0225 Reconsidering the Human Emotional Brain Without Sleep: Is it a ‘Prefrontal-Amygdala Disconnect’ or Reorganization of Amygdala-Centric Networks?

Abstract Introduction It is well known that sleep deprivation (SD) leads to hyper-responsiveness of the amygdala (a key node of the brain’s emotional system). Prior neuroimaging work has suggested that the medial prefrontal cortex (MPFC) provides inhibitory top-down regulation of the amygdala when normally rested. However, this connectivity appears weakened or impaired after a night of total SD. Prior work only examined neuroimaging at two time points (rested and sleep deprived). We sought to further explore this effect by collecting repeated brain scans every 6 hours across a 39-hour period of total SD. Methods Twenty healthy adults (9 female; age=23.6, SD=4.7 years) underwent a night of normal sleep in the lab followed by a 39-hour period of SD. Beginning at 0900, rsFMRI scans were collected at 3T every 6-hours. Data were preprocessed and analyzed using standard pipelines using CONN v22. The effect of SD (time awake) on whole-brain seed-to-voxel rsFC using each amygdala as a seed region (p<.001 uncorrected voxel threshold, p<.05 FDR corrected). Results After controlling for time of day, time awake was linearly associated with increasing rsFC between the amygdala and medial prefrontal cortex. Further examination revealed a larger pattern suggesting that increased SD was associated with greater coupling between the amygdala and core nodes of the salience network, including the anterior cingulate cortex and bilateral insular regions, while leading to anticorrelated connectivity between amygdala and several regions, including sensory-motor cortex, visual cortex, and the precuneus. Conclusion Our findings suggest a more nuanced pattern than the traditional prefrontal–amygdala ‘disconnect’ hypothesis. Across repeated scans, prolonged sleep deprivation was associated with a progressive reorganization of amygdala-centric networks that shifted emotional circuitry toward stronger coupling with salience-network regions involved in threat detection and interoceptive monitoring. As sensory, visual, and attentional systems degrade with increasing sleep loss, the brain may adapt by relying more on amygdala-driven salience signals to maintain defensive hypervigilance despite reduced fidelity of external sensory input. This network shift, marked by weaker top-down control and stronger bottom-up salience processing, offers a dynamic, time-dependent account of how sleep loss reshapes emotional brain function. Support (if any) Army Research Office (ARO): W911NF2210223