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Neurologic Functional Connectivity In Unicoronal Craniosynostosis: A Side-based Comparison
Anusha Singh, BS, Kitae E. Park, BA, Cheryl Lacadie, BS, Omar Allam, BS, Michael Alperovich, MD, MSc, John A. Persing, MD.
Yale School of Medicine, New Haven, CT, USA.

PURPOSE: Unicoronal synostosis has been associated with impaired reading, language, and social function. Functional MRI (fMRI) can evaluate brain connectivity in targeted brain regions to compare imaging analysis to previously published clinical performance. fMRI was used in this study to compare brain function connectivity in unicoronal synostosis (UCS) and compare outcomes by cerebral dominance (left versus right-sided UCS).
METHODS: Twelve adolescents with surgically treated UCS, 7 right-sided and 5 left-sided, were individually matched to age, gender and handedness controls. Resting state fMRI was acquired in a 3T Siemens TIM Trio scanner (Erlangen, Germany). Data was collected with intrinsic connectivity distribution and seed-connectivity analysis with BioImage Suite (Yale School of Medicine). Region of interest (ROI) analysis was performed based on Brodmannís areas (BA) related to emotional, executive, language, motor and visuo-spatial function, left BA5, 6, 7, 18, 19, 37, 39, and 44. BA5, 6, 7 are areas of the frontal and parietal cortex important for visuomotor coordination and complex movement. BA18, 19 are areas of the occipital lobe related to visual information processing. BA 37, 39, and 44 are areas of the fusiform, angular gyri and temporal lobe important for language function. P<0.05 was significant.
RESULTS: Compared to controls, all UCS patients demonstrated decreased connectivity in left BA7, bilateral BA39, and right BA41 (p<0.01) ), which are areas of the parietal and temporal cortices responsible for vision, language function, and motor coordination. Right UCS patients demonstrated increased connectivity in right BA17, BA18, BA19, BA20, BA36 when compared to controls (p<0.05). In the ROI analysis, right UCS exhibited decreased connectivity between the anterior cingulate cortex and right BA18, 19, and 37 compared to controls (p<0.05). The increased connectivity in BA17-20 (visual processing regions) supports our previous neurocognitive study results of increased visual perception abilities in right UCS patients. The subsequent decreased connectivity between BA18-19 and the anterior cingulate cortex (a section of which is implicated in complex motor coordination) is supported by neurocognitive data that shows decreased visual-motor integration ability in right UCS. This decreased connectivity between the aforementioned areas and the anterior cingulate gyrus despite increased intrinsic connectivity may also imply discordance in connecting emotion and executive function to language and visual information in right UCS patients. Connectivity between the left parahippocampus and right BA36, 37, and 54 was increased (p<0.05). Compared to controls and right UCS, left UCS demonstrated decreased connectivity between left BA6 and left BA17 and 18 (p<0.05). Left UCS patients did not demonstrate significantly different intrinsic or seed-based connectivity to right UCS or controls otherwise.
CONCLUSION: Unilateral coronal synostosis had decreased connectivity and greater potential for neurocognitive dysfunction in regions associated with memory, visual information processing, and motor function. Moreover, left-sided UCS had decreased connectivity in circuits crucial in complex motor movement when compared to right-sided UCS. This study provides data suggestive of long-term sequelae of UCS that varies by sidedness, which may underlie the different phenotypes of neurocognitive impairment found in previous cognitive analyses.


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