Autism: a world changing too fast for a mis-wired brain ?

International audienceDisorders in verbal and emotional communication and imitation, social reciprocity and higher order cognition observed in individuals with autism spectrum disorders (ASD) are presented here as phenotypic expressions of temporo-spatial processing disorders (TSPDs). TSPDs include various degrees of disability in (i) processing multi-sensory dynamic stimuli online, (ii) associating them into meaningful and coherent patterns and (iii) producing real-time sensory-motor adjustments and motor outputs. In line with this theory, we found that slowing down the speed opf facial and vocal events enhanced imitative, verbal and cognitive abilities in some ASD children, particularly those with low functioning autism. We then argue that TSPDs may result from Multi-system Brain Disconnectivity-Dissynchrony (MBD), defined as an increase or decrease in functional connectivity and neuronal synchronization within/between multiple neurofunctional territories and pathways. Recent functional magnetic resonance imaging (fMRI) and electrophysiological studies supporting MBD are outlined. Finally, we review the suspected underlying neurobiological mechanisms of MBD as evidenced in neuroimaging, genetic, environmental and epigenetic studies. Overall, our TSPD/MBD approach to ASD may open new promising avenues for a better understanding of neuro-physio-psychopathology of ASD and clinical rehabilitation of people affected by these syndromes

Autism, Movement, Time and Thought E-Motion Mis-Sight and other Temporo-Spatial Processing Disorders in Autism

In this chapter we propose a new approach of autism called E-Motion mis-sight and other temporospatial processing disorders. According to our view, subjects with autistic spectrum disorders (ASD) present more or less disabilities, delays and deviances, to perceive and integrate environmental world's sensory events online and to produce real-time sensorymotor coupling and adequate verbal and nonverbal outputs, from the beginning of their life. In other words, the environmental world is going and changing too fast for persons with ASD.In the first paragraph, we present some biographical self-reports, clinical considerations and neuropsychological arguments, which open windows on the peculiar visual and visuo-motor world of autistic persons. In the second paragraph, we expose the available experimental results in favour of physical and biological motion integration disorders in autistic population, and we expose a first synthesis of our approach. In the third paragraph, we review some results demonstrating other temporo-spatial processing disorders in ASD, and suggest some possible underlying neurobiological mechanisms of our E-Motion mis-sight and other temporospatial processing disorders hypothesis of autism, based on putative multi-system temporal dissynchronization and functional disconnectivity. We think that this approach, which is compatible with the major contemporary theories of ASD, may have new implications for the comprehension and new applications for the rehabilitation of these disorders. In the last paragraph, we propose some psychological and philosophical perspectives of our approach concerning with the integration of movement and time in thought, and the mind-brain relationships in autism in particular, and in human being in general

From neuronal to human communication disorders: A novel approach to autism

International audienceIn this paper we draw the first lines of a novel gene-to-behaviour approach to Autism Spectrum Disorders (ASD). This approach is presented from behaviours and upstream to genes. We first present again our threefold -clinical, experimental and theoretical- approach to autism, the so-called E-Motion mis-sight and other temporospatial processing disorders. According to our view, subjects with ASD present from the beginning of their life different degrees of disability in processing sensory events online and in producing real-time sensory-motor adjustments and motor outputs. The environmental world is changing too fast to be processed on time by the autistic brain, leading to the primary communicative, cognitive and imitative disorders of persons with ASD, and to their secondary adaptive and compensatory strategies. Confirming this view, we present several results demonstrating that slowing down visual and auditory flows around individuals with ASD enhances their performance in imitation, verbal comprehension and facial expression recognition. Then we show that these temporospatial processing disorders are based on multisystem dissynchrony and disconnectivity (MDD), i.e., disorders in neuronal synchronization (hypo- and/or hypersynchronization) and functional connectivity (over- and/or under-connectivity) between multiple neurofunctional territories and pathways. We show that MDD is based itself on structural and functional abnormalities of the brain, and we finally relate these neuronal and synaptic abnormalities to their genetic counterparts.Dans cet article, nous proposons un scénario de la genèse des désordres du spectre autistique (DSA). Nous présentons ce scénario en partant du comportement et en remontant vers les gènes, selon une démarche de clinicien-chercheur. Pour ce faire, nous rappelons d'abord notre triple approche clinique, expérimentale et théorique de l'autisme dite de « Malvoyance de l'E-Motion et autres désordres du traitement temporopatial des flux sensoriels », selon laquelle certains enfants ayant des désordres de la constellation autistique présentent depuis le début de leur vie des difficultés à traiter en ligne les événements du monde environnemental et à produire en temps réel des ajustements sensorimoteurs et moteurs. Le monde environnemental change trop vite pour être traité en temps réel par le cerveau des personnes autistes, ce qui génère leurs désordres communicatifs, cognitifs et imitatifs ainsi que leurs stratégies compensatoires et adaptatives. Nous montrons ensuite que ces troubles du traitement temporospatial sont sous-tendus par une dysconnectivité et dyssynchronie multisystème (DDM), c'est-à-dire des déficits ou excès de connectivité entre de multiples territoires neurofonctionnels, eux-mêmes en rapport avec des anomalies cérébrales structurales et fonctionnelles. Pour finir, nous relions ces anomalies neuronales et synaptiques à leurs contreparties génétiques

Subtle oculomotor difficulties and their relation to motor skill in children with autism spectrum disorder

Objectives Sensorimotor difficulties are often reported in autism spectrum disorders (ASD). Visual and motor skills are linked in that the processing of visual information can help in guiding motor movements. The present study investigated oculomotor skill and its relation to general motor skill in ASD by providing a comprehensive assessment of oculomotor control. Methods Fifty children (25 ASD; 25 typically developing [TD]), aged 7–10 years, completed a motor assessment (comprising fine and gross motor tasks) and oculomotor battery (comprising fixation, smooth pursuit, prosaccade and antisaccade tasks). Results No group differences were found for antisaccade errors, nor saccade latencies in prosaccade and antisaccade tasks, but increased saccade amplitude variability was observed in children with ASD, suggesting a reduced consistency in saccade accuracy. Children with ASD also demonstrated poorer fixation stability than their peers and spent less time in pursuit of a moving target. Motor skill was not correlated with saccade amplitude variability. However, regression analyses revealed that motor skill (and not diagnosis) accounted for variance in fixation performance and fast smooth pursuit. Conclusions The findings highlight the importance of considering oculomotor paradigms to inform the functional impact of neuropathologies in ASD and also assessing the presentation of co-occurring difficulties to further our understanding of ASD. Avenues for future research are suggested

EEG hyper-connectivity in high-risk infants is associated with later autism

- Background: It has been previously reported that structural and functional brain connectivity in individuals with autism spectrum disorders (ASD) is atypical and may vary with age. However, to date, no measures of functional connectivity measured within the first 2 years have specifically associated with a later ASD diagnosis. - Methods: In the present study, we analyzed functional brain connectivity in 14-month-old infants at high and low familial risk for ASD using electroencephalography (EEG). EEG was recorded while infants attended to videos. Connectivity was assessed using debiased weighted phase lag index (dbWPLI). At 36 months, the high-risk infants were assessed for symptoms of ASD. - Results: As a group, high-risk infants who were later diagnosed with ASD demonstrated elevated phase-lagged alpha-range connectivity as compared to both low-risk infants and high-risk infants who did not go on to ASD. Hyper-connectivity was most prominent over frontal and central areas. The degree of hyper-connectivity at 14 months strongly correlated with the severity of restricted and repetitive behaviors in participants with ASD at 3 years. These effects were not attributable to differences in behavior during the EEG session or to differences in spectral power. - Conclusions: The results suggest that early hyper-connectivity in the alpha frequency range is an important feature of the ASD neurophysiological phenotype

Effective connectivity in autism

The aim was to go beyond functional connectivity, by measuring in the first large-scale study differences in effective, that is directed, connectivity between brain areas in autism compared to controls. Resting-state functional magnetic resonance imaging was analyzed from the Autism Brain Imaging Data Exchange (ABIDE) data set in 394 people with autism spectrum disorder and 473 controls, and effective connectivity (EC) was measured between 94 brain areas. First, in autism, the middle temporal gyrus and other temporal areas had lower effective connectivities to the precuneus and cuneus, and these were correlated with the Autism Diagnostic Observational Schedule total, communication, and social scores. This lower EC from areas implicated in face expression analysis and theory of mind to the precuneus and cuneus implicated in the sense of self may relate to the poor understanding of the implications of face expression inputs for oneself in autism, and to the reduced theory of mind. Second, the hippocampus and amygdala had higher EC to the middle temporal gyrus in autism, and these are thought to be back projections based on anatomical evidence and are weaker than in the other direction. This may be related to increased retrieval of recent and emotional memories in autism. Third, some prefrontal cortex areas had higher EC with each other and with the precuneus and cuneus. Fourth, there was decreased EC from the temporal pole to the ventromedial prefrontal cortex, and there was evidence for lower activity in the ventromedial prefrontal cortex, a brain area implicated in emotion-related decision-making. Autism Res 2019, 00: 1-13. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: To understand autism spectrum disorders better, it may be helpful to understand whether brain systems cause effects on each other differently in people with autism. In this first large-scale neuroimaging investigation of effective connectivity in people with autism, it is shown that parts of the temporal lobe involved in facial expression identification and theory of mind have weaker effects on the precuneus and cuneus implicated in the sense of self. This may relate to the poor understanding of the implications of face expression inputs for oneself in autism, and to the reduced theory of mind. [Abstract copyright: © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Molecular Mechanisms Responsible for Functional Cortical Plasticity During Development and after Focal Ischemic Brain Injury

The cerebral cortex is organized into functional representations, or maps, defined by increased activity during specific tasks. In addition, the brain exhibits robust spontaneous activity with spatiotemporal organization that defines the brain’s functional architecture (termed functional connectivity). Task-evoked representations and functional connectivity demonstrate experience-dependent plasticity, and this plasticity may be important in neurological development and disease. An important case of this is in focal ischemic injury, which results in destruction of the involved representations and disruption of functional connectivity relationships. Behavioral recovery correlates with representation remapping and functional connectivity normalization, suggesting functional organization is critical for recovery and a potentially valuable therapeutic target. However, the cellular and molecular mechanisms that drive this systems-level plasticity are unknown, making it difficult to approach therapeutic modulation of functional brain organization. Using cortical neuroimaging in mice, this dissertation explores the role of specific genes in sensory deprivation induced functional brain map plasticity during development and after focal ischemic injury. In the three contained chapters, I demonstrate the following: 1) Arc, an excitatory neuron synaptic-plasticity gene, is required for representation remapping and behavioral recovery after focal cortical ischemia. Further, perilesional sensory deprivation can direct remapping and improve behavioral recovery. 2) Early visual experience modulates functional connectivity within and outside of the visual cortex through an Arc-dependent mechanism. 3) Electrically coupled inhibitory interneuron networks limit spontaneous activity syncrhony between distant cortical regions. This work starts to define the molecular basis for plasticity in functional brain organization and may help develop approaches for therapeutic modulation of functional brain organization

Oscillatory neural networks underlying resting-state, attentional control and social cognition task conditions in children with ASD, ADHD and ASD+ADHD

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common and impairing neurodevelopmental disorders that frequently co-occur. The neurobiological mechanisms involved in ASD and ADHD are not fully understood. However, alterations in large-scale neural networks have been proposed as core deficits in both ASD and ADHD and may help to disentangle the neurobiological basis of these disorders and their co-occurrence. In this study, we examined similarities and differences in large-scale oscillatory neural networks between boys aged 8-13 years with ASD (n = 19), ADHD (n = 18), ASD + ADHD (n = 29) and typical development (Controls, n = 26). Oscillatory neural networks were computed using graph-theoretical methods from electroencephalographic (EEG) data collected during an eyes-open resting-state and attentional control and social cognition tasks in which we previously reported disorder-specific atypicalities in oscillatory power and event-related potentials (ERPs). We found that children with ASD showed significant hypoconnectivity in large-scale networks during all three task conditions compared to children without ASD. In contrast, children with ADHD showed significant hyperconnectivity in large-scale networks during the attentional control and social cognition tasks, but not during the resting-state, compared to children without ADHD. Children with co-occurring ASD + ADHD did not differ from children with ASD when paired with this group and vice versa when paired with the ADHD group, indicating that these children showed both ASD-like hypoconnectivity and ADHD-like hyperconnectivity. Our findings suggest that ASD and ADHD are associated with distinct alterations in large-scale oscillatory networks, and these atypicalities present together in children with both disorders. These alterations appear to be task-independent in ASD but task-related in ADHD, and may underlie other neurocognitive atypicalities in these disorders. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Functional EEG connectivity in infants associates with later restricted and repetitive behaviours in autism; a replication study.

We conducted a replication study of our prior report that increased alpha EEG connectivity at 14-months associates with later autism spectrum disorder (ASD) diagnosis, and dimensional variation in restricted interests/repetitive behaviours. 143 infants at high and low familial risk for ASD watched dynamic videos of spinning toys and women singing nursery rhymes while high-density EEG was recorded. Alpha functional connectivity (7-8 Hz) was calculated using the debiased weighted phase lag index. The final sample with clean data included low-risk infants (N = 20), and high-risk infants who at 36 months showed either typical development (N = 47), atypical development (N = 21), or met criteria for ASD (N = 13). While we did not replicate the finding that global EEG connectivity associated with ASD diagnosis, we did replicate the association between higher functional connectivity at 14 months and greater severity of restricted and repetitive behaviours at 36 months in infants who met criteria for ASD. We further showed that this association is strongest for the circumscribed interests subdomain. We propose that structural and/or functional abnormalities in frontal-striatal circuits underlie the observed association. This is the first replicated infant neural predictor of dimensional variation in later ASD symptoms