1. Ackerman S, Schoenrbun S, Hudac C, Bernier R. {{Interactive Effects of Prenatal Antidepressant Exposure and Likely Gene Disrupting Mutations on the Severity of Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Aug 02)
To examine the interactive effects of two proposed risk factors which may contribute to symptom severity of Autism Spectrum Disorder (ASD): prenatal antidepressant exposure and likely gene-disrupting (LGD) mutations. Participants included 2748 individuals with ASD from the Simons Simplex Collection. We examined the effects of prenatal antidepressant exposure, maternal depression, presence of an LGD mutation and their interaction on ASD severity. We found a significant interactive effect between antidepressant exposure and the presence of an LGD mutation on ASD severity in the ADOS and ADI-R verbal communication domains. We consider a « two-hit » model in which one variable lays the foundation for an initial risk which is compounded by a second variable.
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2. Baker JP, Lang B. {{Eugenics and the Origins of Autism}}. {Pediatrics};2017 (Aug);140(2)
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3. Bauman MD, Schumann CS. {{Advances in nonhuman primate models of autism: Integrating neuroscience and behavior}}. {Exp Neurol};2017 (Jul 31)
Given the prevalence and societal impact of autism spectrum disorders (ASD), there is an urgent need to develop innovative preventative strategies and treatments to reduce the alarming number of cases and improve core symptoms for afflicted individuals. Translational efforts between clinical and preclinical research are needed to (i) identify and evaluate putative causes of ASD, (ii) determine the underlying neurobiological mechanisms, (iii) develop and test novel therapeutic approaches and (iv) ultimately translate basic research into safe and effective clinical practices. However, modeling a uniquely human brain disorder, such as ASD, will require sophisticated animal models that capitalize on unique advantages of diverse species including drosophila, zebra fish, mice, rats, and ultimately, species more closely related to humans, such as the nonhuman primate. Here we discuss the unique contributions of the rhesus monkey (Macaca mulatta) model to ongoing efforts to understand the neurobiology of the disorder, focusing on the convergence of brain and behavior outcome measures that parallel features of human ASD.
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4. Broome K, McCabe P, Docking K, Doble M. {{A Systematic Review of Speech Assessments for Children With Autism Spectrum Disorder: Recommendations for Best Practice}}. {Am J Speech Lang Pathol};2017 (Aug 03):1-19.
Purpose: The purpose of this systematic review was to provide a summary and evaluation of speech assessments used with children with autism spectrum disorders (ASD). A subsequent narrative review was completed to ascertain the core components of an evidence-based pediatric speech assessment, which, together with the results of the systematic review, provide clinical and research guidelines for best practice. Method: A systematic search of eight databases was used to find peer-reviewed research articles published between 1990 and 2014 assessing the speech of children with ASD. Eligible articles were categorized according to the assessment methods used and the speech characteristics described. Results: The review identified 21 articles that met the inclusion criteria, search criteria, and confidence in ASD diagnosis. The speech of prelinguistic participants was assessed in seven articles. Speech assessments with verbal participants were completed in 15 articles with segmental and suprasegmental aspects of speech analyzed. Assessment methods included connected speech samples, single-word naming tasks, speech imitation tasks, and analysis of the production of words and sentences. Conclusions: Clinical and research guidelines for speech assessment of children with ASD are outlined. Future comparisons will be facilitated by the use of consistent reporting methods in research focusing on children with ASD.
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5. Chien YL, Chou MC, Chiu YN, Chou WJ, Wu YY, Tsai WC, Gau SS. {{ADHD-related symptoms and attention profiles in the unaffected siblings of probands with autism spectrum disorder: focus on the subtypes of autism and Asperger’s disorder}}. {Mol Autism};2017;8:37.
BACKGROUND: The presence of attention-deficit/hyperactive disorder (ADHD) symptoms and impaired attention performance are commonly noted in individuals with autism spectrum disorder (ASD). However, little is known about attention performance in their unaffected siblings. This study aimed to investigate the ADHD-related traits and attention performance in unaffected siblings of probands with autism and Asperger syndrome (AS), as well as the clinical correlates of ADHD-related traits. METHODS: We assessed the intention, hyperactivity-impulsivity, and oppositional symptoms, and attention profiles of 199 probands with a diagnosis of ASD (122 autism, 77 AS), their unaffected siblings, and 196 typically developing controls (TD) by their parents’ reports on the ADHD-related symptoms and the Connors’ Continuous Performance Test (CCPT), respectively. RESULTS: Compared to TD, unaffected siblings of ASD probands were more hyperactive/impulsive and oppositional, particularly unaffected siblings of AS probands. In CCPT, unaffected siblings of AS have intermediate levels of performance between probands with AS and TD on focused attention and sustained attention but were not statistically different from AS probands or TD in these attention profiles. In contrast, unaffected siblings of autism probands have significantly better CCPT performance when compared to autism probands but not to TD. In addition, stereotyped behaviors predicted ADHD-related traits in both sibling groups, but distinctive patterns of other correlates for ADHD-related traits were found between the two sibling groups. CONCLUSIONS: This work suggested that unaffected siblings of AS, but not autism, have more hyperactive/impulsive traits and a trend of pervasive attention deficits assessed by CCPT which might serve as potential endophenotypes for genetic studies in AS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01582256.
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6. Dimmock DP. {{Should we implement population screening for fragile X?}}. {Genet Med};2017 (Aug 03)
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7. Ethridge LE, White SP, Mosconi MW, Wang J, Pedapati EV, Erickson CA, Byerly MJ, Sweeney JA. {{Erratum to: Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome}}. {Mol Autism};2017;8:38.
[This corrects the article DOI: 10.1186/s13229-017-0140-1.].
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8. Frye RE, Slattery JC, Quadros EV. {{Folate metabolism abnormalities in autism: potential biomarkers}}. {Biomark Med};2017 (Aug 03)
Autism spectrum disorder (ASD) has been linked to abnormalities in folate metabolism. Polymorphisms in folate genes may act in complex polygenic ways to increase the risk of developing ASD. Autoantibodies that block folate transport into the brain have been associated with ASD and children with ASD and these autoantibodies respond to high doses of a reduced form of folate known as folinic acid (leucovorin calcium). Some of the same abnormalities are also found in mothers of children with ASD and supplementing folate during preconception and gestational periods reduces the risk to the offspring from developing ASD. These data suggest that folate pathway abnormalities may be a major metabolic disturbance underlying ASD that can be leveraged as biomarkers to improve symptoms and prevent ASD.
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9. Horie M, Okamura H. {{Exploring a method for evaluation of preschool and school children with autism spectrum disorder through checking their understanding of the speaker’s emotions with the help of prosody of the voice}}. {Brain Dev};2017 (Jul 31)
PURPOSE: We attempted to evaluate the ability of 125 preschool and school children with autism spectrum disorder (ASD children) to understand the intentions of those speaking to them using prosody of the voice, by comparing it with that of 119 typically developing children (TDC) and 51 development-age-matched children with attention deficit hyperactivity disorder (ADHD children), and to explore, based on the results, a method for objective evaluation of children with ASD in the early and later periods of childhood. METHODS: Phrases routinely used by children were employed in the task administered to the children, with the prosody of the voice speaking these phrases changed to express the four emotions (acceptance, rejection, bluff and fooling). RESULTS: The percentage of children with ASD who could correctly identify the emotion of « fooling » was significantly lower than that of TDC, at each developmental age (corresponding to middle kindergarten class to sixth year of elementary school). On the other hand, in the children with ADHD, while the correct answer rate for identifying the emotion of « fooling » was significantly lower than that in the TDC and higher than that in the ASD children at development ages corresponding to the early years of elementary school, it did not differ significantly from that in the TDC and was higher than that ASD children at development ages corresponding to the later years of elementary school. CONCLUSION: These results indicate that children with ASD find it particularly difficult to understand the emotion of fooling by listening to speech with discrepancy between the meaning of the phrases and the emotion expressed by the voice, although the prosody of the voice may serve as a key to understanding the emotion of the speakers. This finding also suggests that the prosody of the voice expressing this emotion (fooling) may be used for objective evaluation of children with ASD.
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10. Isaacs D. {{Poverty in the USA and asthma, autism and attention deficit disorder}}. {J Paediatr Child Health};2017 (Aug);53(8):824.
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11. Kawada K, Mimori S. {{Implication of Endoplasmic Reticulum Stress in Autism Spectrum Disorder}}. {Neurochem Res};2017 (Aug 02)
Autism spectrum disorder (ASD) is categorized as a neurodevelopmental disorder according to the Diagnostic and Statistical Manual of Disorders, Fifth Edition and is defined as a congenital impairment of the central nervous system. ASD may be caused by a chromosomal abnormality or gene mutation. However, these etiologies are insufficient to account for the pathogenesis of ASD. Therefore, we propose that the etiology and pathogenesis of ASD are related to the stress of the endoplasmic reticulum (ER). ER stress, induced by valproic acid, increased in ASD mouse model, characterized by an unfolded protein response that is activated by this stress. The inhibition of neurite outgrowth and expression of synaptic factors are observed in ASD. Similarly, ER stress suppresses the neurite outgrowth and expression of synaptic factors. Additionally, hyperplasia of the brain is observed in patients with ASD. ER stress also enhances neuronal differentiation. Synaptic factors, such as cell adhesion molecule and shank, play important roles in the formation of neural circuits. Thus, ER stress is associated with the abnormalities of neuronal differentiation, neurite outgrowth, and synaptic protein expression. ER stress elevates the expression of the ubiquitin-protein ligase HRD1 for the degradation of unfolded proteins. HRD1 expression significantly increased in the middle frontal cortex in the postmortem of patients with ASD. Moreover, HRD1 silencing improved the abnormalities induced by ER stress. Because other ubiquitin ligases are related with neurite outgrowth, ER stress may be related to the pathogenesis of neuronal developmental diseases via abnormalities of neuronal differentiation or maturation.
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12. Li X, Wang Q, Wu Y, Wang S, Huang Y, Li T. {{Personality Characteristics and Neurocognitive Functions in Parents of Children with Autism Spectrum Disorder}}. {Shanghai Arch Psychiatry};2017 (Feb 25);29(1):41-47.
BACKGROUND: The increasing prevalence of autism spectrum disorder in children and the huge family burdens have caused concern in the academic field as well as society. AIM: To study the personality characteristics and neurocognitive functions in the Chinese parents of children with autism spectrum disorder (ASD) and compare them with the parents of well-developed children. METHOD: This study recruited 41 Chinese children who met the diagnostic criteria of autism spectrum disorder according to Diagnostic and Statistical Manual of mental disorders-IV (DSM-IV). Their 79 biological parents were evaluated by means of Eysenck Personality Questionnaire (EPQ) and a set of neuropsychological tests. The normal control group consisted of 80 parents of well-developed children, and they were matched by age and gender. RESULTS: We found that the EPQ scores in the P scale for parents of children with ASD were significantly higher than the parents of well-developed children (t=1.68, p=0.039), while their scores in E scale and L scale were significantly lower (t=1.84, p=0.035; t=2.07, p=0.023). We also identified that the parents of children with ASD took significantly longer time than the normal control to complete Trail Making Test (TMT) Part A and Part B-M (t=1.57, p=0.013; t=0.83, p=0.019). CONCLUSION: Compared to the parents of well-developed children, the parents of children with ASD were more likely to be unconcerned, rigid, stubborn, introverted, and reticent. They displayed less novelty and thrill-seeking behaviors, and had limited social skills and maturity. Although the general cognitive functions including IQ were relatively intact in the parents of children with ASD, there were impairments in their planning, flexibility and visual processing functions.
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13. Mackay BA, Shochet IM, Orr JA. {{A Pilot Randomised Controlled Trial of a School-Based Resilience Intervention to Prevent Depressive Symptoms for Young Adolescents with Autism Spectrum Disorder: A Mixed Methods Analysis}}. {J Autism Dev Disord};2017 (Aug 02)
Despite increased depression in adolescents with Autism Spectrum Disorder (ASD), effective prevention approaches for this population are limited. A mixed methods pilot randomised controlled trial (N = 29) of the evidence-based Resourceful Adolescent Program-Autism Spectrum Disorder (RAP-A-ASD) designed to prevent depression was conducted in schools with adolescents with ASD in years 6 and 7. Quantitative results showed significant intervention effects on parent reports of adolescent coping self-efficacy (maintained at 6 month follow-up) but no effect on depressive symptoms or mental health. Qualitative outcomes reflected perceived improvements from the intervention for adolescents’ coping self-efficacy, self-confidence, social skills, and affect regulation. Converging results remain encouraging given this population’s difficulties coping with adversity, managing emotions and interacting socially which strongly influence developmental outcomes.
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14. Murphy SM, Chowdhury U, White SW, Reynolds L, Donald L, Gahan H, Iqbal Z, Kulkarni M, Scrivener L, Shaker-Naeeni H, Press DA. {{Cognitive Behaviour Therapy Versus a Counselling Intervention for Anxiety in Young People with High-Functioning Autism Spectrum Disorders: A Pilot Randomised Controlled Trial}}. {J Autism Dev Disord};2017 (Aug 02)
The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12-18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements in participants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults.
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15. Puglia MH, Morris JP. {{Neural Response to Biological Motion in Healthy Adults Varies as a Function of Autistic-Like Traits}}. {Front Neurosci};2017;11:404.
Perception of biological motion is an important social cognitive ability that has been mapped to specialized brain regions. Perceptual deficits and neural differences during biological motion perception have previously been associated with autism, a disorder classified by social and communication difficulties and repetitive and restricted interests and behaviors. However, the traits associated with autism are not limited to diagnostic categories, but are normally distributed within the general population and show the same patterns of heritability across the continuum. In the current study, we investigate whether self-reported autistic-like traits in healthy adults are associated with variable neural response during passive viewing of biological motion displays. Results show that more autistic-like traits, particularly those associated with the communication domain, are associated with increased neural response in key regions involved in social cognitive processes, including prefrontal and left temporal cortices. This distinct pattern of activation might reflect differential neurodevelopmental processes for individuals with varying autistic-like traits, and highlights the importance of considering the full trait continuum in future work.
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16. Rodas NV, Eisenhower A, Blacher J. {{Structural and Pragmatic Language in Children with ASD: Longitudinal Impact on Anxiety and Externalizing Behaviors}}. {J Autism Dev Disord};2017 (Aug 03)
Children with autism spectrum disorder (ASD) are at heightened risk for developing comorbid psychological disorders, including anxiety disorders, which may be further exacerbated by the presence of externalizing behaviors. Here, we examined how structural language and pragmatic language predicted anxiety and externalizing behaviors. Participants were 159 young children (4-7 years old) with ASD and their mothers. Utilizing structural equation modeling we examined associations among structural language, pragmatic language, anxiety symptoms, and externalizing behaviors. Pragmatic language, was inversely related to child anxiety and co-occurring externalizing behaviors. Structural language skills positively predicted child anxiety. These findings suggest that children with ASD may be at heightened risk for anxiety and externalizing disorders due to their pragmatic language deficits.
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17. Seymour M, Giallo R, Wood CE. {{The psychological and physical health of fathers of children with Autism Spectrum Disorder compared to fathers of children with long-term disabilities and fathers of children without disabilities}}. {Res Dev Disabil};2017 (Aug 01);69:8-17.
BACKGROUND: The psychological and physical health of fathers of children with Autism Spectrum Disorder (ASD) is under-researched. Due to the unique parenting demands, fathers of children with ASD may be at increased risk of experiencing psychological and physical health difficulties compared to fathers of children without disabilities (W/OD) and fathers of children with other long-term disabilities (LTD). What little research there is on fathers of children with ASD is often conducted on small clinical samples, or embeds the experiences of fathers within other groups. AIM: The current study aimed to explore the extent to which fathers of children with ASD experience psychological distress and physical health issues (e.g., general health, smoking, chronic pain) compared to fathers of children W/OD and fathers of children with a LTD. METHOD: From a large, nationally representative sample of children, 159 fathers of children with ASD were identified, along with 45 fathers of children with a LTD and 6578 fathers of children W/OD. RESULTS: The majority of fathers were experiencing good psychological and physical health. Approximately 1 in 6 fathers of children with ASD were experiencing elevated levels of psychological distress and poor global health, and were at significantly greater risk than fathers of children W/OD; although these differences were not found compared to fathers of children with a LTD. CONCLUSIONS: Some fathers of children with ASD may require additional support which not only focuses on their psychological wellbeing but also fathers’ physical health. The current findings encourage health services to check-in with, or reach-out to fathers as they too may require additional support.
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18. Stephen JM, Hill DE, Peters A, Flynn L, Zhang T, Okada Y. {{Development of Auditory Evoked Responses in Normally Developing Preschool Children and Children with Autism Spectrum Disorder}}. {Dev Neurosci};2017 (Aug 04)
The cortical responses to auditory stimuli undergo rapid and dramatic changes during the first 3 years of life in normally developing (ND) children, with decreases in latency and changes in amplitude in the primary peaks. However, most previous studies have focused on children >3 years of age. The analysis of data from the early stages of development is challenging because the temporal pattern of the evoked responses changes with age (e.g., additional peaks emerge with increasing age) and peak latency decreases with age. This study used the topography of the auditory evoked magnetic field (AEF) to identify the auditory components in ND children between 6 and 68 months (n = 48). The latencies of the peaks in the AEF produced by a tone burst (ISI 2 +/- 0.2 s) during sleep decreased with age, consistent with previous reports in awake children. The peak latencies of the AEFs in ND children and children with autism spectrum disorder (ASD) were compared. Previous studies indicate that the latencies of the initial components of the auditory evoked potential (AEP) and the AEF are delayed in children with ASD when compared to age-matched ND children >4 years of age. We speculated whether the AEF latencies decrease with age in children diagnosed with ASD as in ND children, but with uniformly longer latencies before the age of about 4 years. Contrary to this hypothesis, the peak latencies did not decrease with age in the ASD group (24-62 months, n = 16) during sleep (unlike in the age-matched controls), although the mean latencies were longer in the ASD group as in previous studies. These results are consistent with previous studies indicating delays in auditory latencies, and they indicate a different maturational pattern in ASD children and ND children. Longitudinal studies are needed to confirm whether the AEF latencies diverge with age, starting at around 3 years, in these 2 groups of children.
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19. Thomson SR, Seo SS, Barnes SA, Louros SR, Muscas M, Dando O, Kirby C, Wyllie DJA, Hardingham GE, Kind PC, Osterweil EK. {{Cell-Type-Specific Translation Profiling Reveals a Novel Strategy for Treating Fragile X Syndrome}}. {Neuron};2017 (Aug 02);95(3):550-563.e555.
Excessive mRNA translation downstream of group I metabotropic glutamate receptors (mGlu1/5) is a core pathophysiology of fragile X syndrome (FX); however, the differentially translating mRNAs that contribute to altered neural function are not known. We used translating ribosome affinity purification (TRAP) and RNA-seq to identify mistranslating mRNAs in CA1 pyramidal neurons of the FX mouse model (Fmr1-/y) hippocampus, which exhibit exaggerated mGlu1/5-induced long-term synaptic depression (LTD). In these neurons, we find that the Chrm4 transcript encoding muscarinic acetylcholine receptor 4 (M4) is excessively translated, and synthesis of M4 downstream of mGlu5 activation is mimicked and occluded. Surprisingly, enhancement rather than inhibition of M4 activity normalizes core phenotypes in the Fmr1-/y, including excessive protein synthesis, exaggerated mGluR-LTD, and audiogenic seizures. These results suggest that not all excessively translated mRNAs in the Fmr1-/y brain are detrimental, and some may be candidates for enhancement to correct pathological changes in the FX brain.
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20. Van Etten HM, Kaur M, Srinivasan SM, Cohen SJ, Bhat A, Dobkins KR. {{Increased Prevalence of Unusual Sensory Behaviors in Infants at Risk for, and Teens with, Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Aug 02)
The current study investigated the prevalence and pattern of unusual sensory behaviors (USBs) in teens with Autism Spectrum Disorder (ASD) and infants (3-36 months) at risk for ASD. From two different sites (UCSD and UConn), caregivers of infants at high (n = 32) and low risk (n = 33) for ASD, and teenagers with (n = 12) and without ASD (n = 11), completed age-appropriate Sensory Profile questionnaires (Infant/Toddler Sensory Profile; Dunn 2002; Adolescent/Adult Sensory Profile; Brown and Dunn 2002). The results show that high-risk infants and teenagers with ASD exhibit higher-than-typical prevalence of USBs. Results of our distribution analyses investigating the direction of sensory atypicalities (greater-than-typical vs. less-than-typical) revealed a fair degree of consistency amongst teens, however, USB patterns were more varied in high-risk infants.
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21. van Steenburgh JJ, Varvaris M, Schretlen DJ, Vannorsdall TD, Gordon B. {{Balanced bifrontal transcranial direct current stimulation enhances working memory in adults with high-functioning autism: a sham-controlled crossover study}}. {Mol Autism};2017;8:40.
BACKGROUND: Working memory (WM) often is impaired in autism spectrum disorder (ASD). Such impairment may underlie core deficits in cognition and social functioning. Transcranial direct current stimulation (tDCS) has been shown to enhance WM in both healthy adults and clinical populations, but its efficacy in ASD is unknown. We predicted that bifrontal tDCS would improve WM performances of adults with high-functioning autism during active stimulation compared to sham stimulation and that such enhancement would generalize to an untrained task. METHODS: Twelve adults with high-functioning ASD engaged in a battery of WM tasks that included backward spatial span, backward digit span, spatial n-back and letter n-back. While engaged, 40 min of 1.5 mA bifrontal stimulation was applied over the left and the right dorsolateral prefrontal cortices (DLPFC). Using a single-blind crossover design, each participant received left anodal/right cathodal stimulation, right anodal/left cathodal stimulation, or sham stimulation, in randomized counterbalanced order on three separate days. Following tDCS, participants again engaged in letter and spatial n-back tasks before taking the Brief Test of Attention (BTA). We used repeated-measures ANOVA to compare overall performance on the WM battery as measured by a composite of z-scores for all five measures. Post hoc ANOVAs, t tests, Friedman’s tests, and Wilcoxon signed-rank tests were used to measure the online and offline effects of tDCS and to assess performances on individual measures. RESULTS: Compared to sham stimulation, both left DLPFC anodal stimulation (t11 = 5.4, p = 0.0002) and right DLPFC anodal stimulation (t11 = 3.57, p = 0.004) improved overall WM performance. Left anodal stimulation (t11 = 3.9, p = 0.003) and right anodal stimulation (t11 = 2.7, p = 0.019) enhanced performances during stimulation. Enhancement transferred to an untrained task 50 min after right anodal stimulation (z11 = 2.263, p = 0.024). The tasks that showed the largest effects of active stimulation were spatial span backward (z11 = 2.39, p = 0.017) and BTA (z11 = 2.263, p = 0.024). CONCLUSIONS: In adults with high-functioning ASD, active bifrontal tDCS given during WM tasks appears to improve performance. TDCS benefits also transferred to an untrained task completed shortly after stimulation. These results suggest that tDCS can improve WM task performance and could reduce some core deficits of autism. TRIAL REGISTRATION: NCT01602263.
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22. Yerys BE, Herrington JD, Satterthwaite TD, Guy L, Schultz RT, Bassett DS. {{Globally weaker and topologically different: resting-state connectivity in youth with autism}}. {Mol Autism};2017;8:39.
BACKGROUND: There is a lack of agreement about functional connectivity differences in individuals with autism spectrum disorder (ASD). Studies using absolute strength have found reduced connectivity, while those using relative strength–a measure of system topology–reveal mostly enhanced connectivity. We hypothesized that mixed findings may be driven by the metric of functional connectivity. METHODS: Resting-state echo planar 3 T functional magnetic resonance imaging scans were acquired on a Siemens Verio Scanner from 6 to 17-year-old youth with ASD (n = 81) and a matched typically developing control group (n = 82). All functional time series data were preprocessed using a confound regression procedure that has been previously validated in large-scale developmental datasets. It has also been shown to be highly effective at reducing the influence of motion artifact on connectivity data. We extracted time series data from a 333-node parcellation scheme, which was previously mapped to 13 functional systems. A Pearson’s correlation was calculated and transformed to Fisher’s z between every pair of nodes to create a weighted 333 x 333 adjacency matrix. Mean absolute functional connectivity strength was the mean Fisher’s z of the matrix. Relative functional connectivity was corrected for individual differences in mean absolute functional connectivity (i.e., each connection in the matrix was divided by their mean z), and functional connectivity was evaluated within and across each of the functional networks in the parcellation scheme. RESULTS: Absolute functional connectivity strength was lower in ASD, and lower functional connectivity was correlated with greater ASD symptom severity. Relative functional connectivity was higher for the ASD group in the ventral attention and retrosplenial-temporal systems, with lower cross-system functional connectivity between the ventral attention and somatomotor-mouth systems. Functional connectivity within the ventral attention and retro-splenial systems correlated significantly with ASD symptom severity. CONCLUSIONS: Within a context of globally weaker functional connectivity, youth with ASD have an atypical topology of brain systems that support social perception and communication. This study clarifies the mixed results reported previously and demonstrates that the functional connectivity metric influences the observed direction of functional connectivity differences for individuals with ASD.
