0217 Autonomic Correlates of Brain-State Morphometry in Sleep Deprivation

Abstract Introduction People differ widely in their tolerance to extended wakefulness, yet the physiological factors underlying this variability remain unclear. T1-weighted morphometry can vary over short timescales due to transient physiological states rather than structural change. Autonomic activity, particularly parasympathetic vagal modulation indexed by heart-rate variability (HRV), may contribute to these fluctuations. Root Mean Squared Successive Differences (RMSSD) and High-Frequency normalized units (HFnu) capture time- and frequency-domain parasympathetic activity. Methods Sixteen healthy adults (8 females; age = 23.6 ± 4.6) completed 39 hours of sustained wakefulness with six MRI sessions. HRV was derived from pulse plethysmography and used to compute RMSSD (short-term vagal index) and HFnu (respiration-linked vagal modulation). FreeSurfer provided morphometry measures; resting-state connectivity was used to compute graph-theoretic nodal strength. Linear mixed-effects models tested HRV × Hours Awake interactions for each measure, adjusting for circadian phase (sin/cos terms) and including random subject intercepts. Analyses focused on a priori hubs with restricted FDR correction. Morphometry calculations controlled for estimated intracranial volume (eTIV). Results RMSSD significantly moderated changes in left thalamic morphometry (FDR-corrected p < 0.05): higher-RMSSD individuals showed steeper decline in thalamic volume across wakefulness, whereas lower-RMSSD individuals showed flatter slopes. Thalamic nodal strength showed a similar RMSSD × HoursAwake interaction (FDR-corrected p < 0.05). HFnu significantly moderated surface area in salience-frontal regions, including the frontal middle sulcus, anterior cingulate cortex (ACC), and inferior circular insula (all FDR-corrected p < 0.05), with higher HFnu predicting relative preservation and lower HFnu showing decline. These changes were small in magnitude and are best interpreted as short-term physiological fluctuations rather than true structural alterations. Conclusion State-dependent changes in morphometry closely tracked autonomic state. RMSSD was most strongly aligned with thalamic decline over time, whereas HFnu was linked to relative stability in salience-frontal regions, suggesting that HRV indices capture transient physiological influences on morphometry during sleep deprivation. Future work may evaluate whether these fluctuations contribute to cognitive effects of sleep deprivation. Support (if any) Supported by Army Research Office award W911NF2210223, subaward SUBK00016417.