Brain correlates of phasic autonomic response to acupuncture stimulation: an event-related fMRI study

Abstract

Autonomic nervous system (ANS) response to acupuncture has been investigated by multiple studies; however, the brain circuitry underlying this response is not well understood. We applied event-related fMRI (er-fMRI) in conjunction with ANS recording (heart rate, HR; skin conductance response, SCR). Brief manual acupuncture stimuli were delivered at acupoints ST36 and SP9, while sham stimuli were delivered at control location, SH1. Acupuncture produced activation in S2, insula, and mid-cingulate cortex, and deactivation in default mode network (DMN) areas. On average, HR deceleration (HR-) and SCR were noted following both real and sham acupuncture, though magnitude of response was greater following real acupuncture and inter-subject magnitude of response correlated with evoked sensation intensity. Acupuncture events with strong SCR also produced greater anterior insula activation than without SCR. Moreover, acupuncture at SP9, which produced greater SCR, also produced stronger sharp pain sensation, and greater anterior insula activation. Conversely, acupuncture-induced HR- was associated with greater DMN deactivation. Between-event correlation demonstrated that this association was strongest for ST36, which also produced more robust HR-. In fact, DMN deactivation was significantly more pronounced across acupuncture stimuli producing HR-, versus those events characterized by acceleration (HR+). Thus, differential brain response underlying acupuncture stimuli may be related to differential autonomic outflows and may result from heterogeneity in evoked sensations. Our er-fMRI approach suggests that ANS response to acupuncture, consistent with previously characterized orienting and startle/defense responses, arises from activity within distinct subregions of the more general brain circuitry responding to acupuncture stimuli.

Keywords: acupoint; defense response; heart rate; orienting response; skin conductance response.

Figure 1

Experiment design. A: Locations for acupuncture stimulation included acupoints SP9 and ST36, as well as sham location SH1, all on the left leg. B: The event‐related experimental paradigm consisted of a total of nine acupuncture stimulation events per location, with duration of 2 s and an interstimulus interval of 11.0 ± 2.3 s.

Figure 2

ANS response to acupuncture. A: Heart rate decrease was noted following stimulation at SH1, SP9, and ST36, and was most robust for ST36. B: Increased skin conductance response was noted for all locations, most prominently following acupuncture at SP9. n.b. *<0.05, error bars represent standard deviation.

Figure 3

Intersubject correlations between ANS response and acupuncture sensation. A: Skin conductance response increased (r = 0.53, P = 0.004) with increasing sharp pain sensation. B: Heart rate response was, on average, deceleration for all but one subject (gray circle). If this subject is removed from the correlation, a near‐significant trend (r = −0.36, P = 0.06) is found in the correlation between HR response and acupuncture deqi sensation (assessed with the MASS Index, MI).

Figure 4

Differential HR response to acupuncture: HR+ and HR−. Heart rate (HR) change in response to acupuncture stimuli could be separated into accelerator (HR+) and decelerator (HR−) response patterns. n.b. the light dotted lines represent standard deviation. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 5

Brain response to stimuli at different acupoints. A: FMRI response group maps for SH1, SP9, and ST36 stimulation suggested heterogeneity in brain response. B: SP9 stimulation elicited greater activation in right IFG and FIC, compared to ST36. However, ST36 stimulation elicited more deactivation in the PC. n.b. amyg, amygdale; MCC, middle cingulate cortex; IFG, inferior frontal gyrus; mIns, middle insula; PC, precuneus; PCC, posterior cingulate cortex; PCL, paracentral lobule; FIC, fronto‐insular cortex; sgACC, subgenual ACC; vmPFC, ventromedial prefrontal cortex. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 6

Brain correlates of HR responses to acupuncture. A: Difference map contrasting [HR+] – [HR−] demonstrated greater deactivation for HR− in PCL and DMN areas such as PC. Greater activation for HR+ events was noted in a parietal cluster consistent with poG/SPL. B: An intrasubject correlation analysis with HR− response found that compared with SH1, both SP9 and ST36 demonstrated greater significance in the correlation between HR deceleration and deactivation in DMN areas such as PCC, PC, and mPFC. Also, in comparison with ST36, SP9 stimulation produced greater significance in the correlation between HR− and right iPS activity. C: Greater DMN deactivation correlated with greater HR deceleration following verum acupuncture (SP9 and ST36) stimulation, as evidenced in a representative subject. n.b. iPS, intraparietal sulcus; poG, post‐central gyrus; SPL, superior parietal lobule. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 7

Brain correlates of sudomotor response to acupuncture. A: Brain correlates of acupuncture‐induced SCR demonstrated greater brain response to acupuncture stimulation events in MCC and anterior insula when SCR was high, compared with when SCR was low. B: SCR magnitude for “high‐SCR” events was significantly greater than for “low‐SCR” events. n.b. ** = P < 0.01, error bars represent standard deviation. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]