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

Abstract

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 agerelated neural dedifferentiation extends to the auditory cortex and suggest that declining GABA levels may play a role in neural dedifferentiation in older adults. Significance 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 agerelated 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.

Tracking Age Differences in Neural Distinctiveness across Representational Levels

“…For example, using MR spectroscopy to quantify GABA concentrations in occipital voxels, Simmonite et al (2019) found that lower occipital GABA levels in older adults were associated with declines in fluid processing abilities. Furthermore, Chamberlain et al (2019;preprint) reported that individual differences in the category specificity of face versus house representations were linked to individual differences in VVC GABA concentrations in older adults, indicating a role of GABA in age-related neural dedifferentiation (see also Cassady et al, 2019;Gagnon et al, 2019;Lalwani et al, 2019). These findings substantiate the key role of proficient (particularly GABAergic) neuromodulation for high-fidelity (i.e., stable and distinct) neural representations and cognitive performance and lay the ground for future studies aiming to understand how agerelated deficits in neuromodulation are related to neural dedifferentiation across representational levels.…”

Temporal selectivity declines in the aging human auditory cortex

“…Aging has been hypothesized to lead to a neural dedifferentiation in sensory cortices (e.g., Park et al, 2004 ). A more recent unspecific observation is that with age, decoding accuracy of stimulus conditions from auditory cortical fMRI responses declines ( Lalwani et al, 2019 ; but see discussion for contrasting findings in MEG speech tracking, for example Presacco et al, 2016 ). This finding in turn has been linked to an imbalance of excitation and inhibition in older adults, more specifically a reduction of GABA levels in auditory cortex ( Lalwani et al, 2019 ).…”

“…A more recent unspecific observation is that with age, decoding accuracy of stimulus conditions from auditory cortical fMRI responses declines ( Lalwani et al, 2019 ; but see discussion for contrasting findings in MEG speech tracking, for example Presacco et al, 2016 ). This finding in turn has been linked to an imbalance of excitation and inhibition in older adults, more specifically a reduction of GABA levels in auditory cortex ( Lalwani et al, 2019 ). Accumulating evidence supports the theory of an age-related loss of inhibition in sensory cortices ( Caspary et al, 2008 ).…”

Temporal selectivity declines in the aging human auditory cortex

“…Aging has been hypothesized to lead to a neural dedifferentiation in sensory cortices (e.g., Park et al, 2004). A general observation is that with age, decoding accuracy of stimulus conditions from auditory cortical fMRI responses declines (Lalwani et al, 2019) (but see discussion for contrasting findings in EEG speech tracking, e.g., Presacco et al, 2016). This finding in turn has been linked to an imbalance of excitation and inhibition in older adults, more specifically a reduction of GABA levels in auditory cortex.…”