Youth with Down syndrome display widespread increased functional connectivity during rest

Kelsey D Csumitta, Stephen J Gotts, Liv S Clasen, Alex Martin, Nancy Raitano Lee, Kelsey D Csumitta, Stephen J Gotts, Liv S Clasen, Alex Martin, Nancy Raitano Lee

Abstract

Studies of resting-state functional connectivity in young people with Down syndrome (DS) have yielded conflicting results. Some studies have found increased connectivity while others have found a mix of increased and decreased connectivity. No studies have examined whole-brain connectivity at the voxel level in youth with DS during an eyes-open resting-state design. Additionally, no studies have examined the relationship between connectivity and network selectivity in youth with DS. Thus, the current study sought to fill this gap in the literature. Nineteen youth with DS (Mage = 16.5; range 7-23; 13 F) and 33 typically developing (TD) youth (Mage = 17.5; range 6-24; 18 F), matched on age and sex, completed a 5.25-min eyes-open resting-state fMRI scan. Whole-brain functional connectivity (average Pearson correlation of each voxel with every other voxel) was calculated for each individual and compared between groups. Network selectivity was then calculated and correlated with functional connectivity for the DS group. Results revealed that whole-brain functional connectivity was significantly higher in youth with DS compared to TD controls in widespread regions throughout the brain. Additionally, participants with DS had significantly reduced network selectivity compared to TD peers, and selectivity was significantly related to connectivity in all participants. Exploratory behavioral analyses revealed that regions showing increased connectivity in DS predicted Verbal IQ, suggesting differences in connectivity may be related to verbal abilities. These results indicate that network organization is disrupted in youth with DS such that disparate networks are overly connected and less selective, suggesting a potential target for clinical interventions.

Trial registration: ClinicalTrials.gov NCT00001246.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Figure 1
Figure 1
18 ROIs where functional connectivity is greater in participants with DS than TD controls, colored by the Yeo networks. Red = Default Mode; Green = Dorsal Attention; Yellow = Frontoparietal; Orange Limbic; Pink = Ventral Attention; Purple = Visual; Black = Cerebellar.
Figure 2
Figure 2
Connectivity matrices for the 18 ROI-ROI connections, each organized by the Yeo network structure. (A) Connectivity matrix (r-values) for participants with DS. (B) Connectivity matrix (r-values) for TD controls. (C) Connectivity differences for DS vs. TD participants t-test results (t-values) that replicated in a motion-matched subsample. (D) Significant (red) and non-significant (blue) connectivity differences from (C) after FDR correction.
Figure 3
Figure 3
Network selectivity differences for participants with DS vs. TD controls. (A) Participants with DS display greater within- and between-network connectivity than TD controls. (B) Network selectivity (the difference between within-network connectivity and between-network connectivity) is reduced in participants with DS compared to TD controls. (C) Reduced selectivity in DS is not due to group differences in participant motion, indicated by a non-significant interaction between motion and group, p > 0.97.
Figure 4
Figure 4
Increased ROI-ROI functional connectivity is significantly (p < 0.015) related to reduced network selectivity after partialling motion in the complete sample of participants.
Figure 5
Figure 5
ROI-ROI correlation measures from participants with DS significantly predicted their VIQ scores by permutation testing using a leave-one-subject-out cross-validation approach (p < 0.05).

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