Age-Related Neural Dedifferentiation in the Sensorimotor System and its Behavioral Consequences

Abstract

Tens of millions of people experience age-related declines in sensorimotor functioning, but the neurobiological mechanisms underlying this decline are not well understood. Previous studies have linked age-related behavioral declines to decreases in neural differentiation (i.e., dedifferentiation), including decreases in the distinctiveness of neural activation patterns and in the segregation among large-scale neural networks. However, no studies to date have explored the relationship between these two neural measures and whether they explain the same aspects of sensorimotor behavior. Furthermore, no studies have explored the potential neurochemical substrates of age-related neural dedifferentiation. The present research sought to explore the neural and behavioral mechanisms of age-related neural dedifferentiation in the sensorimotor system using multi-voxel pattern analysis to examine the distinctiveness of sensorimotor neural representations, and graph theoretical analysis to examine the segregation of resting state sensorimotor networks in young and older adults. Study 1 demonstrated that these two measures of neural dedifferentiation are related. Segregation also predicted individual differences in sensorimotor performance, particularly in older adults, whereas distinctiveness did not, suggesting that segregation may be a more sensitive predictor of age-related declines in sensorimotor behavior. Study 2 extended this investigation by exploring potential neurochemical causes of age-related dedifferentiation in the sensorimotor system. Using MR spectroscopy to measure the inhibitory neurotransmitter, gamma aminobutyric acid (GABA), the results revealed that sensorimotor network segregation is linked to sensorimotor GABA levels and that these levels decline with age. Furthermore, individual differences in GABA predicted sensorimotor performance and this relationship was mediated by network segregation. These findings link age-related differences in network segregation to age-related differences in GABA levels and sensorimotor performance. In general, they suggest a neurochemical substrate of age-related dedifferentiation at the level of large-scale brain networks. Taken together, the findings from this dissertation advance our understanding of the neural and neurochemical mechanisms that underlie age-related declines in sensorimotor functioning. These findings may help lead to the development of targeted interventions and treatments to combat age-related sensorimotor behavioral decline.