Improved Resting-State Functional Dynamics in Post-stroke Depressive Patients After Shugan Jieyu Capsule Treatment

Abstract

Shugan Jieyu Capsule (SG), a Chinese herbal medicine mainly composed of Acanthopanax and Hypericum perforatum, has been used to ameliorate cognitive impairments and emotional problems induced by post-stroke depression (PSD), while the altered brain dynamics underlying the ameliorative effects of SG have remained unclear. Our study focused on investigating the potential neurobiological mechanisms of SG in improving the cognitive function of PSD patients via resting-state functional magnetic resonance imaging (fMRI). Fifteen PSD patients (mean ages: 64.13 ± 6.01 years) were instructed to take 0.72 g of SG twice a day for 8 weeks. PSD patients underwent fMRIs, the 24-item Hamilton Depression Scale (HAMD-24) and the Montreal Cognitive Assessment (MoCA) at baseline and the end of intervention, and these assessments were also performed on twenty-one healthy controls (HC) (mean ages: 60.67 ± 6.95 years). Additionally, the dynamic amplitude of low-frequency fluctuations (dALFF) and functional connectivity (dFC) were determined to reveal changes in dynamic functional patterns. We found that taking SG significantly reduced the depressive symptoms assessed by HAMD-24 and improved cognitive functions assessed by MoCA in PSD patients. Furthermore, at baseline, PSD patients showed decreased dALFF in the right precuneus and increased dFC between the right precuneus and left angular gyrus, compared with HC. After intervention, the dALFF and dFC variances of the abnormal patterns were reversed. Additionally, the dALFF variance in the right precuneus was positively correlated with MoCA scores in PSD patients after SG treatment. Collectively, our results indicate that SG may improve the cognitive function of PSD patients through alteration of brain dynamics. Our findings lay a foundation for the exploration of the neurobiological mechanisms of SG in ameliorating symptoms of PSD patients.

Keywords: Shugan Jieyu Capsule; cognitive function; dynamic amplitude of low-frequency fluctuations; dynamic functional connectivity; functional magnetic resonance imaging; post-stroke depression.

FIGURE 1

Study flow-chart. Abbreviations are as follows: HC, healthy controls; PSD, post-stroke depression; SG0W, PSD patients before SG treatment; SG8W, PSD patients after 8 weeks of SG treatment; fMRI, functional magnetic resonance imaging; MoCA, Montreal Cognitive Assessment Scale; SG, Shugan Jieyu Capsule.

FIGURE 2

The lesion map for PSD patients. Voxels that are damaged in at least one patient are projected on the standard template in MNI space. Abbreviations are as follows: MNI, Montreal Neurological Institute space; PSD, post-stroke depression.

FIGURE 3

Clinical characteristics of participants. The histograms show HAMD (A) and MoCA (B) scores for each group (FDR correction at p < 0.05). ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001. (A) HAMD: HC vs. SG0W (t = 8.103, p < 0.001), HC vs. SG8W (t = 3.061, p = 0.004), SG0W vs. SG8W (t = 3.911, p = 0.002). (B) MoCA: HC vs. SG0W (t = 3.622, p < 0.001), HC vs. SG8W (t = 1.126, p = 0.268), SG0W vs. SG8W (t = 2.327, p = 0.035). The results are mean ± standard deviation. Abbreviations are as follows: MoCA, Montreal Cognitive Assessment Scale; HAMD, Hamilton Depression Scale; SG0W, PSD patients before SG treatment; SG8W, PSD patients after 8 weeks of SG treatment; HC, healthy controls; PSD, post-stroke depression; SG, Shugan Jieyu Capsule.

FIGURE 4

Differences in dALFF and correlation between dALFF and MoCA. (A) Group differences in the altered dALFF variance for the right precuneus (MNI coordinates, x = 14, y = −78, z = 44, cluster size = 111 voxels, t = 4.460, p < 0.05 GRF correction). (B) The histogram shows the average dALFF variance in the right precuneus (FDR correction at p < 0.05). ^∗∗p < 0.01, ^∗∗∗p < 0.001. HC vs. SG0W (Mann-Whitney U test, p = 0.008), HC vs. SG8W (Mann-Whitney U test, p = 0.102), SG0W vs. SG8W (t = 6.616, p < 0.001). These results are mean ± standard deviation. (C) This correlation diagram shows the correlation between MoCA and average dALFF variance for the right precuneus in SG8W (r = 0.590, p = 0.021). The solid line and dashed line represent the best-fit line and 95% confidence interval of Pearson’s correlation, respectively. Abbreviations are as follows: L, left; R, right; dALFF, dynamic amplitude of low-frequency fluctuation; MoCA, Montreal Cognitive Assessment Scale; SG0W, PSD patients before SG treatment; SG8W, PSD patients after 8 weeks of SG treatment; HC, healthy controls; PSD, post-stroke depression; SG, Shugan Jieyu Capsule.

FIGURE 5

Differences in dFC. (A) Group differences in dFC variance for the right precuneus and left angular gyrus (MNI coordinates: x = −46, y = −68, z = 34, cluster size = 135 voxels, t = −4.270, p < 0.05 GRF correction). (B) The histogram shows the mean dFC variance between the right precuneus and left angular gyrus (FDR correction at p < 0.05). These results are mean ± standard deviation. ^∗∗p < 0.01, ^∗∗∗p < 0.001. HC vs. SG0W (Mann-Whitney U test, p = 0.002), HC vs. SG8W (Mann-Whitney U test, p = 0.505), SG0W vs. SG8W (t = 4.622, p < 0.001). Abbreviations are as follows: L, left; R, right; dFC, dynamic functional connectivity; SG0W, PSD patients before SG treatment; SG8W, PSD patients after 8 weeks of SG treatment; HC, healthy controls; PSD, post-stroke depression; SG, Shugan Jieyu Capsule.