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

Abstract

Age-related neural dedifferentiation-a decline in the 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 nonhuman primates and more recent work in humans, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation in older adults. 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 positively predicted individual differences in neural distinctiveness. 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.

Keywords: Aging; Dedifferentiation; GABA; MR spectroscopy; Multivariate pattern analysis; fMRI.

Figure 1.

MRS voxel placement. Voxel placement in ventral visual cortex across all participants is depicted on the MNI T1 1mm template. Brighter colors (yellow) indicate greater overlap and darker colors (red) indicate less overlap across participants.

Figure 2.

Participant-specific example of ventral visual structural (red) and functional (yellow) ROIs. The functional ROI was created using the 5,000 most activated vertices during the face and house conditions.

Figure3.

Age-related differences in ventral visual cortex GABA+ levels. GABA+ was significantly reduced in older compared to younger adults.

Figure 4.

Age-related differences in neural distinctiveness. Neural distinctiveness was significantly reduced within the ventral visual cortex of older (orange circles) compared to younger adults (green triangles) across a range of mask sizes (from 1,000 vertices up to the Full Anatomical Mask).

Figure 5.

Average GABA+ levels and neural distinctiveness. GABA+ was positively associated with neural distinctiveness in older adults after controlling for gray matter volume, age, sensorimotor GABA+, and auditory GABA+.