Exploring the changes in functional connectivity of the limbic system in Patients with amnestic mild cognitive impairment treated by acupuncture based on fMRI

Abstract

Objective: Brain functional connectivity (FC) of Limbic system plays an important role in maintaining the normal cognitive state. We conduct an investigation of the FC of limbic system networks in amnestic mild cognitive impairment (aMCI) and speculate on the brain effect mechanism of acupuncture therapy based on resting - state Functional Magnetic Resonance Imaging (rs - fMRI).

Method: 50 patients with aMCI and 41 healthy participants (HC group) from the First Affiliated Hospital of Heilongjiang University of Chinese Medicine in Harbin City, Heilongjiang Province, China, were recruited.rs-fMRI data of all participants were collected. Among them, 35 aMCI participants (true-acupoint group) were treated with the Yuanluo Tongjing acupuncture method for two courses of treatment (once a day, needling every 10 min, retaining the needles for 40 min, 6 days of treatment + 1 day of rest, 4 weeks as one course, and starting the second course after an interval of 2 weeks). 15 aMCI participants (sham-acupoint group) received sham acupoint acupuncture intervention, and the specific intervention details were the same as those of the true-acupoint group. After treatment, rs-fMRI data of aMCI subjects were collected again. Thirty seed points of the limbic system were selected based on the Anatomical Automatic Labeling (AAL) template, and the Statistical Parametric Mapping (SPM) software was used for statistical analysis of FC indices between and within groups.

Result: (1) Compared with the HC group, there were significant differences in the FC between Seed14 of the true-acupoint group before acupuncture intervention and multiple brain regions (enhanced with Seed 7 and weakened with Seed 15). There were differences in the FC of Seed4, Seed29, and Seed30 in the sham-acupoint group, indicating that there were baseline differences among aMCI patient groups. (2) After acupuncture in the true-acupoint group, the FC between multiple seed points and brain regions decreased, while the differences before and after the intervention in the sham-acupoint group mostly did not pass the Family-Wise Error (FEW) correction. (3) Compared with the HC group, the FC of seed points in both the true-acupoint group and the sham-acupoint group mainly decreased after acupuncture. The true-acupoint group involved a wider range of brain regions (the middle frontal gyrus, the left medial superior frontal gyrus, the middle part of the left cingulate gyrus and the gyri surrounding its lateral side, the gyri below the bilateral parietal bones except the supramarginal gyrus and the angular gyrus, the precuneus, etc.). (4) The FC between Seed14 and the left superior frontal gyrus medialis (Seed7), as well as the right caudate nucleus of the true-acupoint group was enhanced before acupuncture and decreased after acupuncture, which may serve as an observational indicators for the intervention of aMCI by acupuncture at acupoints. (5) The Montreal Cognitive Assessment (MoCA) score is more representative in characterizing the abnormal FC between brain regions in aMCI patients.

Conclusion: The cerebral effect mechanism of acupuncture at acupoints for aMCI is more complex. It can regulate the functional connections within the limbic system and between the limbic system and other brain regions, mainly manifested as a decrease. Among them, the FC among Seed17-Parietal_Inf_L, Seed25-Frontal_Mid_L, and See25-Frontal_Sup_Medial_L has become a statistically significant detection index.

Keywords: acupuncture; amnestic mild cognitive impairment; functional connectivity; functional magnetic resonance imaging; limbic system.

Figure 1

The acupuncture points for the Yuanluo Tongjing method in this study. LI11 (Quchi): on the lateral aspect of the elbow, at the midpoint of the line connecting LU5 with the lateral epicondyle of the humerus. CV17 (Danzhong): in the anterior thoracic region, at the same level as the fourth intercostal space, on the anterior median line. HT7 (Shenmen): on the anteromedial aspect of the wrist, radial to the flexor carpi ulnaris tendon, on the palmar wrist crease. CV4 (Guanyuan): on the lower abdomen, 3 B-cun inferior to the centre of the umbilicus, on the anterior median line. ST40 (Fenglong): on the anterolateral aspect of the leg, lateral border of the tibialis anterior muscle, 8 B-cun superior to the prominence of the lateral malleolus. K13 (Taixi): On the posteromedial aspect of the ankle, in the depression between the prominence of the medial malleolus and the calcaneal tendon. SP3 (Taibi): on the medial aspect of the foot, in the depression proximal to the first metatarsophalangeal joint, at the border between the red and white flesh. LR3 (Taichong): On the dorsum of the foot, between the first and second metatarsal bones, in the depression distal to the junction of the bases of the two bones, over the dorsalis pedis artery. BL58(Feiyang): On the posterolateral aspect of the leg, between the inferior border of the lateral head of the gastrocnemius muscle and the calcaneal tendon, at the same level as 7 B-cun proximal to BL60. GV14 (Dazhui): in the posterior region of the neck, in the depression inferior to the spinous process of the seventh cervical vertebra (C7), on the posterior median line. GB20 (Fengchi): ferior to the occipital bone, in the depression between the origins of sternocleidomastoid and the trapezius muscles. GV20 (Baihui): on the head, 5 B-cun superior to the anterior hairline, on the anterior median line. GB13 (Benshen): on the head, 0.5 B-cun superior to the anterior hairline, 3 B-cun lateral to the anterior median line. By Figdraw.

Figure 2

3D brain diagram of the significant changes in the functional connectivity among seed 14 in the true-acupoint group before acupuncture, compared with that HC group. The yellow segments indicate the enhancement in functional connectivity, and the blue segments indicate the reduction in functional connectivity.

Figure 3

3D brain diagram of the significant changes in the functional connectivity among seed 4 in the true-acupoint group before acupuncture, compared with that HC group. The blue segments indicate the reduction in functional connectivity. The same below. 3D brain diagram of the significant changes in the functional connectivity among seed 29 in the true-acupoint group before acupuncture, compared with that HC group. 3D brain diagram of the significant changes in the functional connectivity among seed 30 in the true-acupoint group before acupuncture, compared with that HC group.

Figure 4

3D brain diagram of the significant changes in the functional connectivity among 30 selected seed points in the ture-acupoint group after acupuncture, compared with that HC group. This Circos plot shows the differences in functional connectivity (FC) between the seed points of the limbic system and other brain regions (corrected by Family-Wise Error, FEW). The full circular area represents the AAL brain regions included in the analysis after FEW correction, and different colors are used to distinguish various brain regions. On the left side of the plot are 30 seed points of the limbic system in the AAL template (arranged in ascending order of serial numbers), and on the right side are the serial numbers of brain regions outside the limbic system. The arcs connect the left and right brain regions, representing the FC changes between the left seed points and the right brain regions. The brain region names corresponding to the serial numbers can be found in the appendix. The same below.

Figure 5

3D brain diagram of the significant changes in the functional connectivity among 30 selected seed points in the ture-acupoint group after acupuncture, compared with that HC group. The blue line segments indicate the reduction in functional connectivity (compared with the HC group).

Figure 6

Circos diagram of the significant changes in the functional connectivity between 30 select seed points and the brain regions of the AAL template in the whole brain in the sham-acupoint group after acupuncture, compared with that HC group.

Figure 7

3D brain diagram of the significant changes in the functional connectivity among 30 selected seed points in the sham-acupoint group after acupuncture, compared with that HC group. The blue line segments indicate the reduction in functional connectivity.

Figure 8

Circos diagram of the significant changes in the functional connectivity between 30 selected seed points and the brain regions of the AAL template in the whole brain in the true-acupoint group after acupuncture, compared with that before acupuncture.

Figure 9

3D brain diagram of the significant changes in the functional connectivity among 30 selected seed points in the true-acupoint group after acupuncture, compared with that before acupuncture. The blue line segments indicate the reduction in functional connectivity.

Figure 10

3D brain diagram of the significant changes in the functional connectivity among 30 selected seed points in the sham-acupoint group after acupuncture, compared with that before acupuncture. The blue line segments indicate the reduction in functional connectivity (compared with the HC group).

Figure 11

Box - plot of the results of one - way ANOVA for FC values in the HC group, true - acupoint group before and after acupuncture. p < 0.05 indicates statistical significance, which is marked in red font. Blue represents the healthy control group (HC group), green represents the true-acupoint group before acupuncture, and gray represents the true-acupoint group after acupuncture. (A) shows the comparisons of the FC values between Seed17 and Parietal_Inf_L; (B) shows the comparisons of the FC values between Seed25 and Frontal_Mid_L; (C) shows the comparisons of the FC values between Seed25 and Frontal_Sup_Medial_L.

Figure 12

Scatter plot of the correlation analysis between the FC values between the seed points and brain regions after acupuncture and the scores of the neuropsychological scale in the true-acupoint group. p < 0.05 indicates statistical significance, r represents the correlation coefficient, and the red scatter plot indicates a positive correlation. Seed4: Frontal_Mid_Orb_R; Seed14: Cingulum_Ant_R; Seed15: Cingulum_Mid_L. A is a positive correlation analysis diagram of the FC values between seed4 - Frontal_Mid_R and the MMSE; B is a positive correlation analysis diagram of the FC values between seed14 - Seed15 and the MoCA.

Figure 13

Scatter plot of the correlation analysis between the FC values between the seed points and brain regions after acupuncture and the scores of the neuropsychological scale in the sham-acupoint group. p < 0.05 indicates statistical significance, r represents the correlation coefficient, “-” indicates a negative correlation, the red scatter plot indicates a positive correlation, and the blue scatter plot indicates a negative correlation. Seed7: Frontal_Sup_Medial_L; Seed15: Cingulum_Mid_L; Seed17: Cingulum_Post_L. A is a positive correlation analysis diagram of the FC values between seed15 - Seed7 and the MMSE; B is a negative correlation analysis diagram of the FC values between seed17 - Precuneus_L and the MoCA.