Altered cognitive control network is related to psychometric and biochemical profiles in covert hepatic encephalopathy

Abstract

The cognitive control network (CCN) is a network responsible for multiple executive functions, which are impaired in covert hepatic encephalopathy (CHE). We aimed to use functional connectivity (FC) magnetic resonance imaging to test the hypothesis that CHE manifested with disconnection within the CCN, which is associated with impaired neuropsychiatric and biochemical profiles. CHE was detected with abnormally low psychometric hepatic encephalopathy scores (PHES) (total cut-off score <−4). Two seeds in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) were used to calculate the FC map within the CCN. Pearson correlation analysis was performed between the CCN and psychometric, biochemical profiles including ammonia, Interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Eighteen CHE, 36 non-HE (NHE) cirrhotic patients and 36 controls were studied. Significant differences in FC were noted among groups, which revealed CHE patients had a lower FC in the bilateral lateral occipital cortex (seed in the bilateral dACC) and in the right lateral occipital and precuneus cortices (seed in the left DLPFC) (P < 0.05, corrected) compared with NHE. Progressively decreased FC in the left precentral gyrus within the CCN was noted from control, NHE to CHE. PHES positively and biochemistry negatively correlated with FC in the CCN. In conclusion, CHE patients showed aberrant FC within the CCN which is correlated with both cognitive dysfunction and biochemical profiles. Ammonia and pro-inflammatory cytokines may contribute to the occurrence of aberrant connectivity. Impaired FC within the CCN may serve as a complementary biomarker for CHE.

Progressive Disruption of Dynamic Functional Network Connectivity in Patients With Hepatitis B Virus‐related cirrhosis

“…These results suggest that whole-brain dynamic functional connectivity undergoes a progressive disruption in patients with HBV-RC. Progressive impairment of the static network system in HBV-RC patients has been widely verified, 8,9 and our results extend those findings to dynamic network integration.…”

“…7 Alteration of FC in the NHME stage 8 and the progressive deterioration of FC along with progression from NHME to MHE have also detected in patients with HBV-RC. [9][10][11] However, these studies evaluated brain activity averaged over the entire scanning period and, thus, the results [9][10][11] do not reflect the highly dynamic organization of the brain which exhibits time-varying neural activity and quickly changing neural integration. 12 Functional network connectivity (FNC) is based on spatial independent component analysis, which is a multivariate data-driven method.…”

Minimal hepatic encephalopathy is associated to alterations in eye movements

“…Dorsolateral prefrontal cortex (DLPFC) controls the top-down decisional process determining whether to make a prosaccade by signals to the superior colliculus 22 . The functional connectivity between precuneus and DLPFC, within the cognitive control network (CCN) was reduced in patients with MHE compared to patients without MHE 34 . Moreover, we previously showed a reduction of cortical thickness in the precuneus in MHE patients compared with NMHE and control subjects 35 .…”

Through the looking glass: Deep interpretable dynamic directed connectivity in resting fMRI

“…We also see direction of connectivity from cognitive control (CC) to sensorimotor (SM). Existing studies ( Breukelaar et al, 2017 ; Cole and Schneider, 2007 ; Tsai et al, 2019 ) show that cognitive control is responsible for activities like attention, remembering and execution, things which are required when doing a motor task controlled by sensorimotor. Such directionality is important to study brain’s working in more detail and is not present in FNC used by existing methods.…”