Glutamatergic synapse in autism: a complex story for a complex disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathophysiological mechanisms are still unclear. Hypotheses suggest a role for glutamate dysfunctions in ASD development, but clinical studies investigating brain and peripheral glutamate levels showed heterogenous results leading to hypo- and hyper-glutamatergic hypotheses of ASD. Recently, studies proposed the implication of elevated mGluR5 densities in brain areas in the pathophysiology of ASD. Thus, our objective was to characterize glutamate dysfunctions in adult subjects with ASD by quantifying (1) glutamate levels in the cingulate cortex and periphery using proton magnetic resonance spectroscopy and metabolomics, and (2) mGluR5 brain density in this population and in a validated animal model of ASD (prenatal exposure to valproate) at developmental stages corresponding to childhood and adolescence in humans using positron emission tomography. No modifications in cingulate Glu levels were observed between individuals with ASD and controls further supporting the difficulty to evaluate modifications in excitatory transmission using spectroscopy in this population, and the complexity of its glutamate-related changes. Our imaging results showed an overall increased density in mGluR5 in adults with ASD, that was only observed mostly subcortically in adolescent male rats prenatally exposed to valproic acid, and not detected in the stage corresponding to childhood in the same animals. This suggest that clinical changes in mGluR5 density could reflect the adaptation of the glutamatergic dysfunctions occurring earlier rather than being key to the pathophysiology of ASD.

Skin type and nerve effects on cortical tactile processing: a somatosensory evoked potentials study.

Somatosensory evoked potential (SEP) studies typically characterize short-latency components following median nerve stimulations of the wrist. However, these studies rarely considered 1) skin type (glabrous/hairy) at the stimulation site, 2) nerve being stimulated, and 3) middle-latency (>30 ms) components. Our aim was to investigate middle-latency SEPs following simple mechanical stimulation of two skin types innervated by two different nerves. Eighteen adults received 400 mechanical stimulations over four territories of the right hand (two nerves: radial/median; two skin types: hairy/glabrous skin) while their EEG was recorded. Four middle-latency components were identified: P50, N80, N130, and P200. As expected, significantly shorter latencies and larger amplitudes were found over the contralateral hemisphere for all components. A skin type effect was found for the N80; glabrous skin stimulations induced larger amplitude than hairy skin stimulations. Regarding nerve effects, median stimulations induced larger P50 and N80. Latency of the N80 was longer after median nerve stimulation compared with radial nerve stimulation. This study showed that skin type and stimulated nerve influence middle-latency SEPs, highlighting the importance of considering these parameters in future studies. These modulations could reflect differences in cutaneous receptors and somatotopy. Middle-latency SEPs can be used to evaluate the different steps of tactile information cortical processing. Modulation of SEP components before 100 ms possibly reflects somatotopy and differential processing in primary somatosensory cortex.NEW & NOTEWORTHY The current paper highlights the influences of stimulated skin type (glabrous/hairy) and nerve (median/radial) on cortical somatosensory evoked potentials. Mechanical stimulations were applied over four territories of the right hand in 18 adults. Four middle-latency components were identified: P50, N80, N130, and P200. A larger N80 was found after glabrous skin stimulations than after hairy skin ones, regardless of the nerve being stimulated. P50 and N80 were larger after median than radial nerve stimulations.

Heterozygous variants in ZBTB7A cause a neurodevelopmental disorder associated with symptomatic overgrowth of pharyngeal lymphoid tissue, macrocephaly, and elevated fetal hemoglobin.

By clinical whole exome sequencing, we identified 12 individuals with ages 3 to 37 years, including three individuals from the same family, with a consistent phenotype of intellectual disability (ID), macrocephaly, and overgrowth of adenoid tissue. All 12 individuals harbored a rare heterozygous variant in ZBTB7A which encodes the transcription factor Zinc finger and BTB-domain containing protein 7A, known to play a role in lympho- and hematopoiesis. ID was generally mild. Fetal hemoglobin (HbF) fraction was elevated 2.2%-11.2% (reference value <2% in individuals > 6 months) in four of the five individuals for whom results were available. Ten of twelve individuals had undergone surgery at least once for lymphoid hypertrophy limited to the pharynx. In the most severely affected individual (individual 1), airway obstruction resulted in 17 surgical procedures before the age of 13 years. Sleep apnea was present in 8 of 10 individuals. In the nine unrelated individuals, ZBTB7A variants were novel and de novo. The six frameshift/nonsense and four missense variants were spread throughout the gene. This is the first report of a cohort of individuals with this novel syndromic neurodevelopmental disorder.

Adult attention-deficit/hyperactivity disorder among alcohol use disorder inpatients is associated with food addiction and binge eating, but not BMI.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is associated with binge eating (BE), food addiction (FA), and obesity/higher BMI in individuals without alcohol use disorder (AUD). ADHD is highly prevalent in patients with AUD, but it is unknown whether the presence of comorbid AUD might change the nature of the association between ADHD, BE, FA and BMI (food and alcohol may either compete for the same brain neurocircuitry or share vulnerability risk factors). Here, we filled this gap by testing the association between ADHD and FA/BE in adult patients hospitalized for AUD, with the strength of simultaneously assessing childhood and adult ADHD. We also investigated the association between ADHD and BMI, and the other factors associated with BMI (FA/BE, AUD severity). METHODS: We included 149 AUD inpatients between November 2018 and April 2019. We assessed both childhood and adulthood ADHD (Wender Utah Render Scale and Adult ADHD Self-Report Scale), FA (modified Yale Food Addiction Scale 2.0), BE (Binge Eating Scale), and BMI and AUD (clinical assessment). RESULTS: In multivariable analyses adjusted for age, adult ADHD was associated with higher BE scores (p = .048), but not significant BE (9% vs. 7%; p = .70). ADHD was also associated with FA diagnosis and the number or FA symptoms, with larger effect size for adult (ORs: 9.45[95%CI: 2.82-31.74] and 1.38[1.13-1.69], respectively) than childhood ADHD (ORs: 4.45[1.37-14.46] and 1.40[1.13-1.75], respectively). In multivariable analysis, BMI was associated with both significant BE (p < .001) and FA diagnosis (p = .014), but not adult ADHD nor AUD severity. CONCLUSION: In patients hospitalized for AUD, self-reported adult ADHD was associated with FA and BE, but not BMI. Our results set the groundwork for longitudinal research on the link between ADHD, FA, BE, and BMI in AUD inpatients.

Autism spectrum disorder during French COVID-19 lockdown: The importance of individualized support.

AIM: This observational and repeated measures study assesses the impact of the first, most restrictive, COVID-19 lockdown in France on children with autism spectrum disorder (ASD) and their families. METHOD: During the first COVID-19 lockdown, families of ASD children enrolled in the day-care centre of the child and adolescent psychiatry department of the Tours University Hospital were contacted weekly. A total of 95 parents took part in this study between the 18th of March and the 8th of May 2020. Advice and personalized support materials were provided by professionals involved in children's care. Questions regarding clinical outcomes were addressed to parents, and their assessments were reported on a 5-point Likert scale. Two time points were considered: the first 3 weeks and the three last weeks of the lockdown period. RESULTS: No difference was highlighted between clinical scores collected at the beginning and at the end of the lockdown. No effect of intellectual disability, accommodation type (house or apartment) or parental status was observed. The reasons for the relatively minor impact of the COVID-19 lockdown observed in this study are discussed. CONCLUSIONS: Individualized and regular support provided by caregivers, familiar with ASD children's clinical specificities, in the context of a trusted relationship with parents may have contributed to the stability of this population. This 'tailor-made' approach should be promoted, in order to help support families of ASD children in this challenging period.

The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction.

PURPOSE: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. METHODS: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. RESULTS: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55α subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55α but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. CONCLUSION: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported.

The pupil: a window on social automatic processing in autism spectrum disorder children.

BACKGROUND: Faces are crucial social stimuli, eliciting automatic processing associated with increased physiological arousal in observers. The level of arousal can be indexed by pupil diameter (the 'Event-Related Pupil Dilation', ERPD). However, many parameters could influence the arousal evoked by a face and its social saliency (e.g. virtual vs. real, neutral vs. emotional, static vs. dynamic). A few studies have shown an atypical ERPD in autism spectrum disorder (ASD) patients using several kinds of faces but no study has focused on identifying which parameter of the stimulus is the most interfering with face processing in ASD. METHODS: In order to disentangle the influence of these parameters, we propose an original paradigm including stimuli along an ecological social saliency gradient: from static objects to virtual faces to dynamic emotional faces. This strategy was applied to 186 children (78 ASD and 108 typically developing (TD) children) in two pupillometric studies (22 ASD and 47 TD children in the study 1 and 56 ASD and 61 TD children in the study 2). RESULTS: Strikingly, the ERPD in ASD children is insensitive to any of the parameters tested: the ERPD was similar for objects, static faces or dynamic faces. On the opposite, the ERPD in TD children is sensitive to all the parameters tested: the humanoid, biological, dynamic and emotional quality of the stimuli. Moreover, ERPD had a good discriminative power between ASD and TD children: ASD had a larger ERPD than TD in response to virtual faces, while TD had a larger ERPD than ASD for dynamic faces. CONCLUSIONS: This novel approach evidences an abnormal physiological adjustment to socially relevant stimuli in ASD.

Ophthalmological findings in children with autism spectrum disorder.

PURPOSE: Eye pathology could be related to atypical visual behaviours and impaired social communication through visual cues in children with autism spectrum disorder (ASD). The main purpose of this prospective study was to assess ophthalmological disorders in children with ASD and to investigate the relationships with intellectual disability (ID) and ASD severity. METHODS: In this prospective study, comprehensive ophthalmological and oculomotor examinations were performed. ASD severity and verbal and performance intelligence quotients were determined using adapted scales. These clinical data were compared between groups of children based on the presence or absence of ophthalmological disorders and the achievement or not of visual acuity (VA) testing by using non-parametric statistical tests. RESULTS: Amongst a sample of 51 children, ophthalmological disorders were found in 39% of cases, with 35% having significant refractive errors and 10% presenting with strabismus. Children with ASD and ophthalmological disorders had significantly lower verbal (29.8 ± 14.7 compared with 44.3 ± 21.5; p = 0.010) and performance quotients (57.8 ± 18.3 compared with 67.59 ± 20; p = 0.049) but no significant result was found between the presence of ophthalmological disorders and ASD severity, level of communication and social contact, or modulating behaviour when changes occur. Children who did not achieve monocular VA testing (39%) had significantly lower verbal (25.1 ± 9.7 compared with 46.1 ± 20.9; p < 0.001) and performance quotients (52.7 ± 17 compared with 69.8 ± 18.8; p = 0.001), also presented higher social interaction impairment (p = 0.002), and expressed more important behavioural signs (p = 0.007). CONCLUSIONS: Ophthalmological disorders are frequently found in children with ASD, especially in those with ID. Ophthalmologists and child psychiatrists should pay attention to perform ophthalmological examination in children with ASD since eye disorders might remain undetected. A comprehensive examination by a paediatric ophthalmologist would help to improve the individual clinical description and the global intervention. TRIAL REGISTRATION: Clinical trial registration number: NCT02444117.

Inflexibility in Autism Spectrum Disorder: Need for certainty and atypical emotion processing share the blame.

Although ASD (Autism Spectrum Disorder) diagnosis requires the co-occurrence of socio-emotional deficits and inflexible behaviors, the interaction between these two domains remains unexplored. We used an emotional Wisconsin Card Sorting Test adapted to fMRI to explore this question. ASD and control participants matched a central card (a face) with one of four surrounding cards according to one of three rules: frame color, facial identity or expression. Feedback informed participants on whether to change or maintain the current sorting rule. For each rule, we modeled feedback onsets to change, switch (confirming the newly found rule) and maintenance events. "Bias error", which measures participants' willingness to switch, was larger in ASD participants for the emotional sorting rule. Brain activity to change events showed no group differences. In response to switch events significantly larger activity was observed for ASD participants in bilateral Inferior Parietal Sulci. Inflexibility in ASD appears characterized by the unwillingness to switch toward processing socio-emotional information, rather than a major disruption in cognitive flexibility. However, a larger activity to switch events in ASD highlights the need for a higher level of certainty before setting into a stable processing stage, which may be particularly detrimental in the highly changeable socio-emotional environment.

Brain mechanisms involved in angry prosody change detection in school-age children and adults, revealed by electrophysiology.

Voices transmit social signals through speech and/or prosody. Emotional prosody conveys key information about the emotional state of a speaker and is thus a crucial cue that one has to detect in order to develop efficient social communication. Previous studies in adults reported different brain responses to emotional than to neutral prosodic deviancy. The aim of this study was to characterize such specific emotional deviancy effects in school-age children. The mismatch negativity (MMN) and P3a evoked potentials, reflecting automatic change detection and automatic attention orienting, respectively, were obtained for neutral and emotional angry deviants in both school-age children (n = 26) and adults (n = 14). Shorter latencies were found for emotional than for neutral preattentional responses in both groups. However, whereas this effect was observed on the MMN in adults, it appeared in an early discriminative negativity preceding the MMN in children. A smaller P3a amplitude was observed for the emotional than for the neutral deviants at all ages. Overall, the brain responses involved in specific emotional change processing are already present during childhood, but responses have not yet reached an adult pattern. We suggest that these processing differences might contribute to the known improvement of emotional prosody perception between childhood and adulthood.

Disrupted behaviour in grammatical morphology in French speakers with autism spectrum disorders.

Mixed and inconsistent findings have been reported across languages concerning grammatical morphology in speakers with Autism Spectrum Disorders (ASD). Some researchers argue for a selective sparing of grammar whereas others claim to have identified grammatical deficits. The present study aimed to investigate this issue in 26 participants with ASD speaking European French who were matched on age, gender and SES to 26 participants with typical development (TD). The groups were compared regarding their productivity and accuracy of syntactic and agreement categories using the French MOR part-of-speech tagger available from the CHILDES. The groups significantly differed in productivity with respect to nouns, adjectives, determiners, prepositions and gender markers. Error analysis revealed that ASD speakers exhibited a disrupted behaviour in grammatical morphology. They made gender, tense and preposition errors and they omitted determiners and pronouns in nominal and verbal contexts. ASD speakers may have a reduced sensitivity to perceiving and processing the distributional structure of syntactic categories when producing grammatical morphemes and agreement categories. The theoretical and cross-linguistic implications of these findings are discussed.

Impaired Facilitatory Mechanisms of Auditory Attention After Damage of the Lateral Prefrontal Cortex.

There is growing evidence that auditory selective attention operates via distinct facilitatory and inhibitory mechanisms enabling selective enhancement and suppression of sound processing, respectively. The lateral prefrontal cortex (LPFC) plays a crucial role in the top-down control of selective attention. However, whether the LPFC controls facilitatory, inhibitory, or both attentional mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in patients with LPFC damage, by comparing event-related potentials (ERPs) to attended and ignored sounds with ERPs to these same sounds when attention was equally distributed to all sounds. In control subjects, we observed 2 late frontally distributed ERP components: a transient facilitatory component occurring from 150 to 250 ms after sound onset; and an inhibitory component onsetting at 250 ms. Only the facilitatory component was affected in patients with LPFC damage: this component was absent when attending to sounds delivered in the ear contralateral to the lesion, with the most prominent decreases observed over the damaged brain regions. These findings have 2 important implications: (i) they provide evidence for functionally distinct facilitatory and inhibitory mechanisms supporting late auditory selective attention; (ii) they show that the LPFC is involved in the control of the facilitatory mechanisms of auditory attention.

Eye Movement Monitoring and Maturation of Human Face Exploration.

OBJECTIVE: The aim of this study was to characterize ocular exploration of neutral and emotional faces in the typical development of a child. SUBJECTS AND METHOD: In this eye-tracking study, visual exploration of faces (with neutral or emotional expressions: happiness or sadness) was characterized in a population of 52 children (24 girls and 28 boys from 4 to 15 years of age) and 44 adults (22 women and 22 men from 18 to 35 years of age). The time spent on the eyes, nose and mouth of the faces was measured. RESULTS: All participants spent more time on the eyes (13%) rather than the nose and mouth (6%). The youngest participants spent less time exploring the eyes than the older participants, suggesting the progressive establishment of interest in these informative regions of the face during maturation. This process seemed to occur later in females (7-9 years) than males (4-6 years). CONCLUSION: These results confirm the importance of the eye area and the capacity of this region to capture attention. In addition, this study shows that the exploration of this region increases with age and is lower among girls aged 4-6 years compared with boys of the same age.

Metabolomics Study of Urine in Autism Spectrum Disorders Using a Multiplatform Analytical Methodology.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with no clinical biomarker. The aims of this study were to characterize a metabolic signature of ASD and to evaluate multiplatform analytical methodologies in order to develop predictive tools for diagnosis and disease follow-up. Urine samples were analyzed using (1)H and (1)H-(13)C NMR-based approaches and LC-HRMS-based approaches (ESI+ and ESI- on HILIC and C18 chromatography columns). Data tables obtained from the six analytical modalities on a training set of 46 urine samples (22 autistic children and 24 controls) were processed by multivariate analysis (orthogonal partial least-squares discriminant analysis, OPLS-DA). The predictions from each of these OPLS-DA models were then evaluated using a prediction set of 16 samples (8 autistic children and 8 controls) and receiver operating characteristic curves. Thereafter, a data fusion block-scaling OPLS-DA model was generated from the 6 best models obtained for each modality. This fused OPLS-DA model showed an enhanced performance (R(2)Y(cum) = 0.88, Q(2)(cum) = 0.75) compared to each analytical modality model, as well as a better predictive capacity (AUC = 0.91, p-value = 0.006). Metabolites that are most significantly different between autistic and control children (p < 0.05) are indoxyl sulfate, N-α-acetyl-l-arginine, methyl guanidine, and phenylacetylglutamine. This multimodality approach has the potential to contribute to find robust biomarkers and characterize a metabolic phenotype of the ASD population.

Event-related potential and eye tracking evidence of the developmental dynamics of face processing.

Although the wide neural network and specific processes related to faces have been revealed, the process by which face-processing ability develops remains unclear. An interest in faces appears early in infancy, and developmental findings to date have suggested a long maturation process of the mechanisms involved in face processing. These developmental changes may be supported by the acquisition of more efficient strategies to process faces (theory of expertise) and by the maturation of the face neural network identified in adults. This study aimed to clarify the link between event-related potential (ERP) development in response to faces and the behavioral changes in the way faces are scanned throughout childhood. Twenty-six young children (4-10 years of age) were included in two experimental paradigms, the first exploring ERPs during face processing, the second investigating the visual exploration of faces using an eye-tracking system. The results confirmed significant age-related changes in visual ERPs (P1, N170 and P2). Moreover, an increased interest in the eye region and an attentional shift from the mouth to the eyes were also revealed. The proportion of early fixations on the eye region was correlated with N170 and P2 characteristics, highlighting a link between the development of ERPs and gaze behavior. We suggest that these overall developmental dynamics may be sustained by a gradual, experience-dependent specialization in face processing (i.e. acquisition of face expertise), which produces a more automatic and efficient network associated with effortless identification of faces, and allows the emergence of human-specific social and communication skills.

Combined 1H-NMR and 1H-13C HSQC-NMR to improve urinary screening in autism spectrum disorders.

Autism spectrum disorders (ASD) are neurodevelopmental diseases with complex genetic and environmental etiological factors. Although genetic causes play a significant part in the etiology of ASD, metabolic disturbances may also play a causal role or modulate the clinical features of ASD. The number of ASD studies involving metabolomics is increasing, and sometime with conflicting findings. We assessed the metabolomics profiling of urine samples to determine a comprehensive biochemical signature of ASD. Furthermore, to date no study has combined metabolic profiles obtained from different analytical techniques to distinguish patient with ASD from healthy individuals. We obtained (1)H-NMR spectra and 2D (1)H-(13)C HSQC NMR spectra from urine samples of patients with ASD or healthy controls. We analyzed these spectra by multivariate statistical data analysis. The OPLS-DA model obtained from (1)H NMR spectra showed a good discrimination between ASD samples and non-ASD samples (R(2)Y(cum) = 0.70 and Q(2) = 0.51). Combining the (1)H NMR spectra and the 2D (1)H-(13)C HSQC NMR spectra increased the overall quality and predictive value of the OPLS-DA model (R(2)Y(cum) = 0.84 and Q(2) = 0.71), leading to a better sensitivity and specificity. Urinary excretion of succinate, glutamate and 3-methyl-histidine differed significantly between ASD and non-ASD samples. Urinary screening of children with neurodevelopmental disorders by combining NMR spectroscopies (1D and 2D) in multivariate analysis is a better sensitive and a straightforward method that could help the diagnosis ASD.

Gender identity disorder and autism spectrum disorder in a 23-year-old female.

We describe the case of a 23-year-old woman with Gender Identity Disorder (GID) asking for a cross-sex hormonal treatment with sex reassignment surgery and who was recently diagnosed with Autism Spectrum Disorder (ASD). Gender identity clinics are now reporting an overrepresentation of individuals with ASD among GID patients. The prevalence of ASD is 10-fold higher among GID patients than in general population. However, few case reports or studies have explored the co-occurrence of ASD and GID. This co-occurrence is relevant for diagnostic and clinical management and also raises important theoretical issues.

Cranio-Facial Characteristics in Autism Spectrum Disorder: A Scoping Review.

Autism spectrum disorders (ASD) consist of a complex group of neurodevelopmental disorders characterised by qualitative impairments of social interactions, communication abilities, and a limited, stereotyped, and repetitive selection of interests and activities. In light of the imperative to identify a possible biomarker for ASD, it has been determined that craniofacial anomalies serve as significant risk factors for neurodevelopmental disorders. The aim of this scoping review is to deepen the knowledge of the scientific literature related to cranio-facial characteristics in individuals with ASD, with a particular focus on recent research advancements. The review was performed by employing the search strings (("Autism Spectrum Disorder" OR autism OR ASD OR "Autism Spectrum") AND ("facial morphology" OR "facial phenotype")) on the databases PubMed/MEDLINE, Scopus, and ERIC as of March 9, 2023. The review comprised seven studies whose findings were obtained through quantitative analysis of Euclidean distances between anatomical landmarks. The examination of facial abnormalities represents a possible reliable diagnostic biomarker that could aid in the timely identification of ASD. Phenotypic characteristics that may serve as predictive indicators of the severity of autistic symptoms can be observed in certain individuals with ASD by applying anthropometric and instrumental measurements. The presence of a phenotype characterised by an increased intercanthal distance and a reduced facial midline height appears to be associated with a higher degree of severity in autistic symptoms. In addition, it is worth noting that facial asymmetry and facial masculinity can be considered reliable indicators for predicting a more severe manifestation of symptoms.

GC-MS-based urine metabolic profiling of autism spectrum disorders.

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders resulting from multiple factors. Diagnosis is based on behavioural and developmental signs detected before 3 years of age, and there is no reliable biological marker. The purpose of this study was to evaluate the value of gas chromatography combined with mass spectroscopy (GC-MS) associated with multivariate statistical modeling to capture the global biochemical signature of autistic individuals. GC-MS urinary metabolic profiles of 26 autistic and 24 healthy children were obtained by liq/liq extraction, and were or were not subjected to an oximation step, and then were subjected to a persilylation step. These metabolic profiles were then processed by multivariate analysis, in particular orthogonal partial least-squares discriminant analysis (OPLS-DA, R(2)Y(cum) = 0.97, Q(2)(cum) = 0.88). Discriminating metabolites were identified. The relative concentrations of the succinate and glycolate were higher for autistic than healthy children, whereas those of hippurate, 3-hydroxyphenylacetate, vanillylhydracrylate, 3-hydroxyhippurate, 4-hydroxyphenyl-2-hydroxyacetate, 1H-indole-3-acetate, phosphate, palmitate, stearate, and 3-methyladipate were lower. Eight other metabolites, which were not identified but characterized by a retention time plus a quantifier and its qualifier ion masses, were found to differ between the two groups. Comparison of statistical models leads to the conclusion that the combination of data obtained from both derivatization techniques leads to the model best discriminating between autistic and healthy groups of children.

My voice or yours? An electrophysiological study.

This study examined the neural processes underlying own voice discrimination using electrophysiological methods. Event-related potentials were recorded while healthy subjects (n = 17) heard passively three oddball sequences composed of recordings of the French vowel/a/pronounced either by the participant her/himself or by two unknown persons. The results indicated that, although the mismatch negativity (MMN) displayed similar peak latency and amplitude in both conditions, the subsequent P3a clearly distinguished the two conditions since its amplitude was significantly smaller for own voice discrimination than for that of unknown voices. Moreover, the own voice discriminative response was associated with an early pre-MMN response. This early response involved a left inferior frontal component, the activity of which lasted throughout the time course of the discriminative response, which included both MMN and P3a.