Developing Automated Algorithms to Assess Linguistic Variation in Individuals with Autism
Importance: Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition.
Objective: To investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS).
Design, setting, and participants: Cross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ.
Main outcomes and measures: Statistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures.
Results: Relative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction.
Conclusions and relevance: Adolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect immature or aberrant developmental processes in 2 brain networks involved in understanding of others, a domain of impairment in ASD. Further, robust links with sociocommunicative symptoms of ASD implicate atypically increased ToM-MNS connectivity in social deficits observed in ASD.
Neurodevelopmental disconnections have been assumed to cause behavioral alterations in autism spectrum disorders (ASDs). Here, we combined measurements of intrinsic functional connectivity (iFC) from resting-state functional magnetic resonance imaging (fMRI) with task-based fMRI to explore whether altered activity and/or iFC of the right posterior superior temporal sulcus (pSTS) mediates deficits in emotion recognition in ASD. Fifteen adults with ASD and 15 matched-controls underwent resting-state and task-based fMRI, during which participants discriminated emotional states from point light displays (PLDs). Intrinsic FC of the right pSTS was further examined using 584 (278 ASD/306 controls) resting-state data of the Autism Brain Imaging Data Exchange (ABIDE). Participants with ASD were less accurate than controls in recognizing emotional states from PLDs. Analyses revealed pronounced ASD-related reductions both in task-based activity and resting-state iFC of the right pSTS with fronto-parietal areas typically encompassing the action observation network (AON). Notably, pSTS-hypo-activity was related to pSTS-hypo-connectivity, and both measures were predictive of emotion recognition performance with each measure explaining a unique part of the variance. Analyses with the large independent ABIDE dataset replicated reductions in pSTS-iFC to fronto-parietal regions. These findings provide novel evidence that pSTS hypo-activity and hypo-connectivity with the fronto-parietal AON are linked to the social deficits characteristic of ASD.
Keywords: autism spectrum disorders; emotion recognition; functional connectivity; functional magnetic resonance imaging; superior temporal sulcus.
Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.
Keywords: ASD; EEG; MEG; VSDi; circuit; gamma; neurophysiology; translational.
Approximately 30% of hearing children with autism spectrum disorder (ASD) do not acquire expressive language, and those who do often show impairments related to their social deficits, using language instrumentally rather than socially, with a poor understanding of pragmatics and a tendency toward repetitive content. Linguistic abnormalities can be clinically useful as diagnostic markers of ASD and as targets for intervention. Studies have begun to document how ASD manifests in children who are deaf for whom signed languages are the primary means of communication. Though the underlying disorder is presumed to be the same in children who are deaf and children who hear, the structures of signed and spoken languages differ in key ways. This article describes similarities and differences between the signed and spoken language acquisition of children on the spectrum. Similarities include echolalia, pronoun avoidance, neologisms, and the existence of minimally verbal children. Possible areas of divergence include pronoun reversal, palm reversal, and facial grammar.
Previous work has demonstrated that patterns of social attention hold predictive value for language development in typically developing infants. The goal of this research was to explore how patterns of attention in autistic, language delayed, and typically developing children relate to early word learning and language abilities. We tracked patterns of eye movements to faces and objects while children watched videos of a woman teaching them a series of new words. Subsequent test trials measured participants’ recognition of these novel word-object pairings. Results indicated that greater attention to the speaker’s mouth was related to higher scores on standardized measures of language development for autistic and typically developing children (but not for language delayed children). This effect was mediated by age for typically developing, but not autistic children. When effects of age were controlled for, attention to the mouth among language delayed participants was negatively correlated with standardized measures of language learning. Attention to the speaker’s mouth and eyes while she was teaching the new words was also predictive of faster recognition of those words among autistic children. These results suggest that language delays among children with autism may be driven in part by aberrant social attention, and that the mechanisms underlying these delays may differ from those in language delayed participants without autism.
Keywords: attention to faces; autism spectrum disorders; eye tracking; language development; word learning.
Atypical motor behaviors are common among children with autism spectrum disorders (ASD). However, little is known about onset and functional implications of differences in early motor development among infants later diagnosed with ASD. Two prospective experiments were conducted to investigate motor skills among 6-month-olds at increased risk (high risk) for ASD (N1 = 129; N2 = 46). Infants were assessed using the Mullen Scales of Early Learning (MSEL) and during toy play. Across both experiments, high-risk infants exhibited less mature object manipulation in a highly structured (MSEL) context and reduced grasping activity in an unstructured (free-play) context than infants with no family history of ASD. Longitudinal assessments suggest that between 6 and 10 months, grasping activity increases in high-risk infants.
The social difficulties that are a hallmark of autism spectrum disorder (ASD) are thought to arise, at least in part, from atypical attention toward stimuli and their features. To investigate this hypothesis comprehensively, we characterized 700 complex natural scene images with a novel three-layered saliency model that incorporated pixel-level (e.g., contrast), object-level (e.g., shape), and semantic-level attributes (e.g., faces) on 5,551 annotated objects. Compared with matched controls, people with ASD had a stronger image center bias regardless of object distribution, reduced saliency for faces and for locations indicated by social gaze, and yet a general increase in pixel-level saliency at the expense of semantic-level saliency. These results were further corroborated by direct analysis of fixation characteristics and investigation of feature interactions. Our results for the first time quantify atypical visual attention in ASD across multiple levels and categories of objects.
Keywords: attention; autism spectrum disorder; center bias; eye tracking; faces; saliency; semantics; social cognition.
Autism spectrum disorders (ASD) are characterized by social impairments and restricted/stereotyped behaviors and currently affect an estimated 1 in 68 children aged 8 years old. While there has been substantial recent focus on ASD in research, both the biological pathology and, perhaps consequently, a fully effective treatment have yet to be realized. What has remained throughout is the hypothesis that ASD has neurobiological underpinnings and the observation that both the phenotypic expression and likely the underlying etiology is highly heterogeneous. Given the neurodevelopmental basis of ASD, a biologically based marker (biomarker) could prove useful not only for diagnostic and prognostic purposes, but also for stratification and response indices for pharmaceutical development. In this review, we examine the current state of the field for MEG-related biomarkers in ASD. We describe several potential biomarkers (middle latency delays [M50/M100], mismatch negativity latency, gamma-band oscillatory activity), and investigate their relation to symptomology, core domains of dysfunction (e.g., language impairment), and putative biological underpinnings.
Keywords: ASD; Gamma; MEG; biomarker; latency delay; signature; translational.
We report the first study on pronoun use by an under-studied research population, children with autism spectrum disorder (ASD) exposed to American Sign Language from birth by their deaf parents. Personal pronouns cause difficulties for hearing children with ASD, who sometimes reverse or avoid them. Unlike speech pronouns, sign pronouns are indexical points to self and other. Despite this transparency, we find evidence from an elicitation task and parental report that signing children with ASD avoid sign pronouns in favor of names. An analysis of spontaneous usage showed that all children demonstrated the ability to point, but only children with better-developed sign language produced pronouns. Differences in language abilities and self-representation may explain these phenomena in sign and speech.
Objective: Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but few studies have integrated functional with structural connectivity measures. This multimodal investigation examined functional and structural connectivity of the imitation network in children and adolescents with ASD, and its links with clinical symptoms.
Methods: Resting state functional magnetic resonance imaging and diffusion-weighted imaging were performed in 35 participants with ASD and 35 typically developing controls, aged 8 to 17 years, matched for age, gender, intelligence quotient, and head motion.
Results: Within-network analyses revealed overall reduced functional connectivity (FC) between distributed imitation regions in the ASD group. Whole brain analyses showed that underconnectivity in ASD occurred exclusively in regions belonging to the imitation network, whereas overconnectivity was observed between imitation nodes and extraneous regions. Structurally, reduced fractional anisotropy and increased mean diffusivity were found in white matter tracts directly connecting key imitation regions with atypical FC in ASD. These differences in microstructural organization of white matter correlated with weaker FC and greater ASD symptomatology.
Interpretation: Findings demonstrate atypical connectivity of the brain network supporting imitation in ASD, characterized by a highly specific pattern. This pattern of underconnectivity within, but overconnectivity outside the functional network is in contrast with typical development and suggests reduced network integration and differentiation in ASD. Our findings also indicate that atypical connectivity of the imitation network may contribute to ASD clinical symptoms, highlighting the role of this fundamental social cognition ability in the pathophysiology of ASD.
The intraparietal sulcus (IPS), a region in the dorsal attention network (DAN), has been implicated in multi-sensory attention and working memory. Working memory and attention develop across childhood; changes in functional connectivity within the DAN may relate to this maturation. Previous findings regarding fronto-parietal intrinsic functional connectivity age-effects were mixed. Our study aimed to circumvent limitations of previous work using a large cross-sectional sample, 183 typically developing participants 6.5-20 years, from the Autism Brain Imaging Data Exchange, and seed regions along the anterior-to-posterior axis of the IPS. These seeds, IPS0-4, were entered into functional connectivity models. Group-level models investigated differential connectivity along the IPS and relationships with age. Anterior IPS3/4 exhibited greater connectivity with sensorimotor/pre-motor regions. Posterior IPS0/1 demonstrated greater connectivity with dorsal and ventral visual regions. Positive age-effects were found between IPS3-4 and visual regions. Negative age-effects were found between IPS and superior parietal and medial orbitofrontal cortices. Follow-up region of interest analyses were used to estimate age-effects for DAN and anticorrelated default mode network regions. Results suggest age-effects on IPS functional connectivity are relatively modest, and may differ pre- and across-adolescence. Studying typical age-related connectivity variability within this network may help to understand neurodevelopmental disorders marked by impaired attention.
Keywords: Attention; Functional connectivity; IPS; Resting-state fMRI; Visual-spatial; Visuotopic.