Sex differences in brain functional connectivity changes to different energy densities of laser acupuncture at PC6 (Neiguan): a pilot resting-state fMRI study.

Purpose previous studies have suggested that laser acupuncture (LA) may influence autonomic nervous system (ANS) activity and brain functional connectivity (FC); however, the underlying neural mechanisms and potential sex-dependent responses remain to be further investigated. Using resting-state functional magnetic resonance imaging (fMRI), we examined the effects of LA at different energy densities (EDs), hypothesizing that varying dosages elicit differential brain responses influenced by biological sex. Methods we enrolled 60 healthy adults of both sexes aged 18-55 years with a BMI of 18.5-24 kg/m². Participants were randomized into three groups (n = 20 each) receiving LA at EDs of 0, 7.96, or 23.87 J/cm², with male/female distributions of 7/13, 7/13, and 9/11, respectively. Bilateral PC6 (Neiguan) was stimulated, and two 500-second resting-state fMRI scans were acquired before and after LA to analyze FC between ANS-related brainstem regions and other brain areas by sex. Results female-specific analyses more closely resembled previously reported sex-independent results, indicating females as the primary contributing subgroup. Accordingly, in females, LA at 23.87 J/cm² enhanced FC between the rostral ventrolateral medulla and orbitofrontal cortex (OFC), while reducing FC between the caudal ventrolateral medulla (CVLM), nucleus of the solitary tract/nucleus ambiguus, and dorsal motor nucleus of the vagus with the sensorimotor cortex (SMC). In males, 23.87 and 7.96 J/cm² LA decreased FC between the CVLM and OFC, with no significant changes between all regions of interest (ROIs) and SMC. Conclusion different EDs of LA elicited distinct FC changes in males and females between ROIs and other brain areas, while PRV findings showed limited evidence of sex-dependent autonomic modulation.