manual dexterity in individuals with cardiovascular disease. The preliminary findings will form the foundation for an R01 application that will further identify the physiological mechanisms contributing to the impairment of fine motor skills in individuals who have or who are at risk of cardiovascular disease. The outcome of the study will lead to the development of interventions that can ameliorate the impaired manual dexterity in those individuals. [unreadable] [unreadable] [unreadable]

The project provides a systematic means to modify the activity in a specific group of muscles by using a robot, which is expected to lead to wider diagnosis and treatment options for patients than conventional approaches which rely solely on therapists' knowledge and experience. This EAGER project tests this potentially transformative concept in a collaboration between Georgia Institute of Technology (GT) and two institutions in Japan, Nara Institute of Science and Technology (NAIST) and the University of Tokyo Hospital (U-Tokyo) through the support of NSF-JST (Japan Science and Technology Agency) Strategic International Cooperative Program. The primary objective of the US-Japan collaborative research is to develop methodologies to computationally plan and execute various motor-tasks for neuromuscular function test by using an exoskeleton-type robot and quantitatively evaluate the efficacy by measuring various biosignals.

The project produces results that are useful in rehabilitation science, robotics, physical therapy, neuro-muscular science, and athletic training. In addition, international collaboration with Japanese researchers exposes graduate students and faculty to the global research opportunities and capabilities. Moreover, results have the potential to significantly lower health care costs in these domains, which occur quite frequently in the aging population.

The goal of this award is to develop theories, methods, and tools to understand the mechanisms of neuromotor adaptation in human-robot physical interaction. Human power-assisting systems, e.g., powered lifting devices that aid human operators in manipulating heavy or bulky loads, require physical contact between the operator and machine, creating a coupled dynamic system. This coupled dynamic has been shown to introduce inherent instabilities and performance degradation due to a change in human stiffness; when instability is encountered, a human operator often attempts to control the oscillation by stiffening their arm, which leads to a stiffer system with more instability. The project will establish control algorithms for robot co-workers that proactively adjust the contact impedance between the operator and robotic manipulator for achieving higher performance and stability. This research will 1) understand the association between neuromuscular adaptations and system performance limits, 2) develop probabilistic methods to classify and predict the transition of operator's cognitive and physical states from physiological measures, and 3) integrate this knowledge into a structure of shared human-robot and demonstrate the efficacy in a powered lifting device with real-world constraints at vehicle assembly facilities.

If successful, the research will benefit the communities interested in the adaptive shared control approach for advanced manufacturing and process design, including automobile, aerospace, and military. Such next-generation manufacturing is expected to improve productivity and reduce assembly time as well as physical burden of assembly line workers. Research outcomes will be integrated into current courses at both graduate and undergraduate levels. Students will be recruited from interdisciplinary and multicultural groups including under-represented groups. K-12 outreach will be carried out in conjunction with Georgia Tech Student and Teacher Enhancement Partnership Program and a summer robot camp in a local non-profit association. An online portal is maintained for dissemination.

Motor function is compromised with advanced age, and motor impairment is involved in various neuromotor injuries and disorders including stroke, spinal cord injury, amputation, and aging. Development of effective interventions for facilitating neuromotor adaptation is essential for accelerating or augmenting rehabilitation outcomes in the control of impaired limbs. The ultimate goal of the study is to find non-pharmacological and non-invasive neuromodulating interventions for enhancing the rehabilitation outcomes that may be applied to individuals with impaired motor function. In rats, implanted afferent vagus nerve stimulation paired with motor training enhanced neuromotor adaptation and motor recovery most likely through increased release of central neuromodulators that originate from the brainstem. We propose to translate the findings in rats into humans by applying vagus nerve stimulation noninvasively. Transcutaneous VNS (tVNS) can noninvasively activate the brainstem including locus coeruleus, where norepinephrine (i.e. neuromodulator) is synthesized. However, it is unknown whether tVNS leads to increasing neuromodulators and facilitating neuromotor adaptations when combined with motor training in humans. With potential applicability of this novel intervention for facilitating neuromotor adaptation to various clinical human populations in future scope, it is essential to start with the basic understanding about the effect of tVNS on the neuromotor system and training-induced adaptation in neuromotor behavior in non-disabled humans. The overarching hypothesis is that an application of tVNS increases central norepinephrine and facilitates training-induced neuromotor adaptations in humans. The specific aim is to examine the effect of tVNS on central norepinephrine and training-induced neuromotor adaptations in humans. The effect of applying tVNS concurrently to visuomotor training will be investigated by comparing the changes in central norepinephrine and changes in the visuomotor skill and corticospinal excitability due to training with and without tVNS (sham) in non-disabled humans. We expect that subjects with concurrent tVNS during training show greater increases in the visuomotor skill and corticospinal excitability after training. We also expect that tVNS increases central norepinephrine, and the amount of neuromotor adaptations due to training is associated with that of tVNS-induced increase in central norepinephrine. These expected findings will be the first evidence on the efficacy of concurrent tVNS with motor training for upregulating central norepinephrine and facilitating training-induced neuromotor adaptations in humans. They will open new scientific and clinical fields of study that will lead to the creation of motor rehabilitation paired with tVNS that can enhance rehabilitation outcomes in individuals with motor impairment. Demonstration of associated changes between central norepinephrine and neuromotor adaptations due to tVNS in non-disabled humans is a necessary step for applying tVNS to rehabilitation with the understanding of the underlying mechanism and for potentially using central norepinephrine as a predictor of tVNS efficacy in rehabilitation.

SUMMARY Upper limb motor function is often impaired due to neurologic injuries such as stroke and spinal cord injury. The ultimate objective is to innovate effective motor rehabilitation for enhancing clinical outcomes in stroke populations by discovering and applying scientific mechanisms and developing new engineering technologies to facilitate neuromotor adaptation. In stroke rehabilitation, mental practice, such as motor imagery and action observation, is a very effective intervention when performed appropriately. The challenge is that performance quality and efficacy of mental practice are highly variable and can be compromised. It is hypothesized that control and observation of robotic grasp and release actions via synergistic proximal muscle activation will increase neuromotor excitability of the non-activated distal muscles and hand function due to cognitive engagement with the externally present and visible robotic prosthesis. The Specific Aim of this proof of concept and feasibility study is to develop and test robotically augmented mental practice with synergistic proximal muscles for neuromotor facilitation of hand muscles. A robotically augmented mental practice will be developed for individuals to grasp and release an object by controlling the associated actions of a sound- generating robotic prosthesis utilizing surface electromyography (EMG) of shoulder/trunk muscles with deep learning algorithms. To demonstrate the proof of concept of increased neuromotor excitability and hand performance in able-bodied adults, transcranial magnetic stimulation will be applied to the motor cortex for the non-activated hand muscles and reaction time and maximal voluntary contraction performances will be tested with a finger in various practice conditions. The feasibility and possible trends in stroke survivors with upper extremity disabilities will also be examined. The project will be performed at the Georgia Institute of Technology by an interdisciplinary team of experts in fields directly related to the study: an applied physiologist, mechanical and biomedical engineers, a physical therapist, and a clinical neuroscientist. The successful completion of the study will provide augmented mental practice for neuromotor facilitation for distal muscles, and evidence for efficacy will be provided in able-bodied adults and feasibility in post-stroke individuals. The results will lead to the development of a more effective priming intervention before physical practice that can facilitate functional improvement as part of stroke rehabilitation.