Brandon Keehn

Underconnected, but How? A Survey of Functional Connectivity MRI Studies in Autism Spectrum Disorders

Growing consensus suggests that autism spectrum disorders (ASD) are associated with atypical brain networks, thus shifting the focus to the study of connectivity. Many functional connectivity studies have reported underconnectivity in ASD, but results in others have been divergent. We conducted a survey of 32 functional connectivity magnetic resonance imaging studies of ASD for numerous methodological variables to distinguish studies supporting general underconnectivity (GU) from those not consistent with this hypothesis (NGU). Distinguishing patterns were apparent for several data analysis choices. The study types differed significantly with respect to low-pass filtering, task regression, and whole-brain field of view. GU studies were more likely to examine task-driven time series in regions of interest, without the use of low-pass filtering. Conversely, NGU studies mostly applied task regression (for removal of activation effects) and low-pass filtering, testing for correlations across the whole brain. Results thus suggest that underconnectivity findings may be contingent on specific methodological choices. Whereas underconnectivity reflects reduced efficiency of within-network communication in ASD, diffusely increased functional connectivity can be attributed to impaired experience-driven mechanisms (e.g., synaptic pruning). Both GU and NGU findings reflect important aspects of network dysfunction associated with sociocommunicative, cognitive, and sensorimotor impairments in ASD.

Why is visual search superior in autism spectrum disorder

This study investigated the possibility that enhanced memory for rejected distractor locations underlies the superior visual search skills exhibited by individuals with autism spectrum disorder (ASD). We compared the performance of 21 children with ASD and 21 age- and IQ-matched typically developing (TD) children in a standard static search task and a dynamic search task, in which targets and distractors randomly changed locations every 500 ms, precluding the use of memory in search. Children with ASD exhibited overall faster reaction time (RT) relative to TD children, and showed no disruption in search efficiency in the dynamic condition, discounting the possibility that memory for rejected distractors augments their visual search abilities. Analyses of RT x set size functions showed no group differences in slopes but lower intercepts for the ASD group in both static and dynamic search, suggesting that the ASD advantage derived from non-search processes, such as an enhanced ability to discriminate between targets and distractors at the locus of attention. Eye-movement analyses revealed that the ASD and TD groups were similar in the number and spatial distribution of fixations across the search array, but that fixation duration was significantly shorter among children with ASD. Lower intercepts in static search were related to increased symptom severity in children with ASD. In summary, ASD search superiority did not derive from differences in the manner in which individuals with ASD deployed their attention while searching, but from anomalously enhanced perception of stimulus features, which was in turn positively associated with autism symptom severity.

Tract-Specific Analyses of Diffusion Tensor Imaging Show Widespread White Matter Compromise in Autism Spectrum Disorder

BACKGROUND Previous diffusion tensor imaging (DTI) studies have shown white matter compromise in children and adults with autism spectrum disorder (ASD), which may relate to reduced connectivity and impaired function of distributed networks. However, tract-specific evidence remains limited in ASD. We applied tract-based spatial statistics (TBSS) for an unbiased whole-brain quantitative estimation of the fractional anisotropy (FA), mean diffusion (MD) and axial and radial diffusion of the white matter tracts in children and adolescents with ASD. METHODS DTI was performed in 26 ASD and 24 typically developing (TD) participants, aged 9-20 years. Groups were matched for age and IQ. Each participants aligned FA, MD and axial and radial diffusion data were projected onto the mean FA skeleton representing the centers of all tracts and the resulting data fed into voxelwise group statistics. RESULTS TBSS revealed decreased FA and increased MD and radial diffusion in the ASD group compared to the TD group in the corpus callosum, anterior and posterior limbs of the internal capsule, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, cingulum, anterior thalamic radiation, and corticospinal tract. No single site with inverse effects (increased FA, reduced MD or radial diffusion in the ASD group) was detected. In clusters of significant group difference, age was positively correlated with FA and negatively correlated with MD and radial diffusion in the TD, but not the ASD group. CONCLUSIONS Our findings reveal white matter compromise affecting numerous tracts in children and adolescents with ASD. Slightly varying patterns of diffusion abnormalities detected for some tracts may suggest tract-specific patterns of white matter abnormalities associated with ASD. Age-dependent effects further show that maturational changes (increasing FA, decreasing MD and radial diffusion with age) are diminished in ASD from school-age childhood into young adulthood.

Atypical attentional networks and the emergence of autism.

The sociocommunicative impairments that define autism spectrum disorder (ASD) are not present at birth but emerge gradually over the first two years of life. In typical development, basic attentional processes may provide a critical foundation for sociocommunicative abilities. Therefore early attentional dysfunction in ASD may result in atypical development of social communication. Prior research has demonstrated that persons with ASD exhibit early and lifelong impairments in attention. The primary aim of this paper is to provide a review of the extant research on attention in ASD using a framework of functionally independent attentional networks as conceptualized by Posner and colleagues: the alerting, orienting and executive control networks (Posner and Petersen, 1990; Petersen and Posner, 2012). The neural substrates and typical development of each attentional network are briefly discussed, a review of the ASD attention literature is presented, and a hypothesis is proposed that links aberrant attentional mechanisms, specifically impaired disengagement of attention, with the emergence of core ASD symptoms.

Affective response to eye contact and face recognition ability in children with ASD

This study tested the hypothesis that affective arousal in response to eye contact is negatively associated with face identification skills in children with autism spectrum disorder (ASD). Participants were 20 children and adolescents with ASD and 20 age- and IQ-matched typically developing (TD) children. Skin conductance response (SCR), a psychophysiological measure of autonomic arousal, was collected while participants viewed faces with gaze directed toward them and faces with gaze averted away from them. Participants also completed an independent match-to-sample face recognition test. Children with ASD exhibited significantly larger SCRs than TD children to faces with direct and averted gaze. There were no differences between SCRs to direct gaze and averted gaze in either group. Children with ASD exhibited a marginally significant decrease in face recognition accuracy relative to TD children, particularly when face recognition depended on the eye region of the face. Face recognition accuracy among children with ASD was negatively correlated with the amplitude of SCRs to direct gaze but not to averted gaze. There was no association between face recognition accuracy and SCRs to gaze in the TD group. These findings suggest that autonomic reactivity to eye contact may interfere with face identity processing in some children with ASD.

White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study.

OBJECTIVE Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle cerebellar peduncle in children with ASD and typically developing (TD) children. METHOD DTI data were obtained from 26 children with ASD and 24 matched TD children. Fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusion were calculated for the whole brain, the genu, body, and splenium of the corpus callosum, the genu and anterior and posterior limbs of the internal capsule, and the middle cerebellar peduncle. RESULTS Children with ASD had reduced FA and increased radial diffusion for whole-brain white matter and all three segments of the corpus callosum and internal capsule, compared with those in TD children. Increased MD was found for the whole brain and for anterior and posterior limbs of the internal capsule. Reduced axial diffusion was found for the body of corpus callosum. Reduced FA was also found for the middle cerebellar peduncle. CONCLUSIONS Our findings suggest widespread white matter compromise in children with ASD. Abnormalities in the corpus callosum indicate impaired interhemispheric transfer. Results for the internal capsule and middle cerebellar peduncle add to the currently limited DTI evidence on subcortico-cortical tracts in ASD. The robust impairment found in all three segments of the internal capsule is consistent with studies documenting impairment of elementary sensorimotor function in ASD.

Atypical network connectivity for imitation in autism spectrum disorder

Imitation has been considered as one of the precursors for sociocommunicative development. Impairments of imitation in autism spectrum disorder (ASD) could be indicative of dysfunctional underlying neural processes. Neuroimaging studies have found reduced activation in areas associated with imitation, but a functional connectivity MRI network perspective of these regions in autism is unavailable. Functional and effective connectivity was examined in 14 male participants with ASD and 14 matched typically developing (TD) participants. We analyzed intrinsic, low-frequency blood oxygen level dependent (BOLD) fluctuations of three regions in literature found to be associated with imitation (inferior frontal gyrus [IFG], inferior parietal lobule [IPL], superior temporal sulcus [STS]). Direct group comparisons did not show significantly reduced functional connectivity within the imitation network in ASD. Conversely, we observed greater connectivity with frontal regions, particularly superior frontal and anterior cingulate gyri, in the ASD compared to TD group. Structural equation modeling of effective connectivity revealed a significantly reduced effect of IPL on IFG together with an increased influence of a region in dorsal prefrontal cortex (dPFC) on IFG in the ASD group. Our results suggest atypical connectivity of the imitation network with an enhanced role of dPFC, which may relate to behavioral impairments.

Functional differentiation of posterior superior temporal sulcus in autism: a functional connectivity magnetic resonance imaging study.

BACKGROUND Socio-communicative impairments are salient features of autism spectrum disorder (ASD). Abnormal development of posterior superior temporal sulcus (pSTS)--a key processing area for language, biological motion, and social context--could play a role in these deficits. METHODS Functional connectivity magnetic resonance imaging was used to examine the synchronization of low-frequency blood oxygen level-dependent fluctuations during continuous performance on a visual search task. Twenty-one children and adolescents with ASD and 26 typically developing individuals-matched on age and IQ-participated in the study. Three subregions of pSTS were delineated with a data-driven approach, and differentiation of pSTS was examined by comparing the connectivity of each subregion. RESULTS In typically developing individuals, differentiation of networks was positively associated with age and anatomical maturation (cortical thinning in pSTS, greater white matter volume). In the ASD group, differentiation of pSTS connectivity was significantly reduced, and correlations with anatomical measures were weak or absent. Moreover, pSTS differentiation was inversely correlated with autism symptom severity. CONCLUSIONS Atypical maturation of pSTS suggests altered trajectories for functional segregation and integration of networks in ASD, potentially related to impaired cognitive and sensorimotor development. Furthermore, our findings provide a novel explanation for atypically increased connectivity in ASD that has been observed in some functional connectivity magnetic resonance imaging studies.

Microstructural Abnormalities of Short-Distance White Matter Tracts in Autism Spectrum Disorder.

Recent functional connectivity magnetic resonance imaging and diffusion tensor imaging (DTI) studies have suggested atypical functional connectivity and reduced integrity of long-distance white matter fibers in autism spectrum disorder (ASD). However, evidence for short-distance white matter fibers is still limited, despite some speculation of potential sparing of local connectivity in ASD. Short-distance U-fibers are an important component of neural networks and are thought to play a crucial role in cognitive function. In the present study, we applied tract-based spatial statistics to derive short- and long-distance white matter tracts in frontal, parietal, and temporal lobes in both hemispheres. DTI data were acquired from 26 children with ASD and 24 typically developing (TD) children. A mean fractional anisotropy (FA) image was created and thinned to represent centers of all common tracts. Evidence of compromised short-distance tracts for the ASD group was found in frontal lobe (reduced FA, increased mean diffusivity [MD] and radial diffusivity) as well as in temporal and parietal lobes (increased MD and radial diffusivity). Significant positive correlations between age and FA and negative correlations between age and MD and radial diffusivity were also found for short-distance tracts in each lobe in the TD, but not the ASD group. These results suggest white matter compromise in short-distance tracts in ASD. Absence of typical age-related correlations with DTI indices may reflect altered maturation of short-distance tracts in ASD. Our results are inconsistent with a notion of selective sparing of short-distance connectivity in ASD.

Patterns of visual attention to faces and objects in autism spectrum disorder.

This study used eye-tracking to examine visual attention to faces and objects in adolescents with autism spectrum disorder (ASD) and typical peers. Point of gaze was recorded during passive viewing of images of human faces, inverted human faces, monkey faces, three-dimensional curvilinear objects, and two-dimensional geometric patterns. Individuals with ASD obtained lower scores on measures of face recognition and social-emotional functioning but exhibited similar patterns of visual attention. In individuals with ASD, face recognition performance was associated with social adaptive function. Results highlight heterogeneity in manifestation of social deficits in ASD and suggest that naturalistic assessments are important for quantifying atypicalities in visual attention.