Differences in Chemo-signaling Compound-Evoked Brain Activity in Male and Female
Young Adults: A Pilot Study in the Role of Sexual Dimorphism in Olfactory Chemo-
Signaling

ABSTRACT
Previous studies have shown that putative pheromones 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST) cause activation in the preoptic area/anterior hypothalamus in men and women. Sex differences in neural activation patterns have been demonstrated when participants are subject to pheromone stimulation; however, whether other compounds give rise to similar neural activity has not been completely investigated. Twenty-nine young adults [16 female (21.3+/-0.54; mean yrs+/-SE), 13 male (22.85+/- 0.42)] participated in a 3-block design, where participants were exposed to a scent (lavender), a synthetic male pheromone (4,16-androstadien-3b-ol; ALD), and a synthetic female pheromone (1,3,5(10),16-Estratetraen-3-ol; EST) via an automated olfactometer. Whole-brain, high- resolution (1.8mm 3 ) functional MRI data from a Siemens Trio 3T MRI scanner were collected during all blocks. Five adults were excluded due to excessive movement. MANOVA analysis, a 2 × 3 multivariate model and analysis of 2x2 effects between sex and subsets of stimuli was done for activation over the whole brain and small volumes involved in olfaction. Exploratory analysis of 2x2 effects between sex and subsets of stimuli exhibited significant interactions when assessing activations over the whole brain, and small volumes involved in olfaction. The left and right frontal poles (LFP, RFP) shows significant interaction when assessing sex with lavender and EST for whole brain analysis. For small volume analysis, the right orbitofrontal cortex (ROFC) exhibited a sex with lavender and ALD interaction, and a sex with lavender and EST interaction was observed in the left inferior frontal gyrus (LIFG). Main effects of sex, stimulus, or interaction show no differences analyzed using a 2 x 3 multivariate model. The study shows there is a sexually dimorphic response in the olfactory system to pheromones not previously studied. Scents like lavender do not have this same response. These distinct functional differences in activation patterns may be a result of neural development and maturation differences between sexes. Future studies should expand this pilot study and involve a younger demographic to accurately determine the age at which the olfactory response differentiates between males and females.

MRI METHODS
All scans were acquired at the Brigham Young University MRI Research Facility on a Siemens Tim Trio 3T MRI scanner using a 32-channel receive-only head coil. All participants contributed both structural and functional images. Standard-resolution T1-weighted magnetization prepared rapid acquisition with gradient echo (MPRAGE) structural images were acquired with the following parameters: TR = 20 ms, TE = 4.92 ms, flip angle = 25°, FoV = 256 × 256, voxel size = isotropic 1 mm, slices = 192 interleaved. High-resolution multi-band echo-planar T2*-weighted functional images were acquired using a pulse sequence with the following parameters: multi-band factor = 8, TR = 875 ms, TE = 43.6 ms, flip angle = 55°, acquisition matrix = 100 ×100 mm, voxel size = isotropic 1.8 mm, slices = 72 interleaved.