Mismatch Negativity and P3a in Adolescents and Young Adults with Autism Spectrum Disorders: Behavioral Correlates and Clinical Implications.

In a sample of 37 adolescents and young adults with autism spectrum disorder (ASD) and 35 typically-developing controls (TDC), we investigated sensory symptoms by clinical measures, and Mismatch Negativity and P3a component at Fz with the frequency and duration oddball paradigms of event-related potentials. Results showed that compared to TDC, ASD participants reported more sensory symptoms, and presented a shorter P3a peak latency in the duration paradigm, which was correlated with more social awareness deficits. In the frequency paradigm, P3a parameters were correlated with sensation avoiding and attention characteristics of ASD. Our findings suggest that sensory abnormality in ASD may extend into adolescence and young adulthood. P3a latency might be a potential neurophysiological marker for ASD.

Temporal voice areas exist in autism spectrum disorder but are dysfunctional for voice identity recognition.

The ability to recognise the identity of others is a key requirement for successful communication. Brain regions that respond selectively to voices exist in humans from early infancy on. Currently, it is unclear whether dysfunction of these voice-sensitive regions can explain voice identity recognition impairments. Here, we used two independent functional magnetic resonance imaging studies to investigate voice processing in a population that has been reported to have no voice-sensitive regions: autism spectrum disorder (ASD). Our results refute the earlier report that individuals with ASD have no responses in voice-sensitive regions: Passive listening to vocal, compared to non-vocal, sounds elicited typical responses in voice-sensitive regions in the high-functioning ASD group and controls. In contrast, the ASD group had a dysfunction in voice-sensitive regions during voice identity but not speech recognition in the right posterior superior temporal sulcus/gyrus (STS/STG)-a region implicated in processing complex spectrotemporal voice features and unfamiliar voices. The right anterior STS/STG correlated with voice identity recognition performance in controls but not in the ASD group. The findings suggest that right STS/STG dysfunction is critical for explaining voice recognition impairments in high-functioning ASD and show that ASD is not characterised by a general lack of voice-sensitive responses.

Normal P50 Gating in Children with Autism, Yet Attenuated P50 Amplitude in the Asperger Subcategory.

Autism spectrum disorders (ASD) and schizophrenia are separate disorders, but there is evidence of conversion or comorbid overlap. The objective of this paper was to explore whether deficits in sensory gating, as seen in some schizophrenia patients, can also be found in a group of ASD children compared to neurotypically developed children. An additional aim was to investigate the possibility of subdividing our ASD sample based on these gating deficits. In a case-control design, we assessed gating of the P50 and N100 amplitude in 31 ASD children and 39 healthy matched controls (8-12 years) and screened for differences between groups and within the ASD group. We did not find disturbances in auditory P50 and N100 filtering in the group of ASD children as a whole, nor did we find abnormal P50 and N100 amplitudes. However, the P50 amplitude to the conditioning stimulus was significantly reduced in the Asperger subgroup compared to healthy controls. In contrast to what is usually reported for patients with schizophrenia, we found no evidence for sensory gating deficits in our group of ASD children taken as a whole. However, reduced P50 amplitude to conditioning stimuli was found in the Asperger group, which is similar to what has been described in some studies in schizophrenia patients. There was a positive correlation between the P50 amplitude of the conditioning stimuli and anxiety score in the pervasive developmental disorder not otherwise specified group, which indicates a relation between anxiety and sensory registration in this group.

P300 component of event-related potentials in persons with asperger disorder.

In the present study, we investigated auditory event-related potentials in adults with Asperger disorder and normal controls using an auditory oddball task and a novelty oddball task. Task performance and the latencies of P300 evoked by both target and novel stimuli in the two tasks did not differ between the two groups. Analysis of variance revealed that there was a significant interaction effect between group and electrode site on the mean amplitude of the P300 evoked by novel stimuli, which indicated that there was an altered distribution of the P300 in persons with Asperger disorder. In contrast, there was no significant interaction effect on the mean P300 amplitude elicited by target stimuli. Considering that P300 comprises two main subcomponents, frontal-central-dominant P3a and parietal-dominant P3b, our results suggested that persons with Asperger disorder have enhanced amplitude of P3a, which indicated activated prefrontal function in this task.

Motor imagery in Asperger syndrome: testing action simulation by the hand laterality task.

Asperger syndrome (AS) is a neurodevelopmental condition within the Autism Spectrum Disorders (ASD) characterized by specific difficulties in social interaction, communication and behavioural control. In recent years, it has been suggested that ASD is related to a dysfunction of action simulation processes, but studies employing imitation or action observation tasks provided mixed results. Here, we addressed action simulation processes in adolescents with AS by means of a motor imagery task, the classical hand laterality task (to decide whether a rotated hand image is left or right); mental rotation of letters was also evaluated. As a specific marker of action simulation in hand rotation, we assessed the so-called biomechanical effect, that is the advantage for judging hand pictures showing physically comfortable versus physically awkward positions. We found the biomechanical effect in typically-developing participants but not in participants with AS. Overall performance on both hand laterality and letter rotation tasks, instead, did not differ in the two groups. These findings demonstrated a specific alteration of motor imagery skills in AS. We suggest that impaired mental simulation and imitation of goal-less movements in ASD could be related to shared cognitive mechanisms.

GABAergic activity in autism spectrum disorders: an investigation of cortical inhibition via transcranial magnetic stimulation.

Mounting evidence suggests a possible role for γ-aminobutyric acid (GABA) in the neuropathophysiology of autism spectrum disorders (ASD), but the extent of this impairment is unclear. A non-invasive, in vivo measure of GABA involves transcranial magnetic stimulation (TMS) of the primary motor cortex to probe cortical inhibition. Individuals diagnosed with ASD (high-functioning autism or Asperger's disorder) (n = 36 [28 male]; mean age: 26.00 years) and a group of healthy individuals (n = 34 [23 male]; mean age: 26.21 years) (matched for age, gender, and cognitive function) were administered motor cortical TMS paradigms putatively measuring activity at GABAA and GABAB receptors (i.e., short and long interval paired pulse TMS, cortical silent period). All cortical inhibition paradigms yielded no difference between ASD and control groups. There was, however, evidence for short interval cortical inhibition (SICI) deficits among those ASD participants who had experienced early language delay, suggesting that GABA may be implicated in an ASD subtype. The current findings do not support a broad role for GABA in the neuropathophysiology of ASD, but provide further indication that GABAA could be involved in ASD where there is a delay in language acquisition. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.

Age-related change in brain metabolite abnormalities in autism: a meta-analysis of proton magnetic resonance spectroscopy studies.

Abnormal trajectory of brain development has been suggested by previous structural magnetic resonance imaging and head circumference findings in autism spectrum disorders (ASDs); however, the neurochemical backgrounds remain unclear. To elucidate neurochemical processes underlying aberrant brain growth in ASD, we conducted a comprehensive literature search and a meta-analysis of (1)H-magnetic resonance spectroscopy ((1)H-MRS) studies in ASD. From the 22 articles identified as satisfying the criteria, means and s.d. of measure of N-acetylaspartate (NAA), creatine, choline-containing compounds, myo-Inositol and glutamate+glutamine in frontal, temporal, parietal, amygdala-hippocampus complex, thalamus and cerebellum were extracted. Random effect model analyses showed significantly lower NAA levels in all the examined brain regions but cerebellum in ASD children compared with typically developed children (n=1295 at the maximum in frontal, P<0.05 Bonferroni-corrected), although there was no significant difference in metabolite levels in adulthood. Meta-regression analysis further revealed that the effect size of lower frontal NAA levels linearly declined with older mean age in ASD (n=844, P<0.05 Bonferroni-corrected). The significance of all frontal NAA findings was preserved after considering between-study heterogeneities (P<0.05 Bonferroni-corrected). This first meta-analysis of (1)H-MRS studies in ASD demonstrated robust developmental changes in the degree of abnormality in NAA levels, especially in frontal lobes of ASD. Previously reported larger-than-normal brain size in ASD children and the coincident lower-than-normal NAA levels suggest that early transient brain expansion in ASD is mainly caused by an increase in non-neuron tissues, such as glial cell proliferation.

Sensory abnormalities in autism. A brief report.

Sensory abnormalities were assessed in a population-based group of 208 20-54-month-old children, diagnosed with autism spectrum disorder (ASD) and referred to a specialized habilitation centre for early intervention. The children were subgrouped based upon degree of autistic symptoms and cognitive level by a research team at the centre. Parents were interviewed systematically about any abnormal sensory reactions in the child. In the whole group, pain and hearing were the most commonly affected modalities. Children in the most typical autism subgroup (nuclear autism with no learning disability) had the highest number of affected modalities. The children who were classified in an "autistic features" subgroup had the lowest number of affected modalities. There were no group differences in number of affected sensory modalities between groups of different cognitive levels or level of expressive speech. The findings provide support for the notion that sensory abnormality is very common in young children with autism. This symptom has been proposed for inclusion among the diagnostic criteria for ASD in the upcoming DSM-V.

HRV and EEG based indicators of stress in children with Asperger syndrome in audio-visual stimulus test.

Asperger syndrome (AS) is a neurobiological condition which is characterized by poor skills in social communication, and restricted and repetitive patterns of behavior and interests. We studied whether stress-related indices of heart rate variability (HRV) and electroencephalography (EEG) are different in children with AS than normal controls. We analyzed retrospectively the data of the test where audiovisual stimuli were used. We hypothesized that this test is a stressful situation for individuals with AS and they would have a greater reaction than control subjects. EEG and one-channel electrocardiography (ECG) were collected for children with diagnosis of AS (N = 20) and their age-matched controls (N = 21). HRV indices, frontal EEG asymmetry index and brain load index were calculated. HRV based indices revealed increased sympathetic activity during the test in children with AS. EEG based indices increased more in children with AS during the test compared to baseline. Thus, the children with AS seems to have a greater reaction to stressful situation.

The effect of a motor-based, social skills intervention for adolescents with high-functioning autism: two single-subject design cases.

The purpose of this study was to assess the effect of a motor-based, social skills intervention for two adolescents with high-functioning autism (HFA) using single-subject design. A description of the intervention is provided as a first step in the manualization process. The intervention was provided as a 7-week after-school program, once weekly to the paired participants. Intervention consisted of role-play methods in which motor behaviours were linked with their cognitive and emotional meanings. Baseline, intervention and 3-month probe data collection periods were carried out and then compared using visual inspection of graphed data, paired t-tests and a three-standard-deviation-band approach. Both participants displayed a statistically significant increase in targeted social skills behaviours from baseline to intervention and maintained this level at a 3-month post-intervention probe. These single-subject design cases illustrate that motor-based, social skills interventions may be effective for adolescents with HFA and warrant further testing.

Enhanced pure-tone pitch discrimination among persons with autism but not Asperger syndrome.

Persons with Autism spectrum disorders (ASD) display atypical perceptual processing in visual and auditory tasks. In vision, Bertone, Mottron, Jelenic, and Faubert (2005) found that enhanced and diminished visual processing is linked to the level of neural complexity required to process stimuli, as proposed in the neural complexity hypothesis. Based on these findings, Samson, Mottron, Jemel, Belin, and Ciocca (2006) proposed to extend the neural complexity hypothesis to the auditory modality. They hypothesized that persons with ASD should display enhanced performance for simple tones that are processed in primary auditory cortical regions, but diminished performance for complex tones that require additional processing in associative auditory regions, in comparison to typically developing individuals. To assess this hypothesis, we designed four auditory discrimination experiments targeting pitch, non-vocal and vocal timbre, and loudness. Stimuli consisted of spectro-temporally simple and complex tones. The participants were adolescents and young adults with autism, Asperger syndrome, and typical developmental histories, all with IQs in the normal range. Consistent with the neural complexity hypothesis and enhanced perceptual functioning model of ASD (Mottron, Dawson, Soulières, Hubert, & Burack, 2006), the participants with autism, but not with Asperger syndrome, displayed enhanced pitch discrimination for simple tones. However, no discrimination-thresholds differences were found between the participants with ASD and the typically developing persons across spectrally and temporally complex conditions. These findings indicate that enhanced pure-tone pitch discrimination may be a cognitive correlate of speech-delay among persons with ASD. However, auditory discrimination among this group does not appear to be directly contingent on the spectro-temporal complexity of the stimuli.

Speech-feature discrimination in children with Asperger syndrome as determined with the multi-feature mismatch negativity paradigm.

OBJECTIVE: Asperger syndrome, belonging to the autistic spectrum of disorders, involves deficits in social interaction and prosodic use of language but normal development of formal language abilities. Auditory processing involves both hyper- and hypoactive reactivity to acoustic changes. METHODS: Responses composed of mismatch negativity (MMN) and obligatory components were recorded for five types of deviations in syllables (vowel, vowel duration, consonant, syllable frequency, syllable intensity) with the multi-feature paradigm from 8-12-year old children with Asperger syndrome. RESULTS: Children with Asperger syndrome had larger MMNs for intensity and smaller MMNs for frequency changes than typically developing children, whereas no MMN group differences were found for the other deviant stimuli. Furthermore, children with Asperger syndrome performed more poorly than controls in Comprehension of Instructions subtest of a language test battery. CONCLUSIONS: Cortical speech-sound discrimination is aberrant in children with Asperger syndrome. This is evident both as hypersensitive and depressed neural reactions to speech-sound changes, and is associated with features (frequency, intensity) which are relevant for prosodic processing. SIGNIFICANCE: The multi-feature MMN paradigm, which includes variation and thereby resembles natural speech hearing circumstances, suggests abnormal pattern of speech discrimination in Asperger syndrome, including both hypo- and hypersensitive responses for speech features.

Auditory stream segregation in children with Asperger syndrome.

Individuals with Asperger syndrome (AS) often have difficulties in perceiving speech in noisy environments. The present study investigated whether this might be explained by deficient auditory stream segregation ability, that is, by a more basic difficulty in separating simultaneous sound sources from each other. To this end, auditory event-related brain potentials were recorded from a group of school-aged children with AS and a group of age-matched controls using a paradigm specifically developed for studying stream segregation. Differences in the amplitudes of ERP components were found between groups only in the stream segregation conditions and not for simple feature discrimination. The results indicated that children with AS have difficulties in segregating concurrent sound streams, which ultimately may contribute to the difficulties in speech-in-noise perception.

Research note: exceptional absolute pitch perception for spoken words in an able adult with autism.

Autism is a neurodevelopmental disorder, characterised by deficits in socialisation and communication, with repetitive and stereotyped behaviours [American Psychiatric Association (1994). Diagnostic and statistical manual for mental disorders (4th ed.). Washington, DC: APA]. Whilst intellectual and language impairment is observed in a significant proportion of diagnosed individuals [Gillberg, C., & Coleman, M. (2000). The biology of the autistic syndromes (3rd ed.). London: Mac Keith Press; Klinger, L., Dawson, G., & Renner, P. (2002). Autistic disorder. In E. Masn, & R. Barkley (Eds.), Child pyschopathology (2nd ed., pp. 409-454). New York: Guildford Press], the disorder is also strongly associated with the presence of highly developed, idiosyncratic, or savant skills [Heaton, P., & Wallace, G. (2004) Annotation: The savant syndrome. Journal of Child Psychology and Psychiatry, 45 (5), 899-911]. We tested identification of fundamental pitch frequencies in complex tones, sine tones and words in AC, an intellectually able man with autism and absolute pitch (AP) and a group of healthy controls with self-reported AP. The analysis showed that AC's naming of speech pitch was highly superior in comparison to controls. The results suggest that explicit access to perceptual information in speech is retained to a significantly higher degree in autism.

Atypical pattern of discriminating sound features in adults with Asperger syndrome as reflected by the mismatch negativity.

Asperger syndrome, which belongs to the autistic spectrum of disorders, is characterized by deficits of social interaction and abnormal perception, like hypo- or hypersensitivity in reacting to sounds and discriminating certain sound features. We determined auditory feature discrimination in adults with Asperger syndrome with the mismatch negativity (MMN), a neural response which is an index of cortical change detection. We recorded MMN for five different sound features (duration, frequency, intensity, location, and gap). Our results suggest hypersensitive auditory change detection in Asperger syndrome, as reflected in the enhanced MMN for deviant sounds with a gap or shorter duration, and speeded MMN elicitation for frequency changes.

Processing of affective speech prosody is impaired in Asperger syndrome.

Many people with the diagnosis of Asperger syndrome (AS) show poorly developed skills in understanding emotional messages. The present study addressed discrimination of speech prosody in children with AS at neurophysiological level. Detection of affective prosody was investigated in one-word utterances as indexed by the N1 and the mismatch negativity (MMN) of auditory event-related potentials (ERPs). Data from fourteen boys with AS were compared with those for thirteen typically developed boys. These results suggest atypical neural responses to affective prosody in children with AS and their fathers, especially over the RH, and that this impairment can already be seen at low-level information processes. Our results provide evidence for familial patterns of abnormal auditory brain reactions to prosodic features of speech.

Auditory perception and attention as reflected by the brain event-related potentials in children with Asperger syndrome.

OBJECTIVE: Language development is delayed and deviant in individuals with autism, but proceeds quite normally in those with Asperger syndrome (AS). We investigated auditory-discrimination and orienting in children with AS using an event-related potential (ERP) paradigm that was previously applied to children with autism. METHODS: ERPs were measured to pitch, duration, and phonetic changes in vowels and to corresponding changes in non-speech sounds. Active sound discrimination was evaluated with a sound-identification task. RESULTS: The mismatch negativity (MMN), indexing sound-discrimination accuracy, showed right-hemisphere dominance in the AS group, but not in the controls. Furthermore, the children with AS had diminished MMN-amplitudes and decreased hit rates for duration changes. In contrast, their MMN to speech pitch changes was parietally enhanced. The P3a, reflecting involuntary orienting to changes, was diminished in the children with AS for speech pitch and phoneme changes, but not for the corresponding non-speech changes. CONCLUSIONS: The children with AS differ from controls with respect to their sound-discrimination and orienting abilities. SIGNIFICANCE: The results of the children with AS are relatively similar to those earlier obtained from children with autism using the same paradigm, although these clinical groups differ markedly in their language development.

Similarities in the phenotype of the auditory neural substrate in children with Asperger syndrome and their parents.

Asperger syndrome (AS) is a developmental disorder of brain function characterized by deficits in social interaction including difficulties in understanding emotional expressions. Children with AS share some of the behavioural characteristics with their parents and AS seems to run particularly in the male members of the same families. The aim of the present study was to determine whether similarities could be found between children with AS and their parents at central auditory processing. It was found that in children with AS the sound encoding, as reflected by the exogenous components of event-related potentials, was similarly abnormal as in both their mothers and fathers. However, their abnormal cortical auditory discrimination, as indexed by the prolonged latency of the mismatch negativity, resembled that of their fathers but not that of their mothers. The present results suggest that complex genetic mechanisms may contribute to auditory abnormalities encountered in children with AS.

Deficient auditory processing in children with Asperger Syndrome, as indexed by event-related potentials.

Asperger Syndrome (AS) is characterized by normal language development but deficient understanding and use of the intonation and prosody of speech. While individuals with AS report difficulties in auditory perception, there are no studies addressing auditory processing at the sensory level. In this study, event-related potentials (ERP) were recorded for syllables and tones in children with AS and in their control counterparts. Children with AS displayed abnormalities in transient sound-feature encoding, as indexed by the obligatory ERPs, and in sound discrimination, as indexed by the mismatch negativity. These deficits were more severe for the tone stimuli than for the syllables. These results indicate that auditory sensory processing is deficient in children with AS, and that these deficits might be implicated in the perceptual problems encountered by children with AS.