Alterations in cortical volume and complexity in Parkinson's disease with depression.

AIMS: The aim of this study is to investigate differences in gray matter volume and cortical complexity between Parkinson's disease with depression (PDD) patients and Parkinson's disease without depression (PDND) patients. METHODS: A total of 41 PDND patients, 36 PDD patients, and 38 healthy controls (HC) were recruited and analyzed by Voxel-based morphometry (VBM) and surface-based morphometry (SBM). Differences in gray matter volume and cortical complexity were compared using the one-way analysis of variance (ANOVA) and correlated with the Hamilton Depression Scale-17 (HAMD-17) scores. RESULTS: PDD patients exhibited significant cortical atrophy in various regions, including bilateral medial parietal-occipital-temporal lobes, right dorsolateral temporal lobes, bilateral parahippocampal gyrus, and bilateral hippocampus, compared to HC and PDND groups. A negative correlation between the GMV of left precuneus and HAMD-17 scores in the PDD group tended to be significant (r = -0.318, p = 0.059). Decreased gyrification index was observed in the bilateral insular and dorsolateral temporal cortex. However, there were no significant differences found in fractal dimension and sulcal depth. CONCLUSION: Our research shows extensive cortical structural changes in the insular cortex, parietal-occipital-temporal lobes, and hippocampal regions in PDD. This provides a morphological perspective for understanding the pathophysiological mechanism underlying depression in Parkinson's disease.

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

Background: Excessive daytime sleepiness (EDS) is one of the most important non-motor symptoms of Parkinson's disease (PD), and its neuropathologic basis is still unclear. Objective: This study investigated the changes of neuronal activity in PD patients with EDS (PD-EDS) in the resting state. Methods: Forty-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. Results: PD-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. Conclusions: EDS in PD patients may be associated with changes in brain neuron activity and functional connectivity.

Aberrant Changes in Cortical Complexity in Right-Onset Versus Left-Onset Parkinson's Disease in Early-Stage.

There is increasing evidence to show that motor symptom lateralization in Parkinson's disease (PD) is linked to non-motor features, progression, and prognosis of the disease. However, few studies have reported the difference in cortical complexity between patients with left-onset of PD (LPD) and right-onset of PD (RPD). This study aimed to investigate the differences in the cortical complexity between early-stage LPD and RPD. High-resolution T1-weighted magnetic resonance images of the brain were acquired in 24 patients with LPD, 34 patients with RPD, and 37 age- and sex-matched healthy controls (HCs). Cortical complexity including gyrification index, fractal dimension (FD), and sulcal depth was analyzed using surface-based morphometry via CAT12/SPM12. Familywise error (FWE) peak-level correction at p < 0.05 was performed for significance testing. In patients with RPD, we found decreased mean FD and mean sulcal depth in the banks of the left superior temporal sulcus (STS) compared with LPD and HCs. The mean FD in the left superior temporal gyrus (STG) was decreased in RPD compared with HCs. However, in patients with LPD, we did not identify significantly abnormal cortical complex change compared with HCs. Moreover, we observed that the mean FD in STG was negatively correlated with the 17-item Hamilton Depression Scale (HAMD) among the three groups. Our findings support the specific influence of asymmetrical motor symptoms in cortical complexity in early-stage PD and reveal that the banks of left STS and left STG might play a crucial role in RPD.

Alterations of Regional Homogeneity in the Mild and Moderate Stages of Parkinson's Disease.

Objectives: This study aimed to investigate alterations in regional homogeneity (ReHo) in early Parkinson's disease (PD) at different Hoehn and Yahr (HY) stages and to demonstrate the relationships between altered brain regions and clinical scale scores. Methods: We recruited 75 PD patients, including 43 with mild PD (PD-mild; HY stage: 1.0-1.5) and 32 with moderate PD (PD-moderate; HY stage: 2.0-2.5). We also recruited 37 age- and sex-matched healthy subjects as healthy controls (HC). All subjects underwent neuropsychological assessments and a 3.0 Tesla magnetic resonance scanning. Regional homogeneity of blood oxygen level-dependent (BOLD) signals was used to characterize regional cerebral function. Correlative relationships between mean ReHo values and clinical data were then explored. Results: Compared to the HC group, the PD-mild group exhibited increased ReHo values in the right cerebellum, while the PD-moderate group exhibited increased ReHo values in the bilateral cerebellum, and decreased ReHo values in the right superior temporal gyrus, the right Rolandic operculum, the right postcentral gyrus, and the right precentral gyrus. Reho value of right Pre/Postcentral was negatively correlated with HY stage. Compared to the PD-moderate group, the PD-mild group showed reduced ReHo values in the right superior orbital gyrus and the right rectus, in which the ReHo value was negatively correlated with cognition. Conclusion: The right superior orbital gyrus and right rectus may serve as a differential indicator for mild and moderate PD. Subjects with moderate PD had a greater scope for ReHo alterations in the cortex and compensation in the cerebellum than those with mild PD. PD at HY stages of 2.0-2.5 may already be classified as Braak stages 5 and 6 in terms of pathology. Our study revealed the different patterns of brain function in a resting state in PD at different HY stages and may help to elucidate the neural function and early diagnosis of patients with PD.

Changes in Degree Centrality of Network Nodes in Different Frequency Bands in Parkinson's Disease With Depression and Without Depression.

BACKGROUND: Depression induces an early onset of Parkinson's disease (PD), aggravates dyskinesia and cognitive impairment, and accelerates disease progression. However, it is very difficult to identify and diagnose PD with depression (PDD) in the early clinical stage. Few studies have suggested that the changes in neural networks are associated with PDD, while degree centrality (DC) has been documented to be effective in detecting brain network changes. OBJECTIVES: The objectives of this study are to explore DC changes between patients with PDD and without depression (PDND) and to find the key brain hubs involved with depression in PD patients. METHODS: One hundred and four PD patients and 54 healthy controls (HCs) underwent brain resting-state functional magnetic resonance imaging. The Data Processing and Analysis of Brain Imaging and Resting-State Functional Magnetic Resonance Data Analysis Toolkit were used for processing and statistical analysis. The DC value of each frequency band was calculated. One-way analysis of variance and a two-sample t-test for post hoc comparison were used to compare the differences of the DC values in different frequency bands among PDD, PDND, and healthy control group. Gaussian random field was used for multiple comparison correction. Pearson correlation analysis was performed between each individual's DC map and clinical indicators. RESULTS: The DC value of different brain regions changed in PDD and PDND in different frequency bands. The prefrontal lobe, limbic system, and basal ganglia were the main brain regions involved. PDD patients showed a wider range and more abnormal brain areas in the slow-4 frequency band (0.027-0.073 Hz) compared to the HCs. PDD showed a decreased DC value in the medial frontal gyrus, bilateral cuneus gyrus, right lingual gyrus, bilateral supplementary motor area (SMA), bilateral superior frontal gyrus, and left paracentral lobule, but an increased DC value in the bilateral brainstem, midbrain, bilateral parahippocampal gyrus, cerebellum, left superior temporal gyrus, bilateral insula, left fusiform gyrus, and left caudate nucleus in the traditional frequency band (0.01-0.08 Hz) compared to PDND patients. PDND patients displayed more abnormal functions in the basal ganglia in the slow-4 frequency band. CONCLUSION: The DC changes in PDD and PDND are frequency dependent and frequency specific. The medial frontal gyrus, SMA, and limbic system may be the key hubs for depression in PD.

Distinct Changes in Global Brain Synchronization in Early-Onset vs. Late-Onset Parkinson Disease.

Early- and late-onset Parkinson's disease (EOPD and LOPD, respectively) have different risk factors, clinical features, and disease course; however, the functional outcome of these differences have not been well characterized. This study investigated differences in global brain synchronization changes and their clinical significance in EOPD and LOPD patients. Patients with idiopathic PD including 25 EOPD and 24 LOPD patients, and age- and sex-matched healthy control (HC) subjects including 27 younger and 26 older controls (YCs and OCs, respectively) were enrolled. Voxel-based degree centrality (DC) was calculated as a measure of global synchronization and compared between PD patients and HC groups matched in terms of disease onset and severity. DC was decreased in bilateral Rolandic operculum and left insula and increased in the left superior frontal gyrus (SFG) and precuneus of EOPD patients compared to YCs. DC was decreased in the right putamen, mid-cingulate cortex, bilateral Rolandic operculum, and left insula and increased in the right cerebellum-crus1 of LOPD patients compared to OCs. Correlation analyses showed that DC in the right cerebellum-crus1 was inversely associated with the Hamilton Depression Scale (HDS) score in LOPD patients. Thus, EOPD and LOPD patients show distinct alterations in global synchronization relative to HCs. Furthermore, our results suggest that the left SFG and right cerebellum-crus1 play important roles in the compensation for corticostriatal-thalamocortical loop injury in EOPD and LOPD patients, whereas the cerebellum is a key hub in the neural mechanisms underlying LOPD with depression. These findings provide new insight into the clinical heterogeneity of the two PD subtypes.

Changed Resting-State Brain Signal in Parkinson's Patients With Mild Depression.

Background: Depression is reported to occur 5-10 years early than the onset of motor symptoms in Parkinson (PD) patients. However, markers for early diagnosis of PD in individuals with sub-clinical depression still remain to be identified. Purpose: This study utilized Regional Homogeneity (ReHo) to investigate the alterations in resting state brain activities in Parkinson (PD) patients with different degrees of depression. Methods: Twenty non-depressed PD patients, twenty mild to moderately depressed PD patients, and thirteen severely depressed PD patients were recruited. Hamilton Depression Scale (HDS) and the Beck Depression Inventory (BDI) were assessed depression. Resting-state functional magnetic resonance imaging (rs-MRI) was analyzed with ReHo. Results: PD patients with mild to moderate depression had decreased ReHo in the left dorsal anterior cingulate cortex when compared with PD patients without depression. PD patients with severe depression exhibited increased ReHo in the left inferior prefrontal gyrus and right orbitofrontal area when compared with PD patients with mild to moderate depression. ReHo values in the bilateral supplementary motor area (SMA) in PD patients with severe depression was also increased when compared with PD patients without depression. Conclusions: This study suggests that rs-MRI with ReHo analysis can detect early changes in brain function that associate with depression in PD patients, which could be biomarkers for early diagnosis and treatment of PD related depression.

Networks Are Associated With Depression in Patients With Parkinson's Disease: A Resting-State Imaging Study.

BACKGROUND: Disturbance of networks was recently proposed to be associated with the occurrence of depression in Parkinson's disease (PD). However, the neurobiological mechanism of depression underlying PD remains unclear. OBJECTIVE: This study was conducted to investigate whether intra-network and inter-network brain connectivity is differently changed in PD patients with and without depression (PDD and PDND patients, respectively). METHODS: Forty-one PDD patients, 64 PDND patients, and 55 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI). The default mode network (DMN), executive control network (ECN), salience network (SN), precuneus network (PCUN), and sensorimotor network (SMN) were extracted using independent component analysis (ICA), and then the functional connectivity (FC) values within and between these networks were measured. RESULTS: PDD patients exhibited abnormal FC values within the DMN, ECN, SN, PCUN, and SMN. In addition, PDD patients demonstrated decreased connectivity between anterior SN (aSN) and bilateral ECN, between posterior SN (pSN) and dorsal DMN (dDMN), and between PCUN and dDMN/SMN/bilateral ECN. Connectivity within the left hippocampus of dDMN and the right medial superior frontal gyrus of aSN was a significant predictor of depression level in PD patients. CONCLUSIONS: Aberrant intra- and inter-network FC is involved in several important hubs in the large-scale networks, which can be a biomarker for distinguishing PDD from PDND.