Changes in resting-state network functional connectivity and the association with cognitive flexibility in pediatric brain tumor survivors. 

Minarose Ismail, (Noor Al Dahhan1, Elizabeth Cox1,2, Julie Tseng1, Katie Wade Alonso1,2, Sonya Bells1, Cynthia de Medeiros1, Dunja Matic1,2, Suzanne Laughlin1,2, Eric Bouffet1,2, Donald Mabbott1,2) 

The Hospital for Sick Children Toronto, Canada1, Department of Psychology, University of Toronto, Toronto, Canada2 

Abstract

Background 

Pediatric brain tumor survivors (PBTS) exhibit tumor and treatment-related deficits in cognitive flexibility, a capacity that allows one to adjust their behaviour under various contexts. Working memory and information processing are higher-order cognitive processes that act coherently to implement cognitive flexibility and are mediated in the brain by the default mode network (DMN) and the executive control network (ECN). It is unclear whether deficits in working memory and information processing in PBTS are associated with disrupted neural synchrony in the DMN and ECN.  

Objectives 

Our study has three specific aims: 1) To investigate the differences in functional connectivity of the DMN and ECN in pediatric brain tumor survivors 2) To investigate the differences in functional connectivity within age and treatment groups 3) To investigate the relationship between functional connectivity in the DMN and ECN and performance on spatial working memory and visual information processing task.

Methods 

Neural activity was recorded using magnetoencephalography in 38 healthy children (7.28–17.48 yrs.) and 38 PBTS (6.86–18 yrs.) during resting state and filtered into 6 frequency bands. The DMN and ECN were defined using the HCP MMP 1.0 atlas and weighted phase-lag index values were computed to index FC. Group differences were assessed using Network-Based Statistics and Pearson’s correlation tests were used to compare FC with performance on non-verbal WM and IP tests. 

Results 

Compared to healthy controls, PBTS show significantly different frequency-specific patterns of resting-state functional connectivity of the DMN and ECN. PBTS exhibited greater theta connectivity than healthy controls in both hemispheres and across hemispheres. Our within-group age analysis showed that delta connectivity was greater in older healthy controls and PBTS. We also observed that compared to the radiation group, the surgery group exhibited greater theta and low gamma connectivity. Differences in functional connectivity of the DMN and ECN were associated with measures of visual working memory and information processing. Overall, greater theta connectivity between the DMN and ECN within hemispheres was associated with poorer performance on visual working memory and information processing. However, greater theta and lower high gamma connectivity between the DMN and ECN across hemispheres was associated with better performance on visual working memory and information processing.

Conclusions 

This study presents the possibility that differences in FC in the DMN and ECN may contribute to the deficits in cognitive flexibility in children treated for PBTs.