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bioRxiv · 10.1101/2020.01.31.928853

Effects of dopamine agonist treatment on resting-state network connectivity in Parkinson's disease

Cole, D. M.·Mohammadi, B.·Milenkova, M.·Kollewe, K.·Schrader, C.·Samii, A.·Dengler, R.·Muente, T. F.·Beckmann, C. F.
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Abstract

Dopamine agonist (DA) medications commonly used to treat, or normalise, motor symptoms of Parkinsons disease (PD) may lead to cognitive-neuropsychiatric side effects, such as increased impulsivity in decision-making. Subject-dependent variation in the neural response to dopamine modulation within cortico-basal ganglia circuitry is thought to play a key role in these latter, non-motor DA effects. This neuroimaging study combined resting-state functional magnetic resonance imaging (fMRI) with DA modification in patients with idiopathic PD, investigating whether brain resting-state network (RSN) functional connectivity metrics identify disease-relevant effects of dopamine on systems-level neural processing. By comparing patients both On and Off their DA medications with age-matched, un-medicated healthy control subjects (HCs), we identified multiple non-normalising DA effects on frontal and basal ganglia RSN cortico-subcortical connectivity patterns in PD. Only a single isolated, potentially normalising, DA effect on RSN connectivity in sensori-motor systems was observed, within cerebro-cerebellar neurocircuitry. Impulsivity in reward-based decision-making was positively correlated with ventral striatal connectivity within basal ganglia circuitry in HCs, but not in PD patients. Overall, we provide brain systems-level evidence for anomalous DA effects in PD on large-scale networks supporting cognition and motivated behaviour. Moreover, findings suggest that dysfunctional striatal and basal ganglia signalling patterns in PD are compensated for by increased recruitment of other cortico-subcortical and cerebro-cerebellar systems.

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Cole, D. M., Mohammadi, B., Milenkova, M., Kollewe, K., Schrader, C., Samii, A., Dengler, R., Muente, T. F., Beckmann, C. F.. 2020-01-31. Effects of dopamine agonist treatment on resting-state network connectivity in Parkinson's disease. https://doi.org/10.1101/2020.01.31.928853

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