Previous studies have shown that persons with Parkinson’s disease (pwPD) share
specific deficits in learning new sequential movements, but the neural substrates of
this impairment remain unclear. In addition, the degree to which striatal dopaminergic
denervation in PD affects the cortico-striato-thalamo-cerebellar motor learning network
remains unknown. We aimed to answer these questions using fMRI in 16 pwPD and 16
healthy age-matched control subjects while they performed an implicit motor sequence
learning task. While learning was absent in both pwPD and controls assessed with
reaction time differences between sequential and random trials, larger error-rates during
the latter suggest that at least some of the complex sequence was encoded. Moreover,
we found that while healthy controls could improve general task performance indexed
by decreased reaction times across both sequence and random blocks, pwPD could
not, suggesting disease-specific deficits in learning of stimulus-response associations.
Using fMRI, we found that this effect in pwPD was correlated with decreased activity
in the hippocampus over time. Importantly, activity in the substantia nigra (SN) and
adjacent bilateral midbrain was specifically increased during sequence learning in
pwPD compared to healthy controls, and significantly correlated with sequence-specific
learning deficits. As increased SN activity was also associated (on trend) with higher
doses of dopaminergic medication as well as disease duration, the results suggest that
learning deficits in PD are associated with disease progression, indexing an increased
drive to recruit dopaminergic neurons in the SN, however, unsuccessfully. Finally, there
were no differences between pwPD and controls in task modulation of the cortico-striato-thalamo-cerebellar network. However, a restricted nigral-striatal model showed
that negative modulation of SN to putamen connection was larger in pwPD compared
to controls during random trials, while no differences between the groups were found
during sequence learning. We speculate that learning-specific SN recruitment leads to a
relative increase in SN- > putamen connectivity, which returns to a pathological reduced
state when no learning takes place
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84327 |
| Date | 27 March 2023 |
| Creators | Tzvi, Elinor, Bey, Richard, Nitschke, Matthias, Brüggemann, Norbert, Classen, Joseph, Münte, Thomas F., Krämer, Ulrike M., Rumpf, Jost-Julian |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1663-4365, 685168 |
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