Sleep can intrude into the awake human brain when sleep deprived or fatigued, even while performing cognitive tasks. However, how the brain activity associated with sleep onset can co-exist with the activity associated with cognition in the awake humans remains unexplored. Here, we used simultaneous fMRI and EEG to generate fMRI activity maps associated with EEG theta (4-7 Hz) activity associated with sleep onset. We implemented a method to track these fMRI activity maps in individuals performing a cognitive task after well-rested and sleep-deprived nights. We found frequent intrusions of the fMRI maps associated with sleep-onset in the task-related fMRI data. These sleep events elicited a pattern of transient fMRI activity, which was spatially distinct from the task-related activity in the frontal and parietal areas of the brain. They were concomitant with reduced arousal as indicated by decreased pupil size and increased response time. Graph theoretical modelling showed that the activity associated with sleep onset emerges from the basal forebrain and spreads anterior-posteriorly via the brain's structural connectome. We replicated the key findings in an independent dataset, which suggests that the approach can be reliably used in understanding the neuro-behavioural consequences of sleep and circadian disturbances in humans. 3 Brief sleep onsets can intrude into wakefulness when homeostatic sleep drive is elevated due to sleep loss, fatigue, or extended monitoring tasks. These transient sleep intrusions can be local and restricted to the momentary silencing of a few neurons (Krueger JM and G Tononi 2011; Vyazovskiy VV et al. 2011; Nir Y et al. 2017; Quercia A et al. 2018) or on a global scale; characterised by the slowing of neural activity in widespread cortical and sub-cortical regions (Boyle LN et al. 2008; Ong JL et al. 2015; Jonmohamadi Y et al. 2016; Toppi J et al. 2016; Wang C et al. 2016; Poudel GR et al. 2018). While some extreme sleep episodes are associated with behavioural signs of falling asleep such as attentional lapses (Drummond SP et al. 2005; Chee MWL et al. 2008) and slow closing of the eyelids (Poudel GR et al. 2014; Poudel GR et al. 2018), sleep onset can also occur without overt behavioural signs. Sleep onsets are particularly frequent in individuals who are exposed to sleep and circadian disturbances, and can acutely reduce cognitive function (Nir Y et al. 2017). Hence, monitoring sleep onsets while awake has major implications for understanding human behaviour in shiftwork, safety-critical operations including motor vehicle accidents, as well as circadian and sleep disorders.Electroencephalography (EEG), pupil sizes, and response behaviour can be used to monitor overt signs of reduced arousal in humans. Any brief (3-15 s) intrusions of theta waves (4-7 Hz theta) that replace higher-frequency alpha waves (>8 Hz) on EEG recordings are considered to be microsleeps (Boyle LN et al. 2008). In drowsy individuals, response lapses are associated with these microsleeps (Poudel GR et al. 2014;Poud...

Sleep can intrude into the awake human brain when sleep deprived or fatigued, even while performing cognitive tasks. However, how the brain activity associated with sleep onset can co-exist with the activity associated with cognition in the awake humans remains unexplored. Here, we used simultaneous fMRI and EEG to generate fMRI activity maps associated with EEG theta (4-7 Hz) activity associated with sleep onset. We implemented a method to track these fMRI activity maps in individuals performing a cognitive task after well-rested and sleep-deprived nights. We found frequent intrusions of the fMRI maps associated with sleep-onset in the task-related fMRI data. These sleep events elicited a pattern of transient fMRI activity, which was spatially distinct from the task-related activity in the frontal and parietal areas of the brain. They were concomitant with reduced arousal as indicated by decreased pupil size and increased response time. Graph theoretical modelling showed that the activity associated with sleep onset emerges from the basal forebrain and spreads anterior-posteriorly via the brain's structural connectome. We replicated the key findings in an independent dataset, which suggests that the approach can be reliably used in understanding the neuro-behavioural consequences of sleep and circadian disturbances in humans.