Altered dynamic spontaneous neural activity in minimal hepatic encephalopathy

Abstract

Background and aims: Abnormal regional neural activity has been identified by the analysis of the static amplitude of low-frequency fluctuation (ALFF) in the setting of minimal hepatic encephalopathy (MHE). Brain activity is highly dynamic. This work sought to evaluate the temporal variability of ALFF to reveal MHE-related alterations in the dynamics of spontaneous neural activity.

Methods: A total of 29 healthy controls and 49 patients with cirrhosis [including 20 patients with MHE and 29 patients without MHE (NHE)] who underwent resting-state functional magnetic resonance imaging and Psychometric Hepatic Encephalopathy Score (PHES) examination were enrolled in this investigation. Utilizing a sliding-window approach, we calculated the dynamic ALFF (dALFF) variability to reflect the temporal dynamics of regional neural activity. An analysis of the correlation between dALFF variability and PHES was performed, and receiver operating characteristic (ROC) curve analysis to determine the potential of the dALFF variability index in identifying MHE was completed.

Results: The dALFF variability in the bilateral precuneus/posterior cingulate gyrus and left middle frontal gyrus progressively decreased from NHE to MHE group. In cirrhotic patients, the value of dALFF variability in the bilateral precuneus/posterior cingulate gyrus was positively correlated with their neurocognitive performance (r = 0.383 and P = 0.007). The index of dALFF variability in the bilateral precuneus/posterior cingulate gyrus could be used to distinguish NHE and MHE patients, with moderate power (area under the ROC curve = 0.712 and P = 0.012).

Conclusion: Our findings highlight the existence of aberrant dynamic brain function in MHE, which could underlie the neural basis of cognitive impairments and could be associated with the development of the disease. Analyzing dALFF could facilitate new biomarker identification for MHE.

Keywords: amplitude of low-frequency fluctuation; cognition; dynamic; minimal hepatic encephalopathy; spontaneous neural activity.

Figure 1

The distribution pattern of dALFF variability in the healthy control (HC) group, group of patients with minimal hepatic encephalopathy (MHE), and group of patients without MHE (NHE). The red and blue colors, respectively, indicate high and low dALFF variability. “L” denotes the left hemisphere and “R” denotes the right hemisphere.

Figure 2

Brain regions where significant differences in dALFF variability were located across the 3 groups. The combination of violin and box plots shows the distribution and between-group differences of mean dALFF values in these regions. ROI1, bilateral precuneus and posterior cingulate gyrus; ROI2, left middle frontal gyrus. HC, healthy control; MHE, minimal hepatic encephalopathy; NHE, patients without MHE. dALFF, dynamic amplitude of low-frequency fluctuation.

Figure 3

The results of correlation analyses. dALFF, dynamic amplitude of low-frequency fluctuation.

Figure 4

Results of ROC curve analysis. ROI1, bilateral precuneus and posterior cingulate gyrus; ROI2, left middle frontal gyrus.

Figure 5

Results of dALFF analysis with GMV as a covariate.

Figure 6

Results of dALFF analysis with the GSR.

Figure 7

Results of dALFF analyses with the following distinct sliding-window parameter settings: (A) window size of 24 TR, sliding step of 1 TR, and Hamming window type; (B) window size of 32 TR, sliding step of 2 TR, and Hamming window type; (C) window size of 32 TR, sliding step of 4 TR, and Hamming window type; (D) window size of 40 TR, sliding step of 1 TR, and Hamming window type; (E) window size of 50 TR, sliding step of 1 TR, and Hamming window type; and (F) window size of 32 TR, sliding step of 1 TR, and rectangular window type. TR = 2,000 ms.

Figure 8

Brain regions where the significant differences in sALFF were found across the 3 groups.