Abstract
BackgroundPhelan-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).MethodsEleven 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).ResultsPrevious 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.ConclusionsDespite 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-016-9138-9) contains supplementary material, which is available to authorized users.
Highlights
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)
In the PMS group, listening to communicative vocalizations yielded selective activity compared to noncommunicative vocalizations in the right superior temporal gyrus (STG) in a region comparable to that previously observed in typically developing adults [19] (MNI coordinates: x = 64, y = -36, z = 12; Z = 1.89, cluster size (k) = 238 voxels, p < 0.05, corrected; Fig. 1a)
Between-group comparisons confirmed that selective STG activity was significantly greater in the PMS relative to idiopathic ASD (iASD) group (x = 64, y = −38, z = 12; Z = 2.64, k = 6021)
Summary
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). 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. In vitro assays have shown that synaptic deficits in neurons from patients with PMS can be corrected by restoring SHANK3 expression or treatment with IGF-1 [11]. Despite this promising preclinical evidence that synaptic alterations in SHANK3 deficiency may represent therapeutic targets, to date, there is a dearth of data, in humans, on the abnormal neural systems underlying PMS
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