The present study aimed to investigate alterations in the multilayer network combining structural and functional layers between patients with ESKD and healthy controls. Numerous attempts have been made to explain the use of multilayer network analysis in many neurological disorders; however, there have been no approaches using multilayer networks in patients with ESKD. (2, 24, 25) Our study revealed a significant reduction in weighted multiplex participation at both the global and nodal levels among patients with ESKD compared with healthy controls. Furthermore, examination at the nodal level identified several specific brain regions characterized by decreased weighted multiplex participation, highlighting localized deficits in the interlayer interactions within the brain network of patients with ESKD.
At the global level, weighted multiplex participation was lower in patients with ESKD than in healthy controls. Weighted multiplex participation is a quantitative measure of a node’s involvement across multiple network layers determined by evaluating the weighted interactions within each layer. (27–31) Therefore, decreased weighted multiplex participation suggests a diminished level of integration or engagement of brain regions across the structural and functional layers of connectivity in patients with ESKD. This result corresponds to the finding of a deficit in integration within multilayer networks among patients with Alzheimer's disease and mild cognitive disorders. (31)
Additional analysis was conducted at the nodal level of the multilayer network, revealing a decrease in weighted multiplex participation within specific regions, such as the right subcentral gyrus, right opercular part of the inferior frontal gyrus, right occipito-temporal medial lingual gyrus, and right postcentral gyrus, in patients with ESKD compared with healthy controls. The right subcentral gyrus plays a crucial role in sensorimotor integration; somatosensory processing; language and speech; and motor coordination. (32, 33) The right postcentral gyrus, located on the lateral surface of the anterior parietal lobe, plays a role in somatosensory processing and sensorimotor integration. (33, 34) The right opercular part of the inferior frontal gyrus is important for language production, executive functioning, and motor control. (33, 35) The right occipitotemporal medial lingual gyrus plays a role in visual processing and word and face recognition. (33, 36) These findings suggest the possibility that the complementary relationship between structural and functional networks in these nodes had decreased.
Previously, the dominant cerebral hemisphere, which mainly refers to the left side of a left-handed person, was known to play a crucial role in brain function. However, recent research has revealed the importance of the non-dominant cerebral hemisphere, primarily referring to the right side, in brain function. The non-dominant hemisphere plays a significant role in primary cognitive functions, such as visuospatial and social cognition (37). The white matter fiber tract, known as the superior longitudinal fasciculus in the perisylvian area of the right hemisphere, plays a crucial role in cognitive function. The subcentral, inferior frontal, and postcentral gyri, which showed significant changes in this study, correspond to these regions. Accordingly, damage to the multilayer network in these areas may be related to neurological impairments in patients with ESKD. These regions are distinct areas with diverse functions; however, they have interconnected neural networks and functional relationships. Further research utilizing multilayer network analysis may provide valuable insights into the pathophysiology of neurological complications in patients with ESKD, and inform targeted interventions to mitigate these adverse outcomes.
Our study represents the first attempt to conduct a multilayer network analysis in patients with ESKD; however, it has several limitations. First, this study was planned at a single center, and the relatively small sample size is a limitation. This may have led to a selection bias, and we believe that larger-scale studies are necessary in the future. Second, we conducted a multilayer network analysis of patients with ESKD at a group level rather than at an individual level. Therefore, we could not perform a correlation analysis between clinical data and the multilayer network. Third, cognitive function tests were not performed. This represents a limitation in understanding the relationship between cognitive function impairment in patients with ESKD and variables within the multilayer network. Despite these limitations, this study demonstrates the value of multilayer network analysis in understanding the pathophysiology of neurological complications in patients with ESKD and its potential for diverse future applications.