Abnormalities in the Fractional Amplitude of Low-Frequency Fluctuation and Functional Connectivity in Parkinson's Disease With Excessive Daytime Sleepiness

Abstract

BackgroundExcessive daytime sleepiness (EDS) is one of the most important non-motor symptoms of Parkinson's disease (PD), and its neuropathologic basis is still unclear.ObjectiveThis study investigated the changes of neuronal activity in PD patients with EDS (PD-EDS) in the resting state.MethodsForty-three PD patients were recruited and divided into the PD-EDS group (n = 21) and PD-NEDS group (PD patients without excessive daytime sleepiness, n = 22) according to the Epworth sleepiness scale (ESS) scores. Patients in both groups received resting-state functional magnetic resonance imaging (rs-fMRI). The differences in fractional amplitude of low-frequency fluctuation (fALFF) between the two groups, correlations between fALFF and ESS, and functional connection (FC) between the brain regions with different fALFF values and the whole brain were analyzed.ResultsPD-EDS patients exhibited a decreased fALFF in the Cingulum-Ant-R, but an increased fALFF in the Putamen-R and Thalamus-L when compared with PD-NEDS patients; an increased functional connectivity between these three seed regions with different fALFF values and the right medial frontal gyrus, bilateral superior temporal gyrus, left insular, and right precuneus was observed (p < 0.05), but a deceased functional connectivity between these three seed regions and the right cerebellum anterior lobe/right brainstem, right middle temporal gyrus and inferior temporal gyrus, right hippocampus/parahippocampal gyrus, right medial cingulate gyrus and bilateral middle occipital gyrus was observed (p < 0.05). The value of fALFF was negatively correlated with the ESS score in the Cingulum-Ant-R, but positively correlated with the ESS score in the Putamen-R and Thalamus-L.ConclusionsEDS in PD patients may be associated with changes in brain neuron activity and functional connectivity.

Spontaneous brain activity in the hippocampal regions could characterize cognitive impairment in patients with Parkinson's disease

“…Zi performed statistical differences in fALFF between patients in PD with excessive daytime sleepiness and analyzed the changes in the functional connection within the whole brain. It was found that the functional connectivity in the right hippocampus/parahippocampal was decreased, which resulted in damage to the dopaminergic circuits in the limbic system and subsequently inhibited the arousal mechanism 49 . However, Wang found that ALFF was elevated in the hippocampal structure in PD patients, and the hippocampus was an important structure for studying PD 50 …”

“…It was found that the functional connectivity in the right hippocampus/parahippocampal was decreased, which resulted in damage to the dopaminergic circuits in the limbic system and subsequently inhibited the arousal mechanism. 49 However, Wang found that ALFF was elevated in the hippocampal structure in PD patients, and the hippocampus was an important structure for studying PD. 50 By comparing the fALFF of three cognitive groups, we found that the parahippocampal gyrus corresponding to the ROI 5 brain region was the different brain region of the three cognitive groups, and it was also the only brain region to identify MCI from NC.…”

Altered dynamic functional network connectivity in drug-naïve Parkinson’s disease patients with excessive daytime sleepiness

“…The CB may also be associated with EDS symptoms in PD patients. Compared with the patients in the PD-noEDS group, the patients in the PD-EDS group had decreased connectivity within the CB, decreased connectivity between the CB and the insula, frontal lobe, and BG regions, and enhanced connectivity with the postcentral gyrus (Wen et al, 2016;Ashraf-Ganjouei et al, 2019;Zi et al, 2022;Zheng et al, 2023). Strong functional connectivity was observed between the CB and BG after sleep deprivation, which was thought to be a natural response to the decrease in motor alertness (Zhang et al, 2019).…”

“…The amplitude of low-frequency fluctuation (ALFF), fractional ALFF and regional homogeneity methods reflect the intensity and consistency of spontaneous activities among brain regions. Previous studies have displayed increases in spontaneous neural activity in the medial prefrontal cortex, paracentral lobule, thalamus, putamen and pons and decreases in the inferior frontal gyrus, angular gyrus, cingulate cortex and cerebellum in patients of PD with EDS (PD-EDS) ( Wen et al, 2016 ; Wang et al, 2020 ; Zi et al, 2022 ; Zheng et al, 2023 ). Functional connectivity analysis can be used to evaluate correlations and synchronization at brain regions and the whole brain network levels.…”

“…Functional connectivity analysis can be used to evaluate correlations and synchronization at brain regions and the whole brain network levels. Multiple studies have demonstrated that EDS in PD patients may be associated with abnormal functional connectivity among various brain regions, including the default mode network (DMN), cognitive executive network (CEN), salience network (SN) and cerebellum (CB) ( Wen et al, 2016 ; Ooi et al, 2019 ; Wang et al, 2020 ; Zi et al, 2022 ; Zheng et al, 2023 ). However, these static rs-fMRI data were measured under the assumption that the intrinsic fluctuations during MRI scans are stationary, ignoring the temporal dynamic properties of functional connectivity.…”