Michigan Neural Distinctiveness (MiND) project: Investigating the scope, causes, and consequences of age-related neural dedifferentiation

Gagnon, H.; Simmonite, M.; Cassady, K.; Chamberlain, J. D.; Freiburger, E.; Lalwani, P.; Kelley, S.; Foerster, B.; Park, D. C.; Petrou, M.; Seidler, R. D.; Taylor, S. F.; Weissman, D. H.; Polk, T. A.

doi:10.1101/466516

bioRxiv · 10.1101/466516

Michigan Neural Distinctiveness (MiND) project: Investigating the scope, causes, and consequences of age-related neural dedifferentiation

Gagnon, H.·Simmonite, M.·Cassady, K.·Chamberlain, J. D.·Freiburger, E.·Lalwani, P.·Kelley, S.·Foerster, B.·Park, D. C.·Petrou, M.·Seidler, R. D.·Taylor, S. F.·Weissman, D. H.·Polk, T. A.

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Abstract

BackgroundAging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway).\n\nMethods/DesignThe MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy (MRS), and diffusion weighted imaging (DWI) sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take (1) a benzodiazepine (lorazepam) that should increase GABA activity or (2) a placebo.\n\nDiscussionBy collecting multimodal imaging measures (fMRI, MRS, DWI) along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines.

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Gagnon, H., Simmonite, M., Cassady, K., Chamberlain, J. D., Freiburger, E., Lalwani, P., Kelley, S., Foerster, B., Park, D. C., Petrou, M., Seidler, R. D., Taylor, S. F., Weissman, D. H., Polk, T. A.. 2018-11-09. Michigan Neural Distinctiveness (MiND) project: Investigating the scope, causes, and consequences of age-related neural dedifferentiation. https://doi.org/10.1101/466516

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