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Whole-Brain Intrinsic Connectivity in Nonsyndromic Craniosynostosis
Alexander H. Sun, BS1, Jeffrey Eilbott, none1, Carolyn Chuang, BS1, Jenny F. Yang, MD, MHS1, Eric D. Brooks, MD, MHS1, Joel Beckett, MD, MHS1, Derek M. Steinbacher, DMD, MD1, Kevin A. Pelphrey, PhD2, John A. Persing, MD1.
1Yale School of Medicine, New Haven, CT, USA, 2George Washington University, Washington, DC, USA.

PURPOSE: Nonsyndromic craniosynostosis (NSC) has been associated with a greater risk of neurocognitive aberrations such as learning disorders, memory and attention deficits, and visuospatial abilities. Previously, our group has performed resting-state functional MRI (fMRI) studies in patients with sagittal NSC (SSO), and has found altered functional connectivity that may underlie some of the neurocognitive deficits in these patients. This study seeks to determine if different forms of NSC, including metopic synostosis (MSO) and unilateral coronal synostosis (UCS), result in different aberrations of functional brain connectivity.
METHODS: Twenty participants (average age 11.6 years, standard deviation 2.27, 15 males, 5 females) with surgically-treated NSC (10 sagittal, 5 metopic, 5 right unilateral coronal) were recruited from the Yale Craniofacial Clinic and individually matched to controls by age, gender, and handedness. Resting-state functional MR imaging was acquired in a 3T Siemens Tim Trio MR system (Erlangen, Germany) while patients focused on a black digital display with a 1-inch white plus sign. Data was corrected for movement using SPM (University College London), underwent CSF and WM signal regression, and was registered to Montreal Neurological Institute (MNI) space. Whole-brain intrinsic connectivity was analyzed using BioImage Suite (Yale School of Medicine) and resulting group-level t-maps were cluster-corrected for multiple comparisons at FWER p<0.05 (voxel-level threshold p<0.01, k ranging from 20 to 23).
RESULTS: For NSC groups versus controls, SSO demonstrated significantly decreased connectivity in left Brodmann areas (BA) 7, 40 and 9, corresponding to the superior parietal lobule and the dorsolateral prefrontal cortex (DLPFC). MSO had significantly decreased connectivity in the left BA 8, which is also a part of the DLPFC. UCS demonstrated decreased connectivity in left BA 10 (anterior prefrontal cortex, APFC), but had increased connectivity in the right caudate nucleus. When comparing between NSC groups, there were no significant differences between SSO and MSO or UCS and MSO. However, SSO did demonstrate decreased connectivity in left BA 8 and 9 compared to UCS.
CONCLUSION: Intrinsic connectivity analysis demonstrated significantly altered functional connectivity in NSC that varied by suture type. The SSO group demonstrated significant changes in the left supramarginal gyrus, which may correspond to some of the language and learning disorder findings known to occur in this group by neurocognitive testing. This corroborates previous fMRI findings seen in SSO, but now at a more robust significance level. The MSO group did not show changes in the parietal cortex, instead demonstrating significant changes in the DLPFC; this area plays a crucial role in executive functions like working memory and abstract reasoning. Finally, the UCS group was the only form of NSC that demonstrated significantly altered connectivity in the APFC, which has a presumed role in multi-tasking. Neurocognitive testing in previous studies has largely focused on sagittal patients or has not differentiated between different forms of NSC. Thus, it is uncertain how different forms of NSC can lead to differing neurocognitive or behavioral phenotypes. This study is the first to provide evidence of differences in neural activity in NSC patients based on type of synostosis.


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