Cognitive, sensory, and motor function all usually decline with age, but some people age much more gracefully than others. Why? We hypothesize that one important factor is individual differences in neural distinctiveness. In previous work we've repeatedly found that neural activation patterns in response to different stimuli are significantly less distinctive in older compared with younger adults. Furthermore, we've found that older adults with more distinctive neural representations perform significantly better than others on a range of fluid processing tasks. Animal work confirms these age-related reductions in neural distinctiveness and suggests that declines in the neurotransmitter gamma-aminobutyric acid (GABA) may be an important cause. Building on this work, we propose to investigate the scope, cause, and consequences of age-related changes in neural distinctiveness. First, we will use functional MRI to test whether neural distinctiveness declines in auditory cortex, somatosensory cortex, and motor cortex, like it does in visual cortex (Aim 1: Scope). Second, we will use magnetic resonance spectroscopy to measure GABA levels and use the GABA agonist Lorazepam to manipulate GABA levels in order to investigate whether age-related reductions in GABA cause reductions in neural distinctiveness (Aim 2: Cause). Third, we will collect an extensive battery of measures assessing behavioral performance in the same participants in order to assess the relationship between neural distinctiveness and behavior (Aim 3: Consequences). The proposed studies will provide novel insights into how the brain changes with age, whether those changes can predict successful aging, and whether changes in GABA levels are a contributing cause. Such insights could provide the basis for novel interventions to slow, or conceivably even reverse, the behavioral declines seen during normal aging.

Public Health Relevance

Tens of millions of otherwise healthy people experience age-related impairments in functions ranging from memory, to perception, to motor control. In previous work we've found that as people get older, patterns of brain activity in response to different stimuli become less distinctive and more confusable. We propose to investigate the scope, causes, and consequences of these changes in neural distinctiveness in order to inform efforts to slow, or conceivably even reverse, the behavioral declines associated with aging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Cognition and Perception Study Section (CP)
Program Officer
Wagster, Molly V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
Zip Code
Simmonite, Molly; Carp, Joshua; Foerster, Bradley R et al. (2018) Age-Related Declines in Occipital GABA are Associated with Reduced Fluid Processing Ability. Acad Radiol :
Cassady, Kaitlin; Gagnon, Holly; Lalwani, Poortata et al. (2018) Sensorimotor network segregation declines with age and is linked to GABA and to sensorimotor performance. Neuroimage 186:234-244