Diffusion Tensor Imaging Provides Evidence of Possible Axonal Overconnectivity in Frontal Lobes in Autism Spectrum Disorder Toddlers

Abstract

Background: Theories of brain abnormality in autism spectrum disorder (ASD) have focused on underconnectivity as an explanation for social, language, and behavioral deficits but are based mainly on studies of older autistic children and adults.

Methods: In 94 ASD and typical toddlers ages 1 to 4 years, we examined the microstructure (indexed by fractional anisotropy) and volume of axon pathways using in vivo diffusion tensor imaging of fronto-frontal, fronto-temporal, fronto-striatal, and fronto-amygdala axon pathways, as well as posterior contrast tracts. Differences between ASD and typical toddlers in the nature of the relationship of age to these measures were tested.

Results: Frontal tracts in ASD toddlers displayed abnormal age-related changes with greater fractional anisotropy and volume than normal at younger ages but an overall slower than typical apparent rate of continued development across the span of years. Posterior cortical contrast tracts had few significant abnormalities.

Conclusions: Frontal fiber tracts displayed deviant early development and age-related changes that could underlie impaired brain functioning and impact social and communication behaviors in ASD.

Keywords: Autism; DTI; Development; Frontal tracts; Tract FA; Tract volume.

Figure 1

Atlas-based tract reconstructions for a representative single subject showing all primary and contrast tracts examined in the study. IFSF = inferior frontal superior frontal tract; fSCS = frontal projection of the superior corticostriate tract; pSCS = parietal projection of the superior corticostriatal tract; pSLF = parietal portion of the superior longitudinal fasciculus; IFOF = inferior frontal occipital fasciculus; ILF = inferior longitudinal fasciculus.

Figure 2

FA (left panel) and volume (right panel) measures for forceps minor, inferior frontal superior frontal tract (IFSF), uncinate, frontal projection of the superior corticostriatal tract (fSCS), and arcuate fasciculus portion of the superior longitudinal fasciculus (tSLF) by age for male participants (for female participants see Figures S1 & S2). Blue squares and red diamonds represent TD and ASD subjects, respectively. The solid blue and red lines in each plot represent model fits for TD and ASD subjects; dotted lines connect longitudinal measures for individual participants.

Figure 3

Atlas-based tract reconstructions for a representative single subject showing all tracts with abnormal age-related trajectories for FA (left) and/or volume (right). IFSF = inferior frontal superior frontal tract; fSCS = frontal projection of the superior corticostriate tract; IFOF = inferior frontal occipital fasciculus; ILF = inferior longitudinal fasciculus.