title: Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome.
abstract: BACKGROUND
  Phelan-McDermid syndrome (PMS), a neurodevelopmental disorder caused by deletion or mutation in the SHANK3 gene, is one of the more common single-locus causes of autism spectrum disorder (ASD). PMS is characterized by global developmental delay, hypotonia, delayed or absent speech, increased risk of seizures, and minor dysmorphic features. Impairments in language and communication are one of the most consistent characteristics of PMS. Although there is considerable overlap in the social communicative deficits associated with PMS and ASD, there is a dearth of data on underlying abnormalities at the level of neural systems in PMS. No controlled neuroimaging studies of PMS have been reported to date. The goal of this study was to examine the neural circuitry supporting the perception of auditory communicative signals in children with PMS as compared to idiopathic ASD (iASD).
  
  
  METHODS
  Eleven children with PMS and nine comparison children with iASD were scanned using functional magnetic resonance imaging (fMRI) under light sedation. The fMRI paradigm was a previously validated passive auditory task, which presented communicative (e.g., speech, sounds of agreement, disgust) and non-communicative vocalizations (e.g., sneezing, coughing, yawning).
  
  
  RESULTS
  Previous research has shown that the superior temporal gyrus (STG) responds selectively to communicative vocal signals in typically developing children and adults. Here, selective activity for communicative relative to non-communicative vocalizations was detected in the right STG in the PMS group, but not in the iASD group. The PMS group also showed preferential activity for communicative vocalizations in a range of other brain regions associated with social cognition, such as the medial prefrontal cortex (MPFC), insula, and inferior frontal gyrus. Interestingly, better orienting toward social sounds was positively correlated with selective activity in the STG and other "social brain" regions, including the MPFC, in the PMS group. Finally, selective MPFC activity for communicative sounds was associated with receptive language level in the PMS group and expressive language in the iASD group.
  
  
  CONCLUSIONS
  Despite shared behavioral features, children with PMS differed from children with iASD in their neural response to communicative vocal sounds and showed relative strengths in this area. Furthermore, the relationship between clinical characteristics and neural selectivity also differed between the two groups, suggesting that shared ASD features may partially reflect different neurofunctional abnormalities due to differing etiologies.
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, NY 10029 USA ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA ; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY USA ; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors.forename: A Ting
authors.initials: AT
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Rouge Valley Health System, Toronto, Canada.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lim
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, NY 10029 USA ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors.forename: Jesslyn
authors.initials: J
authors.lastname: Jamison
authors.affiliation: Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Bush
authors.affiliation: Rush University Medical Center, Chicago, IL USA.
authors.forename: Latha V
authors.initials: LV
authors.lastname: Soorya
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, NY 10029 USA ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tavassoli
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, NY 10029 USA ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors.forename: Paige M
authors.initials: PM
authors.lastname: Siper
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, NY 10029 USA ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA ; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY USA ; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY USA ; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, NY 10029 USA ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA ; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA ; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kolevzon