The effect of aging and cognitive impairment on prefrontal cortical inputs to motor cortical outputs during standing balance control - PROJECT SUMMARY/ABSTRACT Falls present a significant problem as the leading cause of accidental death in older adults (OA). OA are particularly susceptible to falls due to effects of neurotypical aging, which alters neuromotor pathways important in balance control. Individuals with aging- or pathology-related declines in motor function are thought to leverage inputs from prefrontal cognitive regions to support impaired descending cortical motor circuits during balance challenges. In adults with impaired balance, reliance on attention to control balance poses a problem when the individual becomes distracted, and even more so if they have reduced neuromotor resources for balance. For this reason, individuals with cognitive decline such OA with mild cognitive impairment (MCI) are more susceptible to falls. Despite this increased fall-risk in MCI, there are few effective strategies to rehabilitate balance in MCI, and their poor cognitive abilities reduce the effectiveness of many existing training-based balance interventions. There is a need for rehabilitative strategies to enhance underlying cognitive-motor circuit function to improve balance function in OA with and without MCI. However, our ability to develop more effective balance treatments is limited by our lack of knowledge of the cognitive-motor pathway interactions underlying fall-risk. The objective of this F31 project is to characterize cognitive-motor circuit interactions important in balance control. The proposed research will use non-invasive neurostimulation to characterize effective connectivity from a primary cognitive area, the dorsolateral prefrontal cortex (DLPFC), to the primary motor cortex (M1), as a function of age, balance task difficulty, DLPFC engagement, and cognitive impairment. The rigor of previous work by my sponsors and others has shown correlational evidence that functional connectivity between prefrontal cortex and M1 is modulated as a factor of balance task difficulty in and individual balance ability. I will focus on more directly identifying top-down inputs from the DLPFC (involved in attention allocation and attention-based balance control) to leg areas of M1. Dual-site transcranial magnetic stimulation (TMS) will be used to evaluate effective connectivity, or causal and directional relationships between DLPFC and M1 circuits (DLPFC→M1). I hypothesize that prefrontal cognitive regions are recruited to modulate motor pathways at higher levels of task difficulty as necessitated by individual balance and cognitive ability. I will test this hypothesis by: 1) measuring the effect of balance challenge and aging on DLPFC→M1 in easy and difficult standing balance tasks. 2) Testing the effect of cognitive engagement and aging on DLPFC→M1 across balance tasks using a cognitive-motor dual-task. 3) Testing the effect of cognitive impairment on DLPFC→M1 across balance tasks and cognitive- motor dual-tasks. This paradigm will be the first investigation of DLPFC→ lower limb M1 in the context of functionally relevant standing balance tasks. In the long-term, this work will help develop mechanism-informed neuromodulation treatments to improve balance control, neurophysiological biomarkers to predict falls risk and rehabilitation response, and neurobiology-informed, precision (p)rehabilitation to reduce falls in OA and MCI.
