1. Falck-Ytter T. {{Young children with autism spectrum disorder use predictive eye movements in action observation}}. {Biol Lett}. 2009 Dec 23.

Does a dysfunction in the mirror neuron system (MNS) underlie the social symptoms defining autism spectrum disorder (ASD)? Research suggests that the MNS matches observed actions to motor plans for similar actions, and that these motor plans include directions for predictive eye movements when observing goal-directed actions. Thus, one important question is whether children with ASD use predictive eye movements in action observation. Young children with ASD as well as typically developing children and adults were shown videos in which an actor performed object-directed actions (human agent condition). Children with ASD were also shown control videos showing objects moving by themselves (self-propelled condition). Gaze was measured using a corneal reflection technique. Children with ASD and typically developing individuals used strikingly similar goal-directed eye movements when observing others’ actions in the human agent condition. Gaze was reactive in the self-propelled condition, suggesting that prediction is linked to seeing a hand-object interaction. This study does not support the view that ASD is characterized by a global dysfunction in the MNS.

2. Jiao Y, Chen R, Ke X, Chu K, Lu Z, Herskovits EH. {{Predictive models of autism spectrum disorder based on brain regional cortical thickness}}. {Neuroimage}. 2009 Dec 21.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a wide phenotypic range, often affecting personality and communication. Previous voxel-based morphometry (VBM) studies of ASD have identified both gray- and white-matter volume changes. However, the cerebral cortex is a 2-D sheet with a highly folded and curved geometry, which VBM cannot directly measure. Surface-based morphometry (SBM) has the advantage of being able to measure cortical surface features, such as thickness. The goals of this study were twofold: to construct diagnostic models for ASD, based on regional thickness measurements extracted from SBM, and to compare these models to diagnostic models based on volumetric morphometry. Our study included 22 subjects with ASD (mean age 9.2+/-2.1 years) and 16 volunteer controls (mean age 10.0+/-1.9 years). Using SBM, we obtained regional cortical thicknesses for 66 brain structures for each subject. In addition, we obtained volumes for the same 66 structures for these subjects. To generate diagnostic models, we employed four machine-learning techniques: support vector machines (SVMs), multilayer perceptrons (MLPs), functional trees (FTs), and logistic model trees (LMTs). We found that thickness-based diagnostic models were superior to those based on regional volumes. For thickness-based classification, LMT achieved the best classification performance, with accuracy=87%, area under the receiver operating characteristic (ROC) curve (AUC)=0.93, sensitivity=95%, and specificity=75%. For volume-based classification, LMT achieved the highest accuracy, with accuracy=74%, AUC=0.77, sensitivity=77%, and specificity=69%. The thickness-based diagnostic model generated by LMT included 7 structures. Relative to controls, children with ASD had decreased cortical thickness in the left and right pars triangularis, left medial orbitofrontal gyrus, left parahippocampal gyrus, and left frontal pole, and increased cortical thickness in the left caudal anterior cingulate and left precuneus. Overall, thickness-based classification outperformed volume-based classification across a variety of classification methods.

3. Kishi N, Macklis JD. {{MeCP2 functions largely cell-autonomously, but also non-cell-autonomously, in neuronal maturation and dendritic arborization of cortical pyramidal neurons}}. {Exp Neurol}. 2009 Dec 16.

Rett syndrome is a human neurodevelopmental disorder presenting almost exclusively in female infants; it is the second most common cause of mental retardation in girls, after Down’s syndrome. The identification in 1999 that mutation of the methyl-CpG-binding protein 2 (MECP2) gene on the X chromosome causes Rett syndrome has led to a rapid increase in understanding of the neurobiological basis of the disorder. However, much about the functional role of MeCP2, and the cellular phenotype of both patients with Rett syndrome and mutant Mecp2 mouse models, remains unclear. Building on prior work in which we demonstrated that cortical layer 2/3 pyramidal neurons (primarily interhemispheric « callosal projection neurons » (CPN)) have reduced dendritic complexity and smaller somata in Mecp2-null mice, here we investigate whether Mecp2 loss-of-function affects neuronal maturation cell-autonomously and/or non-cell-autonomously by creating physical chimeras. We transplanted Mecp2-null or wild-type (wt) E17-18 cortical neuroblasts and immature neurons from mice constitutively expressing enhanced green fluorescent protein (eGFP) into wt P2-3 mouse cortices to generate chimeric cortices. Mecp2-null layer 2/3 pyramidal neurons in both Mecp2-null and wt neonatal cortices exhibit equivalent reduction in dendritic complexity, and are smaller than transplanted wt neurons, independent of recipient environment. These results indicate that the phenotype of Mecp2-null pyramidal neurons results largely from cell-autonomous mechanisms, with additional non-cell-autonomous effects. Dysregulation of MeCP2 target genes in individual neuronal populations such as CPN is likely centrally involved in Rett syndrome pathogenesis. Our results indicating MeCP2 function in the centrally affected projection neuron population of CPN themselves provide a foundation and motivation for identification of transcriptionally regulated MeCP2 target genes in developing CPN.

4. Loth E, Gomez JC, Happe F. {{When seeing depends on knowing: Adults with Autism Spectrum Conditions show diminished top-down processes in the visual perception of degraded faces but not degraded objects}}. {Neuropsychologia}. 2009 Dec 21.

Behavioural, neuroimaging and neurophysiological approaches emphasise the active and constructive nature of visual perception, determined not solely by the environmental input, but modulated top-down by prior knowledge. For example, degraded images, which at first appear as meaningless ‘blobs’, can easily be recognized as, say, a face, after having seen the same image un-degraded. This conscious perception of the fragmented stimuli relies on top-down priming influences from systems involved in attention and mental imagery on the processing of stimulus attributes, and feature-binding [Dolan, R. J., Fink, G. R., Rolls, E., Booth, M., Holmes, A., Frackowiak, R. S. J., et al. (1997). How the brain learns to see objects and faces in an impoverished context. Nature, 389, 596-599]. In Autism Spectrum Conditions (ASC), face processing abnormalities are well-established, but top-down anomalies in various domains have also been shown. Thus, we tested two alternative hypotheses: (i) that people with ASC show overall reduced top-down modulation in visual perception, or (ii) that top-down anomalies affect specifically the perception of faces. Participants were presented with sets of three consecutive images: degraded images (of faces or objects), corresponding or non-corresponding grey-scale photographs, and the same degraded images again. In a passive viewing sequence we compared gaze times (an index of focal attention) on faces/objects vs. background before and after viewers had seen the undegraded photographs. In an active viewing sequence, we compared how many faces/objects were identified pre- and post-exposure. Behavioural and gaze tracking data showed significantly reduced effects of prior knowledge on the conscious perception of degraded faces, but not objects in the ASC group. Implications for future work on the underlying mechanisms, at the cognitive and neurofunctional levels, are discussed.

5. McCleery JP, Ceponiene R, Burner KM, Townsend J, Kinnear M, Schreibman L. {{Neural correlates of verbal and nonverbal semantic integration in children with autism spectrum disorders}}. {J Child Psychol Psychiatry}. 2009 Dec 11.

Background: Autism is a pervasive developmental disorder characterized by deficits in social-emotional, social-communicative, and language skills. Behavioral and neuroimaging studies have found that children with autism spectrum disorders (ASD) evidence abnormalities in semantic processing, with particular difficulties in verbal comprehension. However, it is not known whether these semantic deficits are confined to the verbal domain or represent a more general problem with semantic processing. The focus of the current study was to investigate verbal and meaningful nonverbal semantic processing in high-functioning children with autism (mean age = 5.8 years) using event-related potentials (ERPs). Method: ERPs were recorded while children attended to semantically matching and mismatching picture-word and picture-environmental sound pairs. Results: ERPs of typically developing children exhibited evidence of semantic incongruency detection in both the word and environmental sound conditions, as indexed by elicitation of an N400 effect. In contrast, children with ASD showed an N400 effect in the environmental sound condition but not in the word condition. Conclusions: These results provide evidence for a deficiency in the automatic activation of semantic representations in children with ASD, and suggest that this deficit is somewhat more selective to, or more severe in, the verbal than the nonverbal domain.

6. Mostafa GA, El-Hadidi ES, Hewedi DH, Abdou MM. {{Oxidative stress in Egyptian children with autism: relation to autoimmunity}}. {J Neuroimmunol}. 2009 Dec 23.

We are the first to study the relationship between oxidative stress (by measuring plasma F2-isoprostane, as a marker of lipid peroxidation, and glutathione peroxidase, as an antioxidant enzyme) and autoimmunity (as indicated by serum antineuronal antibodies) in a group of 44 Egyptian autistic children and 44 healthy matched-children. Our results showed that oxidative stress was found in 88.64% of autistic children. Oxidative stress, resulting from elevated plasma F2-isoprostane and/or reduced glutathione peroxidase, had significant risk for antineuronal positivity, which was found in 54.5% of autistic children, (odds ratio: 12.38 and 6.43, respectively, confidence interval: 1.37-112.10 and 1.21-34.19, respectively). Conclusions: the strong association between oxidative stress and autoimmunity in autistic children may indicate the possible role of oxidative stress, through induction of autoimmunity, in some autistic patients. Therefore, studies considering the role of antioxidants and immunotherapy in amelioration of autistic manifestations are recommended.

7. Rissone A, Sangiorgio L, Monopoli M, Beltrame M, Zucchi I, Bussolino F, Arese M, Cotelli F. {{Characterization of the neuroligin gene family expression and evolution in zebrafish}}. {Dev Dyn}. 2009 Dec 23.

Neuroligins constitute a family of transmembrane proteins localized at the postsynaptic side of both excitatory and inhibitory synapses of the central nervous system. They are involved in synaptic function and maturation and recent studies have linked mutations in specific human Neuroligins to mental retardation and autism. We isolated the human Neuroligin homologs in Danio rerio. Next, we studied their gene structures and we reconstructed the evolution of the Neuroligin genes across vertebrate phyla. Using reverse-transcriptase polymerase chain reaction, we analyzed the expression and alternative splicing pattern of each gene during zebrafish embryonic development and in different adult organs. By in situ hybridization, we analyzed the temporal and spatial expression pattern during embryonic development and larval stages and we found that zebrafish Neuroligins are expressed throughout the nervous system. Globally, our results indicate that, during evolution, specific subfunctionalization events occurred within paralogous members of this gene family in zebrafish. Developmental Dynamics, 2010. (c) 2009 Wiley-Liss, Inc.

8. Silverman JL, Tolu SS, Barkan CL, Crawley JN. {{Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP}}. {Neuropsychopharmacology}. 2009 Dec 23.

Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that shows robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including well-replicated deficits in reciprocal social interactions and social approach, unusual patterns of ultrasonic vocalization, and high levels of repetitive self-grooming. These phenotypes offer straightforward behavioral assays for translational investigations of pharmacological compounds. Two suggested treatments for autism were evaluated in the BTBR mouse model. Methyl-6-phenylethynyl-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, blocks aberrant phenotypes in the Fmr1 mouse model of Fragile X, a comorbid neurodevelopmental disorder with autistic features. Risperidone has been approved by the United States Food and Drug Administration for the treatment of irritability, tantrums, and self-injurious behavior in autistic individuals. We evaluated the actions of MPEP and risperidone on two BTBR phenotypes, low sociability and high repetitive self-grooming. Open field activity served as an independent control for non-social exploratory activity and motor functions. C57BL/6J (B6), an inbred strain with high sociability and low self-grooming, served as the strain control. MPEP significantly reduced repetitive self-grooming in BTBR, at doses that had no sedating effects on open field activity. Risperidone reduced repetitive self-grooming in BTBR, but only at doses that induced sedation in both strains. No overall improvements in sociability were detected in BTBR after treatment with either MPEP or risperidone. Our findings suggest that antagonists of mGluR5 receptors may have selective therapeutic efficacy in treating repetitive behaviors in autism.Neuropsychopharmacology advance online publication, 23 December 2009; doi:10.1038/npp.2009.201.

9. Tadic V, Pring L, Dale N. {{Are language and social communication intact in children with congenital visual impairment at school age?}}. {J Child Psychol Psychiatry}. 2009 Dec 11.

Background: Development of children with congenital visual impairment (VI) has been associated with vulnerable socio-communicative outcomes often bearing striking similarities to those of sighted children with autism.(1) To date, very little is known about language and social communication in children with VI of normal intelligence. Methods: We examined the presentation of language and social communication of 15 children with VI and normal-range verbal intelligence, age 6-12 years, using a standardised language assessment and parental reports of everyday social and communicative behaviours. Their profiles were compared to those of typically developing sighted children of similar age and verbal ability. Results: Compared to their sighted peers, and relative to their own good and potentially superior structural language skills, children with VI showed significantly poorer use of language for social purposes. Pragmatic language weaknesses were a part of a broader socio-communicative profile of difficulties, present in a substantial proportion of these children and consistent with the pattern found in sighted children with autism. Conclusions: There are ongoing socio-communicative and pragmatic language difficulties in children with congenital VI at school age, despite their good intellectual abilities and advanced linguistic skills. Further research is required to unpack the underlying causes and factors maintaining this vulnerability in such children.

10. Verhoeven WM, Csepan R, Marcelis CL, Lefeber DJ, Egger JI, Tuinier S. {{Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia}}. {Acta Psychiatr Scand}. 2009 Dec 23.

Verhoeven WMA, Csepan R, Marcelis CLM, Lefeber DJ, Egger JIM, Tuinier S. Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia. Objective: Sanfilippo B is a rare autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by a deficiency of N-acetyl-alpha-D-glucosaminidase (NAGLU). Method: A mild mentally retarded elderly female patient is described with a slowly progressive dementia who had given birth to a daughter who developed normally. Results: Metabolic screening revealed an enhanced concentration of heparan sulfate in urine. Enzymatic assay demonstrated deficiency of N-acetyl-alpha-D-glucosaminidase. Mutations in the NAGLU gene were found. One mentally retarded and hospitalized elder brother was also found to have MPS IIIB, whereas a second brother, who had died earlier, is suspected to have had the same metabolic disorder. Prior to the development of dementia, both the patient and her brother showed autistic like features, signs of ideomotor apraxia and weakness in verbal comprehension. Conclusion: Screening for metabolic disorders, in particular MPSes, should always be considered in patients with a history of mental deficit and dementia or progressive functional decline.

11. Warren SF, Brady N, Sterling A, Fleming K, Marquis J. {{Maternal responsivity predicts language development in young children with fragile x syndrome}}. {Am J Intellect Dev Disabil}. Jan;115(1):54-75.

The relationship between early maternal responsivity and later child communication outcomes in young children with fragile X syndrome was investigated. Data were obtained from 55 mother-child dyads over a 36-month period. Performance data were obtained at each measurement point from video observations of four different contexts. These were coded for (a) child communication behaviors, (b) parent responsivity, and (c) behavior management behaviors. Results indicate that early maternal responsivity predicts the level of four important child language outcomes at 36 months of age after controlling for child developmental level and autism symptomology.