Acupuncture modulates resting state connectivity in default and sensorimotor brain networks

Abstract

Previous studies have defined low-frequency, spatially consistent networks in resting fMRI data which may reflect functional connectivity. We sought to explore how a complex somatosensory stimulation, acupuncture, influences intrinsic connectivity in two of these networks: the default mode network (DMN) and sensorimotor network (SMN). We analyzed resting fMRI data taken before and after verum and sham acupuncture. Electrocardiography data were used to infer autonomic modulation through measures of heart rate variability (HRV). Probabilistic independent component analysis was used to separate resting fMRI data into DMN and SMN components. Following verum, but not sham, acupuncture there was increased DMN connectivity with pain (anterior cingulate cortex (ACC), periaqueductal gray), affective (amygdala, ACC), and memory (hippocampal formation, middle temporal gyrus) related brain regions. Furthermore, increased DMN connectivity with the hippocampal formation, a region known to support memory and interconnected with autonomic brain regions, was negatively correlated with acupuncture-induced increase in a sympathetic related HRV metric (LFu), and positively correlated with a parasympathetic related metric (HFu). Following verum, but not sham, acupuncture there was also increased SMN connectivity with pain-related brain regions (ACC, cerebellum). We attribute differences between verum and sham acupuncture to more varied and stronger sensations evoked by verum acupuncture. Our results demonstrate for the first time that acupuncture can enhance the post-stimulation spatial extent of resting brain networks to include anti-nociceptive, memory, and affective brain regions. This modulation and sympathovagal response may relate to acupuncture analgesia and other potential therapeutic effects.

Figure 1. fMRI Scanning Paradigm

The order of SHAM and ACUP runs was pseudo-randomized across subjects and each was flanked by a 5.5 minute rest run. The SHAM and ACUP portions of the scan session were separated by structural and field map scans lasting no less than 15 minutes.

Figure 2. Group Maps for the Default Mode Network (DMN) and Sensorimotor Network (SMN), Before and After Acupuncture

The best-fit components were selected using template masks of the previously defined DMN and SMN shown in the center of each panel [6]. (A) The best fitting component for the DMN primarily involved the lateral parietal cortex, posterior cingulate, precuneus, and areas of the inferior, middle and superior frontal gyri. (B) The best fitting component for the SMN involved bilateral primary somatosensory and motor cortices, secondary somatosensory cortex and the supplementary motor area.

Figure 3. Changes in functional connectivity of the DMN following ACUP and SHAM (After – Before)

(A) Following verum acupuncture there was increased connectivity of the DMN with the amygdala (AMYG), hippocampal formation (HIPPO), middle temporal gyrus (MTG), anterior cingulate cortex (ACC), periaqueductal gray (PAG) and substantia nigra (SN) as well as posterior parietal (BA 7) and primary visual cortex (V1). (B) Following SHAM there was increased connectivity of the DMN with the temporo-occipital junction (TOJ) and decreased connectivity with the middle temporal and inferior temporal gyri (MTG, ITG).

Figure 4. The changes in functional connectivity of the SMN for ACUP and SHAM (After – Before)

(A) Changes in the SMN for acupuncture involved increased connectivity with the ACC, pre-SMA, and the cerebellum (CEREB). (B) Following SHAM there was decreased connectivity for the SMN with the dorsolateral prefrontal cortex (dlPFC).

Figure 5. Changes in connectivity of the DMN following Acupuncture are correlated with HRV

Increased DMN-hippocampal connectivity post-acupuncture was negatively correlated with acupuncture-induced change in LFu (A), and positively correlated with HFu (B), suggesting that increased parasympathetic and decreased sympathetic modulation during ACUP is associated with increased post-stimulation DMN connectivity.

Figure 6. Results of psychophysical analysis

(A) Differences in the types of sensations elicited (expressed as a histogram) were found between ACUP and SHAM. ACUP more frequently induced “aching,” “fullness,” and “dull pain.” (B) MASS index, a measure of deqi intensity, was greater for ACUP compared to SHAM. (C) Results of a psychophysics/imaging correlation analysis: a trend was found for increasing ACUP evoked “soreness” correlating with increasing SMN connectivity with pre-SMA (r = 0.65, p=0.081, Bonferroni corrected), a result consistent with the hypothesis that changes in resting SMN connectivity are related to the sensations evoked by acupuncture stimulation. n.b. Error bars in A represent a 90% confidence interval for binomial distribution. Sensations on the abscissa are in the order presented to the subjects. Error bars in B represent standard deviation. *p<0.05, **p<0.01, ***p<0.005.