Rachael D. Seidler - US grants

learning; neural plasticity; human old age (65+); sensorimotor system; proprioception /kinesthesia; sensory discrimination; visual stimulus; environmental adaptation; behavioral /social science research tag; psychological tests; neuropsychological tests; human subject; clinical research;

[unreadable] DESCRIPTION (provided by applicant): Manual dexterity is fundamental for maintaining independence in many basic and instrumental activities of daily living. Two important components of skill learning are the learning process itself (motor acquisition), and the ability to transfer what has been learned to new conditions and task variants (motor generalization). Many studies have documented declines in the ability of the elderly to learn new manual motor skills. Even though older adults exhibit reduced rates and magnitudes of skill acquisition in comparison to young adults, our recent work demonstrates that they show normal motor generalization. We propose that this newly documented age-related dissociation between acquisition and generalization is fundamentally important to clarifying the mechanisms and course of age-related motor declines. Moreover, this dissociation may provide new insights into acquisition and generalization processes and their neural underpinnings in the young adult. Recent behavioral and brain imaging investigations of skill acquisition suggest that motor learning consists not only of sensorimotor processes but also spatial cognitive processes, particularly during the early stages of learning. In the first aim of this project, we will use both behavioral and brain imaging techniques to investigate whether age-related declines in skill acquisition are associated with deficits in the early, spatial processing stages of learning. We will test this hypothesis using tasks that represent the two major classes of skill learning: sensorimotor adaptation and sequencing behaviors. The second aim will examine whether motor generalization is associated with reduced involvement of these early learning spatial processes for both young and older adults. Thus, the overarching goal of this project is to describe and quantify the neural and behavioral mechanisms of age-related changes in skill acquisition and motor generalization. We predict that age-related declines in both sequence learning and sensorimotor adaptation are a result of deficits in the early, spatial cognitive aspects of skill acquisition. We predict that motor generalization, in comparison to original task learning, results in a reduced reliance on the spatial cognitive processes that are engaged during early skill acquisition, thus allowing for normal motor generalization in older adults. [unreadable] [unreadable]

Both the United States and Europe are preparing for a larger population of older people in the near future. In the United States, the population of adults 65 and older will increase to 88.5 million in 2050, which is more than double the current number. It is expected that by 2050, 35% of Europeans will be over 60 years old, and 11% will be over 80 years old. This is a dramatic increase from current levels of 20% and 4%, respectively. In order for older adults to maintain their independence and function well in an increasingly technological society, it is important for them to be able to retain and develop motor skills. This project comprises a transnational team of investigators from the Netherlands, Germany, and the United States with extensive expertise in the study of motor skill acquisition across the lifespan.

The aim of this project is to delineate age differences in the brain and behavioral mechanisms of motor skill learning. The researchers will collect motor performance and neuroimaging data to identify brain regions contributing to skill learning for young and older adults. In addition, they will assess participants on a range of characteristics such as fitness level, cognitive capacity, health status, and other variables to identify factors contributing to individual differences in successful learning for older adults. They will also evaluate if and how exercise, transcranial brain stimulation, and observing others learn facilitate motor skill acquisition for older adults. Identifying age differences in the mechanisms of skill acquisition, and critically evaluating interventions for their potential effectiveness at improving skill learning abilities, will help to maintain work productivity, health, and daily function for older adults.

? DESCRIPTION (provided by applicant): There is a fundamental gap in understanding the physiological mechanisms of age differences in manual motor control. This is an important problem given the rapidly increasing older adult segment of our society. The long-term goal of my research program is to identify the neural mechanisms for age-related declines in sensorimotor function, allowing me to develop and evaluate targeted interventions to prolong functional independence for older adults. Our recent work leads to the intriguing and novel hypothesis that age declines in manual motor function are due at least in part to reduced distinctiveness of cortical sensorimotor representations. We have shown that motor cortical representations devoted to a single finger muscle are larger in older than young adults, suggestive of reduced intrahemispheric distinctiveness. We have also shown that motor representations for a single hand extend across both hemispheres for older adults, suggestive of reduced interhemispheric distinctiveness. What remains unknown is 1) whether more expansive and bilateral motor representations result in overlapping motor cortical maps for adjacent body parts and for the two hands; 2) whether reduced distinctiveness underlies age declines in uni- and bimanual dexterity, and 3) whether reduced distinctiveness is restricted to the motor system or also applies to somatosensory representations. Elucidating the mechanisms of age-related decline in manual dexterity and somatosensation is critical because activities of daily living require skilled actions that depend on these sensorimotor processes. Our current objective is to quantify distinctiveness of motor and somatosensory representations within cortical hemispheres (Aim 1) and across cortical hemispheres (Aim 2) in individuals aged 20 - 79 years, with age as a continuous variable. We will also evaluate whether distinctiveness of sensorimotor representations-and manual dexterity-can be improved with a targeted training intervention (Aim 3). Our pilot data provide compelling preliminary evidence that training interventions specifically improve individuated hand control during bimanual actions, and result in altered corpus callosum structure as well as more focal sensorimotor representations. Our novel approach integrates precise behavioral measurements and multiple brain imaging techniques in basic science and intervention-based experiments. If successful, this endeavor will elucidate the underlying mechanisms contributing to age-related declines in sensorimotor function, and has high potential to make a significant impact by extending work productivity and prolonging independent living in older adults.

Project Description: Mobility impairments in older adults decrease quality of life and are associated with high societal and economic burden. NIH RFA-AG-18-019 solicits applications ??to investigate the central neural control of mobility in older adults?using innovative and cutting-edge methods.? Current approaches to study the neural control of walking are limited by either the inability to measure people during walking (functional magnetic resonance imaging, fMRI) or the inability to measure activity below the cortex (functional near- infrared spectroscopy, fNIRS). We assert that a full and accurate understanding of the neural control of walking in older adults requires real time measurement of active regions throughout the brain during actual walking. We will achieve this by using innovative mobile brain imaging with high-density electroencephalography (EEG). This approach relies upon innovative hardware and software to deliver three-dimensional localization of active cortical and subcortical brain regions with high spatial and temporal resolution during walking. The result is unprecedented insight into the neural control of walking. Here, our overarching objective is to determine the central neural control of mobility in older adults by collecting EEG during walking and correlating these findings with a comprehensive set of diverse mobility outcomes (clinic-based walking, complex walking and community mobility measures). Our first aim is to evaluate the extent to which brain activity during actual walking explains mobility decline. In both cross sectional and longitudinal designs, we will determine whether poorer walking performance and steeper trajectories of decline are associated with the Compensation Related Utilization of Neural Circuits Hypothesis (CRUNCH). CRUNCH is a well-supported model of brain activity patterns that are seen when older individuals perform tasks of increasing complexity. CRUNCH describes the over-recruitment of frontoparietal brain networks that older adults exhibit in comparison to young adults, even at low levels of task complexity. CRUNCH also describes the limited reserve resources available in the older brain. These factors cause older adults to quickly reach a ceiling in brain resources when performing tasks of increasing complexity. When the ceiling is reached, performance suffers. The RFA also calls for proposals to ?Operationalize and harmonize imaging protocols and techniques for quantifying dynamic gait and motor functions?. In accordance with this call, our second aim is to characterize and harmonize high-density EEG during walking with fNIRS (during actual and imaged walking) and fMRI (during imagined walking). This will allow us to identify the most robust CRUNCH-related hallmarks of brain activity across neuroimaging modalities, which will strengthen our conclusions and allow for widespread application of our findings. Our third aim is to study the mechanisms related to CRUNCH during walking. Thus, our project will address a majority of the objectives in NIH RFA-AG-18-019 and will identify the neural correlates of walking in older adults, leading to unprecedented insight into mobility declines and dysfunction.

PROJECT SUMMARY Without movement, we would be utterly unable to interact with the world. All behaviors, including speech, writing, reaching, grasping, gaze, walking and posture require the coordinated activities of many motor areas. Further, sensory signals provide essential feedback to these motor areas, enabling accurate motor control and motor learning, as well as providing information vital for deciding future behaviors. As a result, understanding the sensorimotor control of even the most basic movements like orienting toward a sudden sound, or reaching to pick up a glass of water is complex. Damage to these sensorimotor pathways can produce a wide range of debilitating neurological disorders including tremor, Parkinson's disease, ataxia, dystonia, and spasticity - all of which markedly decrease quality of life. The Society for the Neural Control of Movement (NCM) is an international community of scientists, clinician-investigators and trainees engaged in research whose common goal is to understand how the brain controls movement and to address the deficits that occur in disease. NCM promotes a broad range of research using interdisciplinary approaches (e.g., neurophysiological, anatomical, molecular, computational, and behavioral), different animal models, and studies of intact subjects and those with neurological disorders. The inaugural NCM Meeting took place in 1991. The success of the society and its annual meeting has led to a continual growth in membership, meeting attendance, and the breadth of scientific content. With support through the NIH, the 2020 NCM meeting will make substantive progress towards furthering three main goals of the society: Aim 1) Stimulate new research approaches and collaborations among NCM meeting attendees by identifying new topics and appropriate scientists as speakers, Aim 2) continue to increase the gender and ethnic diversity within the NCM leadership and in meeting programing, and Aim 3) promote and support the development of the next generation of motor control researchers by providing financial and career support for graduate students and post-doctoral fellows. Overall, the unique format of the annual NCM meeting, with its focus on interdisciplinary approaches, discussion, and scientific interaction in an intimate meeting environment, is of immeasurable value to furthering worldwide understanding of how the brain controls movement in both health and disease.