Recognizing structure in novel tunes: differences between human and rats.

A central feature in music is the hierarchical organization of its components. Musical pieces are not a simple concatenation of chords, but are characterized by rhythmic and harmonic structures. Here, we explore if sensitivity to music structure might emerge in the absence of any experience with musical stimuli. For this, we tested if rats detect the difference between structured and unstructured musical excerpts and compared their performance with that of humans. Structured melodies were excerpts of Mozart's sonatas. Unstructured melodies were created by the recombination of fragments of different sonatas. We trained listeners (both human participants and Long-Evans rats) with a set of structured and unstructured excerpts, and tested them with completely novel excerpts they had not heard before. After hundreds of training trials, rats were able to tell apart novel structured from unstructured melodies. Human listeners required only a few trials to reach better performance than rats. Interestingly, such performance was increased in humans when tonality changes were included, while it decreased to chance in rats. Our results suggest that, with enough training, rats might learn to discriminate acoustic differences differentiating hierarchical music structures from unstructured excerpts. More importantly, the results point toward species-specific adaptations on how tonality is processed.

Actionable and incidental neuroradiological findings in twins with neurodevelopmental disorders.

While previous research has investigated neuroradiological findings in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), the entire range of neurodevelopmental disorders (NDDs) has not yet been well-studied using magnetic resonance imaging (MRI). Considering the overlap among NDDs and simultaneous development of the brain and face, guided by molecular signaling, we examined the relationship of actionable and incidental (non-actionable) MRI findings and NDD diagnoses together with facial morphological variants and genetic copy number variants (CNVs). A cross-sectional study was conducted with a twin cohort 8-36 years of age (57% monozygotic, 40% dizygotic), including 372 subjects (46% with NDDs; 47% female) imaged by MRI, 280 with data for facial morphological variants, and 183 for CNVs. Fifty-one percent of participants had MRI findings. Males had a statistically significantly higher percentage of MRI findings (57.7%) compared with females (43.8%, p = 0.03). Twin zygosity was not statistically significantly correlated with incidence or severity of specific MRI findings. No statistically significant association was found between MRI findings and any NDD diagnosis or facial morphological variants; however, MRI findings were statistically significantly associated with the number of CNVs (OR 1.20, 95% CI 1.00-1.44, p = 0.05, adjusted OR for sex 1.24, 95% CI 1.03-1.50, p = 0.02). When combining the presence of MRI findings, facial morphological variants, and CNVs, statistically significant relationships were found with ASD and ADHD diagnoses (p = 0.0006 and p = 0.002, respectively). The results of this study demonstrate that the ability to identify NDDs from combined radiology, morphology, and CNV assessments may be possible. Additionally, twins do not appear to be at increased risk for neuroradiological variants.

The social brain in female autism: a structural imaging study of twins.

A female advantage in social cognition (SoC) might contribute to women's underrepresentation in autism spectrum disorder (ASD). The latter could be underpinned by sex differences in social brain structure. This study investigated the relationship between structural social brain networks and SoC in females and males in relation to ASD and autistic traits in twins. We used a co-twin design in 77 twin pairs (39 female) aged 12.5 to 31.0 years. Twin pairs were discordant or concordant for ASD or autistic traits, discordant or concordant for other neurodevelopmental disorders or concordant for neurotypical development. They underwent structural magnetic resonance imaging and were assessed for SoC using the naturalistic Movie for the Assessment of Social Cognition. Autistic traits predicted reduced SoC capacities predominantly in male twins, despite a comparable extent of autistic traits in each sex, although the association between SoC and autistic traits did not differ significantly between the sexes. Consistently, within-pair associations between SoC and social brain structure revealed that lower SoC ability was associated with increased cortical thickness of several brain regions, particularly in males. Our findings confirm the notion that sex differences in SoC in association with ASD are underpinned by sex differences in brain structure.

Sex differences in brain structure: a twin study on restricted and repetitive behaviors in twin pairs with and without autism.

Background: Females with autism spectrum disorder have been reported to exhibit fewer and less severe restricted and repetitive behaviors and interests compared to males. This difference might indicate sex-specific alterations of brain networks involved in autism symptom domains, especially within cortico-striatal and sensory integration networks. This study used a well-controlled twin design to examine sex differences in brain anatomy in relation to repetitive behaviors. Methods: In 75 twin pairs (n = 150, 62 females, 88 males) enriched for autism spectrum disorder (n = 32), and other neurodevelopmental disorders (n = 32), we explored the association of restricted and repetitive behaviors and interests-operationalized by the Autism Diagnostic Interview-Revised (C domain) and the Social Responsiveness Scale-2 (Restricted Interests and Repetitive Behavior subscale)-with cortical volume, surface area and thickness of neocortical, sub-cortical, and cerebellar networks. Results: Co-twin control analyses revealed within-pair associations between RRBI symptoms and increased thickness of the right intraparietal sulcus and reduced volume of the right orbital gyrus in females only, even though the mean number of RRBIs did not differ between the sexes. In a sub-sample of ASD-discordant pairs, increased thickness in association with RRBIs was found exclusively in females in the orbitofrontal regions, superior frontal gyrus, and intraparietal sulcus, while in males RRBIs tended to be associated with increased volume of the bilateral pallidum. Limitations: However, due to a small sample size and the small difference in RRBI symptoms within pairs, the results of this exploratory study need to be interpreted with caution. Conclusions: Our findings suggest that structural alterations of fronto-parietal networks in association with RRBIs are found mostly in females, while striatal networks are more affected in males. These results endorse the importance of investigating sex differences in the neurobiology of autism symptoms, and indicate different etiological pathways underlying restricted and repetitive behaviors and interests in females and males.

Sex Differences Along the Autism Continuum: A Twin Study of Brain Structure.

Females might possess protective mechanisms regarding autism spectrum disorder (ASD) and require a higher detrimental load, including structural brain alterations, before developing clinically relevant levels of autistic traits. This study examines sex differences in structural brain morphology in autism and autistic traits using a within-twin pair approach. Twin design inherently controls for shared confounders and enables the study of gene-independent neuroanatomical variation. N = 148 twins (62 females) from 49 monozygotic and 25 dizygotic same-sex pairs were included. Participants were distributed along the whole continuum of autism including twin pairs discordant and concordant for clinical ASD. Regional brain volume, surface area, and cortical thickness were computed. Within-twin pair increases in autistic traits were related to decreases in cortical volume and surface area of temporal and frontal regions specifically in female twin pairs, in particular regions involved in social communication, while only two regions were associated with autistic traits in males. The same pattern was detected in the monozygotic twin pairs only. Thus, non-shared environmental factors seem to impact female more than male cerebral architecture associated with autistic traits. Our results are in line with the hypothesis of a female protective effect in autism and highlights the need to study ASD in females separately from males.

EU-AIMS Longitudinal European Autism Project (LEAP): the autism twin cohort.

EU-AIMS is the largest European research program aiming to identify stratification biomarkers and novel interventions for autism spectrum disorder (ASD). Within the program, the Longitudinal European Autism Project (LEAP) has recruited and comprehensively phenotyped a rare sample of 76 monozygotic and dizygotic twins, discordant, or concordant for ASD plus 30 typically developing twins. The aim of this letter is to complete previous descriptions of the LEAP case-control sample, clinically characterize, and investigate the suitability of the sample for ASD twin-control analyses purposes and share some 'lessons learnt.' Among the twins, a diagnosis of ASD is associated with increased symptom levels of ADHD, higher rates of intellectual disability, and lower family income. For the future, we conclude that the LEAP twin cohort offers multiple options for analyses of genetic and shared and non-shared environmental factors to generate new hypotheses for the larger cohort of LEAP singletons, but particularly cross-validate and refine evidence from it.

Cross-Cultural Validation of the York Measure of Quality of Intensive Behavioral Intervention.

Early intensive behavioral intervention (EIBI) is widely applied in young children with autism spectrum disorder. Little research has addressed the significance of adherence to EIBI practices for treatment outcomes. The York Measure of Quality of Intensive Behavioral Intervention (YMQI) was designed to assess EIBI quality delivery in Ontario, Canada. The objective of this study was to examine the cross-cultural validity of the YMQI in a clinical Swedish community sample of 30 boys and four girls with autism aged 2.5 to 6 years. Internal consistency was alpha = .87 for the full scale YMQI. Interrater reliability among three raters on 97 video-recorded therapy sequences was .71 (intraclass correlation coefficient [ICC]), and intrarater reliability of two raters re-scoring 15 sequences after 6 months was ICC = .87. The convergent validity of the YMQI with EIBI expert ratings was r = .49. Findings endorse the psychometric properties of the YMQI and its usability outside of Anglo-Saxon countries.