Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice.

BACKGROUND: The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRß in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown. RESULTS: Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety. CONCLUSIONS: These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.

A multimodal interface for speech perception: the role of the left superior temporal sulcus in social cognition and autism.

Multimodal integration is crucial for human interaction, in particular for social communication, which relies on integrating information from various sensory modalities. Recently a third visual pathway specialized in social perception was proposed, which includes the right superior temporal sulcus (STS) playing a key role in processing socially relevant cues and high-level social perception. Importantly, it has also recently been proposed that the left STS contributes to audiovisual integration of speech processing. In this article, we propose that brain areas along the right STS that support multimodal integration for social perception and cognition can be considered homologs to those in the left, language-dominant hemisphere, sustaining multimodal integration of speech and semantic concepts fundamental for social communication. Emphasizing the significance of the left STS in multimodal integration and associated processes such as multimodal attention to socially relevant stimuli, we underscore its potential relevance in comprehending neurodevelopmental conditions characterized by challenges in social communication such as autism spectrum disorder (ASD). Further research into this left lateral processing stream holds the promise of enhancing our understanding of social communication in both typical development and ASD, which may lead to more effective interventions that could improve the quality of life for individuals with atypical neurodevelopment.

Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances.

Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of autism spectrum disorder (ASD) pathophysiology. The present study evaluated the daily urinary 6-sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in 20 controls and 20 ASD participants, as well as correlating these measures with sleep disturbances. Although 60% of ASD participants showed a significant night-time rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (P < .05). The remaining 40% of ASD individuals showed no significant increase in nocturnal aMT6s. ASD individuals showed higher nocturnal levels of saliva TNF, but not IL-6. Dysfunction in the initiation and maintenance of sleep, as indicated by the Sleep Disturbance Scale for Children, correlated with night-time aMT6s excretion (r = -.28, P < .05). Dysfunction in sleep breathing was inversely correlated with aMT6s (r = -.31, P < .05) and positively associated with TNF level (r = .42, P < .01). Overall such data indicate immune-pineal axis activation, with elevated TNF but not IL-6 levels associated with disrupted pineal melatonin release and sleep dysfunction in ASD. It is proposed that circadian dysregulation in ASD is intimately linked to heightened immune-inflammatory activity. Such two-way interactions of the immune-pineal axis may underpin many aspects of ASD pathophysiology, including sleep disturbances, as well as cognitive and behavioral alterations.

The methodology of body approach for autists - a case study

Abstract Introduction: The Autistic Spectrum Disorder (ASD) is characterized by persistent deficits in communication and social interaction in multiple contexts and restricted and repetitive patterns of behavior, interests, or activities. Aim: The objective of this work was to present and analyze a program that offers specialized educational service in Physical Education and Art (dance), proposed for a student with ASD, based on a body approach methodology. Methods: A case study was carried out with a student with ASD for three years of corporal intervention practice with two weekly sessions at the Aquatic Activities and Body Expression sessions in a community project. Conclusion: It was possible to observe that the student demonstrated significant improvements in social interaction, communication, and development of the corporal scheme, confirming the effectiveness of the presented corporal intervention.

End-state comfort effect in manipulative motor actions of typical and atypical children: a systematic review / Estado de conforto final de ações motoras manipulativas de crianças típicas e atípicas: revisão sistemática / Estado de confort final de acciones motoras manipuladoras de niños típicos y atípicos: revisión sistemática

ABSTRACT This study aimed to make a systematic review of scientific articles on the planning of manual motor actions of typical and atypical children. To do so, a search of articles published between 1996 and 2017 was done on PubMed, LILACS, Science Direct, and SciElo databases. Original articles in English and Portuguese evaluating the planning of motor actions in typical and atypical children performing manual tasks were selected. For the analysis, the population age, number of children, type of task, main results, site of study and impact of the journal were considered. From the eighteen articles found, twelve were about typical children (from nine months old to twenty years old) and six about atypical children (from three to fourteen years old) diagnosed with autism, hemiplegic cerebral palsy, and developmental coordination disorders. In nine- to ten-year-old typical children, the planning ability of manual motor actions develops over the time and is similar to that of an adult. The atypical children showed motor planning ability lower than that of the typical children, and determining the age when this planning ability is acquired was not possible.

RESUMO O objetivo desse estudo foi realizar uma revisão sistemática de artigos científicos sobre o planejamento de ações motoras manuais de crianças típicas e atípicas. Para isso, foi feita uma busca de artigos publicados entre 1996 e 2017 nas bases de dados PubMed, Lilacs, Science Direct e SciELO. Foram incluídos artigos originais em língua inglesa e portuguesa, que avaliaram o planejamento de ações motoras em crianças típicas e atípicas por meio de tarefas manuais. Para a análise dos artigos, considerou-se a população, a faixa etária, o número de crianças, o tipo de tarefa, os principais resultados, o local de realização do estudo e o fator de impacto da revista. Ao todo, foram encontrados 18 artigos, sendo 12 com crianças típicas (9 meses a 20 anos de idade), e 6 com crianças atípicas (3 a 14 anos) diagnosticadas com autismo, paralisia cerebral hemiplégica e transtornos de déficit de coordenação. Nas crianças típicas, observa-se que a capacidade de planejamento de ações motoras manuais se desenvolve ao longo do tempo e se assemelha a de um adulto entre os 9 e 10 anos de idade. As crianças atípicas apresentaram capacidade de planejamento motor inferior à das crianças típicas e não foi possível determinar a idade em que essa habilidade de planejamento é estabelecida.

RESUMEN El objetivo de este estudio fue realizar una revisión sistemática de artículos científicos sobre la planificación de acciones motoras manuales de niños típicos y atípicos. Para ello, se realizó una búsqueda de artículos publicados entre 1996 y 2017 en las bases de datos PubMed, Lilacs, Science Direct y SciELO. Se incluyeron artículos originales en inglés y portugués que evaluaron la planificación de acciones motoras en niños típicos y atípicos a través de tareas manuales. Para el análisis de los artículos, se consideró la población, el grupo de edad, el número de niños, el tipo de tarea, los principales resultados, el lugar de realización del estudio y el factor de impacto de la revista. En total, se encontraron 18 artículos, 12 con niños típicos (9 meses a 20 años) y 6 con niños atípicos (3 a 14 años) diagnosticados con autismo, parálisis cerebral hemipléjica y trastornos de déficit de coordinación. En los niños típicos, se observa que la capacidad de planificación de acciones motoras manuales se desarrolla a lo largo del tiempo y entre los 9 y 10 años se asemeja a la de un adulto. Los niños atípicos presentaron una capacidad de planificación de motores inferior a la de los niños típicos y no fue posible determinar la edad en que se estableció esta capacidad de planificación.

Autismo: Aspectos genéticos y biológicos / Autism. Genetic and biological aspects

El autismo es un trastorno del neurodesarrollo caracterizado por compromiso en la interacción social y la comunicación, asociado a intereses restringidos y conductas estereotipadas con gran prevalencia poblacional, bases neurobiológicas y alta heredabilidad. Su etiología es heterogénea y se han reconocido numerosas bases genéticas, factores ambientales y mecanismos epigenéticos. Los avances en la genética molecular, así como los estudios epidemiológicos de grandes cohortes, han posibilitado identificar entidades médicas específicas, así como genes y factores ambientales vinculados parcial o totalmente en su patogenia. Estos conocimientos, conforme las características clínicas, permiten orientar los estudios complementarios, las conductas terapéuticas, inferir un pronóstico clínico y propiciar el asesoramiento genético familiar. En este trabajo analizamos las características clínicas de los trastornos del espectro del autismo, las entidades médicas específicas que están fuertemente relacionadas a los mismos, así como los genes reconocidos, los posibles factores ambientales y los resultados epidemiológicos que permiten el adecuado asesoramiento familiar.

Autism is a neurodevelopmental disorder characterized by commitment to social interaction and communication, associated with interests restricted and stereotyped behaviors with a high population prevalence, neurobiological bases and high heritability. Its etiology is heterogeneous, numerous genetic bases, environmental factors and epigenetic mechanisms have been recognized. Advances in molecular genetics, as well as epidemiological studies of large cohorts, have made it possible to identify specific medical entities, as well as genes and environmental factors partially or totally linked in their pathogenesis. This knowledge, according to the clinical characteristics, allows to guide the complementary studies, the therapeutic conducts, to infer a clinical prognosis and to propitiate the familiar genetic advice. In this work, the most prevalent clinical characteristics identified are described; the specific medical entities that are strongly related to autism are stated, as well as the recognized genes, the possible environmental factors and the epidemiological results that allow family counseling.

[Autism. Genetic and biological aspects]. / Autismo. Aspectos genéticos y biológicos.

Autism is a neurodevelopmental disorder characterized by commitment to social interaction and communication, associated with interests restricted and stereotyped behaviors with a high population prevalence, neurobiological bases and high heritability. Its etiology is heterogeneous, numerous genetic bases, environmental factors and epigenetic mechanisms have been recognized. Advances in molecular genetics, as well as epidemiological studies of large cohorts, have made it possible to identify specific medical entities, as well as genes and environmental factors partially or totally linked in their pathogenesis. This knowledge, according to the clinical characteristics, allows to guide the complementary studies, the therapeutic conducts, to infer a clinical prognosis and to propitiate the familiar genetic advice. In this work, the most prevalent clinical characteristics identified are described; the specific medical entities that are strongly related to autism are stated, as well as the recognized genes, the possible environmental factors and the epidemiological results that allow family counseling.

El autismo es un trastorno del neurodesarrollo caracterizado por compromiso en la interacción social y la comunicación, asociado a intereses restringidos y conductas estereotipadas con gran prevalencia poblacional, bases neurobiológicas y alta heredabilidad. Su etiología es heterogénea y se han reconocido numerosas bases genéticas, factores ambientales y mecanismos epigenéticos. Los avances en la genética molecular, así como los estudios epidemiológicos de grandes cohortes, han posibilitado identificar entidades médicas específicas, así como genes y factores ambientales vinculados parcial o totalmente en su patogenia. Estos conocimientos, conforme las características clínicas, permiten orientar los estudios complementarios, las conductas terapéuticas, inferir un pronóstico clínico y propiciar el asesoramiento genético familiar. En este trabajo analizamos las características clínicas de los trastornos del espectro del autismo, las entidades médicas específicas que están fuertemente relacionadas a los mismos, así como los genes reconocidos, los posibles factores ambientales y los resultados epidemiológicos que permiten el adecuado asesoramiento familiar.

El enfoque neuropsicológico del autismo: reto para comprender, diagnosticar y rehabilitar desde la atención temprana / Autism: a neuropsychological perspective

La persona con trastorno del espectro autista presenta desde muy temprano características específicas y persistentes en la comunicación y en la interacción social recíproca, con patrones restringidos y repetitivos de comportamiento, intereses y actividades que le limitan en gran medida. La investigación neuropsicológica nos trajo una visión enriquecedora sobre el desarrollo infantil y la disfunción cerebral permitiéndonos entender y evaluar para una intervención más ajustada y consciente a la persona autista, desde la perspectiva neuropsicológica de evaluación y rehabilitación. Está evaluación nos posibilita trazar nuevos caminos para una mayor comprensión de la funcionalidad y de las funciones ejecutivas en el autismo.

The person with the disorder of autism spectrum presents from very early specific and persistent features in communication and reciprocal social interaction, with restricted and repetitive patterns of behavior, interests and activities which greatly limits and compromises their daily life. Neuropsychological research brought us an enriching insight into child development and brain dysfunctions which allows us to understand and evaluate for a more adjusted and conscious action to the autistic person, a neuropsychological assessment and rehabilitation perspective, enabling us to chart new paths to a greater understanding of functionality and executive functions in autism.

Brain stimulation used as biofeedback in neuronal activation of the temporal lobe area in autistic children.

This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.

Brain stimulation used as biofeedback in neuronal activation of the temporal lobe area in autistic children / Estimulação cerebral usada como biofeedback na ativação neural do lobo temporal em crianças autistas

ABSTRACT This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.

RESUMO O estudo verificou a capacidade funcional dos neurônios-espelho em crianças autistas. 30 indivíduos, sendo 10 portadores da síndrome autista (GCA), 10 com deficiência intelectual (GDI), e 10 não-autistas (GCN) tiveram registrado o eletroencefalograma da área do cérebro relacionada teoricamente com os neurônios espelho. O procedimento de coleta de dados ocorreu antes e após uma sessão de estimulação cerebral. Durante a segunda coleta de dados, os participantes tiveram de processar alternadamente figuras evocando sentimentos neutros, felizes e tristes. Os resultados provaram que, para todos os grupos, o processo de estimulação de fato produziu ativação adicional na área neural em estudo. O nível de ativação foi relacionada com o formato dos estímulos emocionais. Uma vez que o aumento da ativação ocorreu em um modelo semelhante ao observado para o grupo controle, pode-se sugerir que as pessoas com autismo têm dificuldade em expressar emoções não devido à inexistência de neurônios-espelho.

Funciones sensoriales en niños menores de 3 años diagnosticados con trastorno del espectro autista (TEA) / Sensory processing in toddlers diagnosed with autism spectrum disorder (ASD)

Las dificultades de procesamiento sensorial en niños con Trastorno del Espectro Autista (TEA) están ampliamente descritos en la literatura principalmente mediante el uso de encuestas a padres y observaciones. Con menor frecuencia se han descrito las dificultades de procesamiento sensorial en niños menores de 3 años de edad que han sido posteriormente diagnosticados con TEA. Este estudio retrospectivo está basado en 84 niños (28 diagnosticados con TEA, 28 con retraso en el desarrollo, y 28 niños con desarrollo típico) entre 18 y 36 meses de edad que asistieron a un programa de intervención temprana y cuyos padres completaron el cuestionario Infant Toddler Sensory Profile (Dunn & Daniels, 2002). Los resultados obtenidos en esta encuesta revelan que los niños menores de edad con TEA muestran un patrón específico de procesamiento sensorial en comparación con niños con otros retrasos en el desarrollo.

Sensory processing difficulties of children with Autism Spectrum Disorder (ASD) are extensively described in the literature using parent surveys and observations. The sensory processing difficulties of children under 3 years of age who are later diagnosed with ASD have seldom been described. This retrospective study is based on 84 children (28 diagnosed with ASD, 28 with developmental disabilities, and 28 typically developing children) between 18 and 36 months of age attending an early intervention program and whose parents completed the Infant Toddler Sensory Profile questionnaire (Dunn & Daniels, 2002). The results obtained in this survey reveals that toddlers with ASD exhibit a distinct pattern of sensory processing as compared to children with other developmental delays.

Collybistin binds and inhibits mTORC1 signaling: a potential novel mechanism contributing to intellectual disability and autism.

Protein synthesis regulation via mammalian target of rapamycin complex 1 (mTORC1) signaling pathway has key roles in neural development and function, and its dysregulation is involved in neurodevelopmental disorders associated with autism and intellectual disability. mTOR regulates assembly of the translation initiation machinery by interacting with the eukaryotic initiation factor eIF3 complex and by controlling phosphorylation of key translational regulators. Collybistin (CB), a neuron-specific Rho-GEF responsible for X-linked intellectual disability with epilepsy, also interacts with eIF3, and its binding partner gephyrin associates with mTOR. Therefore, we hypothesized that CB also binds mTOR and affects mTORC1 signaling activity in neuronal cells. Here, by using induced pluripotent stem cell-derived neural progenitor cells from a male patient with a deletion of entire CB gene and from control individuals, as well as a heterologous expression system, we describe that CB physically interacts with mTOR and inhibits mTORC1 signaling pathway and protein synthesis. These findings suggest that disinhibited mTORC1 signaling may also contribute to the pathological process in patients with loss-of-function variants in CB.

Anatomic and Functional Connectivity Relationship in Autistic Children During Three Different Experimental Conditions.

A group of 21 autistic children were studied for determining the relationship between the anatomic (AC) versus functional (FC) connectivity, considering short-range and long-range brain networks. AC was assessed by the DW-MRI technique and FC by EEG coherence calculation, in three experimental conditions: basal, watching a popular cartoon with audio (V-A), and with muted audio track (VwA). For short-range connections, basal records, statistical significant correlations were found for all EEG bands in the left hemisphere, but no significant correlations were found for fast EEG frequencies in the right hemisphere. For the V-A condition, significant correlations were mainly diminished for the left hemisphere; for the right hemisphere, no significant correlations were found for the fast EEG frequency bands. For the VwA condition, significant correlations for the rapid EEG frequencies mainly disappeared for the right hemisphere. For long-range connections, basal records showed similar correlations for both hemispheres. For the right hemisphere, significant correlations incremented to all EEG bands for the V-A condition, but these significant correlations disappeared for the fast EEG frequencies in the VwA condition. It appears that in a resting-state condition, AC is better associated with functional connectivity for short-range connections in the left hemisphere. The V-A experimental condition enriches the AC and FC association for long-range connections in the right hemisphere. This might be related to an effective connectivity improvement due to full video stimulation (visual and auditory). An impaired audiovisual interaction in the right hemisphere might explain why significant correlations disappeared for the fast EEG frequencies in the VwA experimental condition.

Análisis neuropsicológico y neurofisiológico en una niña con autismo: estudio longitudinal con resultados de intervención / Neuropsychologic and neurophysiological analysis in autistic girl with results of intervention

El presente estudio es acerca del análisis neuropsicológico y neurofisiológico a partir del trabajo de evaluación e intervención neuropsicológica, en el caso de una niña de edad preescolar con características de espectro autista. La niña fue evaluada por presentar retraso en el desarrollo y ausencia del lenguaje. El diagnóstico de la evaluación neuropsicológica y psicológica permitió precisar los aspectos fuertes y débiles del desarrollo psicológico de la niña y precisar las estrategias de intervención. El programa de intervención fue elaborado de acuerdo a la consideración de la edad psicológica e incluyó varias etapas de introducción y formación de la actividad lúdica con apoyos simbólicos y verbales. Se realizaron estudios neuropsicológicos y electrofisiológico de seguimiento. Los resultados permitieron observar cambios favorables en la actividad de la niña a partir del proceso de corrección neuropsicológica, permitiendo acceso a las actividades escolares y la comunicación social. Se discute que a pesar de presencia de diagnósticos desfavorables en la edad infantil con indicaciones del daño cerebral, la corrección neuropsicológica es un instrumento poderoso para superación de dificultades y desarrollo progresivo en las edades infantiles...

The following study is related to the neuropsychological and neurophysiological analysis from a neuropsychological assessment and intervention of a preschool girl with autism spectrum characteristics. The girl was evaluated due to severe developmental disorders and absence of oral expression. Neuropsychological and psychological diagnosis allowed to determine strong and weak development aspects and to establish strategies for intervention. The intervention program was conducted according to consideration of psychological age of the girl and included diverse stages of game activities with symbolic and verbal means. The result showed improvement in the girl’s activity such as the possibility to take part in school learning and in social communication. We discuss that even in cases of severe diagnosis and probability of brain injury, neuropsychological intervention can play an important role and be powerful instrument for overcoming of developmental difficulties and serve for progressive development in childhood...

Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy.

Autism and Alzheimer's disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-ß precursor protein-α has been shown to be elevated in severe autism, leading to the 'anabolic hypothesis' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria-related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of α-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg(2+)) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed.

The use of listening devices to ameliorate auditory deficit in children with autism.

OBJECTIVES: To evaluate both monaural and binaural processing skills in a group of children with autism spectrum disorder (ASD) and to determine the degree to which personal frequency modulation (radio transmission) (FM) listening systems could ameliorate their listening difficulties. STUDY DESIGN: Auditory temporal processing (amplitude modulation detection), spatial listening (integration of binaural difference cues), and functional hearing (speech perception in background noise) were evaluated in 20 children with ASD. Ten of these subsequently underwent a 6-week device trial in which they wore the FM system for up to 7 hours per day. RESULTS: Auditory temporal processing and spatial listening ability were poorer in subjects with ASD than in matched controls (temporal: P = .014 [95% CI -6.4 to -0.8 dB], spatial: P = .003 [1.0 to 4.4 dB]), and performance on both of these basic processing measures was correlated with speech perception ability (temporal: r = -0.44, P = .022; spatial: r = -0.50, P = .015). The provision of FM listening systems resulted in improved discrimination of speech in noise (P < .001 [11.6% to 21.7%]). Furthermore, both participant and teacher questionnaire data revealed device-related benefits across a range of evaluation categories including Effect of Background Noise (P = .036 [-60.7% to -2.8%]) and Ease of Communication (P = .019 [-40.1% to -5.0%]). Eight of the 10 participants who undertook the 6-week device trial remained consistent FM users at study completion. CONCLUSIONS: Sustained use of FM listening devices can enhance speech perception in noise, aid social interaction, and improve educational outcomes in children with ASD.

Altered semantic integration in autism beyond language: a cross-modal event-related potentials study.

Autism spectrum disorders (ASDs) are characterized by impaired communication, particularly pragmatic and semantic language, resulting in verbal comprehension deficits. Semantic processing in these conditions has been studied extensively, but mostly limited only to linguistic material. Emerging evidence, however, suggests that semantic integration deficits may extend beyond the verbal domain. Here, we explored cross-modal semantic integration using visual targets preceded by musical and linguistic cues. Particularly, we have recorded the event-related potentials to evaluate whether the N400 and late positive potential (LPP) components, two widely studied electrophysiological markers of semantic processing, are differently sensitive to congruence with respect to typically developing children. Seven ASD patients and seven neurotypical participants matched by age, education and intelligence quotient provided usable data. Neuroelectric activity was recorded in response to visual targets that were related or unrelated to a preceding spoken sentence or musical excerpt. The N400 was sensitive to semantic congruence in the controls but not the patients, whereas the LPP showed a complementary pattern. These results suggest that semantic processing in ASD children is also altered in the context of musical and visual stimuli, and point to a functional decoupling between the generators of the N400 and LPP, which may indicate delayed semantic processing. These novel findings underline the importance of exploring semantic integration across multiple modalities in ASDs and provide motivation for further investigation in large clinical samples.

Selective impairment of cognitive empathy for moral judgment in adults with high functioning autism.

Faced with a moral dilemma, conflict arises between a cognitive controlled response aimed at maximizing welfare, i.e. the utilitarian judgment, and an emotional aversion to harm, i.e. the deontological judgment. In the present study, we investigated moral judgment in adult individuals with high functioning autism/Asperger syndrome (HFA/AS), a clinical population characterized by impairments in prosocial emotions and social cognition. In Experiment 1, we compared the response patterns of HFA/AS participants and neurotypical controls to moral dilemmas with low and high emotional saliency. We found that HFA/AS participants more frequently delivered the utilitarian judgment. Their perception of appropriateness of moral transgression was similar to that of controls, but HFA/AS participants reported decreased levels of emotional reaction to the dilemma. In Experiment 2, we explored the way in which demographic, clinical and social cognition variables including emotional and cognitive aspects of empathy and theory of mind influenced moral judgment. We found that utilitarian HFA/AS participants showed a decreased ability to infer other people's thoughts and to understand their intentions, as measured both by performance on neuropsychological tests and through dispositional measures. We conclude that greater prevalence of utilitarianism in HFA/AS is associated with difficulties in specific aspects of social cognition.

Animal model of autism induced by prenatal exposure to valproate: altered glutamate metabolism in the hippocampus.

Autism spectrum disorders (ASD) are characterized by deficits in social interaction, language and communication impairments and repetitive and stereotyped behaviors, with involvement of several areas of the central nervous system (CNS), including hippocampus. Although neurons have been the target of most studies reported in the literature, recently, considerable attention has been centered upon the functionality and plasticity of glial cells, particularly astrocytes. These cells participate in normal brain development and also in neuropathological processes. The present work investigated hippocampi from 15 (P15) and 120 (P120) days old male rats prenatally exposed to valproic acid (VPA) as an animal model of autism. Herein, we analyzed astrocytic parameters such as glutamate transporters and glutamate uptake, glutamine synthetase (GS) activity and glutathione (GSH) content. In the VPA group glutamate uptake was unchanged at P15 and increased 160% at P120; the protein expression of GLAST did not change neither in P15 nor in P120, while GLT1 decreased 40% at P15 and increased 92% at P120; GS activity increased 43% at P15 and decreased 28% at P120; GSH content was unaltered at P15 and had a 27% increase at P120. These data highlight that the astrocytic clearance and destination of glutamate in the synaptic cleft might be altered in autism, pointing out important aspects to be considered from both pathophysiologic and pharmacological approaches in ASD.

Considering responsivity: a proposal for pragmatic analysis in autism spectrum.

PURPOSE: To compare the pragmatic profile referring to the communicative initiatives and the bi-dimensional profile involving the aspects of initiative and responsivity. It also aimed to analyze the most common types of responses presented by the studied individuals. METHODS: Thirty recorded samples of interaction between speech-language therapist and children with autism spectrum disorders (mean age: 9 years and 6 months) sessions were analyzed. The samples were transcribed and data analyzed about number of communicative acts, occupation of the communicative space, use of communicative means (verbal, vocal and gestural) and total number of participations (initiatives and responses). The responses were qualified as "non-answer", "adequate answer", "inadequate answer" and "pragmatically inappropriate answer". RESULTS: Significant differences in the comparison of the numbers of initiatives and total participations and of occupation of communicative space and total number of communicative acts. There was also a significant difference in the number of "adequate answers". CONCLUSION: Results show the need to consider the bi-dimensional communicative profile and qualify the answers in order to determine the child's communication abilities.