GABA levels in ventral visual cortex decline with age and are associated with neural distinctiveness

Abstract

Age-related neural dedifferentiationreduced distinctiveness of neural representations in the aging brain-has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in non-human primates, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults predicted individual differences in neural distinctiveness even after controlling for gray matter volume and age. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex. Significance StatementNeural representations in the ventral visual cortex are less distinguishable in older compared to younger humans, and this neural dedifferentiation is associated with age-related cognitive deficits. Animal models suggest that reductions in the inhibitory neurotransmitter gamma aminobutyric acid (GABA) may play a role. To investigate this hypothesis, we combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) in a study of the human ventral visual cortex. We observed reduced distinctiveness of neural patterns and reduced GABA levels in older compared to younger adults. Furthermore, older adults with higher GABA levels tended to have more distinctive neural representations. These findings suggest that reduced GABA levels contribute to age-related declines in neural distinctiveness in the human ventral visual cortex.

RETRACTED: 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.…”

Age-related decline in cortical inhibitory tone strengthens motor memory

“…In the anatomical control region (occipital cortex), there was a qualitatively similar pattern of age-related inhibitory decline, consistent with previous reports 28,29 . However this was not statistically significant, likely reflecting the impact of quality controls that reduced the size of the occipital dataset and consequently reduced power (Table S1 S5.…”

“…Across cortex, E:I is disrupted because γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter, declines with age, both in animals 16,17 and humans 15,[18][19][20][21][22][23][24][25][26] . Regional decline of cortical GABA causes a loss of inhibitory tone, and this is associated with decrements in functions localized to the affected regions [27][28][29] . For example, in somatosensory cortex lower GABA (i.e., higher E:I) is associated with poorer tactile discrimination, both in young and old adults 20,30 .…”

Effects of Age Differences in Memory Formation on Neural Mechanisms of Consolidation and Retrieval

“…Interestingly, recent studies also demonstrated a relationship between a decline of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and neural distinctiveness. Combining magnetic resonance spectroscopy (MRS) to measure GABA with functional MRI, Chamberlain et al (2019) found that older adults had lower GABA levels (see also Simmonite et al, 2019) and less distinct activation patterns in the ventral visual cortex. Furthermore, individual differences in GABA predicted individual differences in distinctiveness (see for similar results with regard to the discrimination of auditory stimuli and GABA levels in the auditory cortex (see Lalwani et al, 2019, for similar results with regard to the discrimination of auditory stimuli and GABA levels in the auditory cortex).…”

“…Reduced inhibition by GABAergic interneurons might impair the resolution of conflict between neural representations and result in less distinct representations (Chamberlain et al, 2019;Lalwani et al, 2019).…”