Locus coeruleus integrity correlates with inhibitory functions of the fronto-subthalamic 'hyperdirect' pathway in Parkinson's disease.

Abstract	A long-running debate concerns whether dopamine or noradrenaline deficiency drives response disinhibition in Parkinson's disease (PD). This study aimed to investigate whether damage to the locus coeruleus (LC) or substantia nigra (SN) might impact inhibitory functions of the fronto-subthalamic hyperdirect or fronto-striatal indirect pathway. Patients with PD (n = 29, 13 women) and matched healthy controls (n = 29, 15 women) participated in this cross-sectional study. LC and SN integrity was assessed using neuromelanin-sensitive MRI. Response inhibition was measured using fMRI with a stop-signal task. In healthy controls, LC (but not SN) integrity correlated with the stopping-related activity of the right inferior frontal gyrus (IFG) and right subthalamic nucleus (STN), which further correlated with stop-signal reaction time (SSRT). PD patients showed reduced LC integrity, longer SSRT, and lower stopping-related activity over the right IFG, pre-supplementary motor area, and right caudate nucleus than healthy controls. In PD patients, the relationship between SSRT and the fronto-subthalamic pathway was preserved. However, LC integrity no longer correlated with the stopping-related right IFG or right STN activity. No contribution of SN integrity was found during stopping. In conclusion, LC (but not SN) might modulate inhibitory functions of the right IFG-STN pathway. Damage to the LC might impact the right IFG-STN pathway during stopping, leading to response disinhibition in PD.
Authors	Biman Xu, Tingting He, Yuan Lu, Jia Jia, Barbara J Sahakian, Trevor W Robbins, Lirong Jin, Zheng Ye
Journal	NeuroImage. Clinical (Neuroimage Clin) Vol. 36 Pg. 103276 ( 2022) ISSN: 2213-1582 [Electronic] Netherlands
PMID	36510410 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Topics	Humans Female Parkinson Disease (diagnostic imaging, metabolism) Locus Coeruleus (diagnostic imaging) Cross-Sectional Studies Subthalamic Nucleus (diagnostic imaging, physiology) Reaction Time (physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!