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Neuroimage. 2019 Apr 15;190:79-93. doi: 10.1016/j.neuroimage.2018.11.021. Epub 2018 Nov 20.

The role of dopamine in the brain - lessons learned from Parkinson's disease.

Author information

1
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. Electronic address: davidm@drcmr.dk.
2
Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
3
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, UK.
4
Institut du Cerveau et de la Moelle épinière - ICM, Centre de NeuroImagerie de Recherche - CENIR, Sorbonne Université, UPMC Univ Paris 06, Paris, France; Inserm U1127, CNRS UMR 7225, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
5
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.

Abstract

Parkinson's disease causes a characteristic combination of motor symptoms due to progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta. The core impairment of dopaminergic neurotransmission has motivated the use of functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease to elucidate the role of dopamine in motor control and cognition in humans. Here we review the main insights from functional brain imaging in Parkinson's disease. Task-related fMRI revealed many disease-related alterations in brain activation patterns. However, the interpretation of these findings is complicated by the fact that task-dependent activity is influenced by complex interactions between the amount of dopaminergic neurodegeneration in the task-relevant nuclei, the state of medication, genetic factors and performance. Despite these ambiguities, fMRI studies in Parkinson's disease demonstrated a central role of dopamine in the generation of movement vigour (bradykinesia) and the control of excessive movements (dyskinesia), involving changes of both activity and connectivity of the putamen, premotor and motor regions, and right inferior frontal gyrus (rIFG). The fMRI studies addressing cognitive flexibility provided convergent evidence for a non-linear, U-shaped, relationship between dopamine levels and performance. The amount of neurodegeneration in the task-relevant dopaminergic nuclei and pharmacological dopamine replacement can therefore move performance either away or towards the task-specific optimum. Dopamine levels also strongly affect processing of reward and punishment for optimal learning. However, further studies are needed for a detailed understanding of the mechanisms underlying these effects.

KEYWORDS:

Cognitive control; Dopamine; Motor control; Parkinson's disease; Reward

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