Direct Brain Recordings Reveal Impaired Neural Function in Infants With Single-Suture Craniosynostosis: A Future Modality for Guiding Management? Peter W. Hashim, MD, MHS,*† Eric D. Brooks, BS,*† John A. Persing, MD,* Hannah Reuman, BA,† Adam Naples, PhD,† Roberto Travieso, MD,* Jordan Terner, MD,*Derek Steinbacher, MD, DMD,* Nicole Landi, PhD,†§ Linda Mayes, MD,† and James C. McPartland, PhD† Background: Patients with single-suture craniosynostosis (SSC) are at an elevated risk for long-term learning disabilities. Such adverse outcomes indicate that the early development of neural processing in SSC may be abnormal. At present, however, the precise functional de- rangements of the developing brain remain largely unknown. Event- related potentials (ERPs) are a form of noninvasive neuroimaging that provide direct measurements of cortical activity and have shown value in predicting long-term cognitive functioning. The current study used ERPs to examine auditory processing in infants with SSC to help clar- ify the developmental onset of delays in this population. Methods: Fifteen infants with untreated SSC and 23 typically developing controls were evaluated. ERPs were recorded during the presentation of speech sounds. Analyses focused on the P150 and N450 components of auditory processing. Results: Infants with SSC demonstrated attenuated P150 amplitudes relative to typically developing controls. No differences in the N450 component were identified between untreated SSC and controls. Conclusions: Infants with untreated SSC demonstrate abnormal speech sound processing. Atypicalities are detectable as early as 6 months of age and may represent precursors to long-term language delay. Electrophysiological assessments provide a precise examination of neural processing in SSC and hold potential as a future modality to examine the effects of surgical treatment on brain development. Key Words: Event-related potentials, craniosynostosis, neurodevelopment (J Craniofac Surg 2015;26: 60–63) T he impact of single-suture craniosynostosis (SSC) on intellec- tual development remains an important concern for craniofacial specialists, pediatricians, and parents. As the methods of neurologic testing have advanced, associations between cranial deformity and cognitive outcomes have gradually evolved. Previously considered by some as a solely cosmetic condition, SSC is now linked to a number of developmental difficulties. 1–4 In particular, studies using long-term neuropsychological testing have demonstrated that indi- viduals previously treated for SSC exhibit normal intelligence but show an increased risk for learning impairments, most notably in language-related areas. 5–7 Given the growing evidence of long-term intellectual sequelae in SSC, the evaluation of neural functioning in infant patients is criti- cal. Studies examining early development in SSC have often relied on an informative, but limited, standardized measure—the Bayley Scales of Infant Development (BSID). 8–13 The BSID provides a standard se- ries of measurements to score the motor, language, and cognitive devel- opment of children between 1 month and 42 months of age. However, although the BSID allows for evaluative scales in early life, it does not offer adequate insight into future intellectual and academic perfor- mance. In particular, lower scores in infancy have not shown a strong ability to predict long-term developmental or cognitive delays. 14–16 Greater understanding of infant brain abnormalities in SSC is needed, as the early detection of neural dysfunction may help to clarify the etiology of long-term delays and, in turn, guide surgical management. Noninvasive neuroimaging provides a safe and effica- cious means to gain insight into neural networks. The recording of event-related potentials (ERPs) is one such method that has shown value in predicting long-term outcomes from infant readings. 17–19 ERPs are extracted from continuous electroencephalogram (EEG) recordings and measure voltage changes in the brain in response to external stimuli. Of particular benefit is that ERP recordings do not depend on behavioral responses from participants, greatly facil- itating their use in infants. Given their safe application and ability to examine complex patterns of neural functioning, ERPs are well suited to detect developmental abnormalities in very young patients. 20 Electrophysiological brain recordings have previously dem- onstrated utility in evaluating neural functioning in craniosynosto- sis. In particular, auditory brainstem responses have been utilized to identify hearing abnormalities in infants with syndromic cranio- synostosis; such measures may provide a means for the early detec- tion of auditory nerve compression. 21 What Is This Box? A QR Code is a matrix barcode readable by QR scanners, mobile phones with cameras, and smartphones. The QR Code links to the online version of the article. From the *Section of Plastic and Reconstructive Surgery at Yale University School of Medicine, New Haven, †Child Study Center at Yale University School of Medicine, New Haven, ‡Haskins Laboratories, New Haven, and §Department of Psychology at University of Connecticut, Storrs, Connecticut. Received April 1, 2014. Accepted for publication July 1, 2014. Address correspondence and reprint requests to Dr John A. Persing, Yale Plastic and ReconstructiveSurgery, 330 Cedar Street, P.O. Box 208041, New Haven, CT 06520; E-mail: john.persing@yale.edu The authors report no conflicts of interest. Copyright © 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000001195 ORIGINAL ARTICLE 60 The Journal of Craniofacial Surgery • Volume 26, Number 1, January 2015 Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.