Motor Sequence Learning Deficits in Idiopathic Parkinson’s Disease Are Associated With Increased Substantia Nigra Activity

Media type: E-Article

Title: Motor Sequence Learning Deficits in Idiopathic Parkinson’s Disease Are Associated With Increased Substantia Nigra Activity

Contributor: Tzvi, Elinor [Author]; Bey, Richard [Author]; Nitschke, Matthias [Author]; Brüggemann, Norbert [Author]; Classen, Joseph [Author]; Münte, Thomas F. [Author]; Krämer, Ulrike M. [Author]; Rumpf, Jost-Julian [Author]

imprint: Lausanne: Frontiers Research Foundation, [2023]

Language: English

Keywords: Parkinson’s disease ; motor sequence learning ; substantia nigra ; dynamic causal modeling ; hippocampus ; fMRI

Origination:

Footnote:

Description: Previous studies have shown that persons with Parkinson’s disease (pwPD) sharespecific deficits in learning new sequential movements, but the neural substrates ofthis impairment remain unclear. In addition, the degree to which striatal dopaminergicdenervation in PD affects the cortico-striato-thalamo-cerebellar motor learning networkremains unknown. We aimed to answer these questions using fMRI in 16 pwPD and 16healthy age-matched control subjects while they performed an implicit motor sequencelearning task. While learning was absent in both pwPD and controls assessed withreaction time differences between sequential and random trials, larger error-rates duringthe latter suggest that at least some of the complex sequence was encoded. Moreover,we found that while healthy controls could improve general task performance indexedby decreased reaction times across both sequence and random blocks, pwPD couldnot, suggesting disease-specific deficits in learning of stimulus-response associations.Using fMRI, we found that this effect in pwPD was correlated with decreased activityin the hippocampus over time. Importantly, activity in the substantia nigra (SN) andadjacent bilateral midbrain was specifically increased during sequence learning inpwPD compared to healthy controls, and significantly correlated with sequence-specificlearning deficits. As increased SN activity was also associated (on trend) with higherdoses of dopaminergic medication as well as disease duration, the results suggest thatlearning deficits in PD are associated with disease progression, indexing an increaseddrive to recruit dopaminergic neurons in the SN, however, unsuccessfully. Finally, therewere no differences between pwPD and controls in task modulation of the cortico-striato-thalamo-cerebellar network. However, a restricted nigral-striatal model showedthat negative modulation of SN to putamen connection was larger in pwPD comparedto controls during random trials, while no differences between the groups were foundduring sequence learning. We speculate that learning-specific SN recruitment leads to arelative increase in SN- > putamen connectivity, which returns to a pathological reducedstate when no learning takes place

Access State: Open Access

Rights information: Attribution (CC BY)

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