Posterior cingulate cross-hemispheric functional connectivity predicts the level of consciousness in traumatic brain injury

Abstract

Previous studies have demonstrated that altered states of consciousness are related to changes in resting state activity in the default-mode network (DMN). Anatomically, the DMN can be divided into anterior and posterior regions. The anterior DMN includes the perigenual anterior cingulate cortex and other medial prefrontal cortical regions, whereas the posterior DMN includes regions such as the posterior cingulate cortex (PCC) and the temporal parietal junction (TPJ). Although differential roles have been attributed to the anterior and posterior DMN regions, their exact contributions to consciousness levels remain unclear. To investigate the specific role of the posterior DMN in consciousness levels, we investigated 20 healthy controls (7 females, mean age = 33.6 years old) and 20 traumatic brain injury (TBI) patients (5 females, mean age = 43 years old) whose brain lesions were mainly restricted to the bilateral frontal cortex but retained a well-preserved posterior DMN (e.g., the PCC and the TPJ) and who exhibited varying levels of consciousness. We investigated the intra- and cross-functional connectivity strengths (FCSs) between the right/left PCC and the right/left TPJ and their correlation with consciousness levels. Significant reductions in both the intra- and cross-hemispheric FCSs were observed in patients compared with controls. A significant correlation with consciousness levels was observed only for the cross-hemispheric PCC-TPJ FCS but not for the intra-hemispheric PCC-TPJ FCS. Taken together, our results show that the cross-hemispheric posterior DMN is related to consciousness levels in a specific group of patients without posterior structural lesions. We therefore propose that the PCC may be central in maintaining consciousness through its cross-hemispheric FC with the TPJ.

Figure 1

The images show one representative subject’s functional connectivity strength; the region of the PCC was used as the seed for analyzing the following FCSs: the FCS between the left PCC and left TPJ (intra-hemispheric FCS); FCS between the left PCC and right TPJ (cross-hemispheric FCS); FCS between the right PCC and left TPJ (cross-hemispheric FCS); the FCS between right PCC and right TPJ (intra-hemispheric FCS).

Figure 2

The bars represent the relative magnitudes of the FCSs (mean+/− SE). The general linear model (univariate) test showed that there were differences between the controls and patients (F = 99.626; P < 0.01), and the T-test with Bonferroni multiple-comparison correction demonstrated that (1) for the between-group analysis, both the intra- and cross-hemispherical FCSs of the patients decreased compared with controls; (2) for the intra-group analysis, a difference was detected between the left intra-hemispheric (lPCC-lTPJ) FCS and the cross-hemispheric (lPCC-rTPJ) FCS (F = 3.094; P = 0.011, corrected) for the patient group, whereas no significant difference among the PCC-TPJ patterns was observed in the control group (F = 1.215; P = 0.310, corrected). **α = 0.01; *α = 0.05.

Figure 3

Differences in the PCC-TPJ FCSs between the low/medium and high GCS subgroups of patients (low/medium GCS: 9 patients, high GCS: 11 patients) using an independent group analysis. The bars represent the relative magnitudes of the FCSs (mean+/− SE). Low/medium GCS versus high GCS: lPCC-lTPJ (F = 3.932; P = 0.126); lPCC-rTPJ (F = 0.607; P = 0.002 < 0.01); rPCC-lTPJ (F = 0.008; P = 0.004 < 0.01); rPCC-rTPJ (F = 0.072; P = 0.315). The cross-hemispherical FCSs represented the major difference between the low/medium GCS and high GCS groups. **.α = 0.01; *.α = 0.05.

Figure 4

(A,B) The Spearman’s correlation of the PCC-PTJ FCSs with both the GCS scores and the CRS-R scores in the TBI patient group. The cross-hemispherical FCSs were significantly correlated with the consciousness level for both scales. (A,C): Intra-hemispheric functional connectivity (lPCC-lTPJ and rPCC-rTPJ). (B,D): Cross-hemispheric functional connectivity (lPCC-rTPJ and rPCC-lTPJ). **α = 0.01; *α = 0.05.