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L-Dopa Responsiveness Is Associated With Distinctive Connectivity Patterns in Advanced Parkinson's Disease

Akram, H; Wu, C; Hyam, J; Foltynie, T; Limousin, P; De Vita, E; Yousry, T; ... Zrinzo, L; + view all (2017) L-Dopa Responsiveness Is Associated With Distinctive Connectivity Patterns in Advanced Parkinson's Disease. Movement Disorders , 32 (6) pp. 874-883. 10.1002/mds.27017.

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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

Type: Article
Title: L-Dopa Responsiveness Is Associated With Distinctive Connectivity Patterns in Advanced Parkinson's Disease
DOI: 10.1002/mds.27017
Publisher version: http://dx.doi.org/10.1002/mds.27017
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, resting state, connectivity, Parkinson's disease, basal ganglia, L-dopa, STATE FUNCTIONAL CONNECTIVITY, GLOBAL SIGNAL REGRESSION, INFERIOR FRONTAL-CORTEX, DEFAULT MODE NETWORK, RESTING-STATE, BASAL GANGLIA, SUBTHALAMIC NUCLEUS, STRUCTURAL CONNECTIVITY, RESPONSE-INHIBITION, NOISE CORRECTION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
URI: http://discovery.ucl.ac.uk/id/eprint/1559000
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