Corrigendum: Cerebellar volumes and sensorimotor behavior in autism spectrum disorder.

[This corrects the article DOI: 10.3389/fnint.2022.821109.].

Cerebellar Volumes and Sensorimotor Behavior in Autism Spectrum Disorder.

Background: Sensorimotor issues are common in autism spectrum disorder (ASD), though their neural bases are not well understood. The cerebellum is vital to sensorimotor control and reduced cerebellar volumes in ASD have been documented. Our study examined the extent to which cerebellar volumes are associated with multiple sensorimotor behaviors in ASD. Materials and Methods: Fifty-eight participants with ASD and 34 typically developing (TD) controls (8-30 years) completed a structural MRI scan and precision grip testing, oculomotor testing, or both. Force variability during precision gripping as well as absolute error and trial-to-trial error variability of visually guided saccades were examined. Volumes of cerebellar lobules, vermis, and white matter were quantified. The relationships between each cerebellar region of interest (ROI) and force variability, saccade error, and saccade error variability were examined. Results: Relative to TD controls, individuals with ASD showed increased force variability. Individuals with ASD showed a reduced volume of cerebellar vermis VI-VII relative to TD controls. Relative to TD females, females with ASD showed a reduced volume of bilateral cerebellar Crus II/lobule VIIB. Increased volume of Crus I was associated with increased force variability. Increased volume of vermal lobules VI-VII was associated with reduced saccade error for TD controls but not individuals with ASD. Increased right lobule VIII and cerebellar white matter volumes as well as reduced right lobule VI and right lobule X volumes were associated with greater ASD symptom severity. Reduced volumes of right Crus II/lobule VIIB were associated with greater ASD symptom severity in only males, while reduced volumes of right Crus I were associated with more severe restricted and repetitive behaviors only in females. Conclusion: Our finding that increased force variability in ASD is associated with greater cerebellar Crus I volumes indicates that disruption of sensory feedback processing supported by Crus I may contribute to skeletomotor differences in ASD. Results showing that volumes of vermal lobules VI-VII are associated with saccade precision in TD but not ASD implicates atypical organization of the brain systems supporting oculomotor control in ASD. Associations between volumes of cerebellar subregions and ASD symptom severity suggest cerebellar pathological processes may contribute to multiple developmental challenges in ASD.

Visual and somatosensory feedback mechanisms of precision manual motor control in autism spectrum disorder.

BACKGROUND: Individuals with autism spectrum disorder (ASD) show deficits processing sensory feedback to reactively adjust ongoing motor behaviors. Atypical reliance on visual and somatosensory feedback each have been reported during motor behaviors in ASD suggesting that impairments are not specific to one sensory domain but may instead reflect a deficit in multisensory processing, resulting in reliance on unimodal feedback. The present study tested this hypothesis by examining motor behavior across different visual and somatosensory feedback conditions during a visually guided precision grip force test. METHODS: Participants with ASD (N = 43) and age-matched typically developing (TD) controls (N = 23), ages 10-20 years, completed a test of precision gripping. They pressed on force transducers with their index finger and thumb while receiving visual feedback on a computer screen in the form of a horizontal bar that moved upwards with increased force. They were instructed to press so that the bar reached the level of a static target bar and then to hold their grip force as steadily as possible. Visual feedback was manipulated by changing the gain of the force bar. Somatosensory feedback was manipulated by applying 80 Hz tendon vibration at the wrist to disrupt the somatosensory percept. Force variability (standard deviation) and irregularity (sample entropy) were examined using multilevel linear models. RESULTS: While TD controls showed increased force variability with the tendon vibration on compared to off, individuals with ASD showed similar levels of force variability across tendon vibration conditions. Individuals with ASD showed stronger age-associated reductions in force variability relative to controls across conditions. The ASD group also showed greater age-associated increases in force irregularity relative to controls, especially at higher gain levels and when the tendon vibrator was turned on. CONCLUSIONS: Our findings that disrupting somatosensory feedback did not contribute to changes in force variability or regularity among individuals with ASD suggests a reduced ability to integrate somatosensory feedback information to guide ongoing precision manual motor behavior. We also document stronger age-associated gains in force control in ASD relative to TD suggesting delayed development of multisensory feedback control of motor behavior.

Atypical neural processing during the execution of complex sensorimotor behavior in autism.

Stereotyped behavior is rhythmic, repetitive movement that is essentially invariant in form. Stereotypy is common in several clinical disorders, such as autism spectrum disorders (ASD), where it is considered maladaptive. However, it also occurs early in typical development (TD) where it is hypothesized to serve as the foundation on which complex, adaptive motor behavior develops. This transition from stereotyped to complex movement in TD is thought to be supported by sensorimotor integration. Stereotypy in clinical disorders may persist due to deficits in sensorimotor integration. The present study assessed whether differences in sensorimotor processing may limit the expression of complex motor behavior in individuals with ASD and contribute to the clinical stereotypy observed in this population. Adult participants with ASD and TD performed a computer-based stimulus-tracking task in the presence and absence of visual feedback. Electroencephalography was recorded during the task. Groups were compared on motor performance (root mean square error), motor complexity (sample entropy), and neural complexity (multiscale sample entropy of the electroencephalography signal) in the presence and absence of visual feedback. No group differences were found for motor performance or motor complexity. The ASD group demonstrated greater neural complexity and greater differences between feedback conditions than TD individuals, specifically in signals relevant to sensorimotor processing. Motor performance and motor complexity correlated with clinical stereotypy in the ASD group. These findings support the hypothesis that individuals with ASD have differences in sensorimotor processing when executing complex motor behavior and that stereotypy is associated with low motor complexity.

Genomic, Clinical, and Behavioral Characterization of 15q11.2 BP1-BP2 Deletion (Burnside-Butler) Syndrome in Five Families.

The 15q11.2 BP1-BP2 deletion (Burnside-Butler) syndrome is emerging as the most common cytogenetic finding in patients with neurodevelopmental or autism spectrum disorders (ASD) presenting for microarray genetic testing. Clinical findings in Burnside-Butler syndrome include developmental and motor delays, congenital abnormalities, learning and behavioral problems, and abnormal brain findings. To better define symptom presentation, we performed comprehensive cognitive and behavioral testing, collected medical and family histories, and conducted clinical genetic evaluations. The 15q11.2 BP1-BP2 region includes the TUBGCP5, CYFIP1, NIPA1, and NIPA2 genes. To determine if additional genomic variation outside of the 15q11.2 region influences expression of symptoms in Burnside-Butler syndrome, whole-exome sequencing was performed on the parents and affected children for the first time in five families with at least one parent and child with the 15q1l.2 BP1-BP2 deletion. In total, there were 453 genes with possibly damaging variants identified across all of the affected children. Of these, 99 genes had exclusively de novo variants and 107 had variants inherited exclusively from the parent without the deletion. There were three genes (APBB1, GOLGA2, and MEOX1) with de novo variants that encode proteins evidenced to interact with CYFIP1. In addition, one other gene of interest (FAT3) had variants inherited from the parent without the deletion and encoded a protein interacting with CYFIP1. The affected individuals commonly displayed a neurodevelopmental phenotype including ASD, speech delay, abnormal reflexes, and coordination issues along with craniofacial findings and orthopedic-related connective tissue problems. Of the 453 genes with variants, 35 were associated with ASD. On average, each affected child had variants in 6 distinct ASD-associated genes (x¯ = 6.33, sd = 3.01). In addition, 32 genes with variants were included on clinical testing panels from Clinical Laboratory Improvement Amendments (CLIA) approved and accredited commercial laboratories reflecting other observed phenotypes. Notably, the dataset analyzed in this study was small and reported results will require validation in larger samples as well as functional follow-up. Regardless, we anticipate that results from our study will inform future research into the genetic factors influencing diverse symptoms in patients with Burnside-Butler syndrome, an emerging disorder with a neurodevelopmental behavioral phenotype.

Visual feedback during motor performance is associated with increased complexity and adaptability of motor and neural output.

Complex motor behavior is believed to be dependent on sensorimotor integration - the neural process of using sensory input to plan, guide, and correct movements. Previous studies have shown that the complexity of motor output is low when sensory feedback is withheld during precision motor tasks. However, much of this research has focused on motor behavior rather than neural processing, and therefore, has not specifically assessed the role of sensorimotor neural functioning in the execution of complex motor behavior. The present study uses a stimulus-tracking task with simultaneous electroencephalography (EEG) recording to assess the effect of visual feedback on motor performance, motor complexity, and sensorimotor neural processing in healthy adults. The complexity of the EEG signal was analyzed to capture the information content in frequency bands (alpha and beta) and scalp regions (central, parietal, and occipital) that are associated with sensorimotor processing. Consistent with previous literature, motor performance and its complexity were higher when visual feedback was provided relative to when it was withheld. The complexity of the neural signal was also higher when visual feedback was provided. This was most robust at frequency bands (alpha and beta) and scalp regions (parietal and occipital) associated with sensorimotor processing. The findings show that visual feedback increases the information available to the brain when generating complex, adaptive motor output.

Subgrouping Autism Based on Symptom Severity Leads to Differences in the Degree of Convergence Between Core Feature Domains.

Existing models of autism spectrum disorder (ASD) disagree as to whether the core features should be conceptualized as convergent (related) or divergent (unrelated), and the few previous studies addressing this question have found conflicting results. We examined standardized parent ratings of symptoms from three domains (social, communication, repetitive behaviors) in large samples of typically developing children, children with ASD, and ASD subgroups. Our results suggest that the most evidence for divergence lies in typically developing children and lower severity ASD cases, while more evidence for convergence is found in a subset of cases with more severe impairment on any core feature. These results highlight the importance of subgrouping ASD given the degree of phenotypic heterogeneity present across the autism spectrum.

A Cohesive Framework for Motor Stereotypy in Typical and Atypical Development: The Role of Sensorimotor Integration.

Stereotyped motor behavior manifests as rhythmic, repetitive movements. It is common in several neurologic and psychiatric disorders where it is considered maladaptive. However, it also occurs early in typical development where it serves an adaptive function in the development of complex, controlled motor behavior. Currently, no framework accounts for both adaptive and maladaptive forms of motor stereotypy. We propose a conceptual model that implicates sensorimotor mechanisms in the phenomenology of adaptive and maladaptive stereotypy. The extensive structural and functional connectivity between sensory and motor neural circuits evidences the importance of sensory integration in the production of controlled movement. In support of our model, motor stereotypy in normative development occurs when the sensory and motor brain regions are immature and the infant has limited sensory and motor experience. With maturation and experience, complex movements develop and replace simple, stereotyped movements. This developmental increase in motor complexity depends on the availability of sensory feedback indicating that the integration of sensory information with ongoing movement allows individuals to adaptively cater their movements to the environmental context. In atypical development, altered neural function of sensorimotor circuitry may limit an individual's ability to integrate sensory feedback to adapt movements to appropriately respond to environmental conditions. Consequently, the motor repertoire would remain relatively simple, resulting in the persistence of motor stereotypy. A framework that considers motor stereotypy as a manifestation of low motor complexity resulting from poor sensorimotor integration has many implications for research, identification and treatment of motor stereotypy in a variety of developmental disorders.

Social Orienting and Attention Is Influenced by the Presence of Competing Nonsocial Information in Adolescents with Autism.

Background: Our experiences with the world play a critical role in neural and behavioral development. Children with autism spectrum disorder (ASD) spend a disproportionate amount of time seeking out, attending to, and engaging with aspects of their environment that are largely nonsocial in nature. In this study we adapted an established method for eliciting and quantifying aspects of visual choice behavior related to preference to test the hypothesis that preference for nonsocial sources of stimulation diminishes orientation and attention to social sources of stimulation in children with ASD. Method: Preferential viewing tasks can serve as objective measures of preference, with a greater proportion of viewing time to one item indicative of increased preference. The current task used gaze-tracking technology to examine patterns of visual orientation and attention to stimulus pairs that varied in social (faces) and nonsocial content (high autism interest or low autism interest). Participants included both adolescents diagnosed with ASD and typically developing; groups were matched on IQ and gender. Results: Repeated measures ANOVA revealed that individuals with ASD had a significantly greater latency to first fixate on social images when this image was paired with a high autism interest image, compared to a low autism interest image pairing. Participants with ASD showed greater total look time to objects, while typically developing participants preferred to look at faces. Groups also differed in number and average duration of fixations to social and object images. In the ASD group only, a measure of nonsocial interest was associated with reduced preference for social images when paired with high autism interest images. Conclusions: In ASD, the presence of nonsocial sources of stimulation can significantly increase the latency of look time to social sources of information. These results suggest that atypicalities in social motivation in ASD may be context-dependent, with a greater degree of plasticity than is assumed by existing social motivation accounts of ASD.