Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

Canonical babbling trajectories across the first year of life in autism and typical development.

LAY ABSTRACT: Our study examined how babies develop their ability to talk to help identify early signs of autism. We looked at babies' production of babbling with mature syllables across the first year of life. Babies usually start producing mature babbling at 7 months of age before they say their first words. Some studies have suggested that babies who are later diagnosed with autism produce this kind of babbling less frequently in their first year of life, but other studies have shown complicated outcomes. In this new study, we followed 44 autistic babies and compared them to 127 typically developing babies. We recorded the babies once every month, all day long, from the time that they were born until they were around 13 months old. Then, we studied their mature babbling from segments of these recordings. We found that the rate at which babies used mature babbling was lower in boys with autism, and higher in girls with autism, compared to babies without autism. This research helps us understand how babies with autism learn to talk. It also raises important questions about differences between boys and girls with autism. Our study can help us improve how scientists and clinicians can identify autism earlier, which could lead to better communication supports for autistic children and their families.

Clinical Correlates and Prevalence of Food Selectivity in Children with Autism Spectrum Disorder.

OBJECTIVE: To examine clinical correlates and prevalence of food selectivity (FS) - ie, self-restricted diet, reluctance to try new foods - in children with autism spectrum disorder (ASD) ascertained from a general outpatient autism clinic. STUDY DESIGN: A multidisciplinary team (pediatric nurse practitioner, psychologist and dietitian) assessed medical and psychosocial histories and dietary habits in 103 children with ASD (mean age = 5.8 ± 2.2 years; range 2-10). Parents rated child mealtime behavior on the Brief Autism Mealtime Behavior Inventory (BAMBI) and disruptive behavior on the Aberrant Behavior Checklist (ABC). Height and weight measurements were collected. Children were classified as FS or no FS based on parent reported intake and mealtime behavior. A 24-hour dietary recall was used to record intake percentages < 80%. Logistic regression and multivariable modeling were used to evaluate clinical correlates with FS. RESULTS: Of 103 children, 45.6% (n = 47) were classified as FS; 54.4% (n = 56) no FS. After adjusting for potential confounders, the odds of FS increased by 1.91 (95% CI: 1.38, 2.64, P < .001) for every half-SD increase in BAMBI total score and by 1.35 (95% CI: 1.05, 1.74, P = .020) for every half-SD increase in ABC Hyperactivity/Noncompliance. No group differences in anthropometrics or nutritional intake were identified. CONCLUSIONS: Food selectivity (FS) in children with ASD was strongly associated with greater severity of disruptive mealtime and hyperactivity/noncompliance behaviors. FS was not associated with anthropometrics or nutritional intake.

Foundations of Vocal Category Development in Autistic Infants.

The present study compared the infant's tendency in the first year of life to produce clusters of particular vocal types (squeals, vocants, and growls) in typically developing (TD) and autistic infants. Vocal clustering provides evidence of vocal category formation and may establish a foundation for speech development. Specifically, we compared the extent of vocal clustering across outcome groups and age groups. We also examined the associations between the extent of vocal clustering and later outcomes at 2 years within the autistic group. Randomly selected 5-min segments (27,153 5-min segments total) from 1293 all-day home recordings from 103 TD infants and 44 autistic infants across the first year were humancoded (about 9.75 h of data coded per infant on average) to derive vocal clustering patterns. Fisher's exact tests were used to compare the occurrence of squeals versus vocants, as well as growls versus vocants, across coded segments. Infants in both groups demonstrated clear clustering patterns of squeals and growls across all age groups. The extent of vocal clustering in the autistic group did not correlate significantly with later language, repetitive behavior, or autism severity outcomes. These findings highlight the robustness of the systematic production of vocal categories across the first year of life. The similarity of the clustering patterns in the TD and autistic groups suggests that vocal category formation through active infant vocal exploration is a robust feature of early speech development.

Sensorimotor and inhibitory control in aging FMR1 premutation carriers.

Aging FMR1 premutation carriers are at risk of developing neurodegenerative disorders, including fragile X-associated tremor/ataxia syndrome (FXTAS), and there is a need to identify biomarkers that can aid in identification and treatment of these disorders. While FXTAS is more common in males than females, females can develop the disease, and some evidence suggests that patterns of impairment may differ across sexes. Few studies include females with symptoms of FXTAS, and as a result, little information is available on key phenotypes for tracking disease risk and progression in female premutation carriers. Our aim was to examine quantitative motor and cognitive traits in aging premutation carriers. We administered oculomotor tests of visually guided/reactive saccades (motor) and antisaccades (cognitive control) in 22 premutation carriers (73% female) and 32 age- and sex-matched healthy controls. Neither reactive saccade latency nor accuracy differed between groups. FMR1 premutation carriers showed increased antisaccade latencies relative to controls, both when considering males and females together and when analyzing females separately. Reduced saccade accuracy and increased antisaccade latency each were associated with more severe clinically rated neuromotor impairments. Findings indicate that together male and female premutation carriers show a reduced ability to rapidly exert volitional control over prepotent responses and that quantitative differences in oculomotor behavior, including control of visually guided and antisaccades, may track with FXTAS - related degeneration in male and female premutation carriers.

Screening for Caregiver-Reported Feeding Concerns in Children with Autism Spectrum Disorder in a Tertiary-Care Clinic.

OBJECTIVE: Feeding concerns, primarily food selectivity, are commonly observed in children with autism spectrum disorder (ASD). Prevalence rates suggest that at least half of autistic youth have feeding difficulties. METHODS: A retrospective chart review examining records of a large cohort of autistic children (N = 746) referred for ASD evaluation was conducted. Families completed a survey regarding feeding concerns in their children before a diagnostic evaluation. RESULTS: Post hoc analyses based on retrospective chart review revealed approximately 30% of caregivers reported significant difficulty feeding their child. Young age, food selectivity, and concerns about weight were associated with increased likelihood of reported feeding difficulties. There was clear overlap between overall feeding difficulties and specific food selectivity; however, 1 in 5 children whose caregivers did not report feeding difficulties endorsed food selectivity. CONCLUSION: Findings highlight the need for multipronged approaches to screening to facilitate service prioritization by pediatric providers.