EXPERIMENTAL Functional Neuroanatomy of Lexical Processing in Children with Cleft Lip and Palate Devra B. Becker, M.D. Rebecca S. Coalson, B.S. Neil S. Sachanandani, B.S. Damien Fair, P.A. Heather M. Lugar, B.A. Leslie E. Kirchner, M.A., S.L.P.-C.C.C. Bradley L. Schlaggar, M.D., Ph.D. Alex A. Kane, M.D. St. Louis, Mo. Background: Patients with palatal clefts are predisposed to developing speech and language abnormalities. Emerging evidence indicates that children with cleft lip and/or cleft palate have higher rates of learning disabilities than the general population and differences in brain morphology. Methods: Magnetic resonance imaging of 12 individuals with isolated unilateral complete clefts of the lip and palate produced functional images during three lexical processing tasks: generation of verbs, opposites, and rhymes. Direct statistical comparisons were made between subjects with cleft lip and palate and controls (matched for age and performance) from an extant data set, both as a group and individually. Results: Two types of differences were found. Compared with unaffected con- trols, subjects with clefts showed a delayed and elongated blood oxygen level– dependent response in regions found throughout the cerebrum, including in the prefrontal cortex, cingulate gyrus, right precuneus, and right temporal gyrus. A right middle frontal gyrus region was activated by these tasks in controls but not in subjects with clefts. Developmental analysis showed that subjects 14.5 years and older (n = 5) had a larger number of age-related regions differing in blood oxygen level– dependent response from controls than did younger sub- jects (n = 7). Single-patient analysis demonstrated substantial individual vari- ability. Conclusions: Children with cleft lip and palate, performing lexical processing tasks at a comparable level of proficiency, use a similar but nonidentical func- tional neuroanatomy than peers without clefts. Differing neural circuitry for language tasks and differing developmental trajectories could help explain the predisposition to velopharyngeal dysfunction and learning disabilities in this population. (Plast. Reconstr. Surg. 122: 1371, 2008.) C left lip and palate is the one of the most common congenital disabilities, affecting approximately one in 1000 live births. 1 The condition affects integrative function such as lan- guage, and a significant number of patients with cleft lip and palate require speech therapy—some require further surgical intervention—to correct speech. 2–4 What makes speech and language dys- function so compelling in the cleft lip and palate population is that no factors have yet been iden- tified that positively predict who will develop it. Previously, surgeons and other health profession- als assumed that the locus of the speech dysfunc- tion was restricted to the local palatal anatomy. Recently, however, researchers have begun to question whether there may be dysfunction of the central nervous system. The possibility of a central nervous component to speech dysfunction in this population is supported by the observation that the palatal anatomy that is dysfunctional for a speech task is fully functional for a swallowing task. From the Division of Plastic Surgery, Department of Surgery, and the Departments of Neurology, Radiology, Anatomy and Neurobiology, and Pediatrics, Washington University School of Medicine. Received for publication July 27, 2007; accepted April 4, 2008. Aspects of this work were presented at the 62nd Annual Meeting of the American Cleft Palate Association, in Myrtle Beach, South Carolina, April 4 through 9, 2005; at the 50th Annual Meeting of the Plastic Surgery Research Council, in Toronto, Canada, May 18 through 21, 2005; and at the 63rd Annual Meeting of the American Cleft Palate-Craniofacial Association, in Van- couver, British Columbia, Canada, April 3 through 8, 2006. Copyright ©2008 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0b013e3181881f54 Disclosure: None of the authors has a financial interest in any of the products described in the article. www.PRSJournal.com 1371