Background Current state of knowledge suggests that disruption of neuronal information integration may be a unitary mechanism of anesthetic-induced unconsciousness. A neural system central for information integration is the thalamocortical system whose specific and nonspecific divisions may play the roles for representing and integrating information; respectively. How anesthetics affect the function of these systems individually is not completely understood. We studied the effect of propofol on thalamocortical functional connectivity in the specific and nonspecific systems using functional magnetic resonance imaging. Methods Eight healthy volunteers were instructed to listen to and encode 40 English words during wakeful baseline, light sedation, deep sedation, and recovery in the scanner. Functional connectivity was determined as the temporal correlation of blood oxygen level-dependent signals with seed regions defined within the specific and nonspecific thalamic nuclei. Results Thalamocortical connectivity at baseline was dominantly medial and bilateral frontal and temporal for the specific system and medial frontal and medial parietal for the nonspecific system. During deep sedation, propofol reduced functional connectivity by 43% (specific) and 79% (nonspecific), a significantly greater reduction of connections in the nonspecific than in the specific system and in the left hemisphere than in the right. Upon regaining consciousness, functional connectivity increased by 58% (specific) and 123% (nonspecific) during recovery, exceeding their values at baseline. Conclusions Propofol conferred differential changes in functional connectivity of the specific and nonspecific thalamocortical systems. The changes in nonspecific thalamocortical connectivity may correlate with loss and return of consciousness.

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 fMRI-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.

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Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1 Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia.

Opioid sedation does not alter intracranial pressure in head injured patientsPurpose: This study aimed to examine the effects of sedative doses of morphine, fentanyl and sufentanil on intracranial pressure (ICP) in head-injured patients in whom changes in mean arterial pressure (MAP) were minimized. Methods: Fd~een severely head-injured patients (GSC of 28) were randomly assigned to receive either fentanyl, sufentanil or morphine, titrating the drug to a maximal 10% decrease in NAP. The patients were subsequently given an infusion of the same opioid. For four hours, ICP, MAP and heart rate were recorded.Results: in all groups, there were no increases in ICP` There was a decrease in MAP in the sufentanU group at 10 rain (P < 0.05) and 45 rain after the initial opioid bolus. These decreases in MAP were not associated with increases in ICP` Conclusion: The study suggests that when opioids are titrated in head-injured patients, worsening intracranial pressure can be avoided.Objectif : I~tudier les effets de doses s6datives de morphine, de fentanyi et de sufentanil sur la pression intracr~nienne (PIC) chez des traumatis~s du cr~ne dont la pression art6rielle moyenne (PAM) n'avait que 16g6rement vari6.M~thodes : Quinze graves traumatis6s du cr~ne (l~chelle de Glasgow <8) ont d, t6 assignd, s al6.atoirement pour recevoir du fentanyl, du sufentanil, ou de la morphine titr6s de fagon A abaisser la PAIr1 de 1096 ou moins. Les patients ont par la suite regu une perfusion du m~me morphinique. Pendant qudire heures, la PIC, la PAIVl et la fr6quence cardiaclue 6talent enregistr~es. l~ultats : La PIC est demeur~e inchangChe dans tousles groupes. La PAP1 a baiss6 dans le groupe sufentanil la I 0 e minute (P > 0,(35) et/~ la 45 9 minute qui ont suivi I'administration du bolus initial. Ces diminutions de la PAN n'6taient pas associ6es A une augmentation de la PIC.Conclusion : Cette ~tude sugg6re que I'administration titrChe de morphiniques A des traumatis~s du cr~ne ne provoque pas de d6t6rioration de la pression intracr~ienne.