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.
