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Principal Investigator: Zirui Huang
Organization: UNIVERSITY OF MICHIGAN AT ANN ARBOR
Fiscal Year: 2024
Award: $516,464
Funding agency: National Institute of General Medical Sciences
SUMMARY
The overall goal of this work is to understand the neural basis of human consciousness and its modulation by
anesthetic agents. State and contents are two aspects of consciousness that have been mostly studied
independently. State refers to an organism's overall conscious condition that has been traditionally expressed
as the level of consciousness. Contents of consciousness refer to perceptual experiences of various kinds (e.g.,
experiences of a red rose). Recent definitions of state include some element of enabling content, highlighting
the inter-relatedness. However, this has not been formally studied in the context of the brain’s large-scale
functional organizations. We aim to fill this knowledge gap by discovering the neural mechanisms by which the
state and contents are interrelated and how their relationship is altered during anesthetic exposure. Our central
hypothesis is that a change in the state of consciousness can affect the quality of conscious contents. Further,
the state-content interaction is associated with a cooperation between the anterior forebrain mesocircuit and
cortical macrocircuit, and the cooperation is controlled by specific subcortical and cortical areas. The hypothesis
will be tested by three Specific Aims. In Aim 1 we will apply functional magnetic resonance imaging (fMRI) to
determine how conscious contents, assessed by a near-threshold perceptual task, are degraded during
anesthetic exposure. We hypothesize that suppressing the state of consciousness will diminish the quality of
conscious contents, which will be associated with functional alterations in three key brain areas: anterior insular
cortex (AIC) for content-gating, dorsolateral prefrontal cortex (DLPFC) for content-broadcasting, and central
thalamus (CT) for mediating both content gating and broadcasting. In Aim 2 we will test the causal involvement
of these areas in the state-content interaction through a perturbational approach. In participants during light
sedation with propofol (or placebo), we will apply transcranial low intensity focused ultrasound pulsation (LIFUP)
to noninvasively stimulate the CT, AIC or DLPFC and assess their effects on perceptual quality and brain activity
by fMRI. Given our preliminary results, we anticipate that stimulating these areas will lead to differential
perceptual outcomes (e.g., a change in subjective perceptual criterion alone, detection sensitivity alone, or both).
In Aim 3 we will determine if stimulating these brain areas during deep sedation with propofol or
dexmedetomidine titrated to unresponsiveness can restore the state of consciousness. We anticipate that
stimulating the CT will produce behavioral signs of wakefulness and command-following in association with
restoration of the macroscale functional hierarchy across unimodal and transmodal areas. The results should
help gain a principled understanding of the role of functional reorganization of the brain in exogenously induced
restoration of consciousness. Taken together, the proposed research is significant because it is expected to
make major progress towards understanding of the fundamental neural mechanisms of the anesthetic
modulation of human consciousness and clarifying the causal relationship of state vs. contents of consciousness.
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