Brittany G. Travers

Diffusion Tensor Imaging in Autism Spectrum Disorder: A Review

White matter tracts of the brain allow neurons and neuronal networks to communicate and function with high efficiency. The aim of this review is to briefly introduce diffusion tensor imaging methods that examine white matter tracts and then to give an overview of the studies that have investigated white matter integrity in the brains of individuals with autism spectrum disorder (ASD). From the 48 studies we reviewed, persons with ASD tended to have decreased fractional anisotropy and increased mean diffusivity in white matter tracts spanning many regions of the brain but most consistently in regions such as the corpus callosum, cingulum, and aspects of the temporal lobe. This decrease in fractional anisotropy was often accompanied by increased radial diffusivity. Additionally, the review suggests possible atypical lateralization in some white matter tracts of the brain and a possible atypical developmental trajectory of white matter microstructure in persons with ASD. Clinical implications and future research directions are discussed. Autism Res 2012, 5: 289–313.

Longitudinal changes in cortical thickness in autism and typical development.

The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. To clarify age-related trajectories of cortical development, we examined longitudinal changes in cortical thickness within a large mixed cross-sectional and longitudinal sample of autistic subjects and age- and gender-matched typically developing controls. Three hundred and forty-five magnetic resonance imaging scans were examined from 97 males with autism (mean age = 16.8 years; range 3-36 years) and 60 males with typical development (mean age = 18 years; range 4-39 years), with an average interscan interval of 2.6 years. FreeSurfer image analysis software was used to parcellate the cortex into 34 regions of interest per hemisphere and to calculate mean cortical thickness for each region. Longitudinal linear mixed effects models were used to further characterize these findings and identify regions with between-group differences in longitudinal age-related trajectories. Using mean age at time of first scan as a reference (15 years), differences were observed in bilateral inferior frontal gyrus, pars opercularis and pars triangularis, right caudal middle frontal and left rostral middle frontal regions, and left frontal pole. However, group differences in cortical thickness varied by developmental stage, and were influenced by IQ. Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and paracentral, lateral orbitofrontal, and lateral occipital regions. We suggest that abnormal cortical development in autism spectrum disorders undergoes three distinct phases: accelerated expansion in early childhood, accelerated thinning in later childhood and adolescence, and decelerated thinning in early adulthood. Moreover, cortical thickness abnormalities in autism spectrum disorders are region-specific, vary with age, and may remain dynamic well into adulthood.

Longitudinal Volumetric Brain Changes in Autism Spectrum Disorder Ages 6–35 Years

Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high‐quality magnetic resonance imaging [MRI] scans; mean inter‐scan interval 2.7 years) compared to 56 typically developing controls (TDCs) (117 high‐quality scans; mean inter‐scan interval 2.6 years) from childhood into adulthood, for a total of 156 participants scanned over an 8‐year period. This initial analysis includes between one and three high‐quality scans per participant that have been processed and segmented to date, with 21% having one scan, 27% with two scans, and 52% with three scans in the ASD sample; corresponding percentages for the TDC sample are 30%, 30%, and 40%. The proportion of participants with multiple scans (79% of ASDs and 68% of TDCs) was high in comparison to that of large longitudinal neuroimaging studies of typical development. We provide volumetric growth curves for the entire brain, total gray matter (GM), frontal GM, temporal GM, parietal GM, occipital GM, total cortical white matter (WM), corpus callosum, caudate, thalamus, total cerebellum, and total ventricles. Mean volume of cortical WM was reduced significantly. Mean ventricular volume was increased in the ASD sample relative to the TDCs across the broad age range studied. Decreases in regional mean volumes in the ASD sample most often were due to decreases during late adolescence and adulthood. The growth curve of whole brain volume over time showed increased volumes in young children with autism, and subsequently decreased during adolescence to meet the TDC curve between 10 and 15 years of age. The volume of many structures continued to decline atypically into adulthood in the ASD sample. The data suggest that ASD is a dynamic disorder with complex changes in whole and regional brain volumes that change over time from childhood into adulthood. Autism Res 2015, 8: 82–93.

Motor difficulties in autism spectrum disorder: linking symptom severity and postural stability.

Postural stability is a fundamental aspect of motor ability that allows individuals to sustain and maintain the desired physical position of one’s body. The present study examined postural stability in average-IQ adolescents and adults with Autism Spectrum Disorder (ASD). Twenty-six individuals with ASD and 26 age-and-IQ-matched individuals with typical development stood on one leg or two legs with eyes opened or closed on a Wii balance board. Results indicated significant group differences in postural stability during one-legged standing, but there were no significant group differences during two-legged standing. This suggests that static balance during more complex standing postures is impaired in average-IQ individuals with ASD. Further, current ASD symptoms were related to postural stability during two-legged standing in individuals with ASD. Future directions and clinical implications are discussed.

A systems level analysis of the mirror neuron hypothesis and imitation impairments in autism spectrum disorders

Although several studies suggest an imitation deficit as a key feature of autism, questions have been raised about the consistency of this finding and about the component skills involved in imitation. The primary aim of this review is to examine the uneven profile of imitation deficits found in autism in the context of the mirror neuron system (MNS) dysfunction hypothesis. We use the cortical underconnectivity framework (Just et al., 2004) to examine the coordination of brain areas that orchestrate the communication between the component skills underlying imitation. A comprehensive account of imitation deficit in autism should take into account the regions that are at the core of the MNS (e.g., IFG and IPL) and related regions that feed into the MNS (e.g., STS, Cerebellum) in their functioning and in their coordination. Our findings suggest that the MNS may be associated with mediating familiarity, attention, self-other matching, and social relevance, which may be vital in characterizing the imitation deficits in autism. Such an analysis may have greater clinical and therapeutic value.

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

Optimal 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 3 months to 7.5 years 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.

Motor-linked implicit learning in persons with autism spectrum disorders.

Fifteen adolescents and young adults with high‐functioning autism spectrum disorders (ASD) and 18 age‐ and IQ‐matched adults with typical development (TD) completed a serial reaction time task (SRT) to examine possible motor‐linked implicit learning impairments in persons with ASD. Measures were taken to decrease the role of explicit learning in the SRT. Results showed that participants with ASD demonstrated intact motor‐linked implicit learning. Furthermore, the motor‐linked implicit learning appeared to take place at a similar rate across trials in the group with ASD compared to the group with TD. These results suggest that persons with ASD are successful in implicit learning of motor‐linked behavior. The results of this study, coupled with past findings, suggest that people with ASD may be able to learn motor movements without conscious awareness, especially if the individual is older and is learning fine motor sequences.

Neural substrates of interpreting actions and emotions from body postures

Accurately reading the body language of others may be vital for navigating the social world, and this ability may be influenced by factors, such as our gender, personality characteristics and neurocognitive processes. This fMRI study examined the brain activation of 26 healthy individuals (14 women and 12 men) while they judged the action performed or the emotion felt by stick figure characters appearing in different postures. In both tasks, participants activated areas associated with visual representation of the body, motion processing and emotion recognition. Behaviorally, participants demonstrated greater ease in judging the physical actions of the characters compared to judging their emotional states, and participants showed more activation in areas associated with emotion processing in the emotion detection task, whereas they showed more activation in visual, spatial and action-related areas in the physical action task. Gender differences emerged in brain responses, such that men showed greater activation than women in the left dorsal premotor cortex in both tasks. Finally, participants higher in self-reported empathy demonstrated greater activation in areas associated with self-referential processing and emotion interpretation. These results suggest that empathy levels and sex of the participant may affect neural responses to emotional body language.

Longitudinal processing speed impairments in males with autism and the effects of white matter microstructure.

The present study used an accelerated longitudinal design to examine group differences and age-related changes in processing speed in 81 individuals with autism spectrum disorder (ASD) compared to 56 age-matched individuals with typical development (ages 6-39 years). Processing speed was assessed using the Wechsler Intelligence Scale for Children-3rd edition (WISC-III) and the Wechsler Adult Intelligence Scale-3rd edition (WAIS-III). Follow-up analyses examined processing speed subtest performance and relations between processing speed and white matter microstructure (as measured with diffusion tensor imaging [DTI] in a subset of these participants). After controlling for full scale IQ, the present results show that processing speed index standard scores were on average 12 points lower in the group with ASD compared to the group with typical development. There were, however, no significant group differences in standard score age-related changes within this age range. For subtest raw scores, the group with ASD demonstrated robustly slower processing speeds in the adult versions of the IQ test (i.e., WAIS-III) but not in the child versions (WISC-III), even though age-related changes were similar in both the ASD and typically developing groups. This pattern of results may reflect difficulties that become increasingly evident in ASD on more complex measures of processing speed. Finally, DTI measures of whole-brain white matter microstructure suggested that fractional anisotropy (but not mean diffusivity, radial diffusivity, or axial diffusivity) made significant but small-sized contributions to processing speed standard scores across our entire sample. Taken together, the present findings suggest that robust decreases in processing speed may be present in ASD, more pronounced in adulthood, and partially attributable to white matter microstructural integrity.

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.