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Mov Disord. 2017 Jun;32(6):874-883. doi: 10.1002/mds.27017. Epub 2017 May 8.

l-Dopa responsiveness is associated with distinctive connectivity patterns in advanced Parkinson's disease.

Author information

1
Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK.
2
Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
3
Department of Neurosurgery, Jefferson University Hospitals, Philadelphia, Pennsylvania, USA.
4
Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, UK.
5
Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK.
6
Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
7
Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK.
8
Centre for Functional MRI of the Brain (FMRIB), John Radcliffe Hospital, Oxford, UK.

Abstract

BACKGROUND:

Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement.

METHODS:

To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to l-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3 × 3 × 2.5 mm3 voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an l-dopa challenge. False discovery rate-corrected P was set at < 0.05 for a 2-tailed t test.

RESULTS:

A greater improvement in UPDRS-III scores following l-dopa administration was characterized by higher resting-state functional connectivity between the prefrontal cortex and the striatum (P = 0.001) and lower resting-state functional connectivity between the pallidum (P = 0.001), subthalamic nucleus (P = 0.003), and the paracentral lobule (supplementary motor area, mesial primary motor, and primary sensory areas).

CONCLUSIONS:

Our findings show characteristic basal ganglia resting-state functional connectivity patterns associated with different degrees of l-dopa responsiveness in patients with advanced Parkinson's disease. l-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response. © 2017 International Parkinson and Movement Disorder Society.

KEYWORDS:

Parkinson's disease; basal ganglia; connectivity; l-dopa; resting state

PMID:
28597560
DOI:
10.1002/mds.27017
[Indexed for MEDLINE]

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