Introduction: Gray matter (GM) volumes of limbic and striatal structures, including the amygdala (AMY)¹ and the nucleus accumbens (NAcc)², are associated with socioemotional phenotypes. For instance, GM atrophy accompanies some dementias in which socioemotional processing is impaired^2,3. Evidence suggests that intranasally administered oxytocin (OT) exerts a modulatory effect on socioemotional processing4, with the AMY^5,6 and NAcc⁷ constituting strong potential targets for this in the brain modulatory process. There, further, is evidence that AMY volume is associated with endogenous OT levels in young adults⁸. However, the generalizability of this finding to older adults is currently unknown. Additionally, literature describing the effects of long-term OT administration on the aging brain is lacking.

Methods: Twenty-four healthy male participants, aged 55 years and older, were randomly assigned in a double-blind design to self-administer intranasally either 24IUs of OT or placebo (P) twice daily for four weeks as part of an ongoing clinical trial conducted at the University of Florida. A structural T1-weighted magnetization prepared rapid gradient-echo (MPRAGE) (1 mm³ isotropic voxels) scan was acquired at baseline and again posttreatment using a 3T Phillips scanner with a 32-channel head coil. Freesurfer was used for whole-brain structural segmentation⁹. Subcortical segmentation statistics (aseg.stat) volumetrics were extracted and analyses were conducted with Rstudio. The Stats¹⁰ package for R was used to run paired t-tests within each of the two treatment conditions (OT vs. P) to determine volume changes in amygdala and nucleus accumbens pre- to post-treatment. All analyses were conducted blind to the experimental conditions. Unblinding will be undertaken prior to the presentation of the final results.

Results: T-tests resulted in a significant increase in bilateral NAcc GM volume for one (t = -5.60, df = 12, p-value < 0.001 left; t = -4.2851, df = 12, p-value = 0.001 right) but not in the other (t = -1.58, df = 10, p-value = 0.149 left; t = t = -1.78, df = 10, p-value = 0.105 right) treatment condition. Additionally, there was a trend-wise decrease in total GM volume from pre- to post-treatment in the right AMY in one (t = 3.20, df = 12, p-value = 0.008) but not in the other (t = 0.89, df = 10, p-value = 0.396) treatment condition. However, this observation was reversed for the left AMY (t = 1.130, df = 12, p-value = 0.280 and t = 3.2065, df = 10, p-value = 0.009, respectively).

Conclusions: The results of this project suggest that 4-week intranasal OT vs. P administration differentially modulates brain volume in AMY and NAcc in healthy older men, with these modulatory effects possibly lateralized for the AMY. These findings are in line with previous literature showing that there may be hemispheric differences in socioemotional task-related AMY activation. Future extensions of this work will include a larger sample size to confirm the robustness of the findings and investigation into associations with socioemotional functioning.