0211 Baseline White Matter Microstructure Predicts Vulnerability to Inhibitory Control Decline After Sleep Deprivation

Abstract Introduction Sleep deprivation (SD) impairs attention and executive functioning, yet individuals vary in magnitude of cognitive decline. White matter (WM) microstructure may contribute to this, but reliable biomarkers of SD vulnerability have not been established. We examined whether baseline diffusion tensor imaging (DTI) measures predict SD-related changes in inhibitory control on a Go/No-Go (GNG) task, after 28 hours of wakefulness. Methods Thirty healthy adults (ages 20–43) underwent diffusion MRI (dMRI) during rested wakefulness, then remained awake for 28 hours. Inhibitory control was assessed before and during SD, using the GNG task at five different timepoints: two baseline sessions before SD (Tests 1–2) and three sessions during SD (Tests 3–5). dMRI data were acquired on a 3T Siemens system and processed with QSIPrep. Deterministic tractography in QSIRecon was used to reconstruct 56 atlas-defined WM pathways, from which fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were extracted. Based on exploratory findings and prior literature implicating arousal and inhibitory-control circuits, confirmatory analyses focused on two pathways: the medial forebrain bundle (MFB), a key monoaminergic arousal pathway, and the subthalamic fasciculus, which supports the hyperdirect inhibitory-control pathway. Three GNG d′ percentage-change indices were highly correlated (r. 90) ; therefore, a single primary outcome measure (GNGdprimePCTbase₃45₂) was selected to reduce redundancy. False discovery rate (FDR) correction was applied across eight tract–metric comparisons. Results Higher baseline MD, RD, and AD in the right MFB were significantly associated with greater SD decline in inhibitory control (all p. 006, FDR-corrected p. 05). Similarly, higher MD, RD, and AD in the left subthalamic fasciculus predicted larger SD-related performance impairments (all p. 006, FDR-corrected p. 05). FA was not significantly associated with outcomes in either tract. These results indicate that reduced microstructural integrity in both arousal-regulatory and rapid inhibitory-control pathways confers greater vulnerability to SD. Conclusion Baseline WM microstructure in the MFB and subthalamic fasciculus was strongly associated with individual differences in inhibitory-control decline following SD. Greater baseline diffusivity, reflecting reduced microstructural integrity, predicted poorer performance after SD. These findings suggest structural differences in monoaminergic arousal circuits and cortico-subthalamic inhibitory pathways may contribute to cognitive vulnerability. Support (if any)