[The BSE2 scale : A new clinical tool for the diagnostic of ASD within NDDs]. / L'échelle ECA2 : un nouvel outil clinique pour le diagnostic du TSA au sein des TND.

OBJECTIVES: The behavioral summarized evaluation scales, the BSE and its revised version the BSE-R, were developed and validated in the 1980-1990s. The BSE-R is still used daily by clinical teams in France and foreign countries, and it is recommended by the French Health Authority (2018). Having taken into account knowledge improvement in neurodevelopment and autism spectrum disorder (ASD) and the importance of observation by relatives in ecological context, the second version of the BSE was developed. This paper presents the construction and the validation study of the second version of the behavioral summarized evaluation scale, the BSE2 and the BSE2-P rated by parents. METHODS: Construct validity of the BSE2 scale has been studied in a population of 244 children and adolescents with ASD according to DSM-5 criteria, aged from 30 months to 18 years. Discriminant validity has been analyzed using a population of 86 patients of the same age, with neurodevelopmental disorder (NDD) without comorbidity of ASD. RESULTS: BSE2 comprises 30 items and is a two-dimensional scale as was BSE-R. Both dimensions, labelled "Interaction" (11 items) and "Modulation" (11 items), accounted for 41.7 % of the total variance. They describe autism severity and are in accordance with the two DSM-5 dimensions. Internal consistency (0.927 and 0.850 respectively) and inter-rater reliability (0.932 and 0.897 respectively) are good or excellent for both dimensions. Sensibility and specificity (0.758 and 0.767 respectively) range BSE2 among the tools with good psychometric properties. The parent version, BSE2-P, dedicated to ecological context is easily rated by parents. CONCLUSIONS: BSE2 scale for children and adolescents is a clinical tool with good psychometric properties. Its two-dimensional structure is in accordance with DSM-5 criteria. This scale covers all spectrum of ASD clinical forms in both children and adolescents. It can be used to identify ASD in complex neurodevelopmental disorders with several comorbidities and can help to distinguish autism symptomatology from other neurodevelopmental diagnoses. Furthermore, this scale allows to expand the rating context, involving parents to define and adjust the individualized therapeutic project. Thus the BSE2 is a valuable clinical tool for practitioners for both diagnosis and follow-up.

Demographic, clinical, and service-use characteristics related to the clinician's recommendation to transition from child to adult mental health services.

PURPOSE: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians' advice to continue treatment at AMHS. METHODS: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians' transition recommendations. RESULTS: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. CONCLUSION: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services.

[GABAergic approach of postpartum depression: A translational review of literature]. / Approche GABAergique de la dépression du post-partum : une revue critique translationnelle.

INTRODUCTION: Prevalence of postpartum depression (PPD) ranges from 10 to 15 % of parturients. The impact of the PPD is major on the maternal bond and the health of both mother and child. Its physiopathological mechanisms appear to differ from other types of depression. Today, pharmacotherapy is based on nonspecific treatment, and recent therapeutic advances in this field require a comprehensive approach of the implication of the GABAergic system in the development of PPD. Neurosteroid levels during pregnancy and after parturition and the GABA-A-r modulation are thought to be involved in PPD. OBJECTIVE: To evaluate if the GABAergic approach is relevant in postpartum depression management. METHODS: We conducted a systematic review of literature based on the MEDLINE database with the following Medical Subject Headings (MeSH): "postpartum depression", "GABA", "ganaxolone", "brexanolone", "allopregnanolone", prior to September 2019. We selected articles in English: preclinical and clinical studies, literature review, observational and therapeutic studies. RESULTS: Preclinical models (mouse and rat) show changes in GABAergic inhibition in the peripartum period and correlation between allopregnanolone and GABA-A-r plasticity. This plasticity in the peripartum period maintains levels of inhibition adapted despite increased neurosteroid levels. KO models for the GABA-A-r δ subunit develop depression and anxiety symptoms in the postpartum period, and a change in the expression of the gene coding for the GABA-R alpha-4 subunit was found. Artificial inhibition of progesterone metabolism during post-partum increased depression symptoms. GABAergic fluctuation seems to be interrelated with other systems such as those of oxytocins. A synthetic neurosteroid (SGE-516) was tested on mouse models of PPD, KO for δ-GABA-A-r or KCC2, and showed decreased depressive symptoms and better mothering. Clinical studies confirm neurosteroid fluctuation and changes in the GABAergic system during the peripartum period. Allopregnanolone is the neurosteroid the most studied in PPD, and it is elevated in the brain during the pregnancy. Studies disagree on the presence of significant differences in allopregnanolone plasma levels during pregnancy or postpartum between women with PPD or not. Women with a history of PPD have greater susceptibility to neurosteroid withdrawal. Imagery and genetical data also show a link between allopregnanolone and PPD. The GABA-A-r may not recover in time following a reduced number during pregnancy, and this mismatch between neurosteroid levels and their receptor may trigger PPD. Several randomized controlled trials investigated brexanolone administrated IV, a synthetic formulation of allopregnanolone, and demonstrated a rapid and well tolerated reduction in depressive symptoms. In March 2019 brexanolone obtained FDA approval in PPD indication under the name Zulresso. However, there are differences in the time of beginning of PPD, which could constitute different subgroups of this disease, and which physiopathology could respond to different mechanisms. Prenatal depression does not respond to a GABAergic approach, but women without any risk factor or previous mood disorder developing PPD in the weeks following childbirth could be particularly responsive to this kind of treatment. CONCLUSION: Disability to modulate GABA-A-r expression during pregnancy and restore its previous state after parturition appears to trigger PPD. The GABAergic system is a promising pharmacotherapy target. From preclinical to clinical studies for about twenty years the GABAergic system has been incriminated and targeted in this challenging mental disease.

[Sensory-psychomotor evaluation in Autism: A new tool for functional diagnosis]. / L'évaluation sensori-psychomotrice dans l'autisme : un nouvel outil d'aide au diagnostic fonctionnel.

INTRODUCTION: Psychomotor impairments in Autism Spectrum Disorders (ASD) have frequently been described in scientific literature. Such deficits impact upon the development of social motor function and interfere with the ability to adjust to everyday life. The inclusion of sensory-motor signs in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) confirms their importance in the diagnosis of ASD. Previous literature has shown the presence precocity of these signs, sometimes before the alteration of the social communication. To our knowledge, there are no existing clinical tools to measure sensory-psychomotor deficit, specifically in ASD. The current paper presents the construction and validation of a new scale, designed to evaluate sensory-psychomotor signs in Autism: 'the Sensory-psychomotor Particularities Scale in Autism' (SPSA). METHOD: The scale is composed of 160 items describing common sensory-psychomotor signs in autism. These items are grouped into 20 variables: touch, nociception, vestibular sensitivity, proprioceptive sensitivity, vision, auditory, multimodality, tone, posture, balance, global coordination, manual dexterity, body schema, bodily self-consciousness, relational adjustment, emotional expression, use of objects, space, time and tonico-emotional regulation. For each item, the psychomotor therapist evaluated sensori-psychomotor signs according to a five-level Likert scale (0="the sign is never expressed by the person", 1="weakly expressed", 2="moderately expressed", 3="severely expressed" and 4="the sign is very characteristic of the person and very severely expressed"). This is completed by a family interview in order to assess the impact of these signs on everyday situations. The study included 111 children with autism. The presence of neurological and genetic diseases was exclusion criteria. For each child, a global developmental evaluation was carried out by an expert clinical team specializing in ASD. Standardized clinical tools were used: Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), Behavior Summarized Evaluation scale (BSE-R), Repeated and Restricted Behavior scale (RRB), Movement Assessment Battery for Children (M-ABC), Motor Development Rating scale (MDR), Sensory Profile (SP). Developmental quotients (DQ) were evaluated using various tests depending on age and ability. RESULTS: Factor analysis produced three clinically relevant factors: F1: "sensory-emotional synchronization", F2: "multisensory integration" and F3: "motor skills": each containing a similar quantity of items. They account for roughly equal percentages of variance (18.9%, 18.0%, 16.8%, respectively). The factorial structure does not change if the 26 children with comorbid developmental coordination disorder are removed. The three factors show good internal consistency and excellent inter-rater reliability. F1 is comprised of 6 items: touch, nociception, proprioceptive sensitivity, vision, emotional expression and tonico-emotional regulation. This factor is significantly associated with items of the Sensory Profile (touch processing, poor registration, sensory seeking). F2 is comprised of 5 items: multimodality, bodily self-consciousness, relational adjustment, use of objects and space. This factor is associated with ADOS, BSE-R and RRB scores, and the item "touch processing" of the Sensory Profile. F3 is comprised of 4 items: tone, posture, global coordination, manual dexterity. This factor is associated with the M-ABC, the MDR and the item "low endurance" of the Sensory Profile. CONCLUSION: The SPSA is a relevant clinical tool to assess the severity of sensory-psychomotor clinical signs in order to describe the individual profiles of children with ASD. It represents a critical step in advancing knowledge of the complex and heterogeneous pattern of psychomotor development in autism. It could make a valuable contribution to the field, both in research and clinical practice.

Emotional prosodic change detection in autism Spectrum disorder: an electrophysiological investigation in children and adults.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by atypical behaviors in social environments and in reaction to changing events. While this dyad of symptoms is at the core of the pathology along with atypical sensory behaviors, most studies have investigated only one dimension. A focus on the sameness dimension has shown that intolerance to change is related to an atypical pre-attentional detection of irregularity. In the present study, we addressed the same process in response to emotional change in order to evaluate the interplay between alterations of change detection and socio-emotional processing in children and adults with autism. METHODS: Brain responses to neutral and emotional prosodic deviancies (mismatch negativity (MMN) and P3a, reflecting change detection and orientation of attention toward change, respectively) were recorded in children and adults with autism and in controls. Comparison of neutral and emotional conditions allowed distinguishing between general deviancy and emotional deviancy effects. Moreover, brain responses to the same neutral and emotional stimuli were recorded when they were not deviants to evaluate the sensory processing of these vocal stimuli. RESULTS: In controls, change detection was modulated by prosody: in children, this was characterized by a lateralization of emotional MMN to the right hemisphere, and in adults, by an earlier MMN for emotional deviancy than for neutral deviancy. In ASD, an overall atypical change detection was observed with an earlier MMN and a larger P3a compared to controls suggesting an unusual pre-attentional orientation toward any changes in the auditory environment. Moreover, in children with autism, deviancy detection depicted reduced MMN amplitude. In addition in children with autism, contrary to adults with autism, no modulation of the MMN by prosody was present and sensory processing of both neutral and emotional vocal stimuli appeared atypical. CONCLUSIONS: Overall, change detection remains altered in people with autism. However, differences between children and adults with ASD evidence a trend toward normalization of vocal processing and of the automatic detection of emotion deviancy with age.

Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder.

Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology.

[Autism: An early neurodevelopmental disorder]. / L'autisme : un trouble neuro-développemental précoce.

With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation.

Brief Report: Early VEPs to Pattern-Reversal in Adolescents and Adults with Autism.

Autism spectrum disorder (ASD) is characterized by atypical visual perception both in the social and nonsocial domain. In order to measure a reliable visual response, visual evoked potentials were recorded during a passive pattern-reversal stimulation in adolescents and adults with and without ASD. While the present results show the same age-related changes in both autistic and non-autistic groups, they reveal a smaller P100 amplitude in the ASD group compared to controls. These results confirm that early visual responses are affected in ASD even with a simple, non social and passive stimulation and suggest that they should be considered in order to better understand higher-level processes.

GABA/Glutamate synaptic pathways targeted by integrative genomic and electrophysiological explorations distinguish autism from intellectual disability.

Phenotypic and genetic heterogeneity is predominant in autism spectrum disorders (ASD), for which the molecular and pathophysiological bases are still unclear. Significant comorbidity and genetic overlap between ASD and other neurodevelopmental disorders are also well established. However, little is understood regarding the frequent observation of a wide phenotypic spectrum associated with deleterious mutations affecting a single gene even within multiplex families. We performed a clinical, neurophysiological (in vivo electroencephalography-auditory-evoked related potentials) and genetic (whole-exome sequencing) follow-up analysis of two families with known deleterious NLGN4X gene mutations (either truncating or overexpressing) present in individuals with ASD and/or with intellectual disability (ID). Complete phenotypic evaluation of the pedigrees in the ASD individuals showed common specific autistic behavioural features and neurophysiological patterns (abnormal MisMatch Negativity in response to auditory change) that were absent in healthy parents as well as in family members with isolated ID. Whole-exome sequencing in ASD patients from each family identified a second rare inherited genetic variant, affecting either the GLRB or the ANK3 genes encoding NLGN4X interacting proteins expressed in inhibitory or in excitatory synapses, respectively. The GRLB and ANK3 mutations were absent in relatives with ID as well as in control databases. In summary, our findings provide evidence of a double-hit genetic model focused on excitatory/inhibitory synapses in ASD, that is not found in isolated ID, associated with an atypical in vivo neurophysiological pattern linked to predictive coding.

[Theoretical and practical aspects of cognitive remediation in intellectual disabilities: Relevance of the Cognitive Remediation Therapy program (CRT)]. / Aspects théoriques et pratiques de la remédiation cognitive dans la déficience intellectuelle du jeune adulte : La « Cognitive Remediation Therapy ¼ (CRT) peut-elle être adaptée ?

INTRODUCTION: Teenagers and adults with intellectual disabilities are nowadays "over-handicapped", often due to lack of care in self-sufficiency and continued learning, two essential domains for living in a community. Their cognitive limits, particularly on the executive functions, could be an obstacle to their involvement in the daily life activities, through their difficulties to plan, anticipate, shift and maintain information in working memory. These high level mental functions can be taught with the CRT program (Cognitive Remediation Therapy - Wykes and Reader 2005) developed in other pathologies and providing an adaptation regarding the developmental level of the person. METHODS: Firstly, it is essential to determine cognitive developmental levels of the teenager or the adult, using standard tools, such as Wechsler scales. Secondly, functional and/or adaptative levels have to be assessed using specific tools, such as the Vineland Adaptative Behavior Scale 2nd Edition (VABS-II, Sparrow et al., 2005) and the Functional Intervention Scale (EFI, Willaye et al., 2005). Finally, in order to clearly distinguish what are the preserved and impaired cognitive domains, standard tools assessing executive functions such as the Wisconsin Card Sorting Test, the Tower of London, Stroop Test and BADS are used if possible for the patient. The setting of cognitive remediation programs, previously developed for schizophrenic patients, requires adaptation for teenagers and adults with intellectual disabilities, taking into account the limitation of their cognitive abilities. In this paper, we will show that the CRT method for cognitive remediation is particularly relevant for subjects with intellectual disabilities. This method is hence focused on strategies and exercises to improve working memory, categorization and moreover executive functions. Of course this method might need adaptations, with examples based on simplification of the different tasks, notably for verbal materials, and with variations of the media used. These sessions will be part of a wider individualized caring project, allowing the person to transfer the cognitive acquisitions to his/her daily life. CONCLUSION: The use of cognitive programs adapted to people with intellectual disabilities can provide benefits in the development of autonomy and daily life activities, leading to a better quality of life and self-esteem.

Identification of Nine New RAI1-Truncating Mutations in Smith-Magenis Syndrome Patients without 17p11.2 Deletions.

Smith-Magenis syndrome (SMS) is an intellectual disability syndrome with sleep disturbance, self-injurious behaviors and dysmorphic features. It is estimated to occur in 1/25,000 births, and in 90% of cases it is associated with interstitial deletions of chromosome 17p11.2. RAI1 (retinoic acid induced 1; OMIM 607642) mutations are the second most frequent molecular etiology, with this gene being located in the SMS locus at 17p11.2. Here, we report 9 new RAI1-truncating mutations in nonrelated individuals referred for molecular analysis due to a possible SMS diagnosis. None of these patients carried a 17p11.2 deletion. The 9 mutations include 2 nonsense mutations and 7 heterozygous frameshift mutations leading to protein truncation. All mutations map in exon 3 of RAI1 which codes for more than 98% of the protein. RAI1 regulates gene transcription, and its targets are themselves involved in transcriptional regulation, cell growth and cell cycle regulation, bone and skeletal development, lipid and glucide metabolisms, neurological development, behavioral functions, and circadian activity. We report the clinical features of the patients carrying these deleterious mutations in comparison with those of patients carrying 17p11.2 deletions.

fMRI investigation of visual change detection in adults with autism.

People with autism spectrum disorders (ASD) may show unusual reactions to unexpected changes that appear in their environment. Although several studies have highlighted atypical auditory change processing in ASD, little is known in this disorder about the brain processes involved in visual automatic change detection. The present fMRI study was designed to localize brain activity elicited by unexpected visual changing stimuli in adults with ASD compared to controls. Twelve patients with ASD and 17 healthy adults participated in the experiment in which subjects were presented with a visual oddball sequence while performing a concurrent target detection task. Combined results across participants highlight the involvement of both occipital (BA 18/19) and frontal (BA 6/8) regions during visual change detection. However, adults with ASD display greater activity in the bilateral occipital cortex and in the anterior cingulate cortex (ACC) associated with smaller activation in the superior and middle frontal gyri than controls. A psychophysiological interaction (PPI) analysis was performed with ACC as the seed region and revealed greater functionally connectivity to sensory regions in ASD than in controls, but less connectivity to prefrontal and orbito-frontal cortices. Thus, compared to controls, larger sensory activation associated with reduced frontal activation was seen in ASD during automatic visual change detection. Atypical psychophysiological interactions between frontal and occipital regions were also found, congruent with the idea of atypical connectivity between these regions in ASD. The atypical involvement of the ACC in visual change detection can be related to abnormalities previously observed in the auditory modality, thus supporting the hypothesis of an altered general mechanism of change detection in patients with ASD that would underlie their unusual reaction to change.

Cerebral functional asymmetry and phonological performance in dyslexic adults.

Developmental dyslexia is a frequent language-based learning disorder characterized by difficulty in reading. The predominant etiologic view postulates that reading impairment is related to phonological and orthographic dysfunction. The aim of this fMRI study was to evaluate the neural bases of phonological processing impairment in remediated dyslexic adults (DD). We used a rhyming words judgment task contrasted with an unreadable fonts font-matching judgment task to compare patterns of activation and functional asymmetry in DD and normal-reading young adults. We found evidence of a link between asymmetry in inferior frontal gyrus and performance during the phonological processing. We also observed that DD recruit a network including regions involved in articulatory control in order to achieve rhyme judgment suggesting that, due to a lack of hemispheric specialization, DD recruit the latter network to achieve rhyme judgment.

Electrophysiological evidence of atypical visual change detection in adults with autism.

Although atypical change detection processes have been highlighted in the auditory modality in autism spectrum disorder (ASD), little is known about these processes in the visual modality. The aim of the present study was therefore to investigate visual change detection in adults with ASD, taking into account the salience of change, in order to determine whether this ability is affected in this disorder. Thirteen adults with ASD and 13 controls were presented with a passive visual three stimuli oddball paradigm. The findings revealed atypical visual change processing in ASD. Whereas controls displayed a vMMN in response to deviant and a novelty P3 in response to novel stimuli, patients with ASD displayed a novelty P3 in response to both deviant and novel stimuli. These results thus suggested atypical orientation of attention toward unattended minor changes in ASD that might contribute to the intolerance of change.

Discrimination between biological motion with and without social intention: a pilot study using visual scanning in healthy adults.

Human beings have a detailed understanding of others' action and body language allowing them to adapt their behaviour for effective social interaction. A proper selection of human motion deserving a social intention over the many human motion surrounding them may be executed by overt visual-spatial attention. The aim of this study was to characterize eye movements in 32 healthy adults while exploring Social and Non-social human biological motion using an eye tracking method according to two paradigms. The "preferential looking paradigm" revealed that the first fixation is more often on the Non-social Motion than Social Motion but the first fixations duration are longer on Social Motion. Moreover, with the same paradigm, subjects spent a greater looking time percentage on Social Motion than Non-social Motion, no matter whether discrimination between categories was asked for or not. In the "blocks paradigm" the looking time percentage varied by the body parts (chests, pelvis and legs) and its distribution was different between categories. Eye movements revealed a spontaneous, fast and durable bias of overt visual-spatial attention favouring the perception of Social Motion and a different visual scanpath for Social compared to Non-social human biological motion. These findings constitute a basis for the investigation of a 'social intention' bias in perception of human biological motion.

Xq27 FRAXA locus is a strong candidate for dyslexia: evidence from a genome-wide scan in French families.

Dyslexia is a frequent neurodevelopmental learning disorder. To date, nine susceptibility loci have been identified, one of them being DYX9, located in Xq27. We performed the first French SNP linkage study followed by candidate gene investigation in dyslexia by studying 12 multiplex families (58 subjects) with at least two children affected, according to categorical restrictive criteria for phenotype definition. Significant results emerged on Xq27.3 within DYX9. The maximum multipoint LOD score reached 3,884 between rs12558359 and rs454992. Within this region, seven candidate genes were investigated for mutations in exonic sequences (CXORF1, CXORF51, SLITRK2, FMR1, FMR2, ASFMR1, FMR1NB), all having a role during brain development. We further looked for 5'UTR trinucleotide repeats in FMR1 and FMR2 genes. No mutation or polymorphism co-segregating with dyslexia was found. This finding in French families with Dyslexia showed significant linkage on Xq27.3 enclosing FRAXA, and consequently confirmed the DYX9 region as a robust susceptibility locus. We reduced the previously described interval from 6.8 (DXS1227-DXS8091) to 4 Mb also disclosing a higher LOD score.

Minimization of cochlear implant artifact in cortical auditory evoked potentials in children.

OBJECTIVES: In congenitally deaf children fit with a cochlear implant, little is known about the maturation of the auditory cortex. Cortical auditory evoked potentials are a useful methodology to study the auditory cortical system of children with cochlear implants. Nevertheless, these recordings are contaminated by a cochlear implant artifact. The objective of this study was to use independent component analysis to minimize the artifact of the cochlear implant to study cortical auditory evoked potentials. STUDY DESIGN: Prospective study. METHOD: A total of 5 children ranging in age from 21 to 49 months who were fitted with a cochlear implant for at least 6 months were included in this study. The stimuli were pure tones (750 Hz, 200 ms duration, 70 dB SPL) presented with an irregular interstimulus interval (1000-2000 ms) via loud speakers. The cortical auditory evoked potentials were recorded from 17 Ag-AgCl electrodes referenced to the nose. The peak latency and amplitude of each deflection culminating at the fronto-central and temporal sites were analyzed. MAIN OUTCOME MEASURES: The P100-N250 peak latencies and amplitudes of the cortical auditory evoked potentials recorded from children fitted with cochlear implants. Scalp map potentials distributions were done for each child for the N250 wave. RESULTS: The use of independent component analysis permitted to minimize the cochlear implant artifact for the five children. Cortical auditory evoked potentials were recorded at fronto-central and temporal sites. Scalp map potentials distributions for the N2 wave showed activation of temporal generators contralateral at the CI for the five children. CONCLUSION: This preliminary electrophysiological study confirms the value and the limits of independent component analysis. It could allow longitudinal studies in cochlear implant users to examine the maturation of auditory cortex. It could also be used to identify objective cortical electrophysiological measures to help the fitting of CIs in children.

Functional morphological imaging of autism spectrum disorders: current position and theories proposed.

Autism is a pervasive disorder of childhood development. Polymorphous clinical profiles combining various degrees of communication and social interaction with restricted and stereotyped behaviour are grouped under the heading of 'autism spectrum disorders' (ASD). Many teams are trying to pick out the underlying cerebral abnormalities in order to understand the neuronal networks involved in relationships with others. Here we review the morphological, spectroscopic and functional abnormalities in the amygdala-hippocampal circuit, the caudate nuclei, the cerebellum, and the frontotemporal regions, which have been described in subjects with ASD. White matter abnormalities have also been described in diffusion tensor imaging, leading to suspected damage to the subjacent neural networks, such as mirror neurones or the social brain.

[Atypical perception processing and facial emotion disorder in autism]. / Les anomalies du traitement des émotions faciales dans l'autisme : un trouble de la perception globale.

INTRODUCTION: Autistic syndrome is defined by several abnormalities, mainly affecting social interaction skills. Disorders of the processes of processing facial and emotional stimuli, and particularly avoidance of gaze, have also been reported in this disorder. Some authors have suggested that these abnormalities may be explained, or at least contributed to, by the social disorder observed in this syndrome. The aim of this study was therefore to improve the understanding of the processes involved in perception AND the representation of faces expressing emotion in subjects with autism spectrum disorders (ASDs). METHODS: Eleven children with ASDs (mean developmental age 7 years 11 months) and eleven normally developing children (mean age 7 years 9 months) took part in three experiments. The first involved overall discrimination of emotions using photographs of faces expressing six basic emotions, the second required local emotional discrimination on the basis of isolated elements of the face (photographs of eyes and mouths isolated from the rest of the face), and for the third the children were asked to create faces expressing emotions by means of a jig-saw puzzle format, using photographs of isolated elements of the face (overall representation necessitating local discrimination). RESULTS: Our findings revealed that the normally developing children had difficulties with the process of local discrimination of emotions: their performance improved when overall perception was possible. In contrast, and astonishingly, the children with ASD were more able to discriminate isolated eyes expressing emotion than the controls, but their performance declined when overall processing was required. DISCUSSION: Our results suggested that the emotional disorders observed in ASDs might be explained by greater skills in the processing of local information. This might explain the inability of children with ASDs to achieve coherent perception of their social environment and might also lead to the withdrawal that is characteristic of this disorder. These results also suggest that the gaze avoidance that is characteristic of individuals with ASDs is eliminated when eyes are presented alone. This gaze avoidance therefore seems to be related to the complexity and variability of this type of stimulus and not to the social nature of the stimulus.

[Genotype/phenotype correlation in autism: genetic models and phenotypic characterization]. / Correspondances génotype/phénotype et l'autisme : modèles et stratégies.

BACKGROUND: Autism spectrum disorders are a class of conditions categorized by communication problems, ritualistic behaviors, and deficits in social behaviors. This class of disorders merges a heterogeneous group of neurodevelopmental disorders regarding some phenotypic and probably physiopathological aspects. Genetic basis is well admitted, however, considering phenotypic and genotypic heterogeneity, correspondences between genotype and phenotype have yet to be established. LITERATURE FINDINGS: To better identify such correspondences, genetic models have to be identified and phenotypic markers have to be characterized. Recent insights show that a variety of genetic mechanisms may be involved in autism spectrum disorders, i.e. single gene disorders, copy number variations and polygenic mechanisms. These current genetic models are described. Regarding clinical aspects, several approaches can be used in genetic studies. Nosographical approach, especially with the concept of autism spectrum disorders, merges a large group of disorders with clinical heterogeneity and may fail to identify clear genotype/phenotype correlations. Dimensional approach referred in genetic studies to the notion of "Broad Autism Phenotype" related to a constellation of language, personality, and social-behavioral features present in relatives that mirror the symptom domains of autism, but are much milder in expression. Studies of this broad autism phenotype may provide a potentially important complementary approach for detecting the genes involved in these domains. However, control population used in those studies need to be well characterized too. Identification of endophenotypes seems to offer more promising results. Endophenotypes, which are supposed to be more proximal markers of gene action in the same biological pathway, linking genes and complex clinical symptoms, are thought to be less genetically complex than the broader disease phenotype, indexing a limited aspect of genetic risk for the disorder as a whole. However, strategies useful to characterize such phenotypic markers (for example, electrophysiological markers) have to take into account that autism is an early neurodevelopmental disorder occurring during childhood when brain development and maturation are in process. CONCLUSION: Recent genetic results have improved our knowledge in genetic basis in autism. Nevertheless, correspondences with phenotypic markers remain challenging according to phenotypic and genotypic heterogeneity.