Sequential deactivation across the thalamus-hippocampus-mPFC pathway during loss of consciousness

  1. Xiaoai Chen
  2. Samuel R. Cramer
  3. Dennis C.Y. Chan
  4. Xu Han
  5. Nanyin Zhang

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Abstract

How consciousness is lost in states such as sleep or anesthesia remains a mystery. To gain insight into this phenomenon, we conducted concurrent recordings of electrophysiology signals in the anterior cingulate cortex and whole-brain functional magnetic resonance imaging (fMRI) in rats exposed to graded propofol, undergoing the transition from consciousness to unconsciousness. Our results reveal that upon the loss of consciousness (LOC), as indicated by the loss of righting reflex, there is a sharp increase in low-frequency power of the electrophysiological signal. Additionally, simultaneously measured fMRI signals exhibit a cascade of deactivation across a pathway including the hippocampus, thalamus, and medial prefrontal cortex (mPFC) surrounding the moment of LOC, followed by a broader increase in brain activity across the cortex during sustained unconsciousness. Furthermore, sliding window analysis demonstrates a temporary increase in synchrony of fMRI signals across the hippocampus-thalamus-mPFC pathway preceding LOC. These data suggest that LOC might be triggered by sequential activities in the hippocampus, thalamus and mPFC, while wide-spread activity increases in other cortical regions commonly observed during anesthesia-induced unconsciousness might be a consequence, rather than a cause of LOC. Taken together, our study identifies a cascade of neural events unfolding as the brain transitions into unconsciousness, offering critical insight into the systems-level neural mechanisms underpinning LOC.

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  1. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/13372246.

    Does the introduction explain the objective of the research presented in the preprint? Yes
    Are the methods well-suited for this research? Highly appropriate The authors used electrophysiology to determine at what time point in the experiment the subjects were unconscious. This allowed them to mark LOC in the fMRI data so they could study the physiology of multiple brain regions at the point of losing consciousness and afterwards.
    Are the conclusions supported by the data? Highly supported
    Are the data presentations, including visualizations, well-suited to represent the data? Highly appropriate and clear
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Very clearly
    Is the preprint likely to advance academic knowledge? Somewhat likely
    Would it benefit from language editing? No
    Would you recommend this preprint to others? Yes, it's of high quality Easy to read/understand
    Is it ready for attention from an editor, publisher or broader audience? Yes, after minor changes A bit more clarification on how figure 5's correlograms represent synchronous activity. "This notion is further supported by an increased occurrence of synchronization in their BOLD activity before LOC and a subsequent decrease after LOC in our study, as well as in several previous studies."

    Competing interests

    The authors declare that they have no competing interests.

  2. Version published to 10.1101/2024.05.20.594986v1 on bioRxiv