Thursday, November 21, 2024
11/21/2024
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.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
