Bilateral effect of acupuncture on cerebrum and cerebellum in ischaemic stroke patients with hemiparesis: a randomised clinical and neuroimaging trial

Abstract

Background: Acupuncture involving the limb region may be effective for stroke rehabilitation clinically, but the visualised and explanatory evidence is limited. Our objectives were to assess the specific effects of acupuncture for ischaemic stroke (IS) patients with hemiparesis and investigate its therapy-driven modification in functional connectivity.

Methods: IS patients were randomly assigned (2:1) to receive 10 sessions of hand-foot 12 needles acupuncture (HA, n=30) or non-acupoint (NA) acupuncture (n=16), enrolling gender-matched and age-matched healthy controls (HCs, n=34). The clinical outcomes were the improved Fugl-Meyer Assessment scores including upper and lower extremity (ΔFM, ΔFM-UE, ΔFM-LE). The neuroimaging outcome was voxel-mirrored homotopic connectivity (VMHC). Static and dynamic functional connectivity (sFC, DFC) analyses were used to study the neuroplasticity reorganisation.

Results: 46 ISs (mean(SD) age, 59.37 (11.36) years) and 34 HCs (mean(SD) age, 52.88 (9.69) years) were included in the per-protocol analysis of clinical and neuroimaging. In clinical, ΔFM scores were 5.00 in HA group and 2.50 in NA group, with a dual correlation between ΔFM and ΔVMHC (angular: r=0.696, p=0.000; cerebellum: r=-0.716, p=0.000) fitting the linear regression model (R²=0.828). In neuroimaging, ISs demonstrated decreased VMHC in bilateral postcentral gyrus and cerebellum (Gaussian random field, GRF corrected, voxel p<0.001, cluster p<0.05), which fitted the logistic regression model (AUC=0.8413, accuracy=0.7500). Following acupuncture, VMHC in bilateral superior frontal gyrus orbital part was increased with cerebro-cerebellar changes, involving higher sFC between ipsilesional superior frontal gyrus orbital part and the contralesional orbitofrontal cortex as well as cerebellum (GRF corrected, voxel p<0.001, cluster p<0.05). The coefficient of variation of VMHC was decreased in bilateral posterior cingulate gyrus (PPC) locally (GRF corrected, voxel p<0.001, cluster p<0.05), with integration states transforming into segregation states overall (p<0.05). There was no acupuncture-related adverse event.

Conclusions: The randomised clinical and neuroimaging trial demonstrated acupuncture could promote the motor recovery and modified cerebro-cerebellar VMHC via bilateral static and dynamic reorganisations for IS patients with hemiparesis.

Keywords: Cerebral Infarction; Clinical Trial; Magnetic Resonance Imaging; Stroke; Stroke Rehabilitation.

Figure 1

Acupuncture regimens. (A) Location of acupoints and non-acupoints. Standard measuring unit for acupoints was B-cun, which is one equal portion of the length between two points of particular joints. Measuring unit for non-acupoints was F-cun (1 F-cun=20 mm), which is defined as the width of the interphalangeal joint of patient’s thumb. (B) Acupuncture manual manipulation. Measurements involved the needle size and dosage were described with inch (1 inch=25 mm). NA, non-acupoint.

Figure 2

Study flow chart. fMRI, functional MRI.

Figure 3

The pathologically cerebro-cerebellar VMHC captured by logistic regression based on machine learning. (A) The decreased VMHC in postcentral gyrus and cerebellum crus1 among the mild to moderate ISs. Red is increasing and blue is decreasing. (B) The decreased VMHC in cerebellum crus1 and cerebellum_6 among the severe ISs. Red is increasing and blue is decreasing. (C) The ROC of train set. (D) The ROC of test set. (E) The calibration curve of the logistic regression. (F) The test decision curve of the logistic regression. The model 1 is VMHC_Postcentral, and the model 2 is VMHC_Cerebellum. AUC, area under curve; IS, ischaemic stroke; ROC, receiver operating characteristic curve; VMHC, voxel-mirrored homotopic connectivity.

Figure 4

The clinical and neuroimaging outcomes. (A) The improvement of FM scores in HA group across motor-impairment severity subgroups. (B) The increased VMHC_Frontal_Sup_Orb in HA group following acupuncture. Red is increasing and blue is decreasing. (C) The higher VMHC_Cerebellum_8 in HA group compared with NA group in postacupuncture stage. Red is high and blue is low. FM, Fugl-Meyer; HA, hand-foot 12 needles acupuncture; LE, lower extremity; NA, non-acupoint; UE, upper extremity; VMHC, voxel-mirrored homotopic connectivity.

Figure 5

The brain and behaviour effects of acupuncture. (A) The ΔFM was positively correlated with ΔVMHC_Angular and negatively with ΔVMHC_Cerebellum_8. (B) The ΔFM-UE was positively correlated with ΔVMHC_Cerebellum_Crus2 and ΔVMHC_Angular, and negatively with ΔVMHC_Cerebellum_8. (C) The ΔFM-LE was negatively correlated with ΔVMHC_Paracentral_Lobule_R/Cingulum_Mid_L. (D) The fitting curve of true value and predicted value based on the linear regression model. (E) The SHAP values of the ΔVMHC with its predictive values meaning the contribution to the ΔFM. The predicted positive contribution of angular gyrus was smaller than the negative contribution of cerebellum (base value=8.883, predicted value=6.046). FM, Fugl-Meyer; LE, lower extremity; SHAP, shapley additive explanation; UE, upper extremity; VMHC, voxel-mirrored homotopic connectivity.

Figure 6

The static and dynamic modification of acupuncture. (A) Regions reported decreased VMHC in HA group compared with HCs. (B) Changes on sFC with Frontal_Sup_Orb_R as ROI following acupuncture. (C) Changes on sFC with Frontal_Sup_Orb_L as ROI following acupuncture. (D) The decreased CV_VMHC of PCC following acupuncture. Red is increasing and blue is decreasing. (E) FT changes among DFC states following acupuncture. (F) MDT changes among DFC states following acupuncture. (G) The pattern of DFC states clustering in preacupuncture stage. (H) The pattern of DFC states clustering in postacupuncture stage. Red is positive weights and blue is negative weights. CV_VMHC, coefficient of variability of VMHC; DFC, dynamic functional connectivity; HA, hand-foot 12 needles acupuncture; HC, healthy control; PCC, posterior cingulate gyrus; ROI, region of interest; sFC, static function connectivity; VMHC, voxel-mirrored homotopic connectivity.