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Validating ? oscillations and delayed auditory responses as translational biomarkers of autism.

ABSTRACT: Difficulty modeling complex behavioral phenotypes in rodents (e.g., language) has hindered pathophysiological investigation and treatment development for autism spectrum disorders. Recent human neuroimaging studies, however, have identified functional biomarkers that can be more directly related to the abnormal neural dynamics of autism spectrum disorders. This study assessed the translational potential of auditory evoked-response endophenotypes of autism in parallel mouse and human studies of autism.Whole-cortex magnetoencephalography was recorded in 17 typically developing and 25 autistic children during auditory pure-tone presentation. Superior temporal gyrus activity was analyzed in time and frequency domains. Auditory evoked potentials were recorded in mice prenatally exposed to valproic acid (VPA) and analyzed with analogous methods.The VPA-exposed mice demonstrated selective behavioral alterations related to autism, including reduced social interactions and ultrasonic vocalizations, increased repetitive self-grooming, and prepulse inhibition deficits. Autistic subjects and VPA-exposed mice showed a similar 10% latency delay in the N1/M100 evoked response and a reduction in ? frequency (30-50 Hz) phase-locking factor. Electrophysiological measures were associated with mouse behavioral deficits. In mice, ? phase-locking factor was correlated with expression of the autism risk gene neuroligin-3 and neural deficits were modulated by the mGluR5-receptor antagonist MPEP.Results demonstrate a novel preclinical approach toward mechanistic understanding and treatment development for autism.

SUBMITTER: Gandal MJ

PROVIDER: S-EPMC5070466 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Validating γ oscillations and delayed auditory responses as translational biomarkers of autism.

Gandal Michael J MJ Edgar J Christopher JC Ehrlichman Richard S RS Mehta Mili M Roberts Timothy P L TP Siegel Steven J SJ

Biological psychiatry 20101201 12

<h4>Background</h4>Difficulty modeling complex behavioral phenotypes in rodents (e.g., language) has hindered pathophysiological investigation and treatment development for autism spectrum disorders. Recent human neuroimaging studies, however, have identified functional biomarkers that can be more directly related to the abnormal neural dynamics of autism spectrum disorders. This study assessed the translational potential of auditory evoked-response endophenotypes of autism in parallel mouse and ...[more]

PMID: 21130222

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Project description:BackgroundThe development of left and right superior temporal gyrus (STG) 50?ms (M50) and 100?ms (M100) auditory responses in typically developing (TD) children and in children with autism spectrum disorder (ASD) was examined. Reflecting differential development of primary/secondary auditory areas and supporting previous studies, it was hypothesized that whereas left and right M50 STG responses would be observed equally often in younger and older children, left and right M100 STG responses would more often be absent in younger than older children. In ASD, delayed neurodevelopment would be indicated via the observation of a greater proportion of ASD than TD subjects showing missing M100 but not M50 responses in both age groups. Missing M100 responses would be observed primarily in children with ASD with language impairment (ASD?+?LI) (and perhaps concomitantly lower general cognitive abilities).MethodsThirty-five TD controls, 63 ASD without language impairment (ASD?-?LI), and 38 ASD?+?LI were recruited. Binaural tones were presented. The presence or absence of a STG M50 and M100 was scored. Subjects were grouped into younger (6-10?years old) and older groups (11-15?years old).ResultsAlthough M50 responses were observed equally often in older and younger subjects and equally often in TD and ASD, left and right M50 responses were delayed in ASD?-?LI and ASD?+?LI. Group comparisons showed that in younger subjects M100 responses were observed more often in TD than ASD?+?LI (90 versus 66%, p?=?0.04), with no differences between TD and ASD?-?LI (90 versus 76%, p?=?0.14) or between ASD?-?LI and ASD?+?LI (76 versus 66%, p?=?0.53). In older subjects, whereas no differences were observed between TD and ASD?+?LI, responses were observed more often in ASD?-?LI than ASD?+?LI. Findings were similar when splitting the ASD group into lower- and higher-cognitive functioning groups.ConclusionAlthough present in all groups, M50 responses were delayed in ASD. Examining the TD data, findings indicated that by 11?years, a right M100 should be observed in 100% of subjects and a left M100 in 80% of subjects. Thus, by 11?years, lack of a left and especially right M100 offers neurobiological insight into sensory processing that may underlie language or cognitive impairment.

Dataset Information

Validating ? oscillations and delayed auditory responses as translational biomarkers of autism.

Publications

Validating γ oscillations and delayed auditory responses as translational biomarkers of autism.

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