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BackgroundAlthough the study of the neuroanatomical correlates of depression in Parkinson’s Disease (PD) is gaining increasing interest, up to now the cortical gyrification pattern of PD-related depression has not been reported. This study was conducted to investigate the local gyrification index (LGI) in PD patients with depression, and its associations with the severity of depression.MethodsLGI values, as measured using FreeSurfer software, were compared between 59 depressed PD (dPD), 27 non-depressed PD (ndPD) patients and 43 healthy controls. The values were also compared between ndPD and mild-depressed PD (mi-dPD), moderate-depressed PD (mo-dPD) and severe-depressed PD (se-dPD) patients as sub-group analyses. Furthermore, we evaluated the correlation between LGI values and depressive symptom scores within dPD group.ResultsCompared to ndPD, the dPD patients exhibited decreased LGI in the left parietal, the right superior-frontal, posterior cingulate and paracentral regions, and the LGI values within these areas negatively correlated with the severity of depression. Specially, reduced gyrification was observed in mo-dPD and involving a larger region in se-dPD, but not in mi-dPD group.ConclusionThe present study demonstrated that cortical gyrification is decreased within specific brain regions among PD patients with versus without depression, and those changes were associated with the severity of depression. Our findings suggested that cortical gyrification might be a potential neuroimaging marker for the severity of depression in patients with PD.

This study investigated alterations in degree centrality (DC) in different motor subtypes of Parkinson’s disease (PD) and analyzed its clinical significance during disease occurrence. A total of 146 subjects were recruited in the study, including 90 patients with PD [51 and 39 with tremor dominant (TD) and akinetic-rigid dominant (ARD) disease, respectively] and 56 healthy controls (HCs). The resting-state functional magnetic resonance imaging data of all the subjects were obtained by 3.0 T magnetic resonance scans. The DC values, an indicator of whole brain synchronization, were calculated and compared among the TD, ARD, and HC groups. Disparities in DC values among the three groups were evaluated by analysis of variance and post hoc two-sample t-tests. Correlation between brain regions with DC differences and clinical variables were performed using partial correlation analysis after controlling for age, gender, and disease duration. Compared to the HCs, both TD and ARD groups demonstrated increased DC values bilaterally in the cerebellum; DC values were decreased in the left putamen and paracentral lobule in the TD group and in the left anterior cingulate gyrus and right supplementary motor area in the ARD group. Compared to the ARD group, the TD group showed decreased DC values in bilateral cerebellar hemispheres and increased DC values in the left anterior cingulate gyrus and right supplementary motor area. The DC of the whole brain showed inconsistencies and shared neural bases among patients with the two subtypes of PD. The differences between brain regions with abnormal DC values may be closely related to different clinical presentations of the two motor subtypes. Our findings provide new insights into the clinical heterogeneity of PD with respect to different motor subtypes.

ObjectiveThe purpose of this study is to look into the altered functional connectivity of brain networks in Early-Onset Parkinson’s Disease (EOPD) and Late-Onset Parkinson’s Disease (LOPD), as well as their relationship to clinical symptoms.MethodsA total of 50 patients with Parkinson’ disease (28 EOPD and 22 LOPD) and 49 healthy controls (25 Young Controls and 24 Old Controls) were admitted to our study. Employing independent component analysis, we constructed the brain networks of EOPD and Young Controls, LOPD and Old Controls, respectively, and obtained the functional connectivity alterations in brain networks.ResultsCerebellar network (CN), Sensorimotor Network (SMN), Executive Control Network (ECN), and Default Mode Network (DMN) were selected as networks of interest. Compared with their corresponding health controls, EOPD showed increased functional connectivity within the SMN and ECN and no abnormalities of inter-network functional connectivity were found, LOPD demonstrated increased functional connectivity within the ECN while decreased functional connectivity within the CN. Furthermore, in LOPD, functional connectivity between the SMN and DMN was increased. The functional connectivity of the post-central gyrus within the SMN in EOPD was inversely correlated with the Unified Parkinson’s Disease Rating Scale Part III scores. Age, age of onset, and MMSE scores are significantly different between EOPD and LOPD (p < 0.05).ConclusionThere is abnormal functional connectivity of networks in EOPD and LOPD, which could be the manifestation of the associated pathological damage or compensation.

ObjectiveThe aim of this study is to explore the neural network mechanism of Parkinson’s disease (PD) with different degrees of depression using independent component analysis (ICA) of the functional connectivity changes in the forehead, limbic system, and basal ganglia regions.MethodsA total of 106 patients with PD were divided into three groups: PD with moderate-severe depression (PDMSD, n = 42), PD with mild depression (PDMD, n = 29), and PD without depression (PDND, n = 35). Fifty gender- and age-matched healthy subjects were recruited as a control group (HC). Three-dimensional T1-weighted image and resting-state functional magnetic resonance imaging (RS-fMRI) data were collected.ResultsDifferent functional connectivity was observed in the left precentral gyrus, right precuneus, right inferior frontal gyrus, right medial and paracingulate gyrus, left supplementary motor area, right brain insula, and the inferior frontal gyrus of the left orbit among the four groups (ANOVA, P < 0.05, Voxel size > 5). Both PDMD and PDMSD exhibited increased functional connectivity in the superior-posterior default-mode network (spDMN) and left frontoparietal network (LFPN); they also exhibited a decreased functional connectivity in the interior Salience Network (inSN) when compared with the PDND group. The functional connectivity within the inSN network was decreased in the PDMSD group when compared with the PDMD group (Alphasim correction, P < 0.05, voxel size > 5).ConclusionPD with different degrees of depression has abnormal functional connectivity in multiple networks, which is an important neurobiological basis for the occurrence and development of depression in PD. The degree of decreased functional connectivity in the inSN network is related to the degree of depression in patients with PD-D, which can be an imaging marker for PD to judge the severity of depression.

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.

Background: Recently, many studies have shown that low vitamin D (VD) levels may be related to an increased risk of Parkinson’s disease (PD), but the underlying mechanisms remain unclear.Objective: To explore the relationship between PD and VD levels, as well as to analyze the effects of VD on spontaneous brain activity and explore the possible mechanism of its involvement in PD risk.Methods: In a cross-sectional study, we quantified the difference in VD levels between 330 PD patients and 209 healthy controls (HC) to explore the correlation between VD and PD risk. We also acquired resting-state Functional Magnetic Resonance Imaging (rs-fMRI) data from 46 PD patients and 21 HC. The PD patients were divided into three groups according to 25(OH)D levels: PD patients with VD deficiency (PD + VDD), PD patients with VD insufficiency (PD + VDI), and PD patients with normal VD (PD + NVD). The effect of VD status on spontaneous neuronal activity in the whole brain was analyzed by measuring the fraction amplitude of low-frequency fluctuation (fALFF).Results: Compared with HC, the PD patients had lower serum 25(OH)D levels (23.60 ± 7.27 vs. 25.60 ± 5.78, P < 0.001). The 25(OH)D level may have a potential dose-dependent effect on the risk of PD (Ptrend = 0.007). A high risk of PD was associated with VD deficiency [25(OH)D < 20 ng/mL, OR = 2.319], and the lowest quartile of 25(OH)D concentration was associated with a high risk of PD (OR = 1.941). In the rs-fMRI study, PD + VDD patients had wider brain regions with altered fALFF than other PD groups when compared with the corresponding HC groups. Both PD + VDD and PD + VDI showed higher fALFF in the cuneus, left precuneus, calcarine cortex and right lingual, as well as lower fALFF in the left middle temporal gyrus. PD + VDD patients also showed higher fALFF in the left superior, middle and inferior frontal gyri, as well as the left precentral gyrus than HC. Among PD patients, there was only a statistically significant difference in fALFF between the PD + VDD and PD + NVD groups. Compared with the PD + NVD group, PD + VDD patients exhibited higher fALFF in the left precentral and left postcentral gyrus, as well as the left inferior parietal lobule.Conclusion: These results demonstrate that PD patients had lower serum VD levels than HC, and VD may have a potential dose-dependent effect on PD risk. Lower serum VD levels can affect the spontaneous neuronal activity of default-mode network (DMN) and visual pathway neurons in PD patients, providing a possible mechanism for its effect on PD risk.

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.

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.

BackgroundDepression 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.ObjectivesThe 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.MethodsOne 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.ResultsThe 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.ConclusionThe 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.

BackgroundDisturbance 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.ObjectiveThis 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).MethodsForty-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.ResultsPDD 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.ConclusionsAberrant 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.

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.

BackgroundDepression is the most common non-motor symptom in patients with Parkinson’s disease (PD) with unknown mechanisms, but the diagnostic criteria of PD with depression (PDD) are not uniform.PurposeThe aim of the study was to investigate interhemispheric interactions between PDD patients and patients with PD without depression (PDND).MethodsThe voxel-mirrored homotopic connectivity (VMHC) combined with the seed-based method was used to investigate intrinsic resting-state functional connectivity (RSFC) in 33 PDD patients, 60 PDND, and 47 healthy controls (HCs).ResultsPDD patients exhibited a decreased VMHC in the bilateral medial frontal gyrus and paracentral lobule (MFG/PCL) than did PDND patients. Parkinson’s disease with depression had a decreased VMHC in the bilateral precentral gyrus than had PDND and HC (p < 0.05). Parkinson’s disease with depression had a decreased homotopic RSFC from the medial frontal gyrus (MFG)/PCL to the contralateral supplementary motor area (SMA) than had PDND (p < 0.05). The decreased homotopic RSFC from the right MFG/PCL to the left SMA was negatively correlated with Hamilton Depression Rating Scale scores (p < 0.05), but not with illness duration, Beck’s Depression Inventory, and Unified Parkinson’s Disease Rating Scale in PD patients.ConclusionsOur findings indicated that the occurrence of depression in Parkinson’s disease is associated with the dysfunctional connectivity from the MFG/PCL to the contralateral SMA, which could be used as potential neuroimaging markers for the diagnosis of depression in PD patients.

Background: Previous studies have indicated the resting-state default mode network (DMN) related connectivity serving as predictor of sustained attention performance in healthy people. Interestingly, sustained attention deficits as well as DMN-involved functional connectivity (FC) alterations are common in both patients with schizophrenia (SCZ) and with obsessive-compulsive disorder (OCD). Thus, the present study was designed to investigate whether the DMN related resting-state connectivity alterations in these two psychiatric disorders were neural correlates of their sustained attention impairments.Methods: The study included 17 SCZ patients, 35 OCD patients and 36 healthy controls (HCs). Sustained attention to response task was adopted to assess the sustained attention. Resting-state scan was administrated and seed-based whole-brain FC analyses were performed with seeds located in classical DMN regions including bilateral medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC).Results: Both SCZ and OCD patients had poorer sustained attention than HCs. Sustained attention deficits in OCD was negatively correlated with their impaired FC of right mPFC-left superior frontal gyrus (SFG) within DMN, and that in SCZ was significantly correlated with their altered FC of left mPFC-bilateral anterior cingulate cortex (ACC) which indicated interaction between DMN and salience network. In addition, the FC between left mPFC and right parietal lobe indicating the interaction between DMN and frontal-parietal network was correlated with sustained attention in both SCZ and OCD.Conclusion: These findings suggest the importance of DMN-involved connectivity, both within and between networks in underlying sustained attention deficits in OCD and SCZ. Results further support the potential of resting-state FC in complementing information for cognitive deficits in psychiatric disorders.