Abnormal Functional Connectivity at Rest Among Sleeping Infants and Toddlers with ASD

Background: The development of coordinated brain networks is thought to serve as a foundation for sophisticated cognitive and social behavior.  At rest, intrinsic coordinated activity is observed within the so-called default mode network, a system that is also often engaged during social, emotional, and introspective behaviors.  Autism is characterized by deficits in these behaviors, and older children, teenagers, and adults with ASD generally show functional underconnectivity at rest compared to typical individuals.  Little is known, however, about the pattern of coordinated resting brain activity at the youngest ages when ASD is first manifested. 

Objectives: The aim of the study was to characterize potential differences in coordinated brain activity at rest between infants and toddlers with ASD compared to typically developing infants and toddlers. 

Methods: We measured fluctuations in blood oxygenation level dependent (BOLD) signal in the absence of any stimulation for 6 minutes 25 seconds in sleeping infants and toddlers with ASD (n=40) and who were typically developing (TD; n=40).  Participants ranged in age between 12 and 45 months; groups were well-matched on age and gender.  Inter-regional correlations were calculated based on BOLD fluctuations with a frequency between 0.005 and 0.1 Hz that were not related to signal changes in whole brain, cerebral spinal fluid, white matter, or to motion.  Functional connectivity maps were created for 6 different seed regions: 3 from a task-negative or default mode network and 3 from a task-positive network.  Within- and between-group t-tests were used to create whole-brain group connectivity maps and compare ASD and TD groups. Significant clusters were those with a combined extent and voxel t-value threshold that protected a whole-brain probability of false positives less than or equal to 0.05.  

Results: ASD infants and toddlers showed more positive associations than TD infants and toddlers between posterior seed regions of the default mode network (posterior cingulate and lateral parietal) and clusters within the anterior cingulate cortex and inferior frontal gyrus.  Specifically, at rest, the ASD group lacked normal intrinsic anti-correlation between these regions and posterior default mode regions, and instead showed positive correlations.  Abnormal functional connectivity was also found between anterior cingulate and a task-positive network seed (intraparietal sulcus); with weaker anticorrelations in ASD than typical.  Although overconnectivity in the form of more positive or less negative correlations was the most prevalent finding, there were also clusters of underconnectivity (i.e., less positive correlations) found in different regions depending on the seed.  Relationships between these aberrant connectivity patterns and clinical and neuroanatomic measures are currently being explored. 

Conclusions: Abnormal patterns of intrinsic correlations during rest can be observed in infants and toddlers with ASD.   In contrast to findings in older ASD children and adults, we see evidence for more positive correlations (i.e., over-connectivity), particularly in regions that show anticorrelated BOLD response in relation to the seed among typical infants and toddlers.