# Altered static and dynamic functional network connectivity between subcortical nuclei and cortical regions of the default mode network in type 2 diabetes mellitus

## TL;DR

This study finds that type 2 diabetes affects brain networks linked to cognition, with specific changes in connections between subcortical and cortical regions.

## Contribution

The study identifies novel patterns of static and dynamic functional connectivity disruptions in T2DM patients involving subcortical nuclei and the default mode network.

## Key findings

- T2DM patients show decreased resting-state functional connectivity between the basal forebrain and dorsomedial prefrontal cortex.
- Dynamic functional connectivity analysis reveals altered state frequencies and dwell times in T2DM patients compared to healthy controls.
- Reduced connectivity correlates with cognitive scores and disease duration in T2DM patients.

## Abstract

Disruptions in functional connectivity (FC) within the default mode network (DMN) are well established as a key neuropathology underlying cognitive impairment in type 2 diabetes mellitus (T2DM). Subcortical nuclei, including the basal forebrain (BF) and mediodorsal thalamus, play critical roles in regulating DMN-associated cognitive processes and are particularly vulnerable to hyperglycemia and brain insulin resistance. However, the specific FC patterns between these subcortical nuclei and DMN cortical regions in patients with T2DM, as well as their potential associations with cognitive impairment, remain incompletely elucidated.

Eighty-two patients with T2DM and 79 healthy controls (HCs) were enrolled in this study. Clinical data, neuropsychological assessments, and resting-state functional magnetic resonance imaging were collected from all participants. Resting-state (rs-FNC) and dynamic (dFNC) functional network connectivity analyses were performed to characterize connectivity between subcortical nuclei and DMN cortical regions. Correlation analyses explored associations between FNC metrics showing significant intergroup differences and participants’ clinical and cognitive parameters.

rs-FNC analysis revealed decreased FC between the BF and the dorsomedial prefrontal cortex (dMPFC), the BF and the temporal pole, and the dMPFC and the anteromedial prefrontal cortex in patients with T2DM (network-based statistic correction; edge p < 0.001, component p < 0.05). dFNC analyses indicated increased frequency and prolonged mean dwell time (MDT) of State 1 (high-frequency low-connectivity), as well as decreased frequency and shortened MDT of State 2 (high-frequency high-connectivity) compared with HCs (all p < 0.05). Reduced FC between the dMPFC and BF was positively correlated with Montreal Cognitive Assessment scores (r = 0.353, p = 0.001), whereas frequency (r = −0.434, p < 0.001) and MDT (r = −0.376, p = 0.001) of State 2 were negatively correlated with T2DM disease duration after Bonferroni correction.

These findings indicate that T2DM duration correlates with reduced highly efficient DMN connectivity, and that the BF may regulate cognitive function via the dMPFC subsystem. The results reveal temporal and functional specificity in abnormal DMN connectivity in patients with T2DM and enrich the neural atlas of DMN dysfunction in this population.