La revue Brain Research propose dans son numéro du 22 mars 2011 un dossier spécial sur le thème de l’autisme et des neurosciences.

The Emerging Neuroscience of Autism Spectrum Disorders

Le numéro est consultable sur le site de l’éditeur

1. Bernardi S, Anagnostou E, Shen J, Kolevzon A, Buxbaum JD, Hollander E, Hof PR, Fan J. In vivo 1H-magnetic resonance spectroscopy study of the attentional networks in autism. Brain Research ;2011 ;1380(0):198-205.

Attentional dysfunction is one of the most consistent findings in individuals with autism spectrum disorders (ASD). However, the significance of such findings for the pathophysiology of autism is unclear. In this study, we investigated cellular neurochemistry with proton magnetic resonance spectroscopy imaging (1H-MRS) in brain regions associated with networks subserving alerting, orienting, and executive control of attention in patients with ASD. Concentrations of cerebral N-acetyl-aspartate (NAA), creatinine + phosphocreatinine, choline-containing compounds, myo-inositol (Ins) and glutamate + glutamine (Glx) were determined by 3 T 1H-MRS examinations in 14 high-functioning medication-free adults with a diagnosis of ASD and 14 age- and IQ-matched healthy controls (HC) in the anterior cingulate cortex (ACC), thalamus, temporoparietal junction (TPJ), and areas near or along the intraparietal sulcus (IPS). Compared to HC group, the ASD group showed significantly lower Glx concentration in right ACC and reduced Ins concentration in left TPJ. This study provides evidence of abnormalities in neurotransmission related to networks subserving executive control and alerting of attention, functions which have been previously implicated in ASD pathogenesis.

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2. Buxbaum JD, Hof PR. The emerging neuroscience of autism spectrum disorders. Brain Research ;2011 ;1380(0):1-2.

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3. Catalina B. Etiological heterogeneity in autism spectrum disorders : More than 100 genetic and genomic disorders and still counting. Brain Research ;2011 ;1380(0):42-77.

There is increasing evidence that autism spectrum disorders (ASDs) can arise from rare highly penetrant mutations and genomic imbalances. The rare nature of these variants, and the often differing orbits of clinical and research geneticists, can make it difficult to fully appreciate the extent to which we have made progress in understanding the genetic etiology of autism. In fact, there is a persistent view in the autism research community that there are only a modest number of autism loci known. We carried out an exhaustive review of the clinical genetics and research genetics literature in an attempt to collate all genes and recurrent genomic imbalances that have been implicated in the etiology of ASD. We provide data on 103 disease genes and 44 genomic loci reported in subjects with ASD or autistic behavior. These genes and loci have all been causally implicated in intellectual disability, indicating that these two neurodevelopmental disorders share common genetic bases. A genetic overlap between ASD and epilepsy is also apparent in many cases. Taken together, these findings clearly show that autism is not a single clinical entity but a behavioral manifestation of tens or perhaps hundreds of genetic and genomic disorders. Increased recognition of the etiological heterogeneity of ASD will greatly expand the number of target genes for neurobiological investigations and thereby provide additional avenues for the development of pathway-based pharmacotherapy. Finally, the data provide strong support for high-resolution DNA microarrays as well as whole-exome and whole-genome sequencing as critical approaches for identifying the genetic causes of ASDs.

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4. Charman T, Jones CRG, Pickles A, Simonoff E, Baird G, Happé F. Defining the cognitive phenotype of autism. Brain Research ;2011 ;1380(0):10-21.

Although much progress has been made in determining the cognitive profile of strengths and weaknesses that characterise individuals with autism spectrum disorders (ASDs), there remain a number of outstanding questions. These include how universal strengths and deficits are ; whether cognitive subgroups exist ; and how cognition is associated with core autistic behaviours, as well as associated psychopathology. Several methodological factors have contributed to these limitations in our knowledge, including : small sample sizes, a focus on single domains of cognition, and an absence of comprehensive behavioural phenotypic information. To attempt to overcome some of these limitations, we assessed a wide range of cognitive domains in a large sample (N = 100) of 14- to 16-year-old adolescents with ASDs who had been rigorously behaviourally characterised. In this review, we will use examples of some initial findings in the domains of perceptual processing, emotion processing and memory, both to outline different approaches we have taken to data analysis and to highlight the considerable challenges to better defining the cognitive phenotype(s) of ASDs. Enhanced knowledge of the cognitive phenotype may contribute to our understanding of the complex links between genes, brain and behaviour, as well as inform approaches to remediation.

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5. Choi CH, Schoenfeld BP, Bell AJ, Hinchey P, Kollaros M, Gertner MJ, Woo NH, Tranfaglia MR, Bear MF, Zukin RS, McDonald TV, Jongens TA, McBride SMJ. Pharmacological reversal of synaptic plasticity deficits in the mouse model of Fragile X syndrome by group II mGluR antagonist or lithium treatment. Brain Research ;2011 ;1380(0):106-119.

Fragile X syndrome is the leading single gene cause of intellectual disabilities. Treatment of a Drosophila model of Fragile X syndrome with metabotropic glutamate receptor (mGluR) antagonists or lithium rescues social and cognitive impairments. A hallmark feature of the Fragile X mouse model is enhanced mGluR-dependent long-term depression (LTD) at Schaffer collateral to CA1 pyramidal synapses of the hippocampus. Here we examine the effects of chronic treatment of Fragile X mice in vivo with lithium or a group II mGluR antagonist on mGluR-LTD at CA1 synapses. We find that long-term lithium treatment initiated during development (5–6 weeks of age) and continued throughout the lifetime of the Fragile X mice until 9–11 months of age restores normal mGluR-LTD. Additionally, chronic short-term treatment beginning in adult Fragile X mice (8 weeks of age) with either lithium or an mGluR antagonist is also able to restore normal mGluR-LTD. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of Fragile X syndrome is an important advance, in that this identifies and validates these targets as potential therapeutic interventions for the treatment of individuals afflicted with Fragile X syndrome.

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6. Courchesne E, Campbell K, Solso S. Brain growth across the life span in autism : Age-specific changes in anatomical pathology. Brain Research ;2011 ;1380(0):138-145.

Autism is marked by overgrowth of the brain at the earliest ages but not at older ages when decreases in structural volumes and neuron numbers are observed instead. This has led to the theory of age-specific anatomic abnormalities in autism. Here we report age-related changes in brain size in autistic and typical subjects from 12 months to 50 years of age based on analyses of 586 longitudinal and cross-sectional MRI scans. This dataset is several times larger than the largest autism study to date. Results demonstrate early brain overgrowth during infancy and the toddler years in autistic boys and girls, followed by an accelerated rate of decline in size and perhaps degeneration from adolescence to late middle age in this disorder. We theorize that underlying these age-specific changes in anatomic abnormalities in autism, there may also be age-specific changes in gene expression, molecular, synaptic, cellular, and circuit abnormalities. A peak age for detecting and studying the earliest fundamental biological underpinnings of autism is prenatal life and the first three postnatal years. Studies of the older autistic brain may not address original causes but are essential to discovering how best to help the older aging autistic person. Lastly, the theory of age-specific anatomic abnormalities in autism has broad implications for a wide range of work on the disorder including the design, validation, and interpretation of animal model, lymphocyte gene expression, brain gene expression, and genotype/CNV-anatomic phenotype studies.

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7. David G A. The promise and the pitfalls of autism research : An introductory note for new autism researchers. Brain Research ;2011 ;1380(0):3-9.

The last decade has seen an enormous growth in the quantity of research directed at understanding the biological underpinnings of autism spectrum disorders. This increase has been spurred on, in part, by research funding provided through private, parent advocacy groups. While increased funding and entry into autism research by scientists from many disciplines has facilitated the speed of discoveries germane to establishing the etiologies of autism, there remain a number of roadblocks to understanding autism sufficiently well to foster new treatments. This short article provides a brief overview of some of the achievements and some of the difficulties in conducting autism research.

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8. Devlin B, Melhem N, Roeder K. Do common variants play a role in risk for autism ? Evidence and theoretical musings. Brain Research ;2011 ;1380(0):78-84.

Both rare and common genetic variants underlie risk for almost any complex disease. Over the past few years a common tool for identifying common risk variants is genome-wide association or GWA. Our analyses focus on results from GWA targeting common variants affecting risk for autism spectrum disorders (ASD). Thus far three large GWA studies have been published, each of which highlights a single, non-overlapping risk locus. Evaluation of these studies suggests that combination of their data would diminish evidence for all of these loci, making none of them significant. Despite this paucity of findings, statistical theory can be used to infer a plausible distribution of effect sizes for SNPs affecting risk for ASD. We lay out this theory, calculate plausible distributions, and discuss the results in the context of results from GWA studies for schizophrenia.

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9. Frankel F, Whitham C. Parent-assisted group treatment for friendship problems of children with autism spectrum disorders. Brain Research ;2011 ;1380(0):240-245.

Children with Asperger’s Disorder or High Functioning Autism are included in regular education classes but find themselves excluded from the social lives of their classmates. This paper briefly reviews studies which attempt to provide them with training to overcome their social difficulties. These interventions have had limited success and have not systematically incorporated the child’s parents into the intervention. Children’s Friendship Training is a manualized parent-assisted group treatment which teaches social skill through learning and practicing sets of rules of etiquette for key social situations. The treatment approach has been demonstrated to have success in improving friendships of children with autism spectrum disorders. The content of Children’s Friendship Training is briefly described and results of controlled studies are reviewed. Limitations of previous research and future directions are also described.

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10. Ghahramani Seno MM, Hu P, Gwadry FG, Pinto D, Marshall CR, Casallo G, Scherer SW. Gene and miRNA expression profiles in autism spectrum disorders. Brain Research ;2011 ;1380(0):85-97.

Accumulating data indicate that there is significant genetic heterogeneity underlying the etiology in individuals diagnosed with autism spectrum disorder (ASD). Some rare and highly-penetrant gene variants and copy number variation (CNV) regions including NLGN3, NLGN4, NRXN1, SHANK2, SHANK3, PTCHD1, 1q21.1, maternally-inherited duplication of 15q11–q13, 16p11.2, amongst others, have been identified to be involved in ASD. Genome-wide association studies have identified other apparently low risk loci and in some other cases, ASD arises as a co-morbid phenotype with other medical genetic conditions (e.g. fragile X). The progress studying the genetics of ASD has largely been accomplished using genomic analyses of germline-derived DNA. Here, we used gene and miRNA expression profiling using cell-line derived total RNA to evaluate possible transcripts and networks of molecules involved in ASD. Our analysis identified several novel dysregulated genes and miRNAs in ASD compared with controls, including HEY1, SOX9, miR-486 and miR-181b. All of these are involved in nervous system development and function and some others, for example, are involved in NOTCH signaling networks (e.g. HEY1). Further, we found significant enrichment in molecules associated with neurological disorders such as Rett syndrome and those associated with nervous system development and function including long-term potentiation. Our data will provide a valuable resource for discovery purposes and for comparison to other gene expression-based, genome-wide DNA studies and other functional data.

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11. King BH, Lord C. Is schizophrenia on the autism spectrum ?. Brain Research ;2011 ;1380(0):34-41.

With the ongoing consideration of the diagnostic criteria for mental disorders that is active in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and International Classification of Diseases (ICD-11) revision processes, it is timely to review the phenomenological overlap between autism and schizophrenia. These disorders have at various times been regarded alternatively as closely related and as non-overlapping and incompatible. Nevertheless, there are several reports in the literature that have described individuals with both autism and schizophrenia, and the broader phenotypes of these disorders clearly intersect. Recent studies reveal theory of mind deficits in both disorders, and mirror neuron impairments also appear to be shared. There also may be similar connectivity deficits emerging in functional imaging studies, and both disorders share several genetic signals that are being identified through detection of copy number variants. Taken together, these data suggest that it may be time to revisit the possibility that these disorders are related.

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12. Kolevzon A, Cai G, Soorya L, Takahashi N, Grodberg D, Kajiwara Y, Willner JP, Tryfon A, Buxbaum JD. Analysis of a purported SHANK3 mutation in a boy with autism : Clinical impact of rare variant research in neurodevelopmental disabilities. Brain Research ;2011 ;1380(0):98-105.

There is strong evidence for rare, highly penetrant genetic variants playing an etiological role in multiple neurodevelopmental disabilities, including autism spectrum disorders. The rate of discovery of such rare variants is increasing with the advent of larger sample collections, chromosome microarray analyses, and high-throughput sequencing. As the variants that are being discovered can be highly penetrant, they lead immediately to model systems with construct validity, critical for understanding the underlying neurobiology of these conditions, which in turn can provide leads for novel therapeutic targets. Moreover, these discoveries can benefit families with information about recurrence risk, resolve concerns about etiology, provide information about associated medical issues, and engender directed advocacy for specific genetic conditions. For these reasons, diagnostic laboratories are taking advantage of research data as they are produced. In the current report, we present our molecular analysis of a child with a purported disruptive mutation in SHANK3 identified by a commercial genetic testing laboratory and we provide evidence that this was not an etiological variant. The variant was a 1-bp insertion in exon 11 of the RefSeq gene, which we then determined was inherited from a healthy mother and found in 1% of controls. Since the variant would be predicted to disrupt the reference gene, and the penetrance of SHANK3 mutations is very high, we did follow up molecular and bioinformatic analyses and concluded that the presumptive exon containing the variant is not likely to be present in most or all SHANK3 transcripts. The results highlight difficulties that can arise with rapid translation of research findings to clinical practice. Researchers are in a unique position to generate resources with collated and curated information that can inform research, genetic testing, clinicians, and families about the best practices as pertains to rare genetic variants in neurodevelopmental disabilities. Of immediate importance would be a well-curated database of gene variation identified in large numbers of typically developing individuals and in individuals affected with neurodevelopmental disabilities. Such a database would reduce false-positive results in clinical settings, would be helpful in structure–function analyses, and would direct translational research to pathways most likely to benefit families.

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13. Murphy DGM, Beecham J, Craig M, Ecker C. Autism in adults. New biologicial findings and their translational implications to the cost of clinical services. Brain Research ;2011 ;1380(0):22-33.

There is increasing evidence that children with autism spectrum disorder (ASD) have differences in brain growth trajectory. However, the neurobiological basis of ASD in adults is poorly understood. We report evidence that brain anatomy and aging in people with ASD is significantly different as compared to controls—so that in adulthood they no longer have a significantly larger overall brain volume, but they do have anatomical and functional abnormalities in frontal lobe, basal ganglia and the limbic system. Further we present preliminary evidence that females have significantly greater abnormalities in brain than males to express the same symptom severity of ASD (i.e. the female brain is “protective” against developing ASD). Also we present preliminary evidence that, in adults, clinical services for autism in the United Kingdom are experiencing very significantly increased demand ; but that just over 50% of people seeking a diagnosis from one expert service do not have ASD. This consumes very significant health care resources, and so we need to identify new cost-effective methods to aid current diagnostic practice. We present initial evidence offering proof of concept that brain anatomy can be used to accurately distinguish adults with autism from healthy controls, and from some other neurodevelopmental disorders (ADHD). Hence further studies are required to determine if sMRI can become an aid to current diagnostic practice in young adults with ASD. Lastly we report evidence that differences in serotonin, glutamate and GABA may partially explain neuroanatomical and neurofunctional abnormalities in people with ASD, and that genetic influences on brain maturation vary across the lifespan (with 5-HT transporter polymorphisms having significant modulatory effects in children but not adults).

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14. Oblak AL, Gibbs TT, Blatt GJ. Reduced GABAA receptors and benzodiazepine binding sites in the posterior cingulate cortex and fusiform gyrus in autism. Brain Research ;2011 ;1380(0):218-228.

Individuals with autism display deficits in the social domain including the proper recognition of faces and interpretations of facial expressions. There is an extensive network of brain regions involved in face processing including the fusiform gyrus (FFG) and posterior cingulate cortex (PCC). Functional imaging studies have found that controls have increased activity in the PCC and FFG during face recognition tasks, and the FFG has differential responsiveness in autism when viewing faces. Multiple lines of evidence have suggested that the GABAergic system is disrupted in the brains of individuals with autism and it is likely that altered inhibition within the network influences the ability to perceive emotional expressions. On-the-slide ligand binding autoradiography was used to determine if there were alterations in GABAA and/or benzodiazepine binding sites in the brain in autism. Using 3H-muscimol and 3H-flunitrazepam we could determine whether the number (Bmax), binding affinity (Kd), and/or distribution of GABAA receptors and benzodiazepine binding sites (BZD) differed from controls in the FFG and PCC. Significant reductions were found in the number of GABAA receptors and BZD binding sites in the superficial layers of the PCC and FFG, and in the number of BZD binding sites in the deep layers of the FFG. In addition, the autism group had a higher binding affinity in the superficial layers of the GABAA study. Taken together, these findings suggest that the disruption in inhibitory control in the cortex may contribute to the core disturbances of socio-emotional behaviors in autism.

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15. Santos M, Uppal N, Butti C, Wicinski B, Schmeidler J, Giannakopoulos P, Heinsen H, Schmitz C, Hof PR. von Economo neurons in autism : A stereologic study of the frontoinsular cortex in children. Brain Research ;2011 ;1380(0):206-217.

The presence of von Economo neurons (VENs) in the frontoinsular cortex (FI) has been linked to a possible role in the integration of bodily feelings, emotional regulation, and goal-directed behaviors. They have also been implicated in fast intuitive evaluation of complex social situations. Several studies reported a decreased number of VENs in neuropsychiatric diseases in which the “embodied” dimension of social cognition is markedly affected. Neuropathological analyses of VENs in patients with autism are few and did not report alterations in VEN numbers. In this study we re-evaluated the possible presence of changes in VEN numbers and their relationship with the diagnosis of autism. Using a stereologic approach we quantified VENs and pyramidal neurons in layer V of FI in postmortem brains of four young patients with autism and three comparably aged controls. We also investigated possible autism-related differences in FI layer V volume. Patients with autism consistently had a significantly higher ratio of VENs to pyramidal neurons (p = 0.020) than control subjects. This result may reflect the presence of neuronal overgrowth in young patients with autism and may also be related to alterations in migration, cortical lamination, and apoptosis. Higher numbers of VENs in the FI of patients with autism may also underlie a heightened interoception, described in some clinical observations.

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16. Schumann CM, Nordahl CW. Bridging the gap between MRI and postmortem research in autism. Brain Research ;2011 ;1380(0):175-186.

Autism is clearly a disorder of neural development, but when, where, and how brain pathology occurs remain elusive. Typical brain development is comprised of several stages, including proliferation and migration of neurons, creation of dendritic arbors and synaptic connections, and eventually dendritic pruning and programmed cell death. Any deviation at one or more of these stages could produce catastrophic downstream effects. MRI studies of autism have provided important clues, describing an aberrant trajectory of growth during early childhood that is both present in the whole brain and marked in specific structures such as the amygdala. However, given the coarse resolution of MRI, the field must also look towards postmortem human brain research to help elucidate the neurobiological underpinnings of MRI volumetric findings. Likewise, studies of postmortem tissue may benefit by looking to the findings from MRI studies to narrow hypotheses and target specific brain regions and subject populations. In this review, we discuss the strengths, limitations, and major contributions of each approach to autism research. We then describe how they relate and what they can learn from each other. Only by integrating these approaches will we be able to fully explain the neuropathology of autism.

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17. Silverman JL, Turner SM, Barkan CL, Tolu SS, Saxena R, Hung AY, Sheng M, Crawley JN. Sociability and motor functions in Shank1 mutant mice. Brain Research ;2011 ;1380(0):120-137.

Autism is a neurodevelopmental disorder characterized by aberrant reciprocal social interactions, impaired communication, and repetitive behaviors. While the etiology remains unclear, strong evidence exists for a genetic component, and several synaptic genes have been implicated. SHANK genes encode a family of synaptic scaffolding proteins located postsynaptically on excitatory synapses. Mutations in SHANK genes have been detected in several autistic individuals. To understand the consequences of SHANK mutations relevant to the diagnostic and associated symptoms of autism, comprehensive behavioral phenotyping on a line of Shank1 mutant mice was conducted on multiple measures of social interactions, social olfaction, repetitive behaviors, anxiety-related behaviors, motor functions, and a series of control measures for physical abilities. Results from our comprehensive behavioral phenotyping battery indicated that adult Shank1 null mutant mice were similar to their wildtype and heterozygous littermates on standardized measures of general health, neurological reflexes and sensory skills. Motor functions were reduced in the null mutants on open field activity, rotarod, and wire hang, replicating and extending previous findings (Hung et al., 2008). A partial anxiety-like phenotype was detected in the null mutants in some components of the light ↔ dark task, as previously reported (Hung et al., 2008) but not in the elevated plus-maze. Juvenile reciprocal social interactions did not differ across genotypes. Interpretation of adult social approach was confounded by a lack of normal sociability in wildtype and heterozygous littermates. All genotypes were able to discriminate social odors on an olfactory habituation/dishabituation task. All genotypes displayed relatively high levels of repetitive self-grooming. Our findings support the interpretation that Shank1 null mice do not demonstrate autism-relevant social interaction deficits, but confirm and extend a role for Shank1 in motor functions.

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18. Stahmer AC, Schreibman L, Cunningham AB. Toward a technology of treatment individualization for young children with autism spectrum disorders. Brain Research ;2011 ;1380(0):229-239.

Although the etiology of autism spectrum disorders (ASD) and early development of the ASD are not yet well understood, recent research in the field of autism has heavily emphasized the importance of early intervention (i.e. treatment before the age of 4 years). Currently, several methods have been demonstrated to be efficacious with some children however no treatment completely ameliorates the symptoms of ASD or works for all children with the disorder. The heterogeneity and developmental nature of the disorder make it unlikely that one specific treatment will be best for all children, or will work for any one child throughout his or her educational career. Thus, this paper examines early research validating different technologies for individualizing treatment. A discussion of current research on pre-treatment characteristics associated with differential outcomes in treatment, including child, family, and practitioner variables ; and how specific intervention techniques address each of those pre-treatment characteristics is provided. The ultimate goal of this line of research is to enable practitioners to prospectively tailor treatments to specific children and increase the overall rate of positives outcomes for children with autism. Research that furthers understanding of how to match clients with efficacious treatments will decrease the outcome variability that characterizes early intervention research at present, and provide for the most efficient allocation of resources during the critical early intervention time-period. This type of research is in its infancy, but is imperative if we are to determine a priori which treatment method will be most effective for a specific child.

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19. Stigler KA, McDonald BC, Anand A, Saykin AJ, McDougle CJ. Structural and functional magnetic resonance imaging of autism spectrum disorders. Brain Research ;2011 ;1380(0):146-161.

The neurobiology of autism spectrum disorders (ASDs) has become increasingly understood since the advent of magnetic resonance imaging (MRI). Initial observations of an above-average head circumference were supported by structural MRI studies that found evidence of increased total brain volume and early rapid brain overgrowth in affected individuals. Subsequent research revealed consistent abnormalities in cortical gray and white matter volume in ASDs. The structural integrity and orientation of white matter have been further elucidated via diffusion tensor imaging methods. The emergence of functional MRI techniques led to an enhanced understanding of the neural circuitry of ASDs, demonstrating areas of dysfunctional cortical activation and atypical cortical specialization. These studies have provided evidence of underconnectivity in distributed cortical networks integral to the core impairments associated with ASDs. Abnormalities in the default-mode network during the resting state have also been identified. Overall, structural and functional MRI research has generated important insights into the neurobiology of ASDs. Additional research is needed to further delineate the underlying brain basis of this constellation of disorders.

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20. Wiggins JL, Peltier SJ, Ashinoff S, Weng S-J, Carrasco M, Welsh RC, Lord C, Monk CS. Using a self-organizing map algorithm to detect age-related changes in functional connectivity during rest in autism spectrum disorders. Brain Research ;2011 ;1380(0):187-197.

Healthy individuals show robust functional connectivity during rest, which is stronger in adults than in children. Connectivity occurs between the posterior and anterior portions of the default network, a group of structures active in the absence of a task, including the posterior cingulate cortex and the superior frontal gyrus. Previous studies found weaker posterior–anterior connectivity in the default network in adults and adolescents with autism spectrum disorders (ASD). However, these studies used small a priori regions of interest (“seeds”) to calculate connectivity. Since seed location for all participants was chosen based on controls’ brains, these studies’ analyses are more tailored to controls than individuals with ASD. An alternative is to use a data-driven approach, such as self-organizing maps (SOM), to create a reference for each participant to calculate connectivity. We used individualized resting-state clusters identified by an SOM algorithm to corroborate previous findings of weaker posterior–anterior connectivity in the ASD group and examine age-related changes in the ASD and control groups. Thirty-nine adolescents with ASD and 41 controls underwent a 10-minute, eyes-open, resting-state functional MRI scan. The SOM analysis revealed that adolescents with ASD versus controls have weaker connectivity between the posterior hub of the default network and the right superior frontal gyrus. Additionally, controls have larger increases in connectivity with age compared to the ASD group. These findings indicate that SOM is a complementary method for calculating connectivity in a clinical population. Additionally, adolescents with ASD have a different developmental trajectory of the default network compared to controls.

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