A hypothalamic-brainstem activity sequence underlies arousal fluctuations during daytime drowsiness

Abstract

During monotonous tasks, struggling with drowsiness leads to dynamic fluctuations in vigilance and task performance. Whether these moment-to-moment fluctuations are regulated by sleep-wake control circuitry remains unknown. Here, we used high-resolution 7T fMRI optimized for subcortical imaging to resolve activity across the human arousal regulatory system, including the hypothalamus, brainstem nuclei, basal forebrain, and thalamus, during a sustained attention task as subjects spontaneously experienced drowsiness. We identified a coordinated activity pattern locked to behavioral failures: widespread transient suppression during arousal drops and reactivation during recovery across all arousal-promoting regions, with opposite responses in the sleep-promoting hypothalamic preoptic area. These changes unfolded over [~]10-15 s in a 30 consistent sequence, led by the hypothalamic nuclei. Furthermore, suppression of brainstem nuclei preceded cortical infraslow (<0.05 Hz) oscillations, implicating a role in global neurovascular dynamics. These findings provide a temporally resolved, network-level portrait of human subcortical dynamics during drowsiness and identify a hypothalamic-led, brainstem-mediated activity sequence underlying behavioral arousal fluctuations and global cortical hemodynamics.