Altered static and dynamic functional network connectivity between subcortical nuclei and cortical regions of the default mode network in type 2 diabetes mellitus.
Dongsheng Zhang, Xiaoling Zhang, Lei Wang, Xuejiao Yan, Xiaoyan Lei, Min Tang, Jie Gao, Yarong Wang
Frontiers in Neuroscience January 28, 2026 DOI: 10.3389/fnins.2026.1766192 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case-control observational study Peer reviewed |
|---|---|
| Sample size | 161 |
| Population | 82 patients with type 2 diabetes mellitus and 79 healthy controls |
| Measures | Montreal Cognitive Assessment (MoCA) |
| Topics | Default mode network |
| Keywords | Dynamic FMRI Subcortical Resting-state Functional network connectivity |
| Key findings | Patients with type 2 diabetes showed reduced resting-state connectivity between the basal forebrain and dorsomedial prefrontal cortex, temporal pole, and within prefrontal DMN regions, plus altered dynamic connectivity states. Reduced dorsomedial prefrontal-basal forebrain connectivity correlated with lower Montreal Cognitive Assessment scores (r = 0.353), and less time in a high-connectivity state correlated with longer diabetes duration (r = -0.376). The authors argue the basal forebrain may regulate cognition via the dorsomedial prefrontal subsystem. |
Abstract
Introduction: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Comparable studies
Other observational and cohort studies on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A default mode of brain function Normal adult human brain | 2001 | Observational study | |
| Resting-State Functional Connectivity Reflects Structural Connectivity in the Default Mode Network Healthy subjects | 2008 | Observational cohort | |
| Meditation experience is associated with increased cortical thickness Participants with extensive Insight meditation experience and matched controls | 2005 | Observational cohort | n = 20 |
| Meditation experience is associated with differences in default mode network activity and connectivity Experienced meditators and matched meditation-naive controls | 2011 | Observational cohort | |
| The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis Healthy subjects | 2008 | Observational study |
Citations in the library
Cites 4
- Mediodorsal thalamus and ventral pallidum contribute to subcortical regulation of the default mode network Communications Biology July 23, 2024
- Altered dynamic effective connectivity of the default mode network in type 2 diabetes Frontiers in Neurology January 15, 2024
- Subsystem mechanisms of default mode network underlying white matter hyperintensity‐related cognitive impairment Human Brain Mapping February 1, 2023
- Subcortical control of the default mode network: Role of the basal forebrain and implications for neuropsychiatric disorders Brain Research Bulletin May 1, 2022