Hierarchical integrated and segregated processing in the functional brain default mode network within attention-deficit/hyperactivity disorder.

Yongchen Fan,Ying Wu,Pan Lin,Rong Wang,Emmanuel Andreas Stamatakis

doi:10.1371/journal.pone.0222414

Abstract

The hierarchical modular organization of functional networks in the brain is crucial for supporting diverse cognitive functions. Functional disorders in the brain are associated with an abnormal hierarchical modular organization. The default mode network (DMN) is a complex dynamic network that is linked to specialized cognitive functions and clinically relevant information. In this study, we hypothesize that hierarchical functional segregation and integration of the DMN within attention-deficit/hyperactivity disorder (ADHD) is abnormal. We investigated topological metrics of both segregation and integration in different hierarchical subnetworks of the DMN between patients with ADHD and healthy controls. We found that the hierarchical functional integration and segregation of the DMN decreased and increased, respectively, in ADHD. Our results also indicated that the abnormalities in the DMN are intrinsically caused by changes in functional segregation and integration in its higher-level subnetworks. To better understand the temporally dynamic changes in the hierarchical functional integration and segregation of the DMN within ADHD, we further analyzed the dynamic transitions between functional segregation and integration. We found that the adaptive reorganizational ability of brain network states decreased in ADHD patients, which indicated less adaptive regulation between the DMN subnetworks in ADHD for supporting correspondingly normal cognitive function. From the perspective of hierarchical functional segregation and integration, our results further provide evidence to support dysfunctional brain cognitive functions within ADHD linked to brain network segregation and integration.

Highlights

We found an increased shortest path length in the raDMN, right posterior DMN (rpDMN), left anterior DMN (laDMN) and left posterior DMN (lpDMN) in Attention-deficit/hyperactivity disorder (ADHD) patients
By performing the statistical two-sample t-test, we confirmed that the changes in the shortest path length caused by ADHD were significant for the lpDMN and rpDMN (p < 0.05) but not for the laDMN and raDMN (p > 0.05)
Through the analysis of hierarchical dynamic transitions, we found that the states of functional segregation and integration in the ADHD patients are more stable, which means that there is less adaptive regulation between the default mode network (DMN) subnetworks in the ADHD patients

Summary

Methods

Materials and methods fMRI acquisitionThe resting-state fMRI data used in this research were released to the open-access “1000 Functional Connectomes Project” (http://fcon_1000.projects.nitrc.org/indi/CoRR/html/ipcas_1. html.) by Milham and Castellanos in December, 2009. Html.) by Milham and Castellanos in December, 2009. The resting-state fMRI data used in this research were released to the open-access “1000 Functional Connectomes Project” These data were acquired from 24 ADHD patients and 24 healthy subjects (control subjects) in the resting state by a 3T Siemens scanner. It should be noted that we used pwr.t.test, a function in R statistical software, to calculate the power in the present analysis with the following parameters: number of samples in each group = 24, large effect size = 0.8, significance level = 0.05, power of test = 0.86. The sample size is acceptable if the testing power calculated is more than 0.8.

Results

Discussion

Conclusion