Differential effects of deep sedation with propofol on the specific and nonspecific thalamocortical systems: a functional magnetic resonance imaging study

Abstract

Background: The current state of knowledge suggests that disruption of neuronal information integration may be a common mechanism of anesthetic-induced unconsciousness. A neural system critical 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. The authors 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 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, particularly in left hemisphere, consistent with the verbal nature of stimuli and task. The changes in nonspecific thalamocortical connectivity may correlate with the loss and return of consciousness.

Figure 1

Experimental paradigm and the seeding of the specific and nonspecific thalamic nuclei for functional connectivity analysis. (A) Study participants underwent fMRI scans while listening to and encoding a distinct set of English words presented during each of the four experimental sessions in wakeful baseline, light sedation, deep sedation, and recovery. Propofol was administrated by computer-controlled intravenous infusion to target plasma concentrations as indicated. (B) The distribution of the thalamic nuclei in a coronal plane of the right thalamus. Two intralaminar nuclei (centromedian and parafascicular) indicated by the shaded area were used as a seed to calculate nonspecific thalamocortical connectivity. The rest of the thalamus was used as a seed for calculating specific thalamocortical connectivity. (C) Examples of the specific and nonspecific thalamic seeds (red area) overlaid the anatomical image of a coronal slice in one subject.

Figure 2

Differential modification of specific and nonspecific thalamocortical functional connectivity across the states of consciousness. The upper three panels (A, B, and C) and the lower three panels (D, E, and F) illustrate respectively the significant specific and nonspecific thalamic connections derived from one-sample t-tests in the states of wakeful baseline, deep sedation, and recovery. Note the different distributions of specific and nonspecific thalamocortical connectivity at baseline and the greater reduction in nonspecific vs. specific connectivity in deep sedation.

Figure 3

Regional distributions of specific (A) and nonspecific (B) thalamocortical functional connectivity as measured by voxel count in Figure 2. Twenty anatomical regions that primarily account for the distribution of functional connections across the states of wakeful baseline, deep sedation, and recovery were selected and displayed from the left to right in a descending order according to the voxel count of wakeful baseline.

Figure 4

Comparison of the changes of the specific and nonspecific thalamocortical functional connectivities across the states of consciousness. (A) The reduction ratio wakeful baseline to deep sedation. (B) The increase ratio from deep sedation to recovery. (C) The increase ratio from wakeful baseline to recovery. (D) Comparison of the extent of functional connectivity between the left and right hemispheres in the three states of consciousness for the specific system. (E) The same for the nonspecific system. Note the hemispheric asymmetry of connectivity in deep sedation. *: p < 0.05, **: p < 0.01, ***: p <0.001, paired t-test via a leave-one-out test analysis.

Figure 5

Regional association of thalamocortical functional connectivity with changes of the state of consciousness. Indices I_A (E.1)and I_B (E. 2) quantify the reduction in connectivity during sedation relative to wakeful baseline and sedation (symmetric component of change) and the relative difference between in connectivity between recovery and wakeful baseline (asymmetric component of change). Note the clearly segregated distribution of brain regions with specific (blue) and nonspecific (red) thalamic connectivity, implying a qualitatively different behavior between the two systems. The changes in the connectivity of the nonspecific regions show a greater association with alterations of the state of consciousness than those of specific connectivity.