Evidence for Brainstem Contributions to Autism Spectrum Disorders

Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects one in 59 children in the United States. Although there is a mounting body of knowledge of cortical and cerebellar contributions to ASD, our knowledge about the early developing brainstem in ASD is only beginning to accumulate. Understanding how brainstem neurotransmission is implicated in ASD is important because many of this condition’s sensory and motor symptoms are consistent with brainstem pathology. Therefore, the purpose of this review was to integrate epidemiological, behavioral, histological, neuroimaging, and animal evidence of brainstem contributions to ASD. Because ASD is a neurodevelopmental condition, we examined the available data through a lens of hierarchical brain development. The review of the literature suggests that developmental alterations of the brainstem could have potential cascading effects on cortical and cerebellar formation, ultimately leading to ASD symptoms. This view is supported by human epidemiology findings and data from animal models of ASD, showing that perturbed development of the brainstem substructures, particularly during the peak formation of the brainstem’s monoaminergic centers, may relate to ASD or ASD-like behaviors. Furthermore, we review evidence from human histology, psychophysiology, and neuroimaging suggesting that brainstem development and maturation may be atypical in ASD and may be related to key ASD symptoms, such as atypical sensorimotor features and social responsiveness. From this review there emerges the need of future research to validate early detection of the brainstem-based somatosensory and psychophysiological behaviors that emerge in infancy, and to examine the brainstem across the life span, while accounting for age. In all, there is preliminary evidence for brainstem involvement in ASD, but a better understanding of the brainstem’s role would likely pave the way for earlier diagnosis and treatment of ASD

Bimanual Reach to Grasp Movements in Youth With and Without Autism Spectrum Disorder

Reaching and grasping (prehension) is one of the earliest developing motor skills in humans, but continued prehension development in childhood and adolescence enables the performance of increasingly complex manual tasks. In individuals with autism spectrum disorder (ASD) atypical unimanual reaching and grasping has been reported, but to date, no studies have investigated discrete bimanual movements. We examined unimanual and bimanual reach to grasp tasks in youth with ASD to better understand how motor performance might change with increasing complexity. Twenty youth with ASD (10.1 ± 2.4 years) and 17 youth with typical development (TD) (9.6 ± 2.6 years) were instructed to reach and grasp cubes that became illuminated. Participants were asked to reach out with the right and/or left hands to grasp and lift targets located at near (18 cm) and/or far (28 cm) distances. For the unimanual (simplest) condition, participants grasped one illuminated cube (with either the left or right hand). For the bimanual conditions, participants grasped two illuminated cubes located at the same distance from the start position (bimanual symmetric condition) or two illuminated cubes located at different distances (bimanual asymmetric condition). Significant interactions among diagnostic group, task complexity, and age were found for initiation time (IT) and movement time (MT). Specifically, the older children in both groups initiated and performed their movements faster in the unimanual condition than in the bimanual conditions, although the older children with ASD produced slower ITs and MTs compared to typically developing peers across all three conditions. Surprisingly, the younger children with ASD had similar ITs and MTs as their peers for the unimanual condition but did not considerably slow these times to adjust for the complexity of the bimanual tasks. We hypothesize that they chose to re-use the motor plans that were generated for the unimanual trials rather than generate more appropriate motor plans for the bimanual tasks. An atypical spatiotemporal relationship between MT and peak aperture (PA) was also found in the ASD group. Together, our results suggest deficits in motor planning that result in subtle effects on performance in younger children with ASD that become more pronounced with age

Atypical development of white matter microstructure of the corpus callosum in males with autism: a longitudinal investigation

Background: The corpus callosum is the largest white matter structure in the brain, and it is the most consistently reported to be atypical in diffusion tensor imaging studies of autism spectrum disorder. In individuals with typical development, the corpus callosum is known to undergo a protracted development from childhood through young adulthood. However, no study has longitudinally examined the developmental trajectory of corpus callosum in autism past early childhood. Methods: The present study used a cohort sequential design over 9 years to examine age-related changes of the corpus callosum in 100 males with autism and 56 age-matched males with typical development from early childhood (when autism can first be reliably diagnosed) to mid-adulthood (after development of the corpus callosum has been completed) (3 to 41 years of age). Results: The group with autism demonstrated a different developmental trajectory of white matter microstructure in the anterior corpus callosum’s (genu and body) fractional anisotropy, which suggests atypical brain maturation in these regions in autism. When analyses were broken down by age group, atypical developmental trajectories were present only in the youngest participants (10 years of age and younger). Significant main effects for group were found in terms of decreased fractional anisotropy across all three subregions of the corpus callosum (genu, body, and splenium) and increased mean diffusivity, radial diffusivity, and axial diffusivity in the posterior corpus callosum. Conclusions: These longitudinal results suggest atypical early childhood development of the corpus callosum microstructure in autism that transitions into sustained group differences in adolescence and adulthood. This pattern of results provides longitudinal evidence consistent with a growing number of published studies and hypotheses regarding abnormal brain connectivity across the life span in autism. Electronic supplementary material The online version of this article (doi:10.1186/s13229-015-0001-8) contains supplementary material, which is available to authorized users

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A Cross-Cultural View of Adults’ Perceptions of Children’s Rights

This study examined how the need for autonomy may be coexisting with current cultural norms. A total of 264 U.S., 76 Swiss, and 51 British adults completed two perceptions of children\u27s rights surveys. The results showed that Swiss and British participants were significantly more likely to advocate for autonomy or self-determination rights than same-aged U.S. adults. British participants were also more likely to advocate for children\u27s self-determination rights than U.S. and Swiss participants, whereas Swiss adults were more likely to grant children nurturance rights than British and US adults. Generally, parents were less likely to advocate for autonomy than non-parents. The results are discussed in terms of individualism--collectivism, self-determination theories, and parentalism

Unfolding Structure in the Drawings of Cubes

Recent work using neural networks and crowd-sourced perceptual judgements has shown that human figure drawings contain latent structure that can predict many characteristics of the artist including parent-reported motor function and perceived gender. We extend these approaches to two-dimensional renderings of three-dimensional cubes, assessing whether latent structure in these cube drawings likewise predicts demographic characteristics and motor function measured via a paper-folding task. Drawings produced with marker and paper showed a large predictive relationship with paper-folding (accounting for 59% of the offset variance, 62% of the angle variance, ps < .01). We also observed a complex interaction with gender: better cube-drawings predicted better paper-folding for male-identifying participants, but this relationship was reversed for female-identifying participants, who demonstrated better paper folding abilities overall. The results suggest that cube drawings contain richer structure than previously recognized and can provide a useful nonverbal metric for characterizing aspects of cognitive and motor abilities

Tai chi training reduces self-report of inattention in healthy young adults

It is important to identify effective non-pharmacological alternatives to stimulant medications that reduce symptoms of attention deficit hyperactivity disorder (ADHD). In this study of healthy young adults, we measured the effects of training in tai chi, which involves mindful attention to the body during movement. Using a non-randomized, controlled, parallel design, students in a 15-week introductory tai chi course (n=28) and control participants (n=44) were tested for ADHD indicators and cognitive function at three points over the course of the 15 weeks. The tai chi students' self-report of attention, but not hyperactivity-impulsivity, improved compared to controls. At baseline, inattention correlated positively with reaction time variability in an affective go/no-go task across all participants, and improvements in attention correlated with reductions in reaction time variability across the tai chi students. Affective bias changed in the tai chi students, as reaction times to positive- and negative-valenced words equalized over time. These results converge to suggest that tai chi training may help improve attention in healthy young adults. Further studies are needed to confirm these results and to evaluate tai chi as therapy for individuals with ADHD

Mapping an index of the myelin g-ratio in infants using magnetic resonance imaging

AbstractOptimal myelination of neuronal axons is essential for effective brain and cognitive function. The ratio of the axon diameter to the outer fiber diameter, known as the g-ratio, is a reliable measure to assess axonal myelination and is an important index reflecting the efficiency and maximal conduction velocity of white matter pathways. Although advanced neuroimaging techniques including multicomponent relaxometry (MCR) and diffusion tensor imaging afford insight into the microstructural characteristics of brain tissue, by themselves they do not allow direct analysis of the myelin g-ratio. Here, we show that by combining myelin content information (obtained with mcDESPOT MCR) with neurite density information (obtained through NODDI diffusion imaging) an index of the myelin g-ratio may be estimated. Using this framework, we present the first quantitative study of myelin g-ratio index changes across childhood, examining 18 typically developing children 3months to 7.5years of age. We report a spatio-temporal pattern of maturation that is consistent with histological and developmental MRI studies, as well as theoretical studies of the myelin g-ratio. This work represents the first ever in vivo visualization of the evolution of white matter g-ratio indices throughout early childhood

Neurogenetic mechanisms of risk for ADHD: Examining associations of polygenic scores and brain volumes in a population cohort

Abstract Background ADHD polygenic scores (PGSs) have been previously shown to predict ADHD outcomes in several studies. However, ADHD PGSs are typically correlated with ADHD but not necessarily reflective of causal mechanisms. More research is needed to elucidate the neurobiological mechanisms underlying ADHD. We leveraged functional annotation information into an ADHD PGS to (1) improve the prediction performance over a non-annotated ADHD PGS and (2) test whether volumetric variation in brain regions putatively associated with ADHD mediate the association between PGSs and ADHD outcomes. Methods Data were from the Philadelphia Neurodevelopmental Cohort (N = 555). Multiple mediation models were tested to examine the indirect effects of two ADHD PGSs—one using a traditional computation involving clumping and thresholding and another using a functionally annotated approach (i.e., AnnoPred)—on ADHD inattention (IA) and hyperactivity-impulsivity (HI) symptoms, via gray matter volumes in the cingulate gyrus, angular gyrus, caudate, dorsolateral prefrontal cortex (DLPFC), and inferior temporal lobe. Results A direct effect was detected between the AnnoPred ADHD PGS and IA symptoms in adolescents. No indirect effects via brain volumes were detected for either IA or HI symptoms. However, both ADHD PGSs were negatively associated with the DLPFC. Conclusions The AnnoPred ADHD PGS was a more developmentally specific predictor of adolescent IA symptoms compared to the traditional ADHD PGS. However, brain volumes did not mediate the effects of either a traditional or AnnoPred ADHD PGS on ADHD symptoms, suggesting that we may still be underpowered in clarifying brain-based biomarkers for ADHD using genetic measures