The role of insula-cerebellum connection underlying aversive regulation with acupuncture

Abstract

Acupuncture at pericardium 6 (PC6) shows a consistently positive efficacy in nausea response suggested by consensus expert guidelines. Nausea encompasses aversive symptom as well as strong emotional components. Disgust is a subjective emotion of uneasy commonly accompanying with a physiological response that is accompanied by strong visceral sensations (e.g., nausea). Understanding the brain circuitry by which acupuncture influences the disgust emotion may further elucidate the modulation effect of acupuncture on aversive experience. In the present study, a well-established aversive conditioning model on healthy subjects was combined with acupuncture intervention at PC6, as well as different acupoints (both local PC7 and distant GB37) as separate controls, to investigate the brain network involved aversive regulation with acupuncture; 48 healthy subjects were enrolled and randomized into four parallel groups: group 1 received disgust-induced (DI) stimuli only; groups 2, 3, and 4 received acupuncture at three single acupoints separately prior to the DI. Disgust sensations were rated at baseline and following disgust stimuli. Acupuncture PC6 can induce significant attenuations in disgust sensations than that of no intervention and acupuncture at other acupoints. Neuroimaging further showed that increased causal interaction strength between the cerebellum (nodulus) and insula can predict greater attenuations in aversive experiences. We also found evidence for radical reorganizations of local stronger casual interaction patterns to disgust-induced brain responses targeted by acupuncture at different acupoints. This study provided the brain substrate for acupuncture on aversion modulation. The coupling between the cerebellum (nodulus) and insula supported interoception system and vestibular control which provided the specific neural basis.

Keywords: Acupuncture; antiemetic effect; casual interaction; disgust regulation; insula-cerebellum; interoception system; vestibular control.

Figure 1.

Experimental design. Run 1: A non-repeated event-related (NRER) fMRI acupuncture run for 4 min, including 2-min needling manipulations preceded by a 1-min rest, and followed by another 1 min rest scanning. Run 2: Disgust stimulus tasks were presented using a rapid event-related design; 20 trials for each type (disgust and neutral pictures) and 40 null trials (fixation cross) were presented in a random order. Group 1 conducted the disgust stimuli only and groups 2, 3, and 4 received acupuncture treatment first and then disgust stimuli. After each fMRI scanning, deqi sensations, disgust sensations, and anxiety degree were assessed using a 10-point visual analogue scale (VAS) across the four groups.

Figure 2.

Illustration of anatomical locations of three acupoints: PC6 (Neiguan), PC7 (Daling), and GB37 (Guangming).

Figure 3.

Averaged psychophysical response (N = 48). (a) The percentage of subjects who reported having experienced the given sensation (at least one subject experienced the seven sensations listed). (b) The intensity of reported sensations measured by an average score (with standard error bars) on a scale from 0 denoting no sensation to 10 denoting an unbearable sensation.

Figure 4.

Comparison results from PC6 vs. DI, PC7 vs. DI, and GB37 vs. DI under the disgust stimuli task. Statistical significance was thresholded at P < 0.05 (uncorrected) and a minimum cluster size of 10 voxels. PAG: periaqueductal gray; DI: disgust induced.

Figure 5.

Multivariate Granger causality relationships with significant connections (P < 0.05, FDR corrected) during disgust-induced stimuli following non-treatment and acupuncture at PC6, PC7, and GB37. Relative strength of path weights (in arbitrary units) was indicated by the width of the arrows. Phipp: hippocampus; ACC: anterior cingulate cortex; MPFC: medial prefrontal cortex; OFC: orbitofrontal cortex; SOG: supper occipital gyrus; SI: primary somatosensory cortex; SMA: supplementary motor area.