Table of Contents

Introduction …………………………………………………………………………………………………….. 1
Non-syndromic Craniosynostosis ………………………………………………………………………………. 1
Surgical Correction of Craniosynostosis………………………………………………………………………. 2
Long-Term Neurodevelopmental Outcomes ……………………………………………………………….. 3
Predictors of Neurodevelopmental Performance …………………………………………………………. 6
Genetics in Craniosynostosis ……………………………………………………………………………………. 6
Functional Magnetic Resonance Imaging in Craniosynostosis ………………………………………. 7
Event Related Potentials in Craniosynostosis …………………………………………………………….. 8
Purpose …………………………………………………………………………………………………………. 11
Methods ……………………………………………………………………………………………………….. 13
Patient Selection and Individualized Testing Parameters …………………………………………….. 13
Unilateral Coronal Craniosynostosis Categorization …………………………………………………. 13
Metopic Craniosynostosis Categorization ……………………………………………………………….. 14
SMAD6 Comparison ……………………………………………………………………………………………. 14
Functional MRI Analysis ………………………………………………………………………………………. 15
Event Related Potential Analysis …………………………………………………………………………… 15
Neuropsychiatric Testing Battery ………………………………………………………………………….. 16
Neurocognitive Tests ………………………………………………………………………………………….. 16
Parental/Guardian Surveys ………………………………………………………………………………….. 18
Quality of Life Survey ………………………………………………………………………………………….. 19
Computed Tomographic Scan Analysis …………………………………………………………………….. 19
Direct Neuroimaging and Genetic Analysis ……………………………………………………………….. 20
Functional MRI ………………………………………………………………………………………………….. 20
Event Related Potentials ……………………………………………………………………………………… 22
Genetic Analysis…………………………………………………………………………………………………. 23
Statistical Analysis …………………………………………………………………………………………………. 24
Unilateral Coronal Craniosynostosis Neuropsychiatric Outcomes ……………………………….. 24
Metopic Craniosynostosis Neurocognitive Comparison to Severity …………………………….. 25
SMAD6 Comparison to non-SMAD6 Neurocognitive Outcomes ………………………………….. 25
fMRI Comparison ……………………………………………………………………………………………….. 26
ERP and BSID Comparison with Neurocognitive Outcomes………………………………………… 26
Results ………………………………………………………………………………………………………….. 27
Unilateral Coronal Craniosynostosis Neurodevelopmental Outcomes …………………………… 27
Subjects ……………………………………………………………………………………………………………. 27
Neurocognitive Test Performance …………………………………………………………………………. 29
Behavioral Survey Performance ……………………………………………………………………………. 30
Impact of Patient Factors on Neurocognitive Performance ……………………………………….. 31
Post-hoc power …………………………………………………………………………………………………. 33
Metopic Craniosynostosis Neurocognitive Outcomes …………………………………………………. 34
Subjects ……………………………………………………………………………………………………………. 34
Neurocognitive Test Performance …………………………………………………………………………. 35
Analysis of Severity …………………………………………………………………………………………….. 36
Sagittal and Metopic SMAD6 Neurocognitive Outcomes …………………………………………….. 37
Subjects ……………………………………………………………………………………………………………. 37
Head-to-head T-test comparison between SMAD6 and non-SMAD6 controls ……………….. 39
Correlation Analysis ……………………………………………………………………………………………. 40
Controlling for significant patient factors ……………………………………………………………….. 41
Parental Surveys ………………………………………………………………………………………………… 41
Power Analysis…………………………………………………………………………………………………… 41
fMRI Analysis ……………………………………………………………………………………………………….. 42
Demographics ……………………………………………………………………………………………………. 42
Behavioral/Functional Scores ……………………………………………………………………………….. 43
GoNoGo Performance ……………………………………………………………………………………………. 44
fMRI Whole-Brain T-Test and Region of Interest Analysis ………………………………………….. 44
BOLD Signal Analysis …………………………………………………………………………………………… 47
ERP and BSID Analysis …………………………………………………………………………………………. 52
Patient Demographics …………………………………………………………………………………………. 52
Neurocognitive Correlation with Infant ERP/BSID Testing …………………………………………. 53
Controlling for Demographic Confounders ……………………………………………………………… 55
ERP Comparison between Subtypes of Craniosynostosis …………………………………………… 55
Discussion ……………………………………………………………………………………………………… 57
Unilateral Coronal Craniosynostosis Neurodevelopmental Outcomes …………………………… 57
Metopic Craniosynostosis Neurocognitive Outcomes …………………………………………………. 59
Sagittal and Metopic SMAD6 Neurocognitive Outcomes …………………………………………….. 61
fMRI Analysis ……………………………………………………………………………………………………….. 64
ERP and BSID Analysis …………………………………………………………………………………………. 67
Citations ………………………………………………………………………………………………………… 70