Decreased resting-state functional connectivity and brain network abnormalities in the prefrontal cortex of elderly patients with Parkinson's disease accompanied by depressive symptoms

Abstract

This study aimed to explore the brain network characteristics in elderly patients with Parkinson's disease (PD) with depressive symptoms. Thirty elderly PD patients with depressive symptoms (PD-D) and 26 matched PD patients without depressive symptoms (PD-NOD) were recruited based on HAMD-24 with a cut-off of 7. The resting-state functional connectivity (RSFC) was conducted by 53-channel functional near-infrared spectroscopy (fNIRS). There were no statistically significant differences in MMSE scores, disease duration, Hoehn-Yahr stage, daily levodopa equivalent dose, and MDS-UPDRS III between the two groups. However, compared to the PD-NOD group, the PD-D group showed significantly higher MDS-UPDRS II, HAMA-14, and HAMD-24. The interhemispheric FC strength and the FC strength between the left dorsolateral prefrontal cortex (DLPFC-L) and the left frontal polar area (FPA-L) was significantly lower in the PD-D group (FDR p < 0.05). As for graph theoretic metrics, the PD-D group had significantly lower degree centrality (aDc) and node efficiency (aNe) in the DLPFC-L and the FPA-L (FDR, p < 0.05), as well as decreased global efficiency (aEg). Pearson correlation analysis indicated moderate negative correlations between HAMD-24 scores and the interhemispheric FC strength, FC between DLPFC-L and FPA-L, aEg, aDc in FPA-L, aNe in DLPFC-L and FPA-L. In conclusion, PD-D patients show decreased integration and efficiency in their brain networks. Furthermore, RSFC between DLPFC-L and FPA-L regions is negatively correlated with depressive symptoms. These findings propose that targeting DLPFC-L and FPA-L regions via non-invasive brain stimulation may be a potential intervention for alleviating depressive symptoms in elderly PD patients.

Keywords: Parkinson's disease; depressive symptoms; functional connectivity; functional near-infrared spectroscopy; prefrontal lobe.

Figure 1.

The arrangement of channels of the 53-channel near-infrared spectroscopy system according to Brodmann's map of the cortex. Ch, channel; PreM & SMC, Pre-Motor and Supplementary Motor Cortex; Broca, Broca's area; DLPFC, dorsolateral prefrontal cortex; FEF, frontal eye fields; FPA, frontopolar area.

Figure 2.

RSFC strength between regions of interest is lower in PD-D than in the PD-NOD group patients. PD-D, Parkinson's disease with depressive symptoms; PD-NOD, Parkinson's disease without depressive symptoms; RSFC, Resting-state functional connectivity; PreM and SMC-L, left Pre-Motor and Supplementary Motor Cortex; Broca-L, left Broca's area; FEF-L, left frontal eye fields; DLPFC-L, left dorsolateral prefrontal cortex; FPA-L, left frontal polar area; FPA-R, right frontal polar area; DLPFC-R, right dorsolateral prefrontal cortex; FEF-R, right frontal eye fields; Broca-R, right Broca's area; PreM and SMC-R, right Pre-Motor and Supplementary Motor Cortex; PreM & SMC, Pre-Motor and Supplementary Motor Cortex; Broca, Broca's area; DLPFC, dorsolateral prefrontal cortex; FEF, frontal eye fields; FPA, frontopolar area.

Figure 3.

Low strength of FC between DLPFC-L and FPA-L in PD-D group patients compared to PD-NOD. PD-D, Parkinson's disease with depressive symptoms; PD-NOD, Parkinson's disease without depressive symptoms; FC, functional connectivity; DLPFC-L, left dorsolateral prefrontal cortex; FPA-L, left frontal polar area.

Figure 4.

PD-D group patients' brain network properties are different from PD-NOD. PD-D, Parkinson's disease with depressive symptoms; PD-NOD, Parkinson's disease without depressive symptoms; aEg, area under the curve of global efficiency; aDc, area under the curve of degree centrality; aBc, area under the curve of betweenness centrality; aNe, area under the curve of node efficiency; PreM and SMC-L, left Pre- Motor and Supplementary Motor Cortex; Broca-L, left Broca's area; FEF-L, left frontal eye fields; DLPFC-L, left dorsolateral prefrontal cortex; FPA-L, left frontal polar area; FPA-R, right frontal polar area; DLPFC-R, right dorsolateral prefrontal cortex.