Reduced covariation between brain morphometry and local spontaneous activity in young children with ASD.

While disruptions in brain maturation in the first years of life in ASD are well documented, little is known about how the brain structure and function are related in young children with ASD compared to typically developing peers. We applied a multivariate pattern analysis to examine the covariation patterns between brain morphometry and local brain spontaneous activity in 38 toddlers and preschoolers with ASD and 31 typically developing children using T1-weighted structural MRI and resting-state fMRI data acquired during natural sleep. The results revealed significantly reduced brain structure-function correlations in ASD. The resultant brain structure and function composite indices were associated with age among typically developing children, but not among those with ASD, suggesting mistiming of typical brain maturational trajectories early in life in autism. Additionally, the brain function composite indices were associated with the overall developmental and adaptive behavior skills in the ASD group, highlighting the neurodevelopmental significance of early local brain activity in autism.

Functional dysregulation of the auditory cortex in bilateral perisylvian polymicrogyria: Multiparametric case analysis of the absent speech phenotype.

The absence of speech is a clinical phenotype seen across neurodevelopmental syndromes, offering insights for neural language models. We present a case of bilateral perisylvian polymicrogyria (BPP) and complete absence of speech with considerable language comprehension and production difficulties. We extensively characterized the auditory speech perception and production circuitry by employing a multimodal neuroimaging approach. Results showed extensive cortical thickening in motor and auditory-language regions. The auditory cortex lacked sensitivity to speech stimuli despite relatively preserved thalamic projections yet had no intrinsic functional organization. Subcortical structures implicated in early stages of processing exhibited heightened sensitivity to speech. The arcuate fasciculus, a suggested marker of language in BPP, showed similar volume and integrity to a healthy control. The frontal aslant tract, linked to oromotor function, was partially reconstructed. These findings highlight the importance of assessing the auditory cortex beyond speech production structures to understand absent speech in BPP. Despite profound cortical alterations, the intrinsic motor network and motor-speech pathways remained largely intact. This case underscores the need for comprehensive phenotyping using multiple MRI modalities to uncover causes of severe disruption in language development.

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.

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.

Anatomical correlates of category-selective visual regions have distinctive signatures of connectivity in neonates.

The ventral visual stream is shaped during development by innate proto-organization within the visual system, such as the strong input from the fovea to the fusiform face area. In adults, category-selective regions have distinct signatures of connectivity to brain regions beyond the visual system, likely reflecting cross-modal and motoric associations. We tested if this long-range connectivity is part of the innate proto-organization, or if it develops with postnatal experience, by using diffusion-weighted imaging to characterize the connectivity of anatomical correlates of category-selective regions in neonates (N = 445), 1-9 month old infants (N = 11), and adults (N = 14). Using the HCP data we identified face- and place- selective regions and a third intermediate region with a distinct profile of selectivity. Using linear classifiers, these regions were found to have distinctive connectivity at birth, to other regions in the visual system and to those outside of it. The results support an extended proto-organization that includes long-range connectivity that shapes, and is shaped by, experience-dependent development.

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.

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.

Externalizing Behaviors are Associated with Increased Parenting Stress in Caregivers of Young Children with Autism.

Parents of children diagnosed with autism spectrum disorder (ASD) report higher levels of stress than parents of typically developing children. Few studies have examined factors associated with parental stress in early childhood. Even fewer have investigated the simultaneous influence of sociodemographic, clinical, and developmental variables on parental stress. We examined factors associated with stress in parents of young children with ASD. Multiple regression models were used to test for associations between socioeconomic indices, developmental measures, and parental stress. Externalizing behaviors, communication, and socialization skills accounted for variance in parental stress, controlling for ASD diagnosis. Results highlight the importance of interventions aimed at reducing externalizing behaviors in young children as well as addressing stress in caregivers of children with ASD.

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.

Resting state functional networks in 1-to-3-year-old typically developing children.

Brain functional networks undergo substantial development and refinement during the first years of life. Yet, the maturational pathways of functional network development remain poorly understood. Using resting-state fMRI data acquired during natural sleep from 24 typically developing toddlers, ages 1.5-3.5 years, we aimed to examine the large-scale resting-state functional networks and their relationship with age and developmental skills. Specifically, two network organization indices reflecting network connectivity and spatial variability were derived. Our results revealed that reduced spatial variability or increased network homogeneity in one of the default mode network components was associated with age, with older children displaying less spatially variable posterior DMN subcomponent, consistent with the notion of increased spatial and functional specialization. Further, greater network homogeneity in higher-order functional networks, including the posterior default mode, salience, and language networks, was associated with more advanced developmental skills measured with a standardized assessment of early learning, regardless of age. These results not only improve our understanding of brain functional network development during toddler years, but also inform the relationship between brain network organization and emerging cognitive and behavioral skills.

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.

Socioeconomic Factors Account for Variability in Language Skills in Preschoolers with Autism Spectrum Disorders.

OBJECTIVE: Although no longer required for a diagnosis, language delays are extremely common in children diagnosed with autism spectrum disorders (ASD). Factors associated with socioeconomic status (SES) have broad-reaching impact on language development in early childhood. Despite recent advances in characterizing autism in early childhood, the relationship between SES and language development in ASD has not received much attention. THE OBJECTIVE OF THIS STUDY WAS: to examine whether toddlers and preschoolers with ASD from low-resource families are more likely to experience language delays above and beyond those associated with autism itself. METHODS: Developmental and diagnostic assessments including the Mullen Scales of Early Learning, the Autism Diagnostic Observation Schedule, Second Edition, and the Vineland Adaptive Behavior Scales were obtained from 62 young children with ASD and 45 typically developing children aged 15 to 64 months. Sociodemographic information including household income, maternal education, and racial/ethnic identity was obtained from caregivers. Multiple regression models were used to test for associations between socioeconomic indices and language scores. RESULTS: Maternal education accounted for variability in expressive language (EL) and receptive language (RL), with lower SES indices associated with lower language skills, and more so in children with ASD. CONCLUSION: These results demonstrate that variability in EL and RL skills in young children with autism can be accounted for by socioeconomic variables. These findings highlight the necessity for targeted intervention and effective implementation strategies for children with ASD from low-resource households and communities and for policies designed to improve learning opportunities and access to services for these young children and their families.

Impact of the oil load on the oxidation of microencapsulated oil powders.

The effect of the oil load on the oxidation of microencapsulated fish oil powders was investigated. The oil load was varied between 4.95 and 20.33%(w/w) by spray drying O/W emulsions with different oil to matrix ratios (0.05, 0.1, 0.15 and 0.2(w/w)), whereas solid content (45%(w/w)) and soy protein isolate to oil ratio (0.15(w/w)) were kept constant. A standardized size fraction of particles (50-80 µm) was stored for 82 days and hydroperoxides and anisidine value measured in the total- and encapsulated oil. Oxidation was limited by the oxygen amount rather than by the oil load. The absolute amount of oxidation products (per powder mass) increased with the oil load, which was explained by oxygen diffusion. Calculating oxidation products per oil mass resulted in a faster oxidation of the powder with 5% oil, whereas the oxidation rate for oil loads ≥10%(w/w) was similar, due to a scavenging effect of oil droplets.

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.

Impact of the oil droplet size on the oxidative stability of microencapsulated oil.

Microencapsulation aims to protect polyunsaturated fatty acids against oxidation by embedding oil droplets in a solid matrix. The effect of the oil droplet size on the oxidation was evaluated under consideration of the non-encapsulated oil and the powder particle size. An O/W emulsion (1.6%(w/w) soy protein; 30.4%(w/w) maltodextrin DE21; 8%(w/w) fish oil) was homogenised at different pressure levels (4, 8, 17.5 and 30 MPa). Emulsions were spray dried and the size of the obtained powders was standardised. Powders were stored for 147 days at 25 °C and the hydroperoxide concentration and Anisidine Value in the total- and encapsulated oil measured. The volume mean diameter of oil droplets varied between 0.48 ± 0.01 and 1.54 ± 0.07 µm. Powders containing small oil droplets resulted in fewer oxidation products, which was related to a larger specific surface area and therefore a pronounced chemical stabilisation by soy protein isolate rather than oxygen diffusion phenomena or different encapsulation efficiencies.

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.

Oxidation rate of the non-encapsulated- and encapsulated oil and their contribution to the overall oxidation of microencapsulated fish oil particles.

Microencapsulation of fish oil by spray drying is an established method to protect polyunsaturated fatty acids against oxidation by separating the environmental O2 from encapsulated lipids. Some oil droplets are not fully embedded within the matrix and are exposed to the environmental O2. The aim of the study is to determine the oxidation rate of the non-encapsulated- and encapsulated oil as well as the contribution of each lipid fraction to the overall oxidation of the encapsulates. The amount of non-encapsulated oil was varied by changing the preparation of the O/W emulsions (18% fish oil; 27% solids) regarding protein to oil ratio (0.02-0.22 (w/w)) and applied homogenization pressure (0.5/0.1-25/5 MPa). Emulsions were spray dried using a pilot plant drier with a maximal water evaporation rate of 30 kg h-1 operated at an inlet and outlet temperature of 160 °C and 85 °C, respectively. The obtained particles were analyzed in terms of water content, aw, particle size, non-encapsulated oil concentration and encapsulation efficiency. The amount of hydroperoxides in the total-, encapsulated- and non-encapsulated oil was determined over a storage period of 6 weeks. The non-encapsulated oil concentration was in the range of 2.20 and 18.45% which corresponds to an encapsulation efficiency between 53.82 and 93.56%. The sum of hydroperoxides in the non-encapsulated- and encapsulated oil equaled the amount detected in the total oil. The non-encapsulated oil oxidized on average 7.4 ±â€¯2.0 times faster than the encapsulated lipids, whereas its contribution to the overall oxidation was minor, due to its low amount. The encapsulated oil was the main contributor to the overall oxidation and oxidized, even though it was fully embedded within the matrix.