Striatal Dopaminergic Neurotransmission, Striato-Cortical Functional Connectivity, and Motivation in...

Motivation, an important determinant of health and well-being in older adults, often declines in older age leading to negative health outcomes. However, the neurobiological basis of age-related changes in motivation is unclear. We hypothesized that higher striatal dopaminergic neurotransmission is positively related to motivation among community-dwelling older adults, and that striato-cortical functional connectivity explains, at least in part, this relationship.

Dopaminergic neurotransmission was indexed by quantifying Vesicular Monoamine Transporter 2 expression in the striatum using (+)-α-[¹¹C]dihydrotetrabenazine (DTBZ) via positron emission tomography imaging. Resting-state co-activation of the striatum with cortical regions indexed the strength of functional connectivity. Motivation level was assessed using latent class analysis applied to responses on an 18-item questionnaire. Multinomial logistic regression models examined the associations of striatal [¹¹C]DTBZ binding with motivation levels, without and with adjustment for striato-cortical functional connectivity. Structural equation models tested the mediating role of functional connectivity.

Among 234 older adults (mean age 75.2 years [range: 67.2-91.2]; 59.8% female; 91.5% White), three distinct motivation groups were identified: low (N = 30), moderate (N = 89), and high motivation (N = 115). Striatal [¹¹C]DTBZ binding was significantly and inversely associated with motivation (adjusted odds ratio = 0.53; 95% CI: 0.32-0.88). Striato-insular and striato-dorsal visual functional connectivity was positively associated with both [¹¹C]DTBZ and motivation, but did not modify the main association; mediation analyses indicated no mediating role.

Striatal dopaminergic neurotransmission and striato-insular functional connectivity may influence motivational capacity in older adults, perhaps acting through independent pathways.