Mapping access to meaning in adolescents with autism: Atypical lateralization and spatiotemporal patterns as a function of language ability.

Individuals with autism spectrum disorders (ASD) vary in their language abilities, associated with atypical patterns of brain activity. However, few studies have examined the spatiotemporal profiles of lexico-semantic processing in ASD, particularly as a function of language heterogeneity. Thirty-nine high-functioning adolescents with ASD and 21 typically developing (TD) peers took part in a lexical decision task that combined semantic access with demands on cognitive control. Spatiotemporal characteristics of the processing stages were examined with a multimodal anatomically-constrained magnetoencephalography (aMEG) approach, which integrates MEG with structural MRI. Additional EEG data were acquired from a limited montage simultaneously with MEG. TD adolescents showed the canonical left-dominant activity in frontotemporal regions during both early (N250m) and late (N400m) stages of lexical access and semantic integration. In contrast, the ASD participants showed bilateral engagement of the frontotemporal language network, indicative of compensatory recruitment of the right hemisphere. The left temporal N400m was prominent in both groups, confirming preserved attempts to access meaning. In contrast, the left prefrontal N400m was reduced in ASD participants, consistent with impaired semantic/contextual integration and inhibitory control. To further investigate the impact of language proficiency, the ASD sample was stratified into high- and low-performing (H-ASD and L-ASD) subgroups based on their task accuracy. The H-ASD subgroup performed on par with the TD group and showed greater activity in the right prefrontal and bilateral temporal cortices relative to the L-ASD subgroup, suggesting compensatory engagement. The L-ASD subgroup additionally showed reduced and delayed left prefrontal N400m, consistent with more profound semantic and executive impairments in this subgroup. These distinct spatiotemporal activity profiles reveal the neural underpinnings of the ASD-specific access to meaning and provide insight into the phenotypic heterogeneity of language in ASD, which may be a result of different neurodevelopmental trajectories and adoption of compensatory strategies.

Reduced asymmetry of the hand knob area and decreased sensorimotor u-fiber connectivity in middle-aged adults with autism.

Individuals with autism spectrum disorder (ASD) frequently present with impairments in motor skills (e.g., limb coordination, handwriting and balance), which are observed across the lifespan but remain largely untreated. Many adults with ASD may thus experience adverse motor outcomes in aging, when physical decline naturally occurs. The 'hand knob' of the sensorimotor cortex is an area that is critical for motor control of the fingers and hands. However, this region has received little attention in ASD research, especially in adults after midlife. The hand knob area of the precentral (PrChand) and postcentral (PoChand) gyri was semi-manually delineated in 49 right-handed adults (25 ASD, 24 typical comparison [TC] participants, aged 41-70 years). Using multimodal (T1-weighted, diffusion-weighted, and resting-state functional) MRI, we examined the morphology, ipsilateral connectivity and laterality of these regions. We also explored correlations between hand knob measures with motor skills and autism symptoms, and between structural and functional connectivity measures. Bayesian analyses indicated moderate evidence of group effects with greater right PrChand volume and reduced leftward laterality of PrChand and PoChand volume in the ASD relative to TC group. Furthermore, the right PoC-PrChand u-fibers showed increased mean diffusivity in the ASD group. In the ASD group, right u-fiber volume positively correlated with corresponding functional connectivity but did not survive multiple comparisons correction. Correlations of hand knob measures and behavior were observed in the ASD group but did not survive multiple comparisons correction. Our findings suggest that morphological laterality and u-fiber connectivity of the sensorimotor network, putatively involved in hand motor/premotor function, may be diminished in middle-aged adults with ASD, perhaps rendering them more vulnerable to motor decline in old age. The altered morphology may relate to atypical functional motor asymmetries found in ASD earlier in life, possibly reflecting altered functional asymmetries over time.

Blood Oxygen Level-Dependent Lag Patterns Differ Between Rest and Task Conditions, but Are Largely Typical in Autism.

Background/Introduction: Autism spectrum disorder (ASD) is characterized by atypical functional connectivity (FC) within and between distributed brain networks. However, FC findings have often been inconsistent, possibly due to a focus on static FC rather than brain dynamics. Lagged connectivity analyses aim at evaluating temporal latency, and presumably neural propagation, between regions. This approach may, therefore, reveal a more detailed picture of network organization in ASD than traditional FC methods. Methods: The current study evaluated whole-brain lag patterns in adolescents with ASD (n = 28) and their typically developing peers (n = 22). Functional magnetic resonance imaging data were collected during rest and during a lexico-semantic decision task. Optimal lag was calculated for each pair of regions of interest by using cross-covariance, and mean latency projections were calculated for each region. Results: Latency projections did not regionally differ between groups, with the same regions emerging among the "earliest" and "latest." Although many of the longest absolute latencies were preserved across resting-state and task conditions, lag patterns overall were affected by condition, as many regions shifted toward zero-lag during task performance. Lag structure was also strongly associated with literature-derived estimates of arterial transit time. Discussion: Results suggest that lag patterns are broadly typical in ASD but undergo changes during task performance. Moreover, lag patterns appear to reflect a combination of neural and vascular sources, which should be carefully considered when interpreting lagged FC. Impact statement Altered brain dynamics have been proposed in autism spectrum disorder (ASD). Lagged functional connectivity analysis uses cross-correlation between functional magnetic resonance imaging (fMRI) time series to determine regional latency. Few studies have examined blood oxygen level-dependent (BOLD) lag in ASD, and findings have been inconsistent. Using multi-echo fMRI data with improved artifact detection and removal, we find differences in lag structure between task and rest states, but not between adolescents with ASD and typically developing peers. Additional analyses exploring links with arterial transit time, however, highlight the impact of vascular organization on BOLD lag patterns and its potential to confound measures of neural dynamics.

MEG Theta during Lexico-Semantic and Executive Processing Is Altered in High-Functioning Adolescents with Autism.

Neuroimaging studies have revealed atypical activation during language and executive tasks in individuals with autism spectrum disorders (ASD). However, the spatiotemporal stages of processing associated with these dysfunctions remain poorly understood. Using an anatomically constrained magnetoencephalography approach, we examined event-related theta oscillations during a double-duty lexical decision task that combined demands on lexico-semantic processing and executive functions. Relative to typically developing peers, high-functioning adolescents with ASD had lower performance accuracy on trials engaging selective semantic retrieval and cognitive control. They showed an early overall theta increase in the left fusiform cortex followed by greater activity in the left-lateralized temporal (starting at ~250 ms) and frontal cortical areas (after ~450 ms) known to contribute to language processing. During response preparation and execution, the ASD group exhibited elevated theta in the anterior cingulate cortex, indicative of greater engagement of cognitive control. Simultaneously increased activity in the ipsilateral motor cortex may reflect a less lateralized and suboptimally organized motor circuitry. Spanning early sensory-specific and late response selection stages, the higher event-related theta responsivity in ASD may indicate compensatory recruitment to offset inefficient lexico-semantic retrieval under cognitively demanding conditions. Together, these findings provide further support for atypical language and executive functions in high-functioning ASD.

Underconnectivity Between Visual and Salience Networks and Links With Sensory Abnormalities in Autism Spectrum Disorders.

OBJECTIVE: The anterior insular cortex (AI), which is a part of the salience network, is critically involved in visual awareness, multisensory perception, and social and emotional processing, among other functions. In children and adolescents with autism spectrum disorders (ASDs), evidence has suggested aberrant functional connectivity (FC) of AI compared with typically developing peers. While recent studies have primarily focused on the functional connections between salience and social networks, much less is known about connectivity between AI and primary sensory regions, including visual areas, and how these patterns may be linked to autism symptomatology. METHOD: The current investigation implemented functional magnetic resonance imaging to examine resting-state FC patterns of salience and visual networks in children and adolescents with ASDs compared with typically developing controls, and to relate them to behavioral measures. RESULTS: Functional underconnectivity was found in the ASD group between left AI and bilateral visual cortices. Moreover, in an ASD subgroup with more atypical visual sensory profiles, FC was positively correlated with abnormal social motivational responsivity. CONCLUSION: Findings of reduced FC between salience and visual networks in ASDs potentially indicate deficient selection of salient information. Moreover, in children and adolescents with ASDs who show strongly atypical visual sensory profiles, connectivity at seemingly more neurotypical levels may be paradoxically associated with greater impairment of social motivation.

Spontaneity and diversity of movement to music are not uniquely human.

Spontaneous movement to music occurs in every human culture and is a foundation of dance [1]. This response to music is absent in most species (including monkeys), yet it occurs in parrots, perhaps because they (like humans, and unlike monkeys) are vocal learners whose brains contain strong auditory-motor connections, conferring sophisticated audiomotor processing abilities [2,3]. Previous research has shown that parrots can bob their heads or lift their feet in synchrony with a musical beat [2,3], but humans move to music using a wide variety of movements and body parts. Is this also true of parrots? If so, it would constrain theories of how movement to music is controlled by parrot brains. Specifically, as head bobbing is part of parrot courtship displays [4] and foot lifting is part of locomotion, these may be innate movements controlled by central pattern generators which become entrained by auditory rhythms, without the involvement of complex motor planning. This would be unlike humans, where movement to music engages cortical networks including frontal and parietal areas [5]. Rich diversity in parrot movement to music would suggest a strong contribution of forebrain regions to this behavior, perhaps including motor learning regions abutting the complex vocal-learning 'shell' regions that are unique to parrots among vocal learning birds [6]. Here we report that a sulphur-crested cockatoo (Cacatua galerita eleonora) responds to music with remarkably diverse spontaneous movements employing a variety of body parts, and suggest why parrots share this response with humans.

Atypical Local and Distal Patterns of Occipito-frontal Functional Connectivity are Related to Symptom Severity in Autism.

Autism spectrum disorders (ASDs) are increasingly prevalent neurodevelopmental disorders characterized by sociocommunicative impairments. Growing consensus indicates that neurobehavioral abnormalities require explanation in terms of interconnected networks. Despite theoretical speculations about increased local and reduced distal connectivity, links between local and distal functional connectivity have not been systematically investigated in ASDs. Specifically, it remains open whether hypothesized local overconnectivity may reflect isolated versus overly integrative processing. Resting state functional MRI data from 57 children and adolescents with ASDs and 51 typically developing (TD) participants were included. In regional homogeneity (ReHo) analyses, pericalcarine visual cortex was found be locally overconnected (ASD > TD). Using this region as seed in whole-brain analyses, we observed overconnectivity in distal regions, specifically middle frontal gyri, for an ASD subgroup identified through k-means clustering. While in this subgroup local occipital to distal frontal overconnectivity was associated with greater symptom severity, a second subgroup showed the opposite pattern of connectivity and symptom severity correlations. Our findings suggest that increased local connectivity in ASDs is region-specific and may be partially associated with more integrative long-distance connectivity. Results also highlight the need to test for subtypes, as differential patterns of brain-behavior links were observed in two distinct subgroups of our ASD cohort.

Children with ASD show links between aberrant sound processing, social symptoms, and atypical auditory interhemispheric and thalamocortical functional connectivity.

Autism spectrum disorder (ASD) is a complex and prevalent neurodevelopmental disorder characterized by social and communicative deficits, as well as repetitive behaviors and atypical sensitivity to sensory stimulation. Alterations in network connectivity are widely recognized, but their interplay with social and sensory symptoms remains largely unclear. Here, functional magnetic resonance imaging and diagnostic and behavioral assessments were used in a cohort of children and adolescents with ASD (n=40) and matched typically developing (TD, n=38) controls to examine the relation between auditory processing, interhemispheric and thalamocortical network connectivity, and social-behavioral symptom severity. We found that atypical processing of sounds was related to social, cognitive, and communicative impairments. Additionally, severity of sensory processing deficits and lower verbal IQ were related to reduced interhemispheric connectivity of auditory cortices in ASD. Increased connectivity between the thalamus and auditory cortex in ASD, however, was associated with reduced cognitive and behavioral symptomatology, suggesting that thalamocortical overconnectivity might reflect a compensatory mechanism in ASD. These findings provide novel evidence for links between auditory sensory deficits and impairments in social interaction and communication.

Local resting state functional connectivity in autism: site and cohort variability and the effect of eye status.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with prominent impairments in sociocommunicative abilities, which have been linked to anomalous brain network organization. Despite ample evidence of atypical long-distance connectivity, the literature on local connectivity remains small and divergent. We used resting-state functional MRI regional homogeneity (ReHo) as a local connectivity measure in comparative analyses across several well-matched low-motion subsamples from the Autism Brain Imaging Data Exchange and in-house data, with a grand total of 147 ASD and 184 typically developing (TD) participants, ages 7-18 years. We tested for group differences in each subsample, with additional focus on the difference between eyes-open and eyes-closed resting states. Despite selection of highest quality data and tight demographic and motion matching between groups and across samples, few effects in exactly identical loci (voxels) were found across samples. However, there was gross consistency across all eyes-open samples of local overconnectivity (ASD > TD) in posterior, visual regions. There was also gross consistency of local underconnectivity (ASD < TD) in cingulate gyrus, although exact loci varied between mid/posterior and anterior sections. While all eyes-open datasets showed the described gross similarities, the pattern of group differences for participants scanned with eyes closed was different, with local overconnectivity in ASD in posterior cingulate gyrus, but underconnectivity in some visual regions. Our findings suggest that fMRI local connectivity measures may be relatively susceptible to site and cohort variability and that some previous inconsistencies in the ASD ReHo literature may be reconciled by more careful consideration of eye status.

Impaired downregulation of visual cortex during auditory processing is associated with autism symptomatology in children and adolescents with autism spectrum disorder.

Autism spectrum disorders (ASD) are pervasive developmental disorders characterized by impairments in language development and social interaction, along with restricted and stereotyped behaviors. These behaviors often include atypical responses to sensory stimuli; some children with ASD are easily overwhelmed by sensory stimuli, while others may seem unaware of their environment. Vision and audition are two sensory modalities important for social interactions and language, and are differentially affected in ASD. In the present study, 16 children and adolescents with ASD and 16 typically developing (TD) participants matched for age, gender, nonverbal IQ, and handedness were tested using a mixed event-related/blocked functional magnetic resonance imaging paradigm to examine basic perceptual processes that may form the foundation for later-developing cognitive abilities. Auditory (high or low pitch) and visual conditions (dot located high or low in the display) were presented, and participants indicated whether the stimuli were "high" or "low." Results for the auditory condition showed downregulated activity of the visual cortex in the TD group, but upregulation in the ASD group. This atypical activity in visual cortex was associated with autism symptomatology. These findings suggest atypical crossmodal (auditory-visual) modulation linked to sociocommunicative deficits in ASD, in agreement with the general hypothesis of low-level sensorimotor impairments affecting core symptomatology. Autism Res 2017, 10: 130-143. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.