Posterior cingulate cortex-related co-activation patterns: a resting state FMRI study in propofol-induced loss of consciousness

Abstract

Background: Recent studies have been shown that functional connectivity of cerebral areas is not a static phenomenon, but exhibits spontaneous fluctuations over time. There is evidence that fluctuating connectivity is an intrinsic phenomenon of brain dynamics that persists during anesthesia. Lately, point process analysis applied on functional data has revealed that much of the information regarding brain connectivity is contained in a fraction of critical time points of a resting state dataset. In the present study we want to extend this methodology for the investigation of resting state fMRI spatial pattern changes during propofol-induced modulation of consciousness, with the aim of extracting new insights on brain networks consciousness-dependent fluctuations.

Methods: Resting-state fMRI volumes on 18 healthy subjects were acquired in four clinical states during propofol injection: wakefulness, sedation, unconsciousness, and recovery. The dataset was reduced to a spatio-temporal point process by selecting time points in the Posterior Cingulate Cortex (PCC) at which the signal is higher than a given threshold (i.e., BOLD intensity above 1 standard deviation). Spatial clustering on the PCC time frames extracted was then performed (number of clusters = 8), to obtain 8 different PCC co-activation patterns (CAPs) for each level of consciousness.

Results: The current analysis shows that the core of the PCC-CAPs throughout consciousness modulation seems to be preserved. Nonetheless, this methodology enables to differentiate region-specific propofol-induced reductions in PCC-CAPs, some of them already present in the functional connectivity literature (e.g., disconnections of the prefrontal cortex, thalamus, auditory cortex), some others new (e.g., reduced co-activation in motor cortex and visual area).

Conclusion: In conclusion, our results indicate that the employed methodology can help in improving and refining the characterization of local functional changes in the brain associated to propofol-induced modulation of consciousness.

Figure 1. Co-activation patterns (CAPs).

The approach is similar to the ones proposed in and . After the extraction of a seed region, in this case Posterior Cingulate Cortex (PCC), a threshold equal to 1 standard deviation(SD) was applied, as to consider only the time points corresponding to peaks in the BOLD signal; next, the spatial maps (namely, time frames), associated with these time points are collected and clusterized using k-means, with a number of clusters fixed to 8. The centroids were kept fixed as well, to allow cluster comparison between the different clinical conditions. The within-cluster time frames were then averaged to obtain 8 spatial PCC-related co-activation patterns. Finally, the computation was iterated over the 4 different states of consciousness (wakefulness, sedation, unconsciousness, recovery), obtaining 8 PCC-related co-activation patterns for each state.

Figure 2. PCC-CAPs in wakefulness.

Left: PCC co-activation patterns in wakefulness (colormap normalized by BOLD intensity), current dataset (18 subjects). Note the similarity of these patterns with the ones showed in Fig. 2 of . Right: t-test on the same CAPs in the awake state showing statistically significant PCC co-activations. The seven slices shown in the maps are at Z = −21, −9, 3, 15, 27, 39, 51, respectively. The activation of precuneus (PC) appears in all 8 CAPs (see Z = 27); superior frontal gyrus (SFG) is co-activated in CAPs 1, 2, 3, 4, 6, 7 (Z = 39 and 51); the mesial prefrontal cortex (MPC) in CAPs 1, 2, 3, 4, 5, 6, 7 (Z = 3); rectus gyrus (RG) in CAPs 1, 2, 3,4, 5, 6, 7 (Z = −21); thalamus(THA) in CAPs 4 and 7 (Z = 3); caudate nucleus (CN) in CAPs 1, 3, 7 (Z = 15); temporal pole (TP) in all CAPs (slice Z = −21); hippocampus(HC) in CAPs 2, 4, 6, 8 (Z = −21); parahippocampus gyrus(PHG) in CAPs 2 and 4 (Z = −9); intraparietal cortex(IPC) all CAPs (Z = 27); medial frontal gyrus(MFG) in CAPs 3, 6, 7 (Z = 39); cuneus(CS) in CAPs 4 and 5 (Z = 3); rolandic stripe(RS) in CAPs 5 and 8 (Z = 51). Note how all these region-specific PCC co-activations survive to the t-test (e.g. HC for CAPs 2, 4, 6, 8; MFG for CAPs 3, 6, 7; PHG for CAPs 2, 4 etc.)

Figure 3. CAPs at different levels of consciousness.

Co-activation patterns (t-contrast) in wakefulness (left), sedation (middle-left), unconsciousness (middle-right), recovery (right), corrected at FDR p<0.05. Lower panel shows PCC seed-voxel correlation maps for each state. The seven slices shown in the maps are at Z = −21, −9, 3, 15, 27, 39, 51, respectively. Spatial patterns in wakefulness and recovery do not significantly differ from each other. Precuneal (PC) activations are preserved in all CAPs in all conditions (Z = 27 and Z = 39); mesial prefrontal (MPC) cortical activity is preserved in CAPs 1, 2, 3, 4 and 7 during wakefulness, sedation and recovery (Z = 27); intraparietal cortex (IPC) activation is preserved in CAPs 1, 2, 3, 4, 6 and 7 in all conditions (Z = 39); cuneus(CS) in CAPs 4 and 5 in all conditions (Z = 3). Note that PCC-CAPs add spatial region-specific information to the network characterization across the different stages of consciousness, when compared to the equivalent PCC seed-based contrast (last row), which exhibit a prominent drop of frontal activation during sedation and unconsciousness.

Figure 4. Decreases in CAPs.

This figure shows the local decreases in co-activation from wakefulness to unconsciousness, using the same t-contrast as in . All the images report contrast which are significant at p<0.05, FDR corrected. The seven slices shown in the maps are at Z = −21, −9, 3, 15, 27, 39, 51, respectively. CAPs consciousness-dependent deactivations appear in mesial prefrontal cortex (MPC), CAPs 1, 2, 5 (see Z = 15); superior fontal gyrus (SFG) in CAP 2 (Z = 39 and 51); thalamus (THA) in CAPs 3 and 7 (Z = 3); mesencephalon (MP) in CAP 7 (Z = −9); motor area (MA) in CAP 5 and CAP 8 (Z = 51); parahippocampal gyrus (PHG) in CAPs 2, 5, 6 (Z = −21); caudate nucleus (CN) in CAP 7 (Z = 15); visual area (VA) in CAP 6 (Z = 15); auditory cortex (AC) in CAP 8 (Z = 15) and precuneus (PC) in CAP 2 (Z = 39). For details see also Fig. 5 and Table 1.

Figure 5. Region specific consciousness modulation in CAPs.

Parameters estimates for the t-contrast employed, identical as in , for some indicative regions where PCC-related activation correlates with propofol-induced changes in consciousness. (mean ± SE; x axis labels: W = wakefulness; S = sedation; U = unconsciousness; R = recovery). Note how PCC co-activation in these regions significantly follows consciousness modulation (see also Table 1).