To determine the relationship between uric acid (UA) levels and substantia nigra functional connectivity (SN-FC) in REM sleep behavior disorder (RBD) and Parkinson’s disease (PD) patients.

Low levels of the natural antioxidant uric acid (UA) and the presence of RBD are associated with an increased likelihood of developing PD, especially in males. RBD and PD are also accompanied by decreased nigrostriatal and nigrocortical resting state functional connectivity. 

Whole brain resting state fMRI, T1-weighted MRIs, and serum UA were collected from 11 Controls, 23 PD patients, and 32 subjects with RBD. AFNI’s afni_proc.py routine was used to analyze fMRI with motion censoring and regression of confounding signals from ventricles and white matter. Group statistical analysis with AFNI’s 3dGroupInCorr was performed using an average seed time series built from a probabilistic mask of left and right substantia nigra.

In sensorimotor and prefrontal cortical regions of Controls, higher UA levels were accompanied by lower SN-FC, while in occipital cortex and thalamus higher UA levels were accompanied by higher SN-FC. Both RBD and PD patients exhibited opposite relationships in these regions, with higher UA accompanied by higher SN-FC in sensorimotor and prefrontal areas, and higher UA accompanied by lower SN-FC in the thalamus and occipital cortex. 

The positive and negative modulation of thalamic and sensorimotor SN-FC respectively by UA in Controls suggests a healthy state in which thalamus inhibits cortex, whereas a switch in these functional relationships in RBD and PD may reflect neurodegeneration-related changes in cortico-basal ganglia-thalamic connectivity. Comparison of PD and RBD patients revealed a positive relationship between UA and SN-FC including putamen, caudate, and precentral gyrus consistent with a potential role of UA in promoting SN-FC integrity during the later disease stage. These exploratory findings, highlight the importance of exploring relationships among multiple putative biomarkers in prodromal and clinically defined PD.