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.

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.

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.

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.

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.

Transient states of network connectivity are atypical in autism: A dynamic functional connectivity study.

There is ample evidence of atypical functional connectivity (FC) in autism spectrum disorders (ASDs). However, transient relationships between neural networks cannot be captured by conventional static FC analyses. Dynamic FC (dFC) approaches have been used to identify repeating, transient connectivity patterns ("states"), revealing spatiotemporal network properties not observable in static FC. Recent studies have found atypical dFC in ASDs, but questions remain about the nature of group differences in transient connectivity, and the degree to which states persist or change over time. This study aimed to: (a) describe and relate static and dynamic FC in typical development and ASDs, (b) describe group differences in transient states and compare them with static FC patterns, and (c) examine temporal stability and flexibility between identified states. Resting-state functional magnetic resonance imaging (fMRI) data were collected from 62 ASD and 57 typically developing (TD) children and adolescents. Whole-brain, data-driven regions of interest were derived from group independent component analysis. Sliding window analysis and k-means clustering were used to explore dFC and identify transient states. Across all regions, static overconnnectivity and increased variability over time in ASDs predominated. Furthermore, significant patterns of group differences emerged in two transient states that were not observed in the static FC matrix, with group differences in one state primarily involving sensory and motor networks, and in the other involving higher-order cognition networks. Default mode network segregation was significantly reduced in ASDs in both states. Results highlight that dynamic approaches may reveal more nuanced transient patterns of atypical FC in ASDs.

Auditory structural connectivity in preterm and healthy term infants during the first postnatal year.

Assessing language development in the first postnatal year is difficult, as receptive and expressive skills are rudimentary. Although outward manifestations of change are limited, the auditory language system is thought to undergo critical development at this age, as the foundations are laid for the rapid onset of spoken language in the second and third years. We recruited 11 infants, 7 healthy controls (gestational age = 40.69 ± 0.56; range from 40 to 41.43) and preterm babies (gestational age = 28.04 ± 0.95; range from 27.43 to 29.43) who underwent a Magnetic Resonance Imaging study during the first postnatal year (age at scan = 194.18 ± 97.98). We assessed white matter tracts using diffusion-weighted magnetic resonance imaging with probabilistic tractography. Fractional anisotropy was found to be largely mature even at one month, although there was a little further increase during the first postnatal year in both the acoustic radiation and the direct brainstem-Heschl's pathway.

Adult-like processing of naturalistic sounds in auditory cortex by 3- and 9-month old infants.

Functional neuroimaging has been used to show that the developing auditory cortex of very young human infants responds, in some way, to sound. However, impoverished stimuli and uncontrolled designs have made it difficult to attribute brain responses to specific auditory features, and thus made it difficult to assess the maturity of feature tuning in auditory cortex. To address this, we used functional magnetic resonance imaging (fMRI) to measure the brain activity evoked by naturalistic sounds (a series of sung lullabies) in two groups of infants (3 and 9 months) and adults. We developed a novel analysis method - inter-subject regression (ISR) - to quantify the similarity of cortical responses between infants and adults, and to decompose components of the response due to different auditory features. We found that the temporal pattern of activity in infant auditory cortex shared similarity with adults. Some of this shared response could be attributed to simple acoustic features, such as frequency, pitch, envelope, but other parts were not, suggesting that even more complex adult-like features are represented in auditory cortex in early infancy.

Using Functional Magnetic Resonance Imaging to Detect Preserved Function in a Preterm Infant with Brain Injury.

We studied developmental plasticity using functional magnetic resonance imaging (fMRI) in a preterm infant with brain injury on structural MRI. fMRI showed preserved brain function and subsequent neurodevelopment was within the normal range. Multimodal neuroimaging including fMRI can improve understanding of neural plasticity after preterm birth and brain injury.

Advanced characterisation of encapsulated lipid powders regarding microstructure by time domain-nuclear magnetic resonance.

Encapsulation is an established technique to protect sensitive materials from environmental stress. In order to understand the physical protection mechanism against oxidation, knowledge about the powder microstructure is required. Time domain-nuclear magnetic resonance (TD-NMR) has the potential to determine the surface oil (SO) and droplet size distribution by relaxation and restricted self-diffusion, respectively. The amount of SO, the retention and encapsulation efficiency are determined based on a lipid balance. The oil load of the initial powder and after SO removal is measured by TD-NMR. The results correlate with gravimetric and photometric references. The oil droplet size obtained by TD-NMR correlates well with static light scattering. The diameter of droplets in emulsions and dried powder both measured by TD-NMR, correlates (r = 0.998), implying that oil droplets embedded in a solid matrix can be measured. Summarising, TD-NMR allows analysis of the microstructure of encapsulated lipid powders, in a rapid, simple and non-destructive way.

Flexible information coding in human auditory cortex during perception, imagery, and STM of complex sounds.

Auditory cortex is the first cortical region of the human brain to process sounds. However, it has recently been shown that its neurons also fire in the absence of direct sensory input, during memory maintenance and imagery. This has commonly been taken to reflect neural coding of the same acoustic information as during the perception of sound. However, the results of the current study suggest that the type of information encoded in auditory cortex is highly flexible. During perception and memory maintenance, neural activity patterns are stimulus specific, reflecting individual sound properties. Auditory imagery of the same sounds evokes similar overall activity in auditory cortex as perception. However, during imagery abstracted, categorical information is encoded in the neural patterns, particularly when individuals are experiencing more vivid imagery. This highlights the necessity to move beyond traditional "brain mapping" inference in human neuroimaging, which assumes common regional activation implies similar mental representations.

Stimulus-specific suppression preserves information in auditory short-term memory.

Philosophers and scientists have puzzled for millennia over how perceptual information is stored in short-term memory. Some have suggested that early sensory representations are involved, but their precise role has remained unclear. The current study asks whether auditory cortex shows sustained frequency-specific activation while sounds are maintained in short-term memory using high-resolution functional MRI (fMRI). Investigating short-term memory representations within regions of human auditory cortex with fMRI has been difficult because of their small size and high anatomical variability between subjects. However, we overcame these constraints by using multivoxel pattern analysis. It clearly revealed frequency-specific activity during the encoding phase of a change detection task, and the degree of this frequency-specific activation was positively related to performance in the task. Although the sounds had to be maintained in memory, activity in auditory cortex was significantly suppressed. Strikingly, patterns of activity in this maintenance period correlated negatively with the patterns evoked by the same frequencies during encoding. Furthermore, individuals who used a rehearsal strategy to remember the sounds showed reduced frequency-specific suppression during the maintenance period. Although negative activations are often disregarded in fMRI research, our findings imply that decreases in blood oxygenation level-dependent response carry important stimulus-specific information and can be related to cognitive processes. We hypothesize that, during auditory change detection, frequency-specific suppression protects short-term memory representations from being overwritten by inhibiting the encoding of interfering sounds.

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.

Altered development of the Hurst Exponent in medial prefrontal cortex in preschoolers with autism.

BACKGROUND: Atypical balance of excitation (E) and inhibition (I) in the brain is thought to contribute to the emergence and symptomatology of autism spectrum disorders (ASD). E/I ratio can be estimated from resting state functional magnetic resonance imaging (fMRI) using the Hurst Exponent (H). A recent study reported decreased ventromedial prefrontal cortex (vmPFC) H in male adults with ASD. Part of the default mode network (DMN), vmPFC plays an important role in emotion regulation, decision making, and social cognition. It frequently shows altered function and connectivity in autistic individuals. METHODS: The current study presents the first fMRI evidence of altered early development of vmPFC H and its link to DMN functional connectivity (FC) and emotional control in toddlers and preschoolers with ASD. 83 children (n=45 ASD), ages 1½ - 5 years, underwent natural sleep fMRI as part of a longitudinal study. RESULTS: In a cross-sectional analysis, vmPFC H decreased with age in children with ASD, reflecting increasing E/I ratio, but not in typically developing children. This effect remained significant when controlling for gestational age at birth, socioeconomic status, or ethnicity. The same pattern was also observed in a subset of children with longitudinal fMRI data acquired two years apart on average. Lower vmPFC H was further associated with reduced FC within the DMN as well as with higher emotional control deficits (though only significant transdiagnostically). CONCLUSIONS: These results suggest an early onset of E/I imbalances in vmPFC in ASD with likely consequences for the maturation of the DMN.

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.

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.

Seeing different objects in different ways: measuring ventral visual tuning to sensory and semantic features with dynamically adaptive imaging.

A key challenge of object recognition is achieving a balance between selectivity for relevant features and invariance to irrelevant ones. Computational and cognitive models predict that optimal selectivity for features will differ by object, and here we investigate whether this is reflected in visual representations in the human ventral stream. We describe a new real-time neuroimaging method, dynamically adaptive imaging (DAI), that enabled measurement of neural selectivity along multiple feature dimensions in the neighborhood of single referent objects. The neural response evoked by a referent was compared to that evoked by 91 naturalistic objects using multi-voxel pattern analysis. Iteratively, the objects evoking the most similar responses were selected and presented again, to converge upon a subset that characterizes the referent's "neural neighborhood." This was used to derive the feature selectivity of the response. For three different referents, we found strikingly different selectivity, both in individual features and in the balance of tuning to sensory versus semantic features. Additional analyses placed a lower bound on the number of distinct activation patterns present. The results suggest that either the degree of specificity available for object representation in the ventral stream varies by class, or that different objects evoke different processing strategies.

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.

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.