Sensorimotor network segregation declines with age and is linked to GABA and to sensorimotor performance

Abstract

Aging is typically associated with declines in sensorimotor performance. Previous studies have linked some age-related behavioral declines to reductions in network segregation. For example, compared to young adults, older adults typically exhibit weaker functional connectivity within the same functional network but stronger functional connectivity between different networks. Based on previous animal studies, we hypothesized that such reductions of network segregation are linked to age-related reductions in the brain's major inhibitory transmitter, gamma aminobutyric acid (GABA). To investigate this hypothesis, we conducted graph theoretical analyses of resting state functional MRI data to measure sensorimotor network segregation in both young and old adults. We also used magnetic resonance spectroscopy to measure GABA levels in the sensorimotor cortex and collected a battery of sensorimotor behavioral measures. We report four main findings. First, relative to young adults, old adults exhibit both less segregated sensorimotor brain networks and reduced sensorimotor GABA levels. Second, less segregated networks are associated with lower GABA levels. Third, less segregated networks and lower GABA levels are associated with worse sensorimotor performance. Fourth, network segregation mediates the relationship between GABA and performance. These findings link age-related differences in network segregation to age-related differences in GABA levels and sensorimotor performance. More broadly, they suggest a neurochemical substrate of age-related dedifferentiation at the level of large-scale brain networks.

Keywords: Aging; Dedifferentiation; GABA; Network segregation; Sensorimotor.

Fig. 1.

A) Sensorimotor cortex MRS voxel overlap across all participants, with brighter (red) colors representing more participant overlap and darker (blue) colors representing less overlap. B) Edited MR spectra from a representative younger adult participant (black) demonstrating a clearly resolved peak for GABA+ at 3 ppm, with the fitted GABA+ model in red. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2.

214 regions of interest were created using coordinates defined by Power et al (2011) to produce ten resting state networks of interest.

Fig. 3.

Age differences in A) a summary measure of general sensorimotor performance (t = 7.24, p < .001); B) grip strength (t = 1.24, p = .22); C) sensorimotor network segregation (t = 2.23, p = .031); and D) sensorimotor GABA+ levels (t = 4.97, p < .001) between young (blue) and older (red) adults. On each box, the central line indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles, respectively. The whiskers extend to the most extreme data points not considered outliers. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4.

A) Relationship between sensorimotor GABA+ levels and sensorimotor network segregation across all participants (accounting for age and GM volume differences; r = .41, p = .008) and B) within each age group separately (Old: r = 0.45, p = .042; Young: r = 0.37, p = .10).

Fig. 5.

A) Relationship between sensorimotor network segregation and sensorimotor performance across all participants (accounting for age and GM volume differences; r = .38, p = .016) and B) within each age group separately (Old: r = 0.50, p = .026; Young: r = 0.18, p = .44). C) Relationship between sensorimotor network segregation and grip strength across all participants (accounting for age and GM volume differences; r = .27, p = .093) and D) within each age group separately (Old0: r = 0.51, p = .021; Young: r = 0.13, p = .59).

Fig. 6.

A) Relationship between sensorimotor GABA+ levels and sensorimotor performance across all participants (accounting for age and GM volume differences; r = .32, p = .046) and B) within each age group separately (Old: r = 0.48, p = .03; Young: r = −0.14, p = .55). C) Relationship between sensorimotor GABA+ levels and grip strength across all participants (accounting for age and GM volume differences; r = .21, p = .19) and D) within each age group separately (Old: r = 0.23, p = .33; Young: r = 0.20, p = .38).

Fig. 7.

Sensorimotor network segregation mediates the link between sensorimotor GABA+ levels and sensorimotor performance across all participants (accounting for age and GM volume differences). The mediator accounted for 70% of the total effect (P_M = .70).