title: Propofol disrupts functional interactions between sensory and high-order processing of auditory verbal memory.
abstract: Current theories suggest that disrupting cortical information integration may account for the mechanism of general anesthesia in suppressing consciousness. Human cognitive operations take place in hierarchically structured neural organizations in the brain. The process of low-order neural representation of sensory stimuli becoming integrated in high-order cortices is also known as cognitive binding. Combining neuroimaging, cognitive neuroscience, and anesthetic manipulation, we examined how cognitive networks involved in auditory verbal memory are maintained in wakefulness, disrupted in propofol-induced deep sedation, and re-established in recovery. Inspired by the notion of cognitive binding, an functional magnetic resonance imaging-guided connectivity analysis was utilized to assess the integrity of functional interactions within and between different levels of the task-defined brain regions. Task-related responses persisted in the primary auditory cortex (PAC), but vanished in the inferior frontal gyrus (IFG) and premotor areas in deep sedation. For connectivity analysis, seed regions representing sensory and high-order processing of the memory task were identified in the PAC and IFG. Propofol disrupted connections from the PAC seed to the frontal regions and thalamus, but not the connections from the IFG seed to a set of widely distributed brain regions in the temporal, frontal, and parietal lobes (with exception of the PAC). These later regions have been implicated in mediating verbal comprehension and memory. These results suggest that propofol disrupts cognition by blocking the projection of sensory information to high-order processing networks and thus preventing information integration. Such findings contribute to our understanding of anesthetic mechanisms as related to information and integration in the brain.
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
authors.forename: Kathryn K
authors.initials: KK
authors.lastname: Lauer
authors.forename: Barney D
authors.initials: BD
authors.lastname: Ward
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rao
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Li
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Hudetz
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D015742:Propofol / Q000494:pharmacology*
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol