Changes in brain connectivity and neurovascular dynamics during dexmedetomidine-induced loss of consciousness.

Understanding the neurophysiological changes that occur during loss and recovery of consciousness is a fundamental aim in neuroscience and has marked clinical relevance. Here, we utilize multimodal magnetic resonance neuroimaging to investigate changes in regional network connectivity and neurovascular dynamics as the brain transitions from wakefulness to dexmedetomidine-induced unconsciousness, and finally into early-stage recovery of consciousness. We observed widespread decreases in functional connectivity strength across the whole brain, and targeted increases in structure-function coupling (SFC) across select networks- especially the cerebellum-as individuals transitioned from wakefulness to hypnosis. We also observed robust decreases in cerebral blood flow (CBF) across the whole brain-especially within the brainstem, thalamus, and cerebellum. Moreover, hypnosis was characterized by significant increases in the amplitude of low-frequency fluctuations (ALFF) of the resting-state blood oxygen level-dependent signal, localized within visual and somatomotor regions. Critically, when transitioning from hypnosis to the early stages of recovery, functional connectivity strength and SFC-but not CBF-started reverting towards their awake levels, even before behavioral arousal. By further testing for a relationship between connectivity and neurovascular alterations, we observed that during wakefulness, brain regions with higher ALFF displayed lower functional connectivity with the rest of the brain. During hypnosis, brain regions with higher ALFF displayed weaker coupling between structural and functional connectivity. Correspondingly, brain regions with stronger functional connectivity strength during wakefulness showed greater reductions in CBF with the onset of hypnosis. Earlier recovery of consciousness was associated with higher baseline (awake) levels of functional connectivity strength, CBF, and ALFF, as well as female sex. Across our findings, we also highlight the role of the cerebellum as a recurrent marker of connectivity and neurovascular changes between states of consciousness. Collectively, these results demonstrate that induction of, and emergence from dexmedetomidine-induced unconsciousness are characterized by widespread changes in connectivity and neurovascular dynamics. Elucidating the neurophysiological changes underlying loss and recovery of consciousness is a fundamental question in neuroscience. Here, we analyze magnetic resonance imaging data collected across multiple time-points to characterize how the human brain's connectivity and neurovascular dynamics change as it transitions from wakefulness to dexmedetomidine-induced unconsciousness, and early-stage recovery of consciousness. During hypnosis, brain regions become less functionally synchronized to each other; they attain a smaller number of functional configurations compared to wakefulness, and display functional connectivity patterns that are more similar to the underlying structural connectivity. Furthermore, cerebral blood flow significantly decreases across the whole brain, and less metabolically demanding low frequency fluctuations in the hemodynamic signal become more prominent. Collectively, loss of consciousness is accompanied by widespread connectivity and neurovascular changes in the brain, characteristic of less metabolically demanding dynamics.