How Do You Feel Now? The Salience Network Functional Connectivity in End-Stage Renal Disease

Abstract

Objective The network connectivity basis of cognitive declines in end-stage renal disease (ESRD) remains unclear. A triple-network model of the salience (SN), executive control, and default mode networks has been suggested to be critical for efficient cognition. Here, we aimed to test the hypothesis that SN may play a role in cognitive impairment in patients with ESRD. Materials and Methods We investigated functional connectivity (FC) alterations within the SN between 43 ESRD patients (19 females/24 males, 46 ± 10 years) and 43 healthy controls (HC) (19 females/24 males, 47 ± 10 years), and performed linear support vector machine (LSVM) analysis on significant FC pairs within the SN to discriminate the two groups, and tested the accuracy of the classifier. Association and mediation analyses were conducted among the significant FC pairs within the SN nodes, clinical indicators, and neuropsychological tests scores. Results We identified significant between-group FC pairs within the SN and fairly good classification efficiency with significant accuracy (72.09%, p < 0.001). We found that FC between the right supramarginal gyrus and right anterior insula (AISL) was positively correlated with MoCA ( r = 0.4010, p = 0.008); FC between the dorsal anterior cingulate cortex (dACC) and left AISL was positively correlated with the level of hemoglobin ( r = 0.4979, p < 0.001). Mediation analysis found that the indirect effect of hemoglobin on forward digit span test scores via the FC between the dACC and right AISL ( p < 0.05). Conclusion Disrupted SN connectivity may help explain cognitive declines in ESRD patients and act as a potential early biomarker. Moreover, the SN connectivity may interact with anemia to promote cognitive impairment.

Altered resting-state cerebellar-cerebral functional connectivity in patients with end-stage renal disease

“…These alterations were mainly located within DMN, ECN, and ALN. Previous studies have identified impairments in these brain networks [ 10 , 12 , 14 ], which align with the findings of our study. The frontoparietal regions are important components of the DMN and ECN, and the cerebellar-frontoparietal network is involved in various higher cognitive abilities [ 32 , 33 ].…”

“…Brain imaging studies demonstrated that functional and structural brain abnormalities in ESRD patients have been detected in several brain regions, including the prefrontal lobe, inferior parietal lobe, cingulate gyrus, precuneus, temporal lobe, hippocampus/parahippocampal gyrus, and insula [ 5–9 ]. There were also abnormalities in the default mode network (DMN) [ 10–12 ], executive control network (ECN) [ 10 , 12 ], sensorimotor network (SMN) [ 12 , 13 ], salience network (SN) [ 10 , 14 ], and affective-limbic network (ALN) [ 15 , 16 ], which are composed of the brain regions mentioned above. The impairment of these brain regions or networks was related to abnormalities in overall cognitive function, working memory, visuospatial/executive function, attention, processing speed, sensorimotor, and emotional processing in ESRD patients.…”

“…Recent neuroimaging studies also found the cerebellum or cerebellar-cerebral FC play a pivotal role in ensuring cognitive function in healthy individuals as well as contributing to clinical symptoms of neuropsychiatric and metabolic brain diseases, such as Alzheimer’s disease and mild cognitive impairment [ 20 ], hepatic encephalopathy [ 21 ], major depression disorder [ 22 ], and obsessive-compulsive disorder [ 23 ]. Previous brain imaging of ESRD patients also detected alteration in the white matter microstructure of the cerebellar peduncle [ 24–26 ], a reduction in the amplitude of low-frequency fluctuations in the cerebellar cortex [ 27 ], and changed functional and structural connectivity of the cerebellum [ 14 , 28 , 29 ]. The above studies indicated that ESRD patients have structural and functional abnormalities of the cerebellum.…”

Macroscale neurovascular coupling and functional integration in end‐stage renal disease patients with cognitive impairment: A multimodal MRI study

“…The right anterior insular cortex plays a key role in SN, which serves as a switch between DMN and frontal parietal network (FPN) in cognition control (Joo et al, 2016), is particularly vulnerable to inner environmental change and external insults and significantly correlated with cognitive impairment (Chand et al, 2017;Fathy et al, 2020). And the disruption of SN correlated with cognitive decline in our previous ESRD research (Hu et al, 2020).…”

Aberrant brain gray matter and functional networks topology in end stage renal disease patients undergoing maintenance hemodialysis with cognitive impairment

“…Moreover, rs-fMRI can detect low-frequency (0.01–0.08 Hz) fluctuations in blood-oxygen-level-dependent (BOLD) signals and can be used to investigate spontaneous neural activity at rest ( Barkhof et al, 2014 ). In hemodialysis patients, impaired functional integrity of extensive brain regions has been measured by using multiple analytical methods based on rs-fMRI, including regional homogeneity (ReHo), amplitude of low frequency fluctuation (ALFF), and functional connectivity (FC) ( Li et al, 2018 ; Chen et al, 2020 ; Hu et al, 2020 ; Guo et al, 2021 ). Although the above results were inconsistent due to the diverse population cohorts and methodologies used, a correlation between functional abnormalities and cognitive dysfunction was indicated.…”