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Weissman, D. H.

Publications and source records attributed to Weissman, D. H..

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Neural distinctiveness declines with age in auditory cortex and is associated with auditory GABA levels.

Neural activation patterns in the ventral visual cortex in response to different categories of visual stimuli (e.g., faces vs. houses) are less selective, or distinctive, in older adults than in younger adults, a phenomenon known as age-related neural dedifferentiation. Previous work in animals suggests that age-related reductions of the inhibitory neurotransmitter, gamma aminobutyric acid (GABA), may play a role in this age-related decline in neural distinctiveness. In this study, we investigated whether neural dedifferentiation extends to auditory cortex and whether individual differences in GABA are associated with individual differences in neural distinctiveness in humans. 20 healthy young adults (ages 18-29) and 23 healthy older adults (over 65) completed a functional magnetic resonance imaging (fMRI) scan, during which neural activity was estimated while they listened to foreign speech and music. GABA levels in the auditory, ventrovisual and sensorimotor cortex were estimated in the same individuals in a separate magnetic resonance spectroscopy (MRS) scan. Relative to the younger adults, the older adults exhibited both (1) less distinct activation patterns for music vs. speech stimuli and (2) lower GABA levels in the auditory cortex. Also, individual differences in auditory GABA levels (but not ventrovisual or sensorimotor GABA levels) predicted individual differences in neural distinctiveness in the auditory cortex in the older adults. These results demonstrate that age-related neural dedifferentiation extends to the auditory cortex and suggest that declining GABA levels may play a role in neural dedifferentiation in older adults.\n\nSignificance StatementPrior work has revealed age-related neural dedifferentiation in the visual cortex. GABA levels also decline with age in several parts of the human cortex. Here, we report that these two age-related changes are linked; neural dedifferentiation is associated with lower GABA levels in older adults. We also show that age-related neural dedifferentiation extends to auditory cortex, suggesting that it may be a general feature of the aging brain. These findings provide novel insights into the neurochemical basis of age-related neural dedifferentiation in humans and also offer a potential new avenue for investigating age-related declines in central auditory processing.

neuroscience

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

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.

neuroscience