Altered Resting-State Brain Activity and Connectivity in Depressed Parkinson’s Disease

Abstract

Depressive symptoms are common in Parkinson’s disease (PD), but the neurophysiological mechanisms of depression in PD are poorly understood. The current study attempted to examine disrupted spontaneous local brain activities and functional connectivities that underlie the depression in PD. We recruited a total of 20 depressed PD patients (DPD), 40 non-depressed PD patients (NDPD) and 43 matched healthy controls (HC). All the subjects underwent neuropsychological tests and resting-state fMRI scanning. The between-group differences in the amplitude of low frequency fluctuations (ALFF) of BOLD signals were examined using post-hoc tests after the analysis of covariance. Compared with the NDPD and HC, the DPD group showed significantly increased ALFF in the left median cingulated cortex (MCC). The functional connectivity (FC) between left MCC and all the other voxels in the brain were then calculated. Compared with the HC and NDPD group, the DPD patients showed stronger FC between the left MCC and some of the major nodes of the default mode network (DMN), including the post cingulated cortex/precuneus, medial prefrontal cortex, inferior frontal gyrus, and cerebellum. Correlation analysis revealed that both the ALFF values in the left MCC and the FC between the left MCC and the nodes of DMN were significantly correlated with the Hamilton Depression Rating Scale score. Moreover, higher local activities in the left MCC were associated with increased functional connections between the MCC and the nodes of DMN in PD. These abnormal activities and connectivities of the limbic-cortical circuit may indicate impaired high-order cortical control or uncontrol of negative mood in DPD, which suggested a possible neural mechanism of the depression in PD.

Precuneal Thickness and Depression in Parkinson Disease

“…Moreover, a recent study demonstrated altered connectivity in the posterior cingulate cortex/precuneus in PD patients with depression compared to PD without depression [23], and our results may indicate the structural basis of these functional changes in D-PD.…”

Abnormalities of regional brain function in Parkinson’s disease: a meta-analysis of resting state functional magnetic resonance imaging studies

“…After initially screen of the titles and abstracts, 17 ALFF studies were potentially eligible for this meta-analysis. Of these, 6 studies were excluded because of the following reasons: one was an abstract41; one used a method of regions of interest42; one applied an approach of support vector machine training43; one did not perform a direct comparison between PD patients and healthy controls16; and two just reported findings from the on-state of PD patients2244. The remaining 11 studies were included in the meta-analysis.…”

The study of brain functional connectivity in Parkinson’s disease

“…Abnormal prefrontal-limbic network connectivity has been demonstrated in depressed PD patients [31, 42]. PD patients with depression are associated with disrupted functional connectivity between the median cingulate cortex and precuneus, prefrontal cortex, and cerebellum [43]. The cingulate cortex plays key roles in integrating multimodal information that is important for emotional, sensorimotor, and cognitive functions [44].…”

“…Progressive micrographia was also associated with disconnections between the pre-SMA, rostral cingulated motor area and cerebellum18 controlsWu T et al, 2015 [22, 29]22 PD patientsVisuomotor association taskEffective connectivityGranger causality analysis (GCA)The connectivity from the putamen to the motor cortex was decreased in PD22 controlsMa H et al, 2015 [30]50 PD patientsResting stateFunctional connectivityThe bilateral dentate nucleus had higher connectivity with the bilateral cerebellar anterior lobe, and lower connectivity with the bilateral prefrontal cortex in tremor-dominant PD29 age-matched health controlsTessitore A et al, 2012 [32]29 PD patientsResting stateFunctional connectivityReduced connectivity within both executive-attention and visual networks15 controlsLiu H et al, 2013 [34]9 PD patientsResting stateFunctional connectivityDecreased connectivity of the dentate nucleus with the bilateral cerebellar posterior lobe in tremor-dominant PD9 controlsHu X et al, 2015 [35, 43]21 tremor-dominant (TD)-PDResting stateVoxel-mirrored homotopic connectivity (VMHC)TD-PD exhibited significantly lower VMHC values in the posterior lobe of the cerebellum. AR-PD exhibited lower VMHC values in the precentral gyrus.29 akinetic-rigid (AR)-PD patients26 controlsSeibert TM et al, 2012 [36]19 cognitively unimpaired controls, 19 cognitively unimpaired PD patients,Resting stateFunctional connectivityDecreased striato-prefrontal connectivity in patients with dementia18 patients with dementiaGorges M et al, 2015 [37]14 cognitively unimpaired PD patients, 17 cognitively impaired PD patientsResting stateFunctional connectivityDecreased default mode network connectivity in cognitively impaired PD patients.22 controlsDisbrow EA et al, 2014 [38]14 non-demented PD patients, 20 controls.Resting stateFunctional connectivityDecreased default mode network connectivity in PDManza P et al, 2016 [41]62 early-stage PD patientsResting stateFunctional connectivityMot...…”