Altered brain connectivity in sagittal craniosynostosis.

Object: Sagittal nonsyndromic craniosynostosis (sNSC) is the most common form of NSC. The condition is associated with a high prevalence (> 50%) of deficits in executive function. The authors employed diffusion tensor imaging (DTI) and functional MRI to evaluate whether hypothesized structural and functional connectivity differences underlie the observed neurocognitive morbidity of sNSC.

Methods: Using a 3-T Siemens Trio MRI system, the authors collected DTI and resting-state functional connectivity MRI data in 8 adolescent patients (mean age 12.3 years) with sNSC that had been previously corrected via total vault cranioplasty and 8 control children (mean age 12.3 years) without craniosynostosis. Data were analyzed using the FMRIB Software Library and BioImageSuite.

Results: Analyses of the DTI data revealed white matter alterations approaching statistical significance in all supratentorial lobes. Statistically significant group differences (sNSC < control group) in mean diffusivity were localized to the right supramarginal gyrus. Analysis of the resting-state seed in relation to whole-brain data revealed significant increases in negative connectivity (anticorrelations) of Brodmann area 8 to the prefrontal cortex (Montreal Neurological Institute [MNI] center of mass coordinates [x, y, z]: -6, 53, 6) and anterior cingulate cortex (MNI coordinates 6, 43, 14) in the sNSC group relative to controls. Furthermore, in the sNSC patients versus controls, the Brodmann area 7, 39, and 40 seed had decreased connectivity to left angular gyrus (MNI coordinates -31, -61, 34), posterior cingulate cortex (MNI coordinates 13, -52, 18), precuneus (MNI coordinates 10, -55, 54), left and right parahippocampus (MNI coordinates -13, -52, 2 and MNI coordinates 11, -50, 2, respectively), lingual (MNI coordinates -11, -86, -10), and fusiform gyri (MNI coordinates -30, -79, -18). Intrinsic connectivity analysis also revealed altered connectivity between central nodes in the default mode network in sNSC relative to controls; the left and right posterior cingulate cortices (MNI coordinates -5, -35, 34 and MNI coordinates 6, -42, 39, respectively) were negatively correlated to right hemisphere precuneus (MNI coordinates 6, -71, 46), while the left ventromedial prefrontal cortex (MNI coordinates 6, 34, -8) was negatively correlated to right middle frontal gyrus (MNI coordinates 40, 4, 33). All group comparisons (sNSC vs controls) were conducted at a whole brain-corrected threshold of p < 0.05.

Conclusions: This study demonstrates altered neocortical structural and functional connectivity in sNSC that may, in part or substantially, underlie the neuropsychological deficits commonly reported in this population. Future studies combining analysis of multimodal MRI and clinical characterization data in larger samples of participants are warranted.