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Striatal Dopaminergic Neurotransmission, Striato-Cortical Functional Connectivity, and Motivation in Community-Dwelling Older Adults

  • Yixiao Song
  • , Peggy M. Cawthon
  • , Xuetong Zhai
  • , Theodore J. Huppert
  • , Andrea L. Rosso
  • , Meryl A. Butters
  • , Lana M. Chahine
  • , Brian J. Lopresti
  • , Sarah K. Royse
  • , Caterina Rosano
  • University of Pittsburgh
  • University of California at San Francisco
  • Sutter Health

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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

Original languageEnglish
JournalAmerican Journal of Geriatric Psychiatry
DOIs
StateAccepted/In press - 2026

Keywords

  • aging
  • Dopamine
  • DTBZ
  • functional connectivity
  • motivation
  • older adults
  • pet imaging

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