Exploring the role of cortical inhibition in neural distinctiveness and behavior

点击翻译按钮获取中文摘要

Neural activation patterns evoked by separate categories of stimuli are clearly different. The extent to which the evoked patterns are different is referred to as neural distinctiveness. Our research group and others have found that neural distinctiveness tends to decline with age, and that older adults who maintain more distinctive neural representations perform better on a range of cognitive tasks. Additionally, previous animal work has found that pharmacological manipulations of GABA cause changes in neural distinctiveness. Based on those findings, we hypothesize that individual differences in inhibition are associated with individual differences in neural distinctiveness, which in turn are related to cognitive performance. We propose to test this model in humans. Currently in the F99 phase, the candidate is recruiting a large sample of young adults and using transcranial magnetic stimulation to measure cortical inhibition, magnetic resonance spectroscopy to measure GABA levels, functional MRI to measure neural distinctiveness, and a battery of validated tasks to measure cognitive and behavioral performance. The candidate will then test whether individual differences in neural distinctiveness are associated with individual differences in cortical inhibition/GABA concentration. The candidate will also test whether individual differences in neural distinctiveness, in GABA, and in cortical inhibition are associated with individual differences in cognition and behavior. In the K00 phase, the candidate will shift her focus to studying these factors in older adults. Aging is associated with substantial declines in mobility, even in the absence of significant disease. However, some older people experience serious declines while others do not. We hypothesize that individual differences in neural distinctiveness and GABA levels will predict motor performance on various walking tasks. Over the course of two proposed studies the candidate will therefore assess and experimentally manipulate GABA levels in older adults and will measure the effects on both neural distinctiveness and on various walking metrics. The candidate will use MRS to measure GABA levels, functional MRI to assess neural distinctiveness, walking tasks to assess mobility, and high-definition transcranial direct current stimulation (HD-tDCS) and continuous theta burst TMS (cTBS) to respectively decrease or increase GABA levels. The proposed studies afford the opportunity to shed light on the underlying causes of age-related cognitive and behavioral impairments. Such an understanding is the first step in developing interventions that could slow, or conceivably even prevent, the cognitive and motor impairments associated with healthy aging.