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1.  Audiovisual speech integration in autism spectrum disorder: ERP evidence for atypicalities in lexical-semantic processing 
Lay Abstract
Language and communicative impairments are among the primary characteristics of autism spectrum disorders (ASD). Previous studies have examined auditory language processing in ASD. However, during face-to-face conversation, auditory and visual speech inputs provide complementary information, and little is known about audiovisual (AV) speech processing in ASD. It is possible to elucidate the neural correlates of AV integration by examining the effects of seeing the lip movements accompanying the speech (visual speech) on electrophysiological event-related potentials (ERP) to spoken words. Moreover, electrophysiological techniques have a high temporal resolution and thus enable us to track the time-course of spoken word processing in ASD and typical development (TD). The present study examined the ERP correlates of AV effects in three time windows that are indicative of hierarchical stages of word processing. We studied a group of TD adolescent boys (n=14) and a group of high-functioning boys with ASD (n=14). Significant group differences were found in AV integration of spoken words in the 200–300ms time window when spoken words start to be processed for meaning. These results suggest that the neural facilitation by visual speech of spoken word processing is reduced in individuals with ASD.
Scientific Abstract
In typically developing (TD) individuals, behavioural and event-related potential (ERP) studies suggest that audiovisual (AV) integration enables faster and more efficient processing of speech. However, little is known about AV speech processing in individuals with autism spectrum disorder (ASD). The present study examined ERP responses to spoken words to elucidate the effects of visual speech (the lip movements accompanying a spoken word) on the range of auditory speech processing stages from sound onset detection to semantic integration. The study also included an AV condition which paired spoken words with a dynamic scrambled face in order to highlight AV effects specific to visual speech. Fourteen adolescent boys with ASD (15–17 years old) and 14 age- and verbal IQ-matched TD boys participated. The ERP of the TD group showed a pattern and topography of AV interaction effects consistent with activity within the superior temporal plane, with two dissociable effects over fronto-central and centro-parietal regions. The posterior effect (200–300ms interval) was specifically sensitive to lip movements in TD boys, and no AV modulation was observed in this region for the ASD group. Moreover, the magnitude of the posterior AV effect to visual speech correlated inversely with ASD symptomatology. In addition, the ASD boys showed an unexpected effect (P2 time window) over the frontal-central region (pooled electrodes F3, Fz, F4, FC1, FC2, FC3, FC4) which was sensitive to scrambled face stimuli. These results suggest that the neural networks facilitating processing of spoken words by visual speech are altered in individuals with ASD.
doi:10.1002/aur.231
PMCID: PMC3586407  PMID: 22162387
Auditory; ASD; ERP; Language; Multisensory; Visual
2.  Cracking the Language Code: Neural Mechanisms Underlying Speech Parsing 
Word segmentation, detecting word boundaries in continuous speech, is a critical aspect of language learning. Previous research in infants and adults demonstrated that a stream of speech can be readily segmented based solely on the statistical and speech cues afforded by the input. Using functional magnetic resonance imaging (fMRI), the neural substrate of word segmentation was examined on-line as participants listened to three streams of concatenated syllables, containing either statistical regularities alone, statistical regularities and speech cues, or no cues. Despite the participants’ inability to explicitly detect differences between the speech streams, neural activity differed significantly across conditions, with left-lateralized signal increases in temporal cortices observed only when participants listened to streams containing statistical regularities, particularly the stream containing speech cues. In a second fMRI study, designed to verify that word segmentation had implicitly taken place, participants listened to trisyllabic combinations that occurred with different frequencies in the streams of speech they just heard (“words,” 45 times; “partwords,” 15 times; “nonwords,” once). Reliably greater activity in left inferior and middle frontal gyri was observed when comparing words with partwords and, to a lesser extent, when comparing partwords with nonwords. Activity in these regions, taken to index the implicit detection of word boundaries, was positively correlated with participants’ rapid auditory processing skills. These findings provide a neural signature of on-line word segmentation in the mature brain and an initial model with which to study developmental changes in the neural architecture involved in processing speech cues during language learning.
doi:10.1523/JNEUROSCI.5501-05.2006
PMCID: PMC3713232  PMID: 16855090
fMRI; language; speech perception; word segmentation; statistical learning; auditory cortex; inferior frontal gyrus
3.  Age and experience shape developmental changes in the neural basis of language-related learning 
Developmental science  2011;14(6):1261-1282.
Very little is known about the neural underpinnings of language learning across the lifespan and how these might be modified by maturational and experiential factors. Building on behavioral research highlighting the importance of early word segmentation (i.e. the detection of word boundaries in continuous speech) for subsequent language learning, here we characterize developmental changes in brain activity as this process occurs online, using data collected in a mixed cross-sectional and longitudinal design. One hundred and fifty-six participants, ranging from age 5 to adulthood, underwent functional magnetic resonance imaging (fMRI) while listening to three novel streams of continuous speech, which contained either strong statistical regularities, strong statistical regularities and speech cues, or weak statistical regularities providing minimal cues to word boundaries. All age groups displayed significant signal increases over time in temporal cortices for the streams with high statistical regularities; however, we observed a significant right-to-left shift in the laterality of these learning-related increases with age. Interestingly, only the 5- to 10-year-old children displayed significant signal increases for the stream with low statistical regularities, suggesting an age-related decrease in sensitivity to more subtle statistical cues. Further, in a sample of 78 10-year-olds, we examined the impact of proficiency in a second language and level of pubertal development on learning-related signal increases, showing that the brain regions involved in language learning are influenced by both experiential and maturational factors.
doi:10.1111/j.1467-7687.2011.01075.x
PMCID: PMC3717169  PMID: 22010887
4.  Individual Differences in the Real-Time Comprehension of Children with ASD 
Lay Abstract
Spoken language processing is related to language and cognitive skills in typically developing children, but very little is known about how children with autism spectrum disorders (ASD) comprehend words in real time. Studying this area is important because it may help us understand why many children with autism have delayed language comprehension. Thirty-four children with ASD (3–6 years old) participated in this study. They took part in a language comprehension task that involved looking at pictures on a screen and listening to questions about familiar nouns (e.g., Where’s the shoe?). Children as a group understood the familiar words, but accuracy and processing speed varied considerably across children. The children who were more accurate were also faster to process the familiar words. Children’s language processing accuracy was related to processing speed and language comprehension on a standardized test; nonverbal cognition did not explain additional information after accounting for these factors. Additionally, lexical processing accuracy at age 5½ was related to children’s vocabulary comprehension three years earlier, at age 2½. Autism severity and years of maternal education were unrelated to language processing. Words typically acquired earlier in life were processed more quickly than words acquired later. These findings point to similarities in patterns of language development in typically developing children and children with ASD. Studying real-time comprehension in children with ASD may help us better understand mechanisms of language comprehension in this population. Future work may help explain why some children with ASD develop age-appropriate language skills, whereas others experience lasting deficits.
Scientific Abstract
Many children with autism spectrum disorders (ASD) demonstrate deficits in language comprehension, but little is known about how they process spoken language as it unfolds. Real-time lexical comprehension is associated with language and cognition in children without ASD, suggesting that this may also be the case for children with ASD. This study adopted an individual differences approach to characterizing real-time comprehension of familiar words in a group of 34 three- to six-year-olds with ASD. The looking-while-listening paradigm was employed; it measures online accuracy and latency through language-mediated eye movements and has limited task demands. On average, children demonstrated comprehension of the familiar words, but considerable variability emerged. Children with better accuracy were faster to process the familiar words. In combination, processing speed and comprehension on a standardized language assessment explained 63% of the variance in online accuracy. Online accuracy was not correlated with autism severity or maternal education, and nonverbal cognition did not explain unique variance. Notably, online accuracy at age 5½ was related to vocabulary comprehension three years earlier. The words typically learned earliest in life were processed most quickly. Consistent with a dimensional view of language abilities, these findings point to similarities in patterns of language acquisition in typically developing children and those with ASD. Overall, our results emphasize the value of examining individual differences in real-time language comprehension in this population. We propose that the looking-while-listening paradigm is a sensitive and valuable methodological tool that can be applied across many areas of autism research.
doi:10.1002/aur.1304
PMCID: PMC3808474  PMID: 23696214
autism; comprehension; language processing; receptive vocabulary; eye-gaze methodology; individual differences
5.  Altered integration of speech and gesture in children with autism spectrum disorders 
Brain and Behavior  2012;2(5):606-619.
The presence of gesture during speech has been shown to impact perception, comprehension, learning, and memory in normal adults and typically developing children. In neurotypical individuals, the impact of viewing co-speech gestures representing an object and/or action (i.e., iconic gesture) or speech rhythm (i.e., beat gesture) has also been observed at the neural level. Yet, despite growing evidence of delayed gesture development in children with autism spectrum disorders (ASD), few studies have examined how the brain processes multimodal communicative cues occurring during everyday communication in individuals with ASD. Here, we used a previously validated functional magnetic resonance imaging (fMRI) paradigm to examine the neural processing of co-speech beat gesture in children with ASD and matched controls. Consistent with prior observations in adults, typically developing children showed increased responses in right superior temporal gyrus and sulcus while listening to speech accompanied by beat gesture. Children with ASD, however, exhibited no significant modulatory effects in secondary auditory cortices for the presence of co-speech beat gesture. Rather, relative to their typically developing counterparts, children with ASD showed significantly greater activity in visual cortex while listening to speech accompanied by beat gesture. Importantly, the severity of their socio-communicative impairments correlated with activity in this region, such that the more impaired children demonstrated the greatest activity in visual areas while viewing co-speech beat gesture. These findings suggest that although the typically developing brain recognizes beat gesture as communicative and successfully integrates it with co-occurring speech, information from multiple sensory modalities is not effectively integrated during social communication in the autistic brain.
doi:10.1002/brb3.81
PMCID: PMC3489813  PMID: 23139906
Autism spectrum disorders; fMRI; gesture; language; superior temporal gyrus
6.  Non-Specialist Psychosocial Interventions for Children and Adolescents with Intellectual Disability or Lower-Functioning Autism Spectrum Disorders: A Systematic Review 
PLoS Medicine  2013;10(12):e1001572.
In a systematic review, Brian Reichow and colleagues assess the evidence that non-specialist care providers in community settings can provide effective interventions for children and adolescents with intellectual disabilities or lower-functioning autism spectrum disorders.
Please see later in the article for the Editors' Summary
Background
The development of effective treatments for use by non-specialists is listed among the top research priorities for improving the lives of people with mental illness worldwide. The purpose of this review is to appraise which interventions for children with intellectual disabilities or lower-functioning autism spectrum disorders delivered by non-specialist care providers in community settings produce benefits when compared to either a no-treatment control group or treatment-as-usual comparator.
Methods and Findings
We systematically searched electronic databases through 24 June 2013 to locate prospective controlled studies of psychosocial interventions delivered by non-specialist providers to children with intellectual disabilities or lower-functioning autism spectrum disorders. We screened 234 full papers, of which 34 articles describing 29 studies involving 1,305 participants were included. A majority of the studies included children exclusively with a diagnosis of lower-functioning autism spectrum disorders (15 of 29, 52%). Fifteen of twenty-nine studies (52%) were randomized controlled trials and just under half of all effect sizes (29 of 59, 49%) were greater than 0.50, of which 18 (62%) were statistically significant. For behavior analytic interventions, the best outcomes were shown for development and daily skills; cognitive rehabilitation, training, and support interventions were found to be most effective for improving developmental outcomes, and parent training interventions to be most effective for improving developmental, behavioral, and family outcomes. We also conducted additional subgroup analyses using harvest plots. Limitations include the studies' potential for performance bias and that few were conducted in lower- and middle-income countries.
Conclusions
The findings of this review support the delivery of psychosocial interventions by non-specialist providers to children who have intellectual disabilities or lower-functioning autism spectrum disorders. Given the scarcity of specialists in many low-resource settings, including many lower- and middle-income countries, these findings may provide guidance for scale-up efforts for improving outcomes for children with developmental disorders or lower-functioning autism spectrum disorders.
Protocol Registration
PROSPERO CRD42012002641
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Newborn babies are helpless, but over the first few years of life, they acquire motor (movement) skills, language (communication) skills, cognitive (thinking) skills, and social (interpersonal interaction) skills. Individual aspects of these skills are usually acquired at specific ages, but children with a development disorder such as an autism spectrum disorder (ASD) or intellectual disability (mental retardation) fail to reach these “milestones” because of impaired or delayed brain maturation. Autism, Asperger syndrome, and other ASDs (also called pervasive developmental disorders) affect about 1% of the UK and US populations and are characterized by abnormalities in interactions and communication with other people (reciprocal socio-communicative interactions; for example, some children with autism reject physical affection and fail to develop useful speech) and a restricted, stereotyped, repetitive repertoire of interests (for example, obsessive accumulation of facts about unusual topics). About half of individuals with an ASD also have an intellectual disability—a reduced overall level of intelligence characterized by impairment of the skills that are normally acquired during early life. Such individuals have what is called lower-functioning ASD.
Why Was This Study Done?
Most of the children affected by developmental disorders live in low- and middle-income countries where there are few services available to help them achieve their full potential and where little research has been done to identify the most effective treatments. The development of effective treatments for use by non-specialists (for example, teachers and parents) is necessary to improve the lives of people with mental illnesses worldwide, but particularly in resource-limited settings where psychiatrists, psychologists, and other specialists are scarce. In this systematic review, the researchers investigated which psychosocial interventions for children and adolescents with intellectual disabilities or lower-functioning ASDs delivered by non-specialist providers in community settings produce improvements in development, daily skills, school performance, behavior, or family outcomes when compared to usual care (the control condition). A systematic review identifies all the research on a given topic using predefined criteria; psychosocial interventions are defined as therapy, education, training, or support aimed at improving behavior, overall development, or specific life skills without the use of drugs.
What Did the Researchers Do and Find?
The researchers identified 29 controlled studies (investigations with an intervention group and a control group) that examined the effects of various psychosocial interventions delivered by non-specialist providers to children (under 18 years old) who had a lower-functioning ASD or intellectual disability. The researchers retrieved information on the participants, design and methods, findings, and intervention characteristics for each study, and calculated effect sizes—a measure of the effectiveness of a test intervention relative to a control intervention—for several outcomes for each intervention. Across the studies, three-quarters of the effect size estimates were positive, and nearly half were greater than 0.50; effect sizes of less than 0.2, 0.2–0.5, and greater than 0.5 indicate that an intervention has no, a small, or a medium-to-large effect, respectively. For behavior analytic interventions (which aim to improve socially significant behavior by systematically analyzing behavior), the largest effect sizes were seen for development and daily skills. Cognitive rehabilitation, training, and support (interventions that facilitates the relearning of lost or altered cognitive skills) produced good improvements in developmental outcomes such as standardized IQ tests in children aged 6–11 years old. Finally, parental training interventions (which teach parents how to provide therapy services for their child) had strong effects on developmental, behavioral, and family outcomes.
What Do These Findings Mean?
Because few of the studies included in this systematic review were undertaken in low- and middle-income countries, the review's findings may not be generalizable to children living in resource-limited settings. Moreover, other characteristics of the included studies may limit the accuracy of these findings. Nevertheless, these findings support the delivery of psychosocial interventions by non-specialist providers to children who have intellectual disabilities or a lower-functioning ASD, and indicate which interventions are likely to produce the largest improvements in developmental, behavioral, and family outcomes. Further studies are needed, particularly in low- and middle-income countries, to confirm these findings, but given that specialists are scarce in many resource-limited settings, these findings may help to inform the implementation of programs to improve outcomes for children with intellectual disabilities or lower-functioning ASDs in low- and middle-income countries.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001572.
This study is further discussed in a PLOS Medicine Perspective by Bello-Mojeed and Bakare
The US Centers for Disease Control and Prevention provides information (in English and Spanish) on developmental disabilities, including autism spectrum disorders and intellectual disability
The US National Institute of Mental Health also provides detailed information about autism spectrum disorders, including the publication “A Parent's Guide to Autism Spectrum Disorder”
Autism Speaks, a US non-profit organization, provides information about all aspects of autism spectrum disorders and includes information on the Autism Speaks Global Autism Public Health Initiative
The National Autistic Society, a UK charity, provides information about all aspects of autism spectrum disorders and includes personal stories about living with these conditions
The UK National Health Service Choices website has an interactive guide to child development and information about autism and Asperger syndrome, including personal stories, and about learning disabilities
The UK National Institute for Health and Care Excellence provides clinical guidelines for the management and support of children with autism spectrum disorders
The World Health Organization provides information on its Mental Health Gap Action Programme (mhGAP), which includes recommendations on the management of developmental disorders by non-specialist providers; the mhGAP Evidence Resource Center provides evidence reviews for parent skills training for management of children with intellectual disabilities and pervasive developmental disorders and interventions for management of children with intellectual disabilities
PROSPERO, an international prospective register of systematic reviews, provides more information about this systematic review
doi:10.1371/journal.pmed.1001572
PMCID: PMC3866092  PMID: 24358029
7.  Deviant fMRI patterns of brain activity to speech in 2–3 year-old children with autism spectrum disorder 
Biological psychiatry  2008;64(7):589-598.
Background
A failure to develop normal language is one of the most common first signs that a toddler might be at risk for autism. Currently the neural bases underlying this failure to develop language are unknown.
Methods
In this study, functional magnetic resonance imaging (fMRI) was utilized to identify the brain regions involved in speech perception in 12 2–3 year-old children with autism spectrum disorder (ASD) during natural sleep. We also recorded fMRI data from two typically developing control groups: a mental age-matched (MA) (n=11) and a chronological age-matched (CA) (n=12) group. During fMRI data acquisition, forward and backward speech stimuli were presented with intervening periods of no sound presentation.
Results
Direct statistical comparison between groups revealed significant differences in regions recruited to process speech. In comparison to their MA-matched controls, the ASD group showed reduced activity in an extended network of brain regions, which are recruited in typical early language acquisition. In comparison to their CA-matched controls, ASD participants showed greater activation primarily within right and medial frontal regions. Laterality analyses revealed a trend towards greater recruitment of right hemisphere regions in the ASD group and left hemisphere regions in the CA group during the forward speech condition. Furthermore, correlation analyses revealed a significant positive relationship between right hemisphere frontal and temporal activity to forward speech and receptive language skill.
Conclusions
These findings suggest that at 2–3 years, children with ASD may be on a deviant developmental trajectory characterized by a greater recruitment of right hemisphere regions during speech perception.
doi:10.1016/j.biopsych.2008.05.020
PMCID: PMC2879340  PMID: 18672231
language; development; laterality; fMRI; pediatric; sleep
8.  The Neural Basis of Speech Parsing in Children and Adults 
Developmental science  2010;13(2):385-406.
Word segmentation, detecting word boundaries in continuous speech, is a fundamental aspect of language learning that can occur solely by the computation of statistical and speech cues. Fifty-four children underwent functional magnetic resonance imaging (fMRI) while listening to three streams of concatenated syllables, which contained either high statistical regularities, high statistical regularities and speech cues, or no easily-detectable cues. Significant signal increases over time in temporal cortices suggest that children utilized the cues to implicitly segment the speech streams. This was confirmed by the findings of a second fMRI run where children displayed reliably greater activity in left inferior frontal gyrus when listening to ‘words’ that occurred more frequently in the streams of speech they just heard. Finally, comparisons between activity observed in these children vs. previously-studied adults indicate significant developmental changes in the neural substrate of speech parsing.
doi:10.1111/j.1467-7687.2009.00895.x
PMCID: PMC3229831  PMID: 20136936
fMRI; language; development; speech perception; word segmentation; statistical learning
9.  An unbiased Bayesian approach to functional connectomics implicates social-communication networks in autism 
NeuroImage : Clinical  2015;8:356-366.
Resting-state functional magnetic resonance imaging (rsfMRI) studies reveal a complex pattern of hyper- and hypo-connectivity in children with autism spectrum disorder (ASD). Whereas rsfMRI findings tend to implicate the default mode network and subcortical areas in ASD, task fMRI and behavioral experiments point to social dysfunction as a unifying impairment of the disorder. Here, we leverage a novel Bayesian framework for whole-brain functional connectomics that aggregates population differences in connectivity to localize a subset of foci that are most affected by ASD. Our approach is entirely data-driven and does not impose spatial constraints on the region foci or dictate the trajectory of altered functional pathways. We apply our method to data from the openly shared Autism Brain Imaging Data Exchange (ABIDE) and pinpoint two intrinsic functional networks that distinguish ASD patients from typically developing controls. One network involves foci in the right temporal pole, left posterior cingulate cortex, left supramarginal gyrus, and left middle temporal gyrus. Automated decoding of this network by the Neurosynth meta-analytic database suggests high-level concepts of “language” and “comprehension” as the likely functional correlates. The second network consists of the left banks of the superior temporal sulcus, right posterior superior temporal sulcus extending into temporo-parietal junction, and right middle temporal gyrus. Associated functionality of these regions includes “social” and “person”. The abnormal pathways emanating from the above foci indicate that ASD patients simultaneously exhibit reduced long-range or inter-hemispheric connectivity and increased short-range or intra-hemispheric connectivity. Our findings reveal new insights into ASD and highlight possible neural mechanisms of the disorder.
Graphical abstract
Highlights
•Our Bayesian model localizes the central foci of altered brain networks in ASD.•The method is entirely data-driven and suitable for a whole-brain analysis.•We demonstrate our approach on data from the Autism Brain Imaging Data Exchange.•We identify two abnormal networks, with foci in the temporal lobe and default mode.•High-level functional correlates include language, comprehension, social and person.
doi:10.1016/j.nicl.2015.04.021
PMCID: PMC4474177  PMID: 26106561
Functional MRI; Bayesian analysis; Autism; Brain networks
10.  Portable Intermodal Preferential Looking (IPL): Investigating Language Comprehension in Typically Developing Toddlers and Young Children with Autism 
One of the defining characteristics of autism spectrum disorder (ASD) is difficulty with language and communication.1 Children with ASD's onset of speaking is usually delayed, and many children with ASD consistently produce language less frequently and of lower lexical and grammatical complexity than their typically developing (TD) peers.6,8,12,23 However, children with ASD also exhibit a significant social deficit, and researchers and clinicians continue to debate the extent to which the deficits in social interaction account for or contribute to the deficits in language production.5,14,19,25
Standardized assessments of language in children with ASD usually do include a comprehension component; however, many such comprehension tasks assess just one aspect of language (e.g., vocabulary),5 or include a significant motor component (e.g., pointing, act-out), and/or require children to deliberately choose between a number of alternatives. These last two behaviors are known to also be challenging to children with ASD.7,12,13,16
We present a method which can assess the language comprehension of young typically developing children (9-36 months) and children with autism.2,4,9,11,22 This method, Portable Intermodal Preferential Looking (P-IPL), projects side-by-side video images from a laptop onto a portable screen. The video images are paired first with a 'baseline' (nondirecting) audio, and then presented again paired with a 'test' linguistic audio that matches only one of the video images. Children's eye movements while watching the video are filmed and later coded. Children who understand the linguistic audio will look more quickly to, and longer at, the video that matches the linguistic audio.2,4,11,18,22,26
This paradigm includes a number of components that have recently been miniaturized (projector, camcorder, digitizer) to enable portability and easy setup in children's homes. This is a crucial point for assessing young children with ASD, who are frequently uncomfortable in new (e.g., laboratory) settings. Videos can be created to assess a wide range of specific components of linguistic knowledge, such as Subject-Verb-Object word order, wh-questions, and tense/aspect suffixes on verbs; videos can also assess principles of word learning such as a noun bias, a shape bias, and syntactic bootstrapping.10,14,17,21,24 Videos include characters and speech that are visually and acoustically salient and well tolerated by children with ASD.
doi:10.3791/4331
PMCID: PMC3570064  PMID: 23271456
Medicine; Issue 70; Neuroscience; Psychology; Behavior; Intermodal preferential looking; language comprehension; children with autism; child development; autism
11.  Testing the Limits of Statistical Learning for Word Segmentation 
Developmental science  2010;13(2):339-345.
Past research has demonstrated that infants can rapidly extract syllable distribution information from an artificial language and use this knowledge to infer likely word boundaries in speech. However, artificial languages are extremely simplified with respect to natural language. In this study, we ask whether infants’ ability to track transitional probabilities between syllables in an artificial language can scale up to the challenge of natural language. We do so by testing both 5.5- and 8-month-olds’ ability to segment an artificial language containing four words of uniform length (all CVCV) or four words of varying length (two CVCV, two CVCVCV). The transitional probability cues to word boundaries were held equal across the two languages. Both age groups segmented the language containing words of uniform length, demonstrating that even 5.5-month-olds are extremely sensitive to the conditional probabilities in their environment. However, neither age group succeeded in segmenting the language containing words of varying length, despite the fact that the transitional probability cues defining word boundaries were equally strong in the two languages. We conclude that infants’ statistical learning abilities may not be as robust as earlier studies have suggested.
doi:10.1111/j.1467-7687.2009.00886.x
PMCID: PMC2819668  PMID: 20136930
artificial language; statistical learning; infant word segmentation
12.  Children with ASD can use gaze in support of word recognition and learning 
Background
Many children with autism spectrum disorders (ASD) struggle to understand familiar words and learn unfamiliar words. We explored the extent to which these problems reflect deficient use of probabilistic gaze in the extra-linguistic context.
Method
Thirty children with ASD and 43 with typical development (TD) participated in a spoken word recognition and mapping task. They viewed photographs of a woman behind three objects and simultaneously heard a word. For word recognition, the objects and words were familiar and the woman gazed ahead (neutral), toward the named object (facilitative), or toward an un-named object (contradictory). For word mapping, the objects and words were unfamiliar and only the neutral and facilitative conditions were employed. The children clicked on the named object, registering accuracy and reaction time.
Results
Speed of word recognition did not differ between groups but varied with gaze such that responses were fastest in the facilitative condition and slowest in the contradictory condition. Only the ASD group responded slower to low frequency than high-frequency words. Accuracy of word mapping did not differ between groups, but accuracy varied with gaze with higher performance in the facilitative than neutral condition. Both groups scored above single-trial chance levels in the neutral condition by tracking cross-situational information. Only in the ASD group did mapping vary with receptive vocabulary.
Conclusions
Under laboratory conditions, children with ASD can monitor gaze and judge its reliability as a cue to word meaning as well as typical peers. The use of cross-situational statistics to support word learning may be problematic for those who have weak language abilities.
doi:10.1111/jcpp.12073
PMCID: PMC4232219  PMID: 23574387
Autistic disorder; language
13.  Redox metabolism abnormalities in autistic children associated with mitochondrial disease 
Translational Psychiatry  2013;3(6):e273-.
Research studies have uncovered several metabolic abnormalities associated with autism spectrum disorder (ASD), including mitochondrial disease (MD) and abnormal redox metabolism. Despite the close connection between mitochondrial dysfunction and oxidative stress, the relation between MD and oxidative stress in children with ASD has not been studied. Plasma markers of oxidative stress and measures of cognitive and language development and ASD behavior were obtained from 18 children diagnosed with ASD who met criteria for probable or definite MD per the Morava et al. criteria (ASD/MD) and 18 age and gender-matched ASD children without any biological markers or symptoms of MD (ASD/NoMD). Plasma measures of redox metabolism included reduced free glutathione (fGSH), oxidized glutathione (GSSG), the fGSH/GSSG ratio and 3-nitrotyrosine (3NT). In addition, a plasma measure of chronic immune activation, 3-chlorotyrosine (3CT), was also measured. Language was measured using the preschool language scale or the expressive one-word vocabulary test (depending on the age), adaptive behaviour was measured using the Vineland Adaptive Behavior Scale (VABS) and core autism symptoms were measured using the Autism Symptoms Questionnaire and the Social Responsiveness Scale. Children with ASD/MD were found to have lower scores on the communication and daily living skill subscales of the VABS despite having similar language and ASD symptoms. Children with ASD/MD demonstrated significantly higher levels of fGSH/GSSG and lower levels of GSSG as compared with children with ASD/NoMD, suggesting an overall more favourable glutathione redox status in the ASD/MD group. However, compare with controls, both ASD groups demonstrated lower fGSH and fGSH/GSSG, demonstrating that both groups suffer from redox abnormalities. Younger ASD/MD children had higher levels of 3CT than younger ASD/NoMD children because of an age-related effect in the ASD/MD group. Both ASD groups demonstrated significantly higher 3CT levels than control subjects, suggesting that chronic inflammation was present in both groups of children with ASD. Interestingly, 3NT was found to correlate positively with several measures of cognitive function, development and behavior for the ASD/MD group, but not the ASD/NoMD group, such that higher 3NT concentrations were associated with more favourable adaptive behaviour, language and ASD-related behavior. To determine whether difference in receiving medications and/or supplements could account for the differences in redox and inflammatory biomarkers across ASD groups, we examined differences in medication and supplements across groups and their effect of redox and inflammatory biomarkers. Overall, significantly more participants in the ASD/MD group were receiving folate, vitamin B12, carnitine, co-enzyme Q10, B vitamins and antioxidants. We then determined whether folate, carnitine, co-enzyme Q10, B vitamins and/or antioxidants influenced redox or inflammatory biomarkers. Antioxidant supplementation was associated with a significantly lower GSSG, whereas antioxidants, co-enzyme Q10 and B vitamins were associated with a higher fGSH/GSSG ratio. There was no relation between folate, carnitine, co-enzyme Q10, B vitamins and antioxidants with 3NT, 3CT or fGSH. Overall, our findings suggest that ASD/MD children with a more chronic oxidized microenvironment have better development. We interpret this finding in light of the fact that more active mitochondrial can create a greater oxidized microenvironment especially when dysfunctional. Thus, compensatory upregulation of mitochondria which are dysfunctional may both increase activity and function at the expense of a more oxidized microenvironment. Although more ASD/MD children were receiving certain supplements, the use of such supplements were not found to be related to the redox biomarkers that were related to cognitive development or behavior in the ASD/MD group but could possibly account for the difference in glutathione metabolism noted between groups. This study suggests that different subgroups of children with ASD have different redox abnormalities, which may arise from different sources. A better understanding of the relationship between mitochondrial dysfunction in ASD and oxidative stress, along with other factors that may contribute to oxidative stress, will be critical to understanding how to guide treatment and management of ASD children. This study also suggests that it is important to identify ASD/MD children as they may respond differently to specific treatments because of their specific metabolic profile.
doi:10.1038/tp.2013.51
PMCID: PMC3693408  PMID: 23778583
autism; inflammation; endophenotypes; mitochondrial disease; oxidative stress
14.  The Psychologist as an Interlocutor in Autism Spectrum Disorder Assessment: Insights From a Study of Spontaneous Prosody 
Purpose
The purpose of this study was to examine relationships between prosodic speech cues and autism spectrum disorder (ASD) severity, hypothesizing a mutually interactive relationship between the speech characteristics of the psychologist and the child. The authors objectively quantified acoustic-prosodic cues of the psychologist and of the child with ASD during spontaneous interaction, establishing a methodology for future large-sample analysis.
Method
Speech acoustic-prosodic features were semiautomatically derived from segments of semistructured interviews (Autism Diagnostic Observation Schedule, ADOS; Lord, Rutter, DiLavore, & Risi, 1999; Lord et al., 2012) with 28 children who had previously been diagnosed with ASD. Prosody was quantified in terms of intonation, volume, rate, and voice quality. Research hypotheses were tested via correlation as well as hierarchical and predictive regression between ADOS severity and prosodic cues.
Results
Automatically extracted speech features demonstrated prosodic characteristics of dyadic interactions. As rated ASD severity increased, both the psychologist and the child demonstrated effects for turn-end pitch slope, and both spoke with atypical voice quality. The psychologist’s acoustic cues predicted the child’s symptom severity better than did the child’s acoustic cues.
Conclusion
The psychologist, acting as evaluator and interlocutor, was shown to adjust his or her behavior in predictable ways based on the child’s social-communicative impairments. The results support future study of speech prosody of both interaction partners during spontaneous conversation, while using automatic computational methods that allow for scalable analysis on much larger corpora.
doi:10.1044/2014_JSLHR-S-13-0062
PMCID: PMC4326041  PMID: 24686340
autism spectrum disorder; children; prosody; social communication; assessment; dyadic interaction
15.  Multisensory Temporal Integration in Autism Spectrum Disorders 
The Journal of Neuroscience  2014;34(3):691-697.
The new DSM-5 diagnostic criteria for autism spectrum disorders (ASDs) include sensory disturbances in addition to the well-established language, communication, and social deficits. One sensory disturbance seen in ASD is an impaired ability to integrate multisensory information into a unified percept. This may arise from an underlying impairment in which individuals with ASD have difficulty perceiving the temporal relationship between cross-modal inputs, an important cue for multisensory integration. Such impairments in multisensory processing may cascade into higher-level deficits, impairing day-to-day functioning on tasks, such as speech perception. To investigate multisensory temporal processing deficits in ASD and their links to speech processing, the current study mapped performance on a number of multisensory temporal tasks (with both simple and complex stimuli) onto the ability of individuals with ASD to perceptually bind audiovisual speech signals. High-functioning children with ASD were compared with a group of typically developing children. Performance on the multisensory temporal tasks varied with stimulus complexity for both groups; less precise temporal processing was observed with increasing stimulus complexity. Notably, individuals with ASD showed a speech-specific deficit in multisensory temporal processing. Most importantly, the strength of perceptual binding of audiovisual speech observed in individuals with ASD was strongly related to their low-level multisensory temporal processing abilities. Collectively, the results represent the first to illustrate links between multisensory temporal function and speech processing in ASD, strongly suggesting that deficits in low-level sensory processing may cascade into higher-order domains, such as language and communication.
doi:10.1523/JNEUROSCI.3615-13.2014
PMCID: PMC3891950  PMID: 24431427
audiovisual; autism spectrum disorders; multisensory integration; sensory processing; speech perception; temporal processing
16.  Memory in language-impaired children with and without autism 
Background
A subgroup of young children with autism spectrum disorders (ASD) have significant language impairments (phonology, grammar, vocabulary), although such impairments are not considered to be core symptoms of and are not unique to ASD. Children with specific language impairment (SLI) display similar impairments in language. Given evidence for phenotypic and possibly etiologic overlap between SLI and ASD, it has been suggested that language-impaired children with ASD (ASD + language impairment, ALI) may be characterized as having both ASD and SLI. However, the extent to which the language phenotypes in SLI and ALI can be viewed as similar or different depends in part upon the age of the individuals studied. The purpose of the current study is to examine differences in memory abilities, specifically those that are key “markers” of heritable SLI, among young school-age children with SLI, ALI, and ALN (ASD + language normal).
Methods
In this cross-sectional study, three groups of children between ages 5 and 8 years participated: SLI (n = 18), ALI (n = 22), and ALN (n = 20). A battery of cognitive, language, and ASD assessments was administered as well as a nonword repetition (NWR) test and measures of verbal memory, visual memory, and processing speed.
Results
NWR difficulties were more severe in SLI than in ALI, with the largest effect sizes in response to nonwords with the shortest syllable lengths. Among children with ASD, NWR difficulties were not associated with the presence of impairments in multiple ASD domains, as reported previously. Verbal memory difficulties were present in both SLI and ALI groups relative to children with ALN. Performance on measures related to verbal but not visual memory or processing speed were significantly associated with the relative degree of language impairment in children with ASD, supporting the role of verbal memory difficulties in language impairments among early school-age children with ASD.
Conclusions
The primary difference between children with SLI and ALI was in NWR performance, particularly in repeating two- and three-syllable nonwords, suggesting that shared difficulties in early language learning found in previous studies do not necessarily reflect the same underlying mechanisms.
Electronic supplementary material
The online version of this article (doi:10.1186/s11689-015-9111-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s11689-015-9111-z
PMCID: PMC4472418  PMID: 26097521
Autism spectrum disorders; Specific language impairment; Verbal memory; Nonword repetition; Verbal working memory; Narrative; Processing speed
17.  Functional Brain Networks and White Matter Underlying Theory-of-Mind in Autism 
Human beings constantly engage in attributing causal explanations to one’s own and to others’ actions, and theory-of-mind (ToM) is critical in making such inferences. Although children learn causal attribution early in development, children with autism spectrum disorders (ASDs) are known to have impairments in the development of intentional causality. This functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) study investigated the neural correlates of physical and intentional causal attribution in people with ASDs. In the fMRI scanner, 15 adolescents and adults with ASDs and 15 age- and IQ-matched typically developing peers made causal judgments about comic strips presented randomly in an event-related design. All participants showed robust activation in bilateral posterior superior temporal sulcus at the temporo-parietal junction (TPJ) in response to intentional causality. Participants with ASDs showed lower activation in TPJ, right inferior frontal gyrus and left premotor cortex. Significantly weaker functional connectivity was also found in the ASD group between TPJ and motor areas during intentional causality. DTI data revealed significantly reduced fractional anisotropy in ASD participants in white matter underlying the temporal lobe. In addition to underscoring the role of TPJ in ToM, this study found an interaction between motor simulation and mentalizing systems in intentional causal attribution and its possible discord in autism.
doi:10.1093/scan/nss106
PMCID: PMC3871731  PMID: 22977198
functional MRI; theory-of-mind; intentional causality; physical causality; causal attribution; diffusion tensor imaging; fractional anisotropy; functional connectivity; autism
18.  Oxytocin and vasopressin in children and adolescents with autism spectrum disorders: Sex differences and associations with symptoms 
There has been intensified interest in the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in autism spectrum disorders (ASD) given their role in affiliative and social behavior in animals, positive results of treatment studies using OT, and findings that genetic polymorphisms in the AVP-OT pathway are present in individuals with ASD. Nearly all such studies in humans have focused only on males. With this preliminary study, we provide basic and novel information on the involvement of OT and AVP in autism with an investigation of blood plasma levels of these neuropeptides in 75 preadolescent and adolescent girls and boys ages 8–18: 40 with high-functioning ASD (19 girls, 21 boys) and 35 typically developing children (16 girls, 19 boys). We related neuropeptide levels to social, language, repetitive behavior, and internalizing symptom measures in these individuals. There were significant gender effects: Girls showed higher levels of OT while boys had significantly higher levels of AVP. There were no significant effects of diagnosis on OT or AVP. Higher OT values were associated with greater anxiety in all girls and with better pragmatic language in all boys and girls. AVP levels were positively associated with restricted and repetitive behaviors in girls with ASD but negatively (non-significantly) associated with these behaviors in boys with ASD. Our results challenge the prevailing view that plasma OT levels are lower in individuals with ASD and suggest there are distinct and sexually dimorphic mechanisms of action for OT and AVP underlying anxiety and repetitive behaviors.
Lay Abstract
Oxytocin (OT) and arginine vasopressin (AVP) are neuropeptides that are involved in affiliative and social behavior. Previous studies have shown that boys with autism spectrum disorders (ASD) have lower levels of OT than boys without ASD, and treatment studies have found that intranasal infusions of OT increase social behaviors in mostly males with ASD. With this study, we provide basic and novel information on the involvement of OT and AVP in ASD with an investigation of blood plasma levels of these neuropeptides in 75 preadolescent and adolescent girls and boys ages 8–18: 40 with high-functioning ASD and 35 typically developing children. We related OT and AVP levels to social, language, repetitive behavior, and internalizing symptom measures in these individuals. Girls had higher levels of OT while boys had higher levels of AVP. There were no differences in OT or AVP levels between the ASD and typically developing groups. Higher OT values were associated with greater anxiety in all girls and with less impaired social language in all boys and girls. Higher levels of AVP were associated with greater restricted and repetitive behaviors in girls with ASD whereas lower levels of AVP levels were associated with lower levels of these behaviors in boys with ASD. Results challenge the prevailing view that OT levels are lower in individuals with ASD, and suggest there are distinct mechanisms of action for OT and AVP underlying anxiety and repetitive behavior symptoms for boys versus girls.
doi:10.1002/aur.1270
PMCID: PMC3657571  PMID: 23413037
Neuropeptides; oxytocin; vasopressin; autism; sex differences; repetitive behaviors; anxiety
19.  Abnormalities in gamma-band responses to language stimuli in first-degree relatives of children with autism spectrum disorder: an MEG study 
BMC Psychiatry  2012;12:213.
Background
Synchronous neural oscillatory activity in the gamma range (30–80 Hz) has been shown to be abnormal in individuals with autism spectrum disorders (ASD) and their first-degree relatives in response to simple auditory stimuli. Gamma-band abnormalities in ASD probands have been seen in response to language stimuli, but this has not been investigated in first-degree relatives. This is of particular interest given that language impairments are a core symptom of ASD and may be part of the broad autism phenotype (BAP) seen in relatives.
Methods
Magnetoencephalography recordings during a continuous word recognition task were obtained for 23 parents of a child with ASD (pASD) and 28 adult control participants. Total and evoked gamma-band activity, as well as inter-trial phase-locking factor (PLF), were measured in response to the task. Beta-band activity was also measured, due to its suggested role in language processing. Participants completed a series of language measures to assess the relationship between brain activity and language function, and lateralization of task-related activity was assessed.
Results
The pASD group showed increased evoked gamma and beta activity, while controls had decreased evoked activity. Additionally, while both groups showed a reduction in total gamma power (commonly seen in language tasks), this reduction was more prominent in the control group. The pASD group demonstrated significantly worse performance on a measure of phonology compared to controls. Significant but distinct relationships were found between gamma/beta activity and language measures within the two groups. In addition, while the overall task generally elicited left lateralized responses, pASD showed greater left lateralization than controls in some regions of interest.
Conclusions
Abnormalities in oscillatory responses to language were seen in pASD that are consistent with previous findings in ASD probands. Gamma-band responses to language stimuli have not previously been assessed in first-degree relatives of ASD probands and these findings are supportive of gamma-band activity as a heritable, neurophysiological biomarker of ASD. The possible relationship seen between language function and neural activity in the current study should be investigated further to assess if oscillatory response abnormalities may contribute to behavioural manifestations of the BAP.
doi:10.1186/1471-244X-12-213
PMCID: PMC3557147  PMID: 23194079
20.  Deficient Brainstem Encoding of Pitch in Children with Autism Spectrum Disorders 
Objective
Deficient prosody is a hallmark of the pragmatic (socially contextualized) language impairment in Autism Spectrum Disorders (ASD). Prosody communicates emotion and intention and is conveyed through acoustic cues such as pitch contour. Thus, the objective of this study was to examine the subcortical representations of prosodic speech in children with ASD.
Methods
Using passively-evoked brainstem responses to speech syllables with descending and ascending pitch contours, we examined sensory encoding of pitch in children with ASD who had normal intelligence and hearing and were age-matched with typically-developing (TD) control children.
Results
We found that some children on the autism spectrum show deficient pitch tracking (evidenced by increased frequency and slope errors and reduced phase locking) compared with TD children.
Conclusions
This is the first demonstration of subcortical involvement in prosody encoding deficits in this population of children.
Significance
Our findings may have implications for diagnostic and remediation strategies in a subset of children with ASD and open up an avenue for future investigations.
doi:10.1016/j.clinph.2008.01.108
PMCID: PMC2536645  PMID: 18558508
auditory brainstem; autism; pitch tracking; prosody
21.  White matter impairment in the speech network of individuals with autism spectrum disorder☆ 
NeuroImage : Clinical  2013;3:234-241.
Impairments in language and communication are core features of Autism Spectrum Disorder (ASD), and a substantial percentage of children with ASD do not develop speech. ASD is often characterized as a disorder of brain connectivity, and a number of studies have identified white matter impairments in affected individuals. The current study investigated white matter integrity in the speech network of high-functioning adults with ASD. Diffusion tensor imaging (DTI) scans were collected from 18 participants with ASD and 18 neurotypical participants. Probabilistic tractography was used to estimate the connection strength between ventral premotor cortex (vPMC), a cortical region responsible for speech motor planning, and five other cortical regions in the network of areas involved in speech production. We found a weaker connection between the left vPMC and the supplementary motor area in the ASD group. This pathway has been hypothesized to underlie the initiation of speech motor programs. Our results indicate that a key pathway in the speech production network is impaired in ASD, and that this impairment can occur even in the presence of normal language abilities. Therapies that result in normalization of this pathway may hold particular promise for improving speech output in ASD.
Highlights
•We used diffusion tensor imaging to measure white matter (WM) tracts in autism.•Autistic participants were high-functioning individuals with normal language skills.•WM between left supplementary motor and premotor areas is impaired in autism.•This tract is believed to be involved in the initiation of speech articulation.•Speech production may be impaired in the absence of language deficits in autism.
doi:10.1016/j.nicl.2013.08.011
PMCID: PMC3815014  PMID: 24273708
Autism; ASD; Speech; Diffusion tensor imaging; Tractography; Communication
22.  Isolated words enhance statistical language learning in infancy 
Developmental Science  2011;14(6):1323-1329.
Infants are adept at tracking statistical regularities to identify word boundaries in pause-free speech. However, researchers have questioned the relevance of statistical learning mechanisms to language acquisition, since previous studies have used simplified artificial languages that ignore the variability of real language input. The experiments reported here embraced a key dimension of variability in infant-directed speech. English-learning infants (8–10 months) listened briefly to natural Italian speech that contained either fluent speech only or a combination of fluent speech and single-word utterances. Listening times revealed successful learning of the statistical properties of target words only when words appeared both in fluent speech and in isolation; brief exposure to fluent speech alone was not sufficient to facilitate detection of the words’ statistical properties. This investigation suggests that statistical learning mechanisms actually benefit from variability in utterance length, and provides the first evidence that isolated words and longer utterances act in concert to support infant word segmentation.
doi:10.1111/j.1467-7687.2011.01079.x
PMCID: PMC3280507  PMID: 22010892
23.  The frequency modulated auditory evoked response (FMAER), a technical advance for study of childhood language disorders: cortical source localization and selected case studies 
BMC Neurology  2013;13:12.
Background
Language comprehension requires decoding of complex, rapidly changing speech streams. Detecting changes of frequency modulation (FM) within speech is hypothesized as essential for accurate phoneme detection, and thus, for spoken word comprehension. Despite past demonstration of FM auditory evoked response (FMAER) utility in language disorder investigations, it is seldom utilized clinically. This report's purpose is to facilitate clinical use by explaining analytic pitfalls, demonstrating sites of cortical origin, and illustrating potential utility.
Results
FMAERs collected from children with language disorders, including Developmental Dysphasia, Landau-Kleffner syndrome (LKS), and autism spectrum disorder (ASD) and also normal controls - utilizing multi-channel reference-free recordings assisted by discrete source analysis - provided demonstratrions of cortical origin and examples of clinical utility. Recordings from inpatient epileptics with indwelling cortical electrodes provided direct assessment of FMAER origin. The FMAER is shown to normally arise from bilateral posterior superior temporal gyri and immediate temporal lobe surround. Childhood language disorders associated with prominent receptive deficits demonstrate absent left or bilateral FMAER temporal lobe responses. When receptive language is spared, the FMAER may remain present bilaterally. Analyses based upon mastoid or ear reference electrodes are shown to result in erroneous conclusions. Serial FMAER studies may dynamically track status of underlying language processing in LKS. FMAERs in ASD with language impairment may be normal or abnormal. Cortical FMAERs can locate language cortex when conventional cortical stimulation does not.
Conclusion
The FMAER measures the processing by the superior temporal gyri and adjacent cortex of rapid frequency modulation within an auditory stream. Clinical disorders associated with receptive deficits are shown to demonstrate absent left or bilateral responses. Serial FMAERs may be useful for tracking language change in LKS. Cortical FMAERs may augment invasive cortical language testing in epilepsy surgical patients. The FMAER may be normal in ASD and other language disorders when pathology spares the superior temporal gyrus and surround but presumably involves other brain regions. Ear/mastoid reference electrodes should be avoided and multichannel, reference free recordings utilized. Source analysis may assist in better understanding of complex FMAER findings.
doi:10.1186/1471-2377-13-12
PMCID: PMC3582442  PMID: 23351174
Frequency modulation; Auditory evoked response; FMAER; Cortical; Source analysis; Language disorder; Landau-Kleffner syndrome; Autism; Children; Epilepsy surgery
24.  Brainstem transcription of speech is disrupted in children with autism spectrum disorders 
Developmental science  2009;12(4):557-567.
Language impairment is a hallmark of autism spectrum disorders (ASD). The origin of the deficit is poorly understood although deficiencies in auditory processing have been detected in both perception and cortical encoding of speech sounds. Little is known about the processing and transcription of speech sounds at earlier (brainstem) levels or about how background noise may impact this transcription process. Unlike cortical encoding of sounds, brainstem representation preserves stimulus features with a degree of fidelity that enables a direct link between acoustic components of the speech syllable (e.g., onsets) to specific aspects of neural encoding (e.g., waves V and A). We measured brainstem responses to the syllable /da/, in quiet and background noise, in children with and without ASD. Children with ASD exhibited deficits in both the neural synchrony (timing) and phase locking (frequency encoding) of speech sounds, despite normal click-evoked brainstem responses. They also exhibited reduced magnitude and fidelity of speech-evoked responses and inordinate degradation of responses by background noise in comparison to typically developing controls. Neural synchrony in noise was significantly related to measures of core and receptive language ability. These data support the idea that abnormalities in the brainstem processing of speech contribute to the language impairment in ASD. Because it is both passively-elicited and malleable, the speech-evoked brainstem response may serve as a clinical tool to assess auditory processing as well as the effects of auditory training in the ASD population.
doi:10.1111/j.1467-7687.2008.00790.x
PMCID: PMC2718770  PMID: 19635083
auditory brainstem; autism spectrum disorder; speech; language; evoked potentials
25.  Reading Affect in the Face and Voice 
Archives of general psychiatry  2007;64(6):698-708.
Context
Understanding a speaker’s communicative intent in everyday interactions is likely to draw on cues such as facial expression and tone of voice. Prior research has shown that individuals with autism spectrum disorders (ASD) show reduced activity in brain regions that respond selectively to the face and voice. However, there is also evidence that activity in key regions can be increased if task demands allow for explicit processing of emotion.
Objectives
To examine the neural circuitry underlying impairments in interpreting communicative intentions in ASD using irony comprehension as a test case, and to determine whether explicit instructions to attend to facial expression and tone of voice will elicit more normative patterns of brain activity.
Design, Setting, and Participants
Eighteen boys with ASD (aged 7–17 years, full-scale IQ >70) and 18 typically developing (TD) boys underwent functional magnetic resonance imaging at the Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles.
Main Outcome Measures
Blood oxygenation level– dependent brain activity during the presentation of short scenarios involving irony. Behavioral performance (accuracy and response time) was also recorded.
Results
Reduced activity in the medial prefrontal cortex and right superior temporal gyrus was observed in children with ASD relative to TD children during the perception of potentially ironic vs control scenarios. Importantly, a significant group X condition interaction in the medial prefrontal cortex showed that activity was modulated by explicit instructions to attend to facial expression and tone of voice only in the ASD group. Finally, medial prefrontal cortex activity was inversely related to symptom severity in children with ASD such that children with greater social impairment showed less activity in this region.
Conclusions
Explicit instructions to attend to facial expression and tone of voice can elicit increased activity in the medial prefrontal cortex, part of a network important for understanding the intentions of others, in children with ASD. These findings suggest a strategy for future intervention research.
doi:10.1001/archpsyc.64.6.698
PMCID: PMC3713233  PMID: 17548751

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