Impaired Prefrontal Hemodynamic Maturation in Autism and Unaffected Siblings

BACKGROUND: Dysfunctions of the prefrontal cortex have been previously reported in individuals with autism spectrum disorders (ASD). Previous studies reported that first-degree relatives of individuals with ASD show atypical brain activity during tasks associated with social function. However, developmental changes in prefrontal dysfunction in ASD and genetic influences on the phenomena remain unclear. In the present study, we investigated the change in hemoglobin concentration in the prefrontal cortex as measured with near-infrared spectroscopy, in children and adults with ASD during the letter fluency test. Moreover, to clarify the genetic influences on developmental changes in the prefrontal dysfunction in ASD, unaffected siblings of the ASD participants were also assessed. METHODOLOGY/PRINCIPAL FINDINGS: Study participants included 27 individuals with high-functioning ASD, age- and IQ-matched 24 healthy non-affected siblings, and 27 unrelated healthy controls aged 5 to 39 years. The relative concentration of hemoglobin ([Hb]) in the prefrontal cortex was measured during the letter fluency task. For children, neither the [oxy-Hb] change during the task nor task performances differed significantly among three groups. For adults, the [oxy-Hb] increases during the task were significantly smaller in the bilateral prefrontal cortex in ASD than those in control subjects, although task performances were similar. In the adult siblings the [oxy-Hb] change was intermediate between those in controls and ASDs. CONCLUSION/SIGNIFICANCE: Although indirectly due to a cross-sectional design, the results of this study indicate altered age-related change of prefrontal activity during executive processing in ASD. This is a first near-infrared spectroscopy study that implies alteration in the age-related changes of prefrontal activity in ASD and genetic influences on the phenomena

The individual's data in ASD group.

<p>CARS, Childhood Autism Rating Scale; EIQ, estimated IQ; VIQ, verbal IQ; PIQ, performance IQ; FIQ, Full-scale IQ; LFT, the number of words generated during the letter fluency task; L, left; R, right; f, female; m, male; Au, autistic disorder; As, asperger disorder; PDD-NOS, pervasive developmental disorder not otherwise specified.</p>*<p>The dosages for Case 3 and 7 were unavailable.</p

Grand average waveforms of hemoglobin concentration changes during the letter fluency task.

<p>Top: Autism spectrum disorder, Middle: Unaffected siblings, bottom: healthy control, right: adult group, left: child group. Line: red, oxyhemoglobin; blue, deoxyhemoglobin. The period of the activation task is between two dot-lines.</p

The scatter plot of age and the mean [oxy-Hb] change between hemispheres.

<p>Red: autism spectrum disorder, blue: unaffected siblings, black: healthy control.</p

Characteristics of Participants.

<p>CARS, Childhood Autism Rating Scale; f, female; m, male;</p>a<p>IQ was evaluated with the WISC-III, except for 1 ASD child estimated IQ by four subtests of the WAIS-R.</p>b<p>For all ASDs and 4 siblings IQs were evaluated with the WAIS-R, for 8 siblings and all controls IQs were estimated by four subtests of the WAIS-R.</p