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Postmenopausal women (POST) have increased muscle sympathetic nerve activity (MSNA) at rest compared to premenopausal women (PRE). While MSNA is generated by nuclei in the medulla oblongata, several forebrain regions can influence the generation of sympathetic activity. Still, functional differences in central autonomic brain regions have yet to be compared between PRE and POST. We tested the hypothesis that blood oxygen level dependent (BOLD) functional MRI signal intensity change in medullary and supramedullary regions which promote sympathetic activity occur at a larger magnitude in POST relative to PRE during handgrip exercise. We examined BOLD signal intensity changes in response to 3 trials of 2-minute isometric handgrip exercise at 30% of maximal voluntary contraction in 14 PRE (32±9 yr, 23±3 kg/m 2 ) and 13 POST (54±5 yr, 22±3 kg/m 2 ). A voxel-based analysis was performed using FSL with corrected voxel threshold of P <0.05. Region of interest analyses on bilateral forebrain areas including the amygdala, insula, and ventromedial prefrontal cortex (vmPFC) as well as the rostral ventrolateral medulla (RVLM) were then performed. BOLD signal intensity change was calculated in 10-sec bins as a percent change from the mean BOLD signal intensity over a 2-min baseline. Statistical analyses were performed using unpaired t-tests and 2-way repeated measures ANOVAs. Data are presented as mean±SD. Resting mean arterial pressure (PRE: 82±5 vs. POST: 90±9 mm Hg, P <0.01) was greater in POST. Robust increases BOLD signal intensity were observed in the contralateral primary motor cortex which were similar between groups (Time: P <0.01, Group: P =0.78, Interaction: P =0.85). The increases in BOLD signal intensity in the left insula (Time: P <0.01, Group: P =0.95, Interaction: P =0.99), left amygdala (Time: P <0.01, Group: P =0.40, Interaction: P =0.27), right amygdala (Time: P <0.05, Group: P =0.14, Interaction: P =0.35), left vmPFC (Time: P <0.01, Group: P =0.94, Interaction: P =0.55), right vmPFC (Time: P =0.05, Group: P =0.46, Interaction: P =0.98), and right RVLM (Time: P <0.05, Group: P =0.64, Interaction: P =0.99) did not differ between groups. Conversely, there were significant groups interactions with increases in BOLD signal intensity within the right insula (Time: P =0.05, Group: P =0.13, Interaction: P =0.05) and left RVLM (Time: P <0.05, Group: P =0.65, Interaction: P <0.01). These preliminary data suggest that there may be exaggerated activation of the RVLM, and blunted activation of the right insula, in POST relative to PRE in response to handgrip exercise. Supported by NIH Grant 5P20GM103653 and University of Delaware Department of Kinesiology and Applied Physiology PhD Research Grant This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.