Subthalamic nucleus shows opposite functional connectivity pattern in Huntington's and Parkinson's disease.

Autor:	Evangelisti S; FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK.; Department of Biomedical and Neuromotor Sciences, University of Bologna, 40127 Bologna, Italy., Boessenkool S; FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK., Pflanz CP; FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK.; Stroke Research Group, Department of Clinical Neuroscience, University of Cambridge, CB2 0QQ Cambridge, UK., Basting R; FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK.; Department of Experimental Psychology, University of Oxford, OX2 6GG Oxford, UK., Betts JF; FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK., Jenkinson M; FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK.; School of Computer Science, Faculty of Engineering, University of Adelaide, 5005 Adelaide, Australia., Clare S; FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK., Muhammed K; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK., LeHeron C; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK.; New Zealand Brain Research Institute, 8011 Christchurch, New Zealand., Armstrong R; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK., Klein JC; FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK., Husain M; FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK.; Department of Experimental Psychology, University of Oxford, OX2 6GG Oxford, UK., Nemeth AH; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK., Hu MT; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK., Douaud G; FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, University of Oxford, OX3 9DU Oxford, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DU Oxford, UK.
Jazyk:	angličtina
Zdroj:	Brain communications [Brain Commun] 2023 Dec 06; Vol. 5 (6), pp. fcad282. Date of Electronic Publication: 2023 Dec 06 (Print Publication: 2023).
DOI:	10.1093/braincomms/fcad282
Abstrakt:	Huntington's and Parkinson's disease are two movement disorders representing mainly opposite states of the basal ganglia inhibitory function. Despite being an integral part of the cortico-subcortico-cortical circuitry, the subthalamic nucleus function has been studied at the level of detail required to isolate its signal only through invasive studies in Huntington's and Parkinson's disease. Here, we tested whether the subthalamic nucleus exhibited opposite functional signatures in early Huntington's and Parkinson's disease. We included both movement disorders in the same whole-brain imaging study, and leveraged ultra-high-field 7T MRI to achieve the very fine resolution needed to investigate the smallest of the basal ganglia nuclei. Eleven of the 12 Huntington's disease carriers were recruited at a premanifest stage, while 16 of the 18 Parkinson's disease patients only exhibited unilateral motor symptoms (15 were at Stage I of Hoehn and Yahr off medication). Our group comparison interaction analyses, including 24 healthy controls, revealed a differential effect of Huntington's and Parkinson's disease on the functional connectivity at rest of the subthalamic nucleus within the sensorimotor network, i.e. an opposite effect compared with their respective age-matched healthy control groups. This differential impact in the subthalamic nucleus included an area precisely corresponding to the deep brain stimulation 'sweet spot'-the area with maximum overall efficacy-in Parkinson's disease. Importantly, the severity of deviation away from controls' resting-state values in the subthalamic nucleus was associated with the severity of motor and cognitive symptoms in both diseases, despite functional connectivity going in opposite directions in each disorder. We also observed an altered, opposite impact of Huntington's and Parkinson's disease on functional connectivity within the sensorimotor cortex, once again with relevant associations with clinical symptoms. The high resolution offered by the 7T scanner has thus made it possible to explore the complex interplay between the disease effects and their contribution on the subthalamic nucleus, and sensorimotor cortex. Taken altogether, these findings reveal for the first time non-invasively in humans a differential, clinically meaningful impact of the pathophysiological process of these two movement disorders on the overall sensorimotor functional connection of the subthalamic nucleus and sensorimotor cortex. Competing Interests: The authors report no competing interests. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
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