Grant: Discovery Grants Program - Individual

Everyone envisions themselves as robust and agile in their old age. Agility is the ability to move quickly and easily without losing balance, requiring a combination of strength, power and neuromuscular coordination. However, the shift from being agile to frail is imperceptible and differs based on sex, with females more likely to become frail. Age-related declines in agility could be a result of age-associated muscle atrophy or because of deterioration of the central nervous system (CNS), which controls complex dynamic movement, or both. Our previous experiments validate the use of neurophysiological and functional brain imaging techniques to probe the relationships between the CNS and human performance. Excitatory and inhibitory integrity of the corticospinal tract can be indexed using transcranial magnetic stimulation (TMS). Functional near-infrared spectroscopy (fNIRS) elucidates cortical hemodynamic responses during real and imagined movements. Further, we have validated a propulsive bipedal hopping agility test using an electronic walkway which provides precise spatiotemporal variables that map to strength (hop length) and interlimb coordination (coefficient of variability). Pairing measurement of performance during complex and demanding tasks, like bipedal hopping, with TMS and fNIRS permits deep phenotyping and advancement of fundamental knowledge of individual (human) performance variability. The LONG-TERM OBJECTIVE of the proposed program expands our understanding of interindividual differences in human agility, the specific CNS mechanisms underlying age- and sex-related differences in agility, and how these variables underpin confidence in activities of daily living. Such a program will enhance our understanding of the sex-specific "normal" aging process. To reach this long-term vision, we will focus on the three short-term objectives: Objective 1: Determine sex- and age-related differences in the contributions of muscle strength versus integrity of the corticospinal tract on agility and balance. Objective 2: Ascertain brain activation patterns during agility and balance tasks and the influence of age and sex. Objective 3: Quantify to what extent modifiable (i.e. agility performance, physical activity, corticospinal tract integrity, or cortical activation) and non-modifiable (i.e., age and sex) factors predict loss of balance confidence. The proposed program is intended to make transformative advances in our understanding of how age and sex influence the CNS during complex human movement, such as agility. The proposed research lays the foundation for future research testing neuromodulation and training interventions that enhance neuroplasticity and performance with attention to important and often overlooked sex differences.