Objective
To test whether more physiologically assessed hot flashes were associated with more connectivity in the default mode network (DMN), the network of brain regions active during rest. We particularly focus on DMN networks supporting the hippocampus as this region is rich in estrogen (E) receptors (ER) and has previously been linked to hot flashes.
Design
Women underwent 24 hours of physiologic and diary hot flash monitoring, functional magnetic resonance imaging (MRI), 72 hours of sleep actigraphy monitoring, a blood draw, questionnaires, and physical measures.
Setting
University medical center.
Patient(s)
Twenty midlife women aged 40–60 years who had their uterus and both ovaries and were not taking hormone therapy (HT).
Intervention(s)
None.
Main Outcome Measure(s)
The DMN functional connectivity.
Result(s)
Controlling for age, race, and education, more physiologically-monitored hot flashes were associated with greater DMN connectivity (beta, B [SE] = 0.004 [0.002]), particularly hippocampal DMN connectivity (B [SE] = 0.005 [0.002]). Findings were most pronounced for sleep physiologic hot flashes (with hippocampal DMN, B [SE] = 0.02 [0.007]). Associations also persisted controlling for sleep, depressive symptoms, and serum E2 concentrations.
Conclusion(s)
More physiologically-monitored hot flashes were associated with more DMN connectivity, particularly networks supporting the hippocampus. Findings were most pronounced for sleep hot flashes. Findings underscore the importance of continued investigation of the central nervous system in efforts to understand this classic menopausal phenomenon.

Parasympathetic nervous system (PNS) activity is important to physiological regulation. Limbic structures are important in determining what information the PNS receives, potentially influencing concurrent physiological responsivity and, ultimately, shaping PNS development. Yet, whether individual differences in these structures are linked to PNS activity in early childhood remains unclear. Here, in an exploratory capacity, we examined the association between neonatal limbic structures (i.e., the left and right amygdala and hippocampus) and preschoolers’ resting-state respiratory sinus arrhythmia (RSA). RSA is a measure of heart-rate variability, a physiological marker that reflects fluctuation in the PNS and is often found predictive of emotion regulation and psychological wellbeing. Data were extracted from the “Growing Up in Singapore towards Healthy Outcomes” (GUSTO) cohort (n = 73, 39 girls). Neonatal limbic volume was collected within two weeks after birth while infants were asleep. Resting-state RSA was collected during a coloring session at 42 months of age. After controlling for potential confounders, a Bonferroni-corrected significant association between neonatal left hippocampal volume and resting-state RSA emerged wherein larger hippocampal volume was associated with higher resting-state RSA. No significant associations were present between resting-state RSA and right or left amygdala, or right hippocampal volume. These findings contribute to an increasing body of evidence aiming at enhancing our understanding of neurobiological underpinnings of parasympathetic activity and modulation. Results are also discussed with reference to ideas concerning biological sensitivity to context, as both left hippocampal volume and resting-state RSA were previously found to moderate associations between adversity and psychological function.