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

Oxford University Press (OUP) https://doi.org/10.1093/braincomms/fcad282 Brain Commun 2024-01-25T08:40:40Z 2023 2022-11-25 2024-01-25T08:40:39Z

Acknowledgements: The authors would like to thank in particular our participants and their families, the radiographers Jon Campbell, Mike Sanders, David Parker and Caroline Young, as well as Jess Myring and Jane Rumbold. We would also like to thank Prof. Amedi’s group for sharing their somatotopic maps with us, and Prof. Anderson Winkler for statistical advice.
Funder: Wellcome Principal Research Fellowship
Funder: National Institute for Health and Care Research Oxford Biomedical Research Centre
Funder: National Institute for Health and Care Research Oxford Health Clinical Research Facility
Funder: National Institute for Health and Care Research Clinical Lectureship
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 resolutio

Huntington’s; Parkinson’s; differential effect; functional connectivity; subthalamic nucleus; Article

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