Free water imaging reveals asynchronous dopaminergic degeneration in substantia nigra and ventral tegmental area in prodromal and early Parkinson's disease
Kaiyue Ding , Yu Shen , Yan Bai , Wei Wei , Neil Roberts , Ningli Wang , Xinhui Wang , Guofeng Shen , Xianchang Zhang , Chaowei Sun , Xiaosheng Song , Meiyun Wang
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Abstract
Purpose
The ventral tegmental area (VTA), which is rich in dopaminergic neurons, may play a role in influencing clinical symptoms in Parkinson's Disease (PD). However, the degeneration dynamics of the VTA during the early and prodromal stages of PD remain unclear. This study aims to explore microstructural changes in the VTA among prodromal PD patients with idiopathic REM sleep behavior disorder (iRBD) and early-stage PD patients using free water imaging (FWI) to assess free water (FW) and its correlation with clinical symptoms.
Method
Diffusion tensor imaging data from 238 participants, including 69 healthy controls (HC), 54 iRBD patients, and 115 PD patients. FW values were computed using a bi-tensor model, and comparisons were done between the HC, iRBD, and PD groups. Additionally, the relationship between FW values in the VTA and substantia nigra pars compacta (SNc) and clinical symptoms was explored through baseline assessments and longitudinal tracking of iRBD patients.
Results
FW values in the SNc significantly increased in iRBD and PD patients compared to HC, with the PD group exhibiting even higher FW values. Initially, the FW values in the VTA in iRBD patients did not significantly differ from those of HC but increased in early PD, correlating with anxiety and motor deficits. Longitudinal tracking revealed FW increases in the SNc and VTA in iRBD patients over time.
Conclusion
The present findings revealed a desynchronized degeneration pattern between the VTA and SNc, with no degeneration observed in the prodromal phase but gradual changes over time, leading to pronounced VTA degeneration in early PD. This underscores the impact of early VTA changes on PD symptoms, contributing to understanding of PD pathophysiology.
期刊介绍：
The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.
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