Plastic Surgery Research Council

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Comparing Language Associated Neural Responses Between Subtypes of Nonsyndromic Craniosynostosis
Robin T. Wu, BS, Taylor A. Halligan, BS, Alexander H. Sun, BS, Carolyn Chuang, MD, Jenny F. Yang, MD, Peter W. Hashim, MD, Raysa Cabrejo, BS, Linda C. Mayes, MD, James C. McPartland, PhD, John A. Persing, MD.
Yale University School of Medicine, New Haven, CT, USA.

Purpose: Nonsyndromic craniosynostosis has been associated with a multitude of language deficits. Essential in language remediation is early detection and prevention. Auditory event-related potentials (ERPs) measure passive neurological responses to speech sounds, suggesting a promising avenue for studying infant speech development. In particular, the mismatch negativity (MMN) quantifies perceptual narrowing and can predict future language development. We present a cohort comparisons between sagittal synostosis (SSO), unilateral coronal synostosis (CSO), and metopic synostosis (MSO), both pre and post operatively.
Methods: Nonsyndromic craniosynostosis and typically developing (TD) infants were recruited from the Yale Autism Program and Yale Craniofacial Clinic. Participants were presented both pre-operatively and post-operatively with a non-native phoneme discrimination paradigm involving the Hindi retroflex phoneme /da/ and the dental phoneme /da/ in random order. Auditory stimuli were set at 80 dB, and EEG was recorded at 250 Hz with a 128-channel HydroCel Geodesic Sensor Net. Analysis focused on four electrode clusters: left and right frontal, and left and right central electrodes. The MMN component was calculated as the largest negative amplitude in the difference wave between 80-300ms after stimulus presentation. Statistical comparisons were performed with ANOVA and student T-tests.
Results: Pre-operatively, 16 SSO, 13 MSO, 4 CSO, and 34 TD patients were included. SSO patients had attenuated left frontal MMN amplitudes compared to controls (p=0.003). MSO patients had attenuate left frontal and central amplitudes compared to controls (p=0.003; p=0.013). CSO patients had no differences compared to controls. In comparison with one another, there were no pre-operative differences among craniosynostosis groups. Post-operatively, 12 SSO, 8 MSO, 3CSO, and 24 TD patients were re-scanned. Attenutated left frontal responses were no longer presents in the SSO cohort. MSO patients retained attenuations in left frontal and central clusters (p=0.041; p=0.001). CSO patients remained comparable to controls. With inter-group comparison, MSO patients had attenuations in the left frontal and central clusters in comparison to SSO (p=0.041; p<0.001). No differences were found between CSO and SSO or CSO and MSO.
Conclusions: This study represents the largest ERP comparison between different subtypes of nonsyndromic craniosynostosis. SSO and MSO infants manifested early signs of language delay in the left brain, classically responsible for language production. While surgical changes mollified these delays in SSO infants, MSO infants retained similar attenuated responses. Pre-operatively, all three groups had similar language profiles. However, following significant improvments in SSO and no changes in MSO, SSO patients had improved left brain language acquisition in comparison to MSO. Importantely, CSO infants may represent an intermediary phenotype between SSO and MSO cohorts. This study begins to develop the early language profiles of nonsyndromic craniosynostosis infants, encouraging early intervention for MSO patients.


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