Functional Activity, Functional Connectivity and Complex Network Biomarkers of Progressive Hyposmia Parkinson’s Disease with No Cognitive Impairment: Evidences from Resting-state fMRI Study

Abstract

Background: Olfactory dysfunction stands as one of the most prevalent non-motor symptoms in the initial stage of Parkinson's disease (PD). Nevertheless, the intricate mechanisms underlying olfactory deficits in Parkinson's disease still remain elusive. Methods: This study collected rs-fMRI data from 30 PD patients (15 with severe hyposmia (PD-SH) and 15 with no/mild hyposmia (PD-N/MH)) and 15 healthy controls (HC). To investigate functional segregation, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were utilized. Functional connectivity (FC) analysis was performed to explore the functional integration across diverse brain regions. Additionally, the graph theory-based network analysis was employed to assess functional networks in PD patients. Furthermore, Pearson correlation analysis was conducted to delve deeper into the relationship between the severity of olfactory dysfunction and various functional metrics. Results: Firstly, PD patients showed significantly higher ALFF values in the superior temporal gyrus compared to HC, especially in the PD-SH group versus PD-N/MH. Meanwhile, ALFF values in this region negatively correlated with olfactory testing scores. Secondly, PD patients had higher ReHo in middle temporal gyrus and superior frontal gyrus than HC, especially PD-SH. Meanwhile, olfactory scores negatively correlated with these ReHo values. Thirdly, we observed a negative correlation between superior cerebellar-insula connectivity and olfactory scores, suggesting a neural circuit link to olfactory dysfunction. Lastly, the PD patients' brain networks consistently showed small-world attributes, with the PD-N/MH group having significantly higher nodal betweenness in the superior cerebellum than the PD-SH group. There's also a positive link between superior cerebellum's betweenness and olfactory scores. Additionally, there is a notable difference in the node degree of the superior temporal gyrus when comparing the PD-SH group to the PD-N/MH group. Conclusion: Using fMRI, our study analyzed brain function in PD-SH, PD-N/MH, and HC groups, revealing impaired segregation and integration in PD-SH and PD-N/MH. We hypothesize that changes in temporal, frontal, occipital, and cerebellar activities, along with aberrant cerebellum-insula connectivity and node degree and betweenness disparities, may be linked to olfactory dysfunction in PD patients.