Journal Article

FZJ-2024-03548

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Resting state changes in aging and Parkinson’s disease are shaped by underlying neurotransmission – a normative modeling study

Kasper, J.FZJ* ; Caspers, S.FZJ* ; Lotter, L. D.FZJ* ; Hoffstaedter, F.FZJ* ; Eickhoff, S. B.FZJ* ; Dukart, J. (Corresponding author)FZJ*

2024
Elsevier Inc. Amsterdam [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/j.bpsc.2024.04.010  doi:10.34734/FZJ-2024-03548

Abstract: BackgroundHuman healthy and pathological aging is linked to a steady decline in brain resting-state activity and connectivity measures. The neurophysiological mechanisms that underlie these changes remain poorly understood.MethodsMaking use of recent developments in normative modeling and availability of in vivo maps for various neurochemical systems, we tested in the UK Biobank cohort (n = 25,917) whether and how age- and Parkinson’s disease–related resting-state changes in commonly applied local and global activity and connectivity measures colocalize with underlying neurotransmitter systems.ResultsWe found that the distributions of several major neurotransmitter systems including serotonergic, dopaminergic, noradrenergic, and glutamatergic neurotransmission correlated with age-related changes across functional activity and connectivity measures. Colocalization patterns in Parkinson’s disease deviated from normative aging trajectories for these, as well as for cholinergic and GABAergic (gamma-aminobutyric acidergic) neurotransmission. The deviation from normal colocalization of brain function and GABAA correlated with disease duration.ConclusionsThese findings provide new insights into molecular mechanisms underlying age- and Parkinson’s-related brain functional changes by extending the existing evidence elucidating the vulnerability of specific neurochemical attributes to normal aging and Parkinson’s disease. The results particularly indicate that alongside dopamine and serotonin, increased vulnerability of glutamatergic, cholinergic, and GABAergic systems may also contribute to Parkinson’s disease–related functional alterations. Combining normative modeling and neurotransmitter mapping may aid future research and drug development through deeper understanding of neurophysiological mechanisms that underlie specific clinical conditions.

Note: This work was supported by the European Union’s Horizon 2020 research and innovation program (Grant No. 826421 [to JD]); TheVirtualBrain-Cloud; the European Union’s Horizon 2020 research and innovation program (Grant No. 945539 [to SC and SBE]) (Human Brain Project SGA3); and the Federal Ministry of Education and Research and the Max Planck Society, Germany (to LDL).

---

Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)
2. Gehirn & Verhalten (INM-7)

Research Program(s):

1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)
2. HBP SGA3 - Human Brain Project Specific Grant Agreement 3 (945539) (945539)

Appears in the scientific report 2024

---

Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---