Youth with Down syndrome display widespread increased functional connectivity during rest

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.

Altered spontaneous brain activity in Down syndrome and its relation with cognitive outcome

“…They also found indirect relationships between communication skills and decreased FC in the left posterior insula and right sensorimotor cortex. These results are in accordance with Csumitta et al 20 , who demonstrated that differences found in connectivity in DS could be related to verbal abilities.…”

“…For instance, the temporal and frontal lobes seem to play an important role in language and executive functions 53 , as well as the frontoparietal brain regions in memory 54 . In addition, we expected the differences in fALFF and ReHo between DS and controls to be related to cognitive outcomes, as in other studies 20 , 29 .…”

“…A cognitive test, KBIT-2 55 , and a simple verbal fluency test were performed. The KBIT-2 test has been used to evaluate people with DS and controls in multiple studies 20 , 29 and was chosen because of its ability to ensure items were age-appropriate, as the age rank for the administration is sufficiently large. Moreover, it evaluates verbal and nonverbal IQ.…”

“…Finally, they found weaker strength in frontal regions, consistent with other studies 29 . Recently, Csumitta et al 20 found increased whole-brain FC in DS.…”

“…The majority of studies using rs- f MRI in this population have focused on specific areas or predetermined networks, such as the default mode network 17 – 19 (DMN) or the hippocampus 7 . However, few studies have focused on the whole brain 20 .…”