Altered functional connectivity and regional brain activity in a triple-network model in minimally conscious state and vegetative-state/unresponsive wakefulness syndrome patients: A resting-state functional magnetic resonance imaging study

Abstract

The purpose of this study was to investigate changes in functional connectivity and regional brain activity between and within the default mode network (DMN), salience network (SN), and executive control network (ECN) among individuals with disorders of consciousness (DOC) in the conditions of minimally conscious state (MCS) and vegetative-state/unresponsive wakefulness syndrome (VS/UWS). Twenty-five VS/UWS patients, 14 MCS patients, and 30 healthy individuals as normal control, completed resting-state fMRI scans. ROI-wise functional connectivity and fractional amplitude of low-frequency fluctuation (fALFF) were implemented to examine group differences. All ROI-wise and fALFF analyses masks were identified from the triple-network model. ROI-wise analyses indicated significantly decreased functional connectivity between posterior cingulate cortex (DMN)-left anterior insula (SN), right anterior insula (SN)-left dorsolateral prefrontal cortex (ECN), and right anterior insula (SN)-right amygdala (SN) in VS/UWS patients compared to MCS patients. Moreover, fALFF were observed reduced in the triple-network across all DOC patients, and as the clinical manifestations of DOC deteriorated from MCS to VS/UWS, fALFF in dorsal DMN, anterior/posterior SN, and left ECN became significantly reduced. Moreover, a positive correlation between fALFF of the left ECN and Coma Recovery Scale-Revised (CRS-R) total scores was found across all DOC patients. These findings contribute to a better understanding of the underlying neural mechanism of functional connectivity and regional brain activity in DOC patients, and this triple-network model provides new connectivity pattern changes that may be integrated in future diagnostic tools based on the neural signatures of conscious states.

Keywords: fractional amplitude of low-frequency fluctuation (fALFF); functional connectivity; minimally conscious state (MCS); resting-state fMRI; triple-network model; vegetative state/unresponsive wakefulness syndrome (VS/UWS).

FIGURE 1

Connectivity differences between MCS and VS/UWS patient groups and NC group in ROI-wise analyses. Between-group comparisons of the ROI-wise analyses indicated significantly decreased functional connectivity between PCC-LAI (A), RAI-LDLPFC (B), and RAI-RAMY (C) during rest, in the VS/UWS group relative to MCS and NC groups. The graphs illustrate the differences in functional connectivity of PCC-LAI, RAI-LDLPFC, and RAI-RAMY in MCS, VS/UWS patients and NC groups (AI, anterior insula; PCC, posterior cingulate cortex; DLPFC, dorsolateral prefrontal cortex; AMY, amygdala; L, left; R, right; NC, healthy control individuals; MCS, minimally conscious state; VS/UWS, vegetative-state/unresponsive wakefulness syndrome; *p < 0.05; ^**p < 0.01; error bars represent the standard error of measurement).

FIGURE 2

fALFF differences within the triple-network model and correlations with CRS-R total scores in MCS and VS/UWS patient groups and NC group. Reduced fALFF within the masks of dorsal/ventral DMN (A), anterior/posterior SN (B), and left/right ECN (C) were shown. As the clinical manifestations of DOC deteriorated from MCS to VS/UWS, fALFF within dorsal DMN (A top), anterior/posterior SN (B top/bottom), and left ECN (C top) became significantly reduced. Correlations between fALFF of the left ECN and CRS-R total scores were found across all DOC patients (D) (fALFF, fractional amplitude of low-frequency fluctuation; CRS-R, Coma Recovery Scale-Revised; DOC, disorders of consciousness; NC, healthy control individuals; MCS, minimally conscious state; VS/UWS, vegetative-state/unresponsive wakefulness syndrome; *p < 0.05; ^**p < 0.01; ^***p < 0.001; error bars represent the standard error of measurement).