The effects of acupuncture on the brain networks for emotion and cognition: an observation of gender differences

Abstract

Acupuncture modulates brain activity at the limbic-paralimbic-neocortical network (LPNN) and the default mode network (DMN). Since these brain networks show gender differences when mediating emotional and cognitive tasks, we thus hypothesize that women and men may also respond differently to acupuncture procedure at these brain regions. In order to test this hypothesis, we retrieved the data of 38 subjects, 19 females and 19 males, who had brain fMRI during acupuncture from previous studies and reanalyzed them based on sex status. Deactivation at the LPNN/DMN during needle manipulation of acupuncture was more extensive in females than in males, particularly in the posterior cingulate (BA31), precuneus (BA7m) and angular gyrus (BA39). The functional correlations between the right BA31 and pregenual cingulate (BA32), hippocampus or contralateral BA31 were significantly stronger in females than in males. The angular gyrus (BA39) was functionally correlated with BA31 in females; in contrast, it was anticorrelated with BA31 in males. Soreness, a major component of the psychophysical responses to needle manipulation, deqi, was correlated in intensity with deactivation of the angular gyrus in females; no such relationships were observed in males. In contrast to lesser deactivation at the LPNN/DMN networks, needle manipulation during acupuncture induced greater activation at the secondary somatosensory cortex and stronger functional connectivity with the anterior-middle cingulate (BA32/24) in males than in females. Our study suggests that brains with sex dimorphism may process the acupuncture stimulation differently between women and men.

Fig. 1

fMRI signal changes during acupuncture in females and males: right paramidsagittal section, x=2 and coronal brain sections from anterior to posterior, y=34 to −54 are shown. The identified brain regions are the following: 1) posterior cingulate (BA31); 2) subgenual area (SG25), subgenual cingulate (BA32/24) and ventromedial prefrontal cortex (BA11); 3) cerebellar vermis; 4) sensorimotor area (SMA, BA6); 5) posterior cingulate (BA23 dorsal); 6) pregenual cingulate (BA32/24); 7) orbitofrontal cortex; 8) temporal pole; 9) anterior insula; 10) medial temporal lobe (amygdala, hippocampus, parahippocampus); 11) precuneus and 12) angular gyrus.

Fig. 2

Comparisons of fMRI signal changes at the representative brain regions during acupuncture between females vs. males: female vs. male deactivation/actiona signals (bars) and the comparisons between two genders (p<0.0001) by imagings (circles) are illustrated. A) Paramidsagittal sections, x=6 for left brain (L) and B) x=−6 for right brain (R), the identified brain regions (1) posterior cingulate (BA31) and (2) precuneus (PCN) and their average signal changes are shown. Paramidsagittal sections, C) x=44 and D) x=−42, are illustrated. Both L and R angular gyrus (3) and their signal changes are shown. (4) illustrates secondary somatosensory cortex, SII (BA40). E) Axial brain section, z=25, with identified regions of SII (BA40) and BA31, and signal changes of SII between female and male are shown.

Fig. 3

Comparisons of average signal changes at different brain structures during acupuncture on LV3 between females vs. males: To use one acupoint, LV3, female vs. male deactivation/actiona signals (bars) and the comparisons between two genders are illustrated. The identified bilateral brain regions, posterior cingulate (BA31), precuneus (PCN), angular gyrus and secondary somatosensory cortex, SII (BA40) between female and male are shown. *p<0.05; **p<0.001; ***p<0.0001.

Fig. 4

Cross-correlation analysis (CCA) of brain networks during acupuncture: the correlations between the seed (masked) and the other brain regions in both female and male brains are shown, and the orange colors represent positive correlation vs. the blue colors which represent negative correlations. T-test for the gender comparisons is also shown, and the labeled orange colors in the t-test pictures of 5A represent statistically significant difference (the deactivation of female was more significant compared with male) vs. blue colors in the t-test pictures of 5B which represent a statistically significant difference (the activation of male was more significant compared with female) on the voxel numbers induced by acupuncture. 5A illustrates the function connectivities in the task-negative network. Seed: right posterior cingulate (BA31), 4.5 mm radius around peak voxel (x, y, z) 9, −46, 39 for females and 14, −43, 48 for males. a) y=−5: correlation between BA31 and the pregenual cingulate (BA32) (1); b) y=−11: correlation between BA31 and hippocampus (2); c) x=6: correlation between right BA31 and the contralateral posterior cingulate (BA31) (3); d) x=46: correlation between BA31 and the angular gyrus (BA39) (4). 5B illustrates task-positive network. Seed: left (contralateral) secondary somatosensory cortex, SII (BA40), 4.5 mm radius around peak voxel (x, y, z) −58, −21, 23 for females and −58, −18, −16 for males. a) y=−10: correlations between left SII and right SII. (1) or the anterior middle cingulate (BA32/24) (2); b) z=44: correlation between left SII and the anterior middle cingulate (BA32/24).

Fig. 5

Gender differences in correlations between average BOLD signals in the brain regions and soreness induced by acupuncture: the severity of soreness induced by acupuncture (x-axis) and its correlation with the average BOLD signal change (%) (y-axis) in females (A and C) vs. males (B and D) are shown for each individual subject. Negative values below zero represent deactivation; positive values above zero represent activation at the brain regions. A and B: the angular gyrus (BA39); C and D: the visual cortex (BA18/19). Correlation coefficient factors, r, and p values for statistical significance are indicated.

Fig. 6

Acupuncture experiment: 1A shows that manual acupuncture was administered to the LI4, ST36, and LV3 acupoints on the right side. 1B shows the paradigm of acupuncture: after remaining in place for 2 min (R1), the needle was rotated with an even motion for 2 min (M1) at the rate of 1 Hz. Needle manipulation was repeated in like manner (M2) after 3 min rest with the needle in place (R2).