Associations between atypical intracortical myelin content and neuropsychological functions in middle to older aged adults with ASD.

INTRODUCTION: In vivo myeloarchitectonic mapping based on Magnetic Resonance Imaging (MRI) provides a unique view of gray matter myelin content and offers information complementary to other morphological indices commonly employed in studies of autism spectrum disorder (ASD). The current study sought to determine if intracortical myelin content (MC) and its age-related trajectories differ between middle aged to older adults with ASD and age-matched typical comparison participants. METHODS: Data from 30 individuals with ASD and 36 age-matched typical comparison participants aged 40-70 years were analyzed. Given substantial heterogeneity in both etiology and outcomes in ASD, we utilized both group-level and subject-level analysis approaches to test for signs of atypical intracortical MC as estimated by T1w/T2w ratio. RESULTS: Group-level analyses showed no significant differences in average T1w/T2w ratio or its associations with age between groups, but revealed significant positive main effects of age bilaterally, with T1w/T2w ratio increasing with age across much of the cortex. In subject-level analyses, participants were classified into subgroups based on presence or absence of clusters of aberrant T1w/T2w ratio, and lower neuropsychological function was observed in the ASD subgroup with atypically high T1w/T2w ratio in spatially heterogeneous cortical regions. These differences were observed across several neuropsychological domains, including overall intellectual functioning, processing speed, and aspects of executive function. CONCLUSIONS: The group-level and subject-level approaches employed here demonstrate the value of examining inter-individual variability and provide important preliminary insights into relationships between brain structure and cognition in the second half of the lifespan in ASD, suggesting shared factors contributing to atypical intracortical myelin content and poorer cognitive outcomes for a subset of middle aged to older autistic adults. These atypicalities likely reflect diverse histories of neurodevelopmental deficits, and possible compensatory changes, compounded by processes of aging, and may serve as useful markers of vulnerability to further cognitive decline in older adults with ASD.

Assessing Predictive Ability of Dynamic Time Warping Functional Connectivity for ASD Classification.

Functional connectivity MRI (fcMRI) is a technique used to study the functional connectedness of distinct regions of the brain by measuring the temporal correlation between their blood oxygen level-dependent (BOLD) signals. fcMRI is typically measured with the Pearson correlation (PC), which assumes that there is no lag between time series. Dynamic time warping (DTW) is an alternative measure of similarity between time series that is robust to such time lags. We used PC fcMRI data and DTW fcMRI data as predictors in machine learning models for classifying autism spectrum disorder (ASD). When combined with dimension reduction techniques, such as principal component analysis, functional connectivity estimated with DTW showed greater predictive ability than functional connectivity estimated with PC. Our results suggest that DTW fcMRI can be a suitable alternative measure that may be characterizing fcMRI in a different, but complementary, way to PC fcMRI that is worth continued investigation. In studying different variants of cross validation (CV), our results suggest that, when it is necessary to tune model hyperparameters and assess model performance at the same time, a K-fold CV nested within leave-one-out CV may be a competitive contender in terms of performance and computational speed, especially when sample size is not large.

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.

Sleep Problems in Preschoolers With Autism Spectrum Disorder Are Associated With Sensory Sensitivities and Thalamocortical Overconnectivity.

BACKGROUND: Projections between the thalamus and sensory cortices are established early in development and play an important role in regulating sleep as well as in relaying sensory information to the cortex. Atypical thalamocortical functional connectivity frequently observed in children with autism spectrum disorder (ASD) might therefore be linked to sensory and sleep problems common in ASD. METHODS: Here, we investigated the relationship between auditory-thalamic functional connectivity measured during natural sleep functional magnetic resonance imaging, sleep problems, and sound sensitivities in 70 toddlers and preschoolers (1.5-5 years old) with ASD compared with a matched group of 46 typically developing children. RESULTS: In children with ASD, sleep problems and sensory sensitivities were positively correlated, and increased sleep latency was associated with overconnectivity between the thalamus and auditory cortex in a subsample with high-quality magnetic resonance imaging data (n = 29). In addition, auditory cortex blood oxygen level-dependent signal amplitude was elevated in children with ASD, potentially reflecting reduced sensory gating or a lack of auditory habituation during natural sleep. CONCLUSIONS: These findings indicate that atypical thalamocortical functional connectivity can be detected early in development and may play a crucial role in sleep problems and sensory sensitivities in ASD.

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.

Cortical myelination in toddlers and preschoolers with autism spectrum disorder.

Intracortical myelin is thought to play a significant role in the development of neural circuits and functional networks, with consistent evidence of atypical network connectivity in children with autism spectrum disorder (ASD). However, little is known about the development of intracortical myelin in the first years of life in ASD, during the critical neurodevelopmental period when autism symptoms first emerge. Using T1-weighted (T1w) and T2w structural magnetic resonance imaging (MRI) in 21 young children with ASD and 16 typically developing (TD) children, ages 1.5-5.5 years, we demonstrate the feasibility of estimating intracortical myelin in vivo using the T1w/T2w ratio as a proxy. The resultant T1w/T2w maps were largely comparable with those reported in prior T1w/T2w studies in TD children and adults, and revealed no group differences between TD children and those with ASD. However, differential associations between T1w/T2w and age were identified in several early myelinated regions (e.g., visual, posterior cingulate, precuneus cortices) in the ASD and TD groups, with age-related increase in estimated myelin content across the toddler and preschool years detected in TD children, but not in children with ASD. The atypical age-related effects in intracortical myelin, suggesting a disrupted myelination in the first years of life in ASD, may be related to the aberrant brain network connectivity reported in young children with ASD in some of the same cortical regions and circuits.

EEG microstates suggest atypical resting-state network activity in high-functioning children and adolescents with autism spectrum development.

EEG microstates represent transient electrocortical events that reflect synchronized activities of large-scale networks, which allows investigations of brain dynamics with sub-second resolution. We recorded resting EEG from 38 children and adolescents with Autism Spectrum Development (ASD) and 48 age, IQ, sex, and handedness-matched typically developing (TD) participants. The EEG was segmented into a time series of microstates using modified k-means clustering of scalp voltage topographies. The frequency and global explained variance (GEV) of a specific microstate (type C) were significantly lower in the ASD group compared to the TD group while the duration of the same microstate was correlated with the presence of ASD-related behaviors. The duration of this microstate was also positively correlated with participant age in the TD group, but not in the ASD group. Further, the frequency and duration of the microstate were significantly correlated with the overall alpha power only in the TD group. The signal strength and GEV for another microstate (type G) was greater in the ASD group than the TD group, and the associated topographical pattern differed between groups with greater variations in the ASD group. While more work is needed to clarify the underlying neural sources, the existing literature supports associations between the two microstates and the default mode and salience networks. The current study suggests specific alterations of temporal dynamics of the resting cortical network activities as well as their developmental trajectories and relationships to alpha power, which has been proposed to reflect reduced neural inhibition in ASD.

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.

Morphometry and functional connectivity of auditory cortex in school-age children with profound language disabilities: Five comparative case studies.

Many neurodevelopmental conditions imply absent or severely reduced language capacities at school age. Evidence from functional magnetic resonance imaging is highly limited. We selected a series of five cases scanned with the same fMRI paradigm and the aim of relating individual language profiles onto underlying patterns of functional connectivity (FC) across auditory language cortex: three with neurogenetic syndromes (Coffin-Siris, Landau-Kleffner, and Fragile-X), one with idiopathic intellectual disability, one with autism spectrum disorder (ASD). Compared to both a group with typical development (TD) and a verbal ASD group (total N = 110), they all showed interhemispheric FC below two standard deviations of the TD mean. Children with higher language scores showed higher intrahemispheric FC between Heschl's gyrus and other auditory language regions, as well as an increase of FC during language stimulation compared to rest. An increase of FC in forward vs. reversed speech in the posterior and middle temporal gyri was seen across all cases. The Coffin-Siris case, the most severe, also had the most anomalous FC patterns and showed reduced myelin content, while the Landau-Kleffner case showed reduced cortical thickness. These results suggest potential for neural markers and mechanisms of severe language processing deficits under highly heterogeneous etiological conditions.

Functional connectivity within an anxiety network and associations with anxiety symptom severity in middle-aged adults with and without autism.

Anxiety is highly prevalent in autism spectrum disorders (ASDs). However, few functional magnetic resonance imaging (fMRI) studies of ASDs have focused on anxiety (and fewer still on anxiety in middle-aged adults). Thus, relationships between atypical connectivity and anxiety in this population are poorly understood. The current study contrasted functional connectivity within anxiety network regions across adults (40-64 years) with and without autism, and tested for group by functional connectivity interactions on anxiety. Twenty-two adults with ASDs (16 males) and 26 typical control (TC) adults (22 males) completed the Beck Anxiety Inventory and a resting-state fMRI scan. An anxiety network consisting of 12 regions of interest was defined, based on a meta-analysis in TC individuals and two studies on anxiety in ASDs. We tested for main effects of group and group by anxiety interactions on connectivity within this anxiety network, controlling for head motion using ANCOVA. Results are reported at an FDR adjusted threshold of q < 0.1 (corrected) and p < 0.05 (uncorrected). Adults with ASDs showed higher anxiety and underconnectivity within the anxiety network, mostly involving bilateral insula. Connectivity within the anxiety network in the ASD group showed distinct relationships with anxiety symptoms that did not relate to ASD symptom severity. Functional connectivity involving the bilateral posterior insula was positively correlated with anxiety in the ASD (but not the TC) group. Increased anxiety in middle-aged adults with ASD is associated with atypical functional connectivity, predominantly involving bilateral insula. Results were not related to ASD symptom severity suggesting independence of anxiety-related effects. LAY SUMMARY: Anxiety is very common in adults with autism but the brain basis of this difference is not well understood. We compared functional connectivity between anxiety-related brain regions in middle-aged adults with and without autism. Adults with autism were more anxious and showed weaker functional connections between these regions. Some relationships between functional connectivity and higher anxiety were specific to the autism group. Results suggest that anxiety functions differently in autism.

Performance of machine learning classification models of autism using resting-state fMRI is contingent on sample heterogeneity.

Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental conditions. In fMRI studies, including most machine learning studies seeking to distinguish ASD from typical developing (TD) samples, cohorts differing in gender and symptom severity composition are often treated statistically as one "ASD group". Using resting-state functional connectivity (FC) data, we implemented random forest to build diagnostic classifiers in 4 ASD samples including a total of 656 participants (NASD = 306, NTD = 350, ages 6-18). Groups were manipulated to titrate heterogeneity of gender and symptom severity and partially overlapped. Each sample differed on inclusionary criteria: (1) all genders, unrestricted severity range; (2) only male participants, unrestricted severity; (3) all genders, higher severity only; (4) only male participants, higher severity. Each set consisted of 200 participants per group (ASD, TD; matched on age and head motion), 160 for training and 40 for validation. FMRI time series from 237 regions of interest (ROIs) were Pearson correlated in a 237×237 FC matrix and classifiers were built using random forest in training samples. Classification accuracies in validation samples were 62.5%, 65%, 70% and 73.75%, respectively for samples 1-4. Connectivity within cingulo-opercular task control (COTC) network, and between COTC ROIs and default mode and dorsal attention network contributed overall most informative features, but features differed across sets. Findings suggest that diagnostic classifiers vary depending on ASD sample composition. Specifically, greater homogeneity of samples regarding gender and symptom severity enhances classifier performance. However, given the true heterogeneity of ASDs, performance metrics alone may not adequately reflect classifier utility.

Supplementary and Premotor Aspects of the Corticospinal Tract Show Links with Restricted and Repetitive Behaviors in Middle-Aged Adults with Autism Spectrum Disorder.

Individuals with autism spectrum disorder (ASD) show motor impairment into adulthood and risk decline during aging, but little is known about brain changes in aging adults with ASD. Few studies of ASD have directly examined the corticospinal tract (CST)-the major descending pathway in the brain responsible for voluntary motor behavior-outside its primary motor (M1) connections. In 26 middle-aged adults with ASD and 26 age-matched typical comparison participants, we used diffusion imaging to examine the microstructure and volume of CST projections from M1, dorsal premotor (PMd), supplementary motor area (SMA), and primary somatosensory (S1) cortices with respect to age. We also examined relationships between each CST sub-tract (-cst), motor skills, and autism symptoms. We detected no significant group or age-related differences in tracts extending from M1 or other areas. However, sub-tracts of the CST extending from secondary (but not primary) motor areas were associated with core autism traits. Increased microstructural integrity of left PMd-cst and SMA-cst were associated with less-severe restricted and repetitive behaviors (RRB) in the ASD group. These findings suggest that secondary motor cortical areas, known to be involved in selecting motor programs, may be implicated in cognitive motor processes underlying RRB in ASD.

Greater functional connectivity between sensory networks is related to symptom severity in toddlers with autism spectrum disorder.

BACKGROUND: Symptoms of autism spectrum disorder (ASD) emerge in the first years of life. Yet, little is known about the organization and development of functional brain networks in ASD proximally to the symptom onset. Further, the relationship between brain network connectivity and emerging ASD symptoms and overall functioning in early childhood is not well understood. METHODS: Resting-state fMRI data were acquired during natural sleep from 24 young children with ASD and 23 typically developing (TD) children, aged 17-45 months. Intrinsic functional connectivity (iFC) within and between resting-state functional networks was derived with independent component analysis (ICA). RESULTS: Increased iFC between visual and sensorimotor networks was found in young children with ASD compared to TD participants. Within the ASD group, the degree of overconnectivity between visual and sensorimotor networks was associated with greater autism symptoms. Age-related weakening of the visual-auditory between-network connectivity was observed in the ASD but not the TD group. CONCLUSIONS: Taken together, these results provide evidence for disrupted functional network maturation and differentiation, particularly involving visual and sensorimotor networks, during the first years of life in ASD. The observed pattern of greater visual-sensorimotor between-network connectivity associated with poorer clinical outcomes suggests that disruptions in multisensory brain circuitry may play a critical role for early development of behavioral skills and autism symptomatology in young children with ASD.

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.

Sex-related patterns of intrinsic functional connectivity in children and adolescents with autism spectrum disorders.

LAY SUMMARY: We investigated whether children and adolescents with autism spectrum disorders show sex-specific patterns of brain function (using functional magnetic resonance imaging) that are well documented in typically developing males and females. We found, unexpectedly, that boys and girls with autism do not differ in their brain functional connectivity, whereas typically developing boys and girls showed differences in a brain network involved in thinking about self and others (the default mode network). Results suggest that autism may be characterized by a lack of brain sex differentiation.

Atypical Relationships Between Spontaneous EEG and fMRI Activity in Autism.

Autism spectrum disorders (ASDs) have been linked to atypical communication among distributed brain networks. However, despite decades of research, the exact nature of these differences between typically developing (TD) individuals and those with ASDs remains unclear. ASDs have been widely studied using resting-state neuroimaging methods, including both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). However, little is known about how fMRI and EEG measures of spontaneous brain activity are related in ASDs. In the present study, two cohorts of children and adolescents underwent resting-state EEG (n = 38 per group) or fMRI (n = 66 ASD, 57 TD), with a subset of individuals in both the EEG and fMRI cohorts (n = 17 per group). In the EEG cohort, parieto-occipital EEG alpha power was found to be reduced in ASDs. In the fMRI cohort, blood oxygen level-dependent (BOLD) power was regionally increased in right temporal regions and there was widespread overconnectivity between the thalamus and cortical regions in the ASD group relative to the TD group. Finally, multimodal analyses indicated that while TD children showed consistently positive relationships between EEG alpha power and regional BOLD power, these associations were weak or negative in ASDs. These findings suggest atypical links between alpha rhythms and regional BOLD activity in ASDs, possibly implicating neural substrates and processes that coordinate thalamocortical regulation of the alpha rhythm.

Impaired motor skills and atypical functional connectivity of the sensorimotor system in 40- to 65-year-old adults with autism spectrum disorders.

Impairments in fine and gross motor function, coordination, and balance in early development are common in autism spectrum disorders (ASDs). It is unclear whether these deficits persist into adulthood and whether they may be exacerbated by additional motor problems that often emerge in typical aging. We assessed motor skills and used resting-state functional magnetic resonance imaging to study intrinsic functional connectivity of the sensorimotor network in 40- to 65-year-old adults with ASDs (n = 17) and typically developing matched adults (n = 19). Adults with ASDs scored significantly lower on assessments of motor skills compared with an age-matched group of typical control adults. In addition, functional connectivity of the sensorimotor system was reduced and the pattern of connectivity was more heterogeneous in adults with ASDs. A negative correlation between functional connectivity of the motor system and motor skills, however, was only found in the typical control group. Findings suggest behavioral impairment and atypical brain organization of the motor system in middle-age adults with ASDs, accompanied by pronounced heterogeneity.

Dopaminergic hypo-activity and reduced theta-band power in autism spectrum disorder: A resting-state EEG study.

BACKGROUND: Prior studies using a variety of methodologies have reported inconsistent dopamine (DA) findings in individuals with autism spectrum disorder (ASD), ranging from dopaminergic hypo- to hyper-activity. Theta-band power derived from scalp-recorded electroencephalography (EEG), which may be associated with dopamine levels in frontal cortex, has also been shown to be atypical in ASD. The present study examined spontaneous eye-blink rate (EBR), an indirect, non-invasive measure of central dopaminergic activity, and theta power in children with ASD to determine: 1) whether ASD may be associated with atypical DA levels, and 2) whether dopaminergic dysfunction may be associated with aberrant theta-band activation. METHOD: Participants included thirty-two children with ASD and thirty-two age-, IQ-, and sex-matched typically developing (TD) children. Electroencephalography and eye-tracking data were acquired while participants completed an eyes-open resting-state session. Blinks were counted and EBR was determined by dividing blink frequency by session duration and theta power (4-7.5 Hz) was extracted from midline leads. RESULTS: Eye-blink rate and theta-band activity were significantly reduced in children with ASD as compared to their TD peers. For all participants, greater midline theta power was associated with increased EBR (related to higher DA levels). CONCLUSIONS: These results suggest that ASD may be associated with dopaminergic hypo-activity, and that this may contribute to atypical theta-band power. Lastly, EBR may be a useful tool to non-invasively index dopamine levels in ASD and could potentially have many clinical applications, including selecting treatment options and monitoring treatment response.

Regionally decreased gyrification in middle-aged adults with autism spectrum disorders.

OBJECTIVE: To examine changing features of cortical morphology in middle-aged adults with autism spectrum disorders (ASDs) vs typical comparison (TC) participants, hypothesizing regionally decreased local gyrification index (lGI), given our previous findings of accelerated lGI decline during adolescence. METHODS: After quality assurance, T1-weighted MRI sequences from 20 participants with ASD and 21 TC participants (40-61 years) matched on age were analyzed. lGI, cortical thickness (CT), and surface area (SA) were measured with FreeSurfer version 5.3. Statistical analyses used a general linear model including age, nonverbal IQ, and total brain volume as covariates. Clusters of significant group effects were used as regions of interest for behavioral analyses. RESULTS: Clusters of decreased lGI were observed bilaterally in the ASD group with large effect sizes in insular and anterior cingulate (ACC), left postcentral, and middle frontal and right orbitofrontal and supramarginal regions. lGI was also shown to decline with age across groups in bilateral precentral and right supramarginal clusters. No significant group, age, or group-by-age interaction effects were observed for CT or SA in this age group. lGI showed a significant correlation with Social Responsiveness Scale total scores in a right caudal ACC cluster in the TC group only, while several correlations were found in the ASD group between executive function scores and clusters in the bilateral insula and right orbitofrontal cortex. CONCLUSION: The pattern of regionally decreased lGI observed here in middle-aged adults with ASDs is consistent with an abnormal trajectory of cortical folding changes across different stages of life in ASDs, as shown in previous studies.