Junko Matsuzaki1, Jeffrey I Berman1, Lisa Blaskey1, Emily S Kuschner1, Leah Gaetz1, Pratik Mukherjee2, Randy L Buckner3, Srikantan S Nagarajan2, Wendy K Chung4, Elliott H Sherr5, Timothy P L Roberts6. 1. Lurie Family Foundations MEG Imaging Center, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 2. Department of Radiology, University of California, San Francisco School of Medicine, San Francisco, California. 3. Department of Psychology, Harvard University, Cambridge, Massachusetts. 4. Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, New York; Simons Foundation, New York, New York. 5. Department of Neurology, University of California, San Francisco School of Medicine, San Francisco, California. 6. Lurie Family Foundations MEG Imaging Center, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Linguistics, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: robertstim@email.chop.edu.
Abstract
BACKGROUND: Individuals with either deletion or duplication of the BP4-BP5 segment of chromosome 16p11.2 have varied behavioral phenotypes that may include autistic features, mild to moderate intellectual disability, and/or language impairment. However, the neurophysiological correlates of auditory language discrimination processing in individuals with 16p11.2 deletion and 16p11.2 duplication have not been investigated. METHODS: Magnetoencephalography was used to measure magnetic mismatch fields (MMFs) arising from the left and right superior temporal gyrus during an auditory oddball paradigm with vowel stimuli (/a/ and /u/) in children and adolescents with 16p11.2 deletion or 16p11.2 duplication and in typically developing peers. One hundred twenty-eight participants ranging from 7 to 17 years of age were included in the final analysis (typically developing: n = 61, 12.08 ± 2.50 years of age; 16p11.2 deletion: n = 45, 11.28 ± 2.51 years of age; and 16p11.2 duplication: n = 22, 10.73 ± 2.49 years of age). RESULTS: Delayed MMF latencies were found in both 16p11.2 deletion and 16p11.2 duplication groups compared with typically developing subjects. In addition, these delayed MMF latencies were associated with language and cognitive ability, with prolonged latency predicting greater impairment. CONCLUSIONS: Our findings suggest that auditory MMF response delays are associated with clinical severity of language and cognitive impairment in individuals with either 16p11.2 deletion or 16p11.2 duplication, indicating a correlate of their shared/overlapping behavioral phenotype (and not a correlate of gene dosage).
BACKGROUND: Individuals with either deletion or duplication of the BP4-BP5 segment of chromosome 16p11.2 have varied behavioral phenotypes that may include autistic features, mild to moderate intellectual disability, and/or language impairment. However, the neurophysiological correlates of auditory language discrimination processing in individuals with 16p11.2 deletion and 16p11.2 duplication have not been investigated. METHODS: Magnetoencephalography was used to measure magnetic mismatch fields (MMFs) arising from the left and right superior temporal gyrus during an auditory oddball paradigm with vowel stimuli (/a/ and /u/) in children and adolescents with 16p11.2 deletion or 16p11.2 duplication and in typically developing peers. One hundred twenty-eight participants ranging from 7 to 17 years of age were included in the final analysis (typically developing: n = 61, 12.08 ± 2.50 years of age; 16p11.2 deletion: n = 45, 11.28 ± 2.51 years of age; and 16p11.2 duplication: n = 22, 10.73 ± 2.49 years of age). RESULTS: Delayed MMF latencies were found in both 16p11.2 deletion and 16p11.2 duplication groups compared with typically developing subjects. In addition, these delayed MMF latencies were associated with language and cognitive ability, with prolonged latency predicting greater impairment. CONCLUSIONS: Our findings suggest that auditory MMF response delays are associated with clinical severity of language and cognitive impairment in individuals with either 16p11.2 deletion or 16p11.2 duplication, indicating a correlate of their shared/overlapping behavioral phenotype (and not a correlate of gene dosage).