Evangelos A. Christou - US grants

[unreadable] DESCRIPTION (provided by applicant): NIA Pilot Research Program, Topic 14: Sensory and Motor Processing. Older adults exhibit a reduced ability to perform accurate goal-directed movements with various muscle groups. This impairment is often observed with movements of the index finger and attributed to a reduced capacity to exert consistent movement trajectories (Enoka et al. 2003). Recent findings however, provide evidence that the ability of older adults to match the target movement trajectory with the index finger is impaired despite lower fluctuations (more consistent) in the movement trajectory (Christou et al. 2003). Although the physiological mechanisms that contribute to movement accuracy are largely unexplored, the impaired accuracy in older adults may be due to: (1) inconsistent movement trajectory caused by an altered activation of the motor units in the agonist muscle (2) impaired acceleration of the index finger caused by altered co-activation of the agonist and antagonist muscles. Based on the preliminary findings, it is hypothesized that the reduced accuracy of older adults with goal-directed movements is due to altered levels of co-activation. Two specific aims will test this hypothesis: The first aim will determine the association between fluctuations in movement trajectory and the accuracy of a pointing task with the index finger during interventions that impair (movement speed) or enhance (practice) accuracy in young and older adults. The second aim will establish the contributions of motor unit discharge and co-activation of the agonist and antagonist muscles to the difference in the pointing accuracy. The findings of this RO3 application will constitute novel information on the physiological mechanisms that impair movement accuracy in older adults. These preliminary findings will form the foundation for an RO1 application that will further explore the mechanisms contributing to the impaired movement accuracy in older adults. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): Older adults are expected to comprise 25% of the workforce in the US by the year 2050. Successful employment of older adults and subsequent maintenance of their independence and health depends on their ability to perform and learn novel motor tasks with accuracy. The effects of human aging on cognition and fine motor performance have been studied extensively. Nonetheless, the interaction of the age-associated motor impairments and ability to learn and retain novel motor tasks is not well understood. Based on our preliminary work, we hypothesize that the ability of older adults to learn novel fine motor tasks is compromised due to altered agonist-antagonist activation and that training that emphasizes alternating agonist- antagonist activity will improve the ability of older adults to retain and transfer novel motor tasks. The hypothesis will be tested with three specific aims. The first two specific aims will identify neuromuscular mechanisms that contribute to the impaired ability of older adults to learn and transfer novel motor tasks during single-joint movements. The first experiment (Aim 1) will identify the agonist-antagonist adaptations that occur in young and older adults at the single motor unit level when learning and transferring dexterous motor tasks with the index finger. The second experiment (Aim 2) will identify the neural adaptations that occur in young and older adults at the agonist-antagonist muscle level when learning and transferring novel aiming motor tasks. The third experiment (Aim 3) will extend the findings to a multi-joint task and determine the efficacy of a speed-progressive light-load training protocol in improving the ability of older adults to learn and transfer fine novel motor tasks with single-joint and multi-joint movements. We expect to find that the ability of older adults to learn, retain, and transfer fine novel motor tasks with accuracy is impaired because of altered activation of the agonist-antagonist motor neuron pool. This impairment in activation will be evident at the single motor unit and whole muscle level and will be exacerbated during multi-joint movements. Finally, we expect that the proposed speed-progressive light-load training will improve the ability of older adults to perform, retain, and transfer fine novel motor tasks with single-joint and multi-joint movements. The findings of this project, therefore, could have a significant impact on the development of motor rehabilitation strategies for young and older adults, as well for individuals who suffer from neurological disorders that impair movement accuracy. PUBLIC HEALTH RELEVANCE The ability to learn new motor tasks is a fundamental adaptive component of life. Consequently older adults who cannot adapt to changing environments by learning new motor tasks will loose their independence and health. Furthermore, older adults are expected to comprise 25% of the workforce in the US by the year 2050. It is crucial, therefore, to understand how the healthy aging neuromuscular system learns to accomplish accurate movements and identify ways to improve the ability of older adults to learn and perform motor tasks with accuracy. The findings of this project, therefore, will identify neuromuscular mechanisms that contribute to motor learning and could have a significant impact on the development of training protocols and motor rehabilitation strategies for young and old adults. [unreadable] [unreadable] [unreadable] [unreadable]

PROJECT SUMMARY Here, our multidisciplinary group with expertise in movement disorders and motor physiology, proposes to study the effects of deep brain stimulation of the ventralis intermedius nucleus (VIM DBS) on balance and gait tasks of patients with Essential Tremor (ET). Although VIM DBS is effective in controlling upper limb tremor, it does not address balance and gait disturbances in ET. This is a significant problem because balance and gait disturbances occur in >40% of ET patients, who exhibit lower quality of life and increased risk for falls and mortality. The inability to mitigate balance and gait disturbances may be a consequence of the DBS targeting a location within the VIM that reduces hand tremor but not tremor relevant to balance and gait. Our preliminary data show that only when VIM DBS reduced midline tremor, balance and gait improved. These findings are based on measurements of midline tremor with sensitive accelerometers during balance and gait tasks. In contrast, current measures of midline tremor are based on qualitative clinical assessments and have never been performed during balance and gait tasks. Thus, current measures of midline tremor are not task-relevant and lack sensitivity. In this proposal, therefore, we will determine if midline tremor is a marker for balance and gait impairments using sensitive accelerometry and electromyography (EMG) of postural muscles and innovative analyses. We will test the central hypothesis that when thalamic neurostimulation reduces midline tremor amplitude, balance and gait improve and risk for falls decreases. In Aim 1, we propose to characterize the effects of neurostimulation on tremor at multiple body locations during static and dynamic balance tasks and during straight and obstacle overground walking tasks (task-relevant tremor). We will quantify tremor using sensitive accelerometers and EMG when ET patients perform balance and gait tasks with their DBS ON or OFF. We test the hypothesis that only the VIM DBS-induced reduction of midline tremor will relate to balance and gait improvements. In Aim 2, we examine the association between the change in risk for falls (pre/post DBS surgery) and the change in tremor quantified at various locations during balance and gait tasks (DBS ON/OFF). We will quantify the risk for falls before and after DBS surgery by using the Activities Specific Balance Confidence scale (ABC), a validated and sensitive scale for risk for falls. In addition, we will quantify performance during the Berg Balance Test (BBS) and Timed Up and Go Test (TUG) with DBS ON and OFF. We will test the hypothesis that a greater VIM DBS-induced reduction in midline tremor amplitude will relate to decreased risk for falls. If successful, the outcomes of this proposal are clinically impactful because they will advance the use of DBS for treating balance and gait disturbances in ET and in other disorders.