An Observed Assessment of Sensory Responsivity in Autism Spectrum Disorders: Associations with Diagnosis, Age, and Parent Report.

Sensory features are common and impairing in autism spectrum disorder (ASD), but there are few observational sensory assessments that are valid across ages. We used the Sensory Processing 3-Dimensional (SP3-D) observed Assessment and parent-reported Inventory to examine sensory responsivity in 41 ASD and 33 typically-developing (TD) youth across 7-17 years. ASD youth had higher and more variable observed and reported sensory responsivity symptoms compared to TD, but the two measures were not correlated. Observed sensory over-responsivity (SOR) and sensory craving (SC) decreased with age in ASD, though SOR remained higher in ASD versus TD through adolescence. Results suggest that in ASD, the SP3-D Assessment can identify SOR through adolescence, and that there is value in integrating multiple sensory measures.

Atypical cerebellar functional connectivity at 9 months of age predicts delayed socio-communicative profiles in infants at high and low risk for autism.

BACKGROUND: While the cerebellum is traditionally known for its role in sensorimotor control, emerging research shows that particular subregions, such as right Crus I (RCrusI), support language and social processing. Indeed, cerebellar atypicalities are commonly reported in autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by socio-communicative impairments. However, the cerebellum's contribution to early socio-communicative development remains virtually unknown. METHODS: Here, we characterized functional connectivity within cerebro-cerebellar networks implicated in language/social functions in 9-month-old infants who exhibit distinct 3-year socio-communicative developmental profiles. We employed a data-driven clustering approach to stratify our sample of infants at high (n = 82) and low (n = 37) familial risk for ASD into three cohorts-Delayed, Late-Blooming, and Typical-who showed unique socio-communicative trajectories. We then compared the cohorts on indices of language and social development. Seed-based functional connectivity analyses with RCrusI were conducted on infants with fMRI data (n = 66). Cohorts were compared on connectivity estimates from a-priori regions, selected on the basis of reported coactivation with RCrusI during language/social tasks. RESULTS: The three trajectory-based cohorts broadly differed in social communication development, as evidenced by robust differences on numerous indices of language and social skills. Importantly, at 9 months, the cohorts showed striking differences in cerebro-cerebellar circuits implicated in language/social functions. For all regions examined, the Delayed cohort exhibited significantly weaker RCrusI connectivity compared to both the Late-Blooming and Typical cohorts, with no significant differences between the latter cohorts. CONCLUSIONS: We show that hypoconnectivity within distinct cerebro-cerebellar networks in infancy predicts altered socio-communicative development before delays overtly manifest, which may be relevant for early detection and intervention. As the cerebellum is implicated in prediction, our findings point to probabilistic learning as a potential intermediary mechanism that may be disrupted in infancy, cascading into alterations in social communication.

Impact of autism genetic risk on brain connectivity: a mechanism for the female protective effect.

The biological mechanisms underlying the greater prevalence of autism spectrum disorder in males than females remain poorly understood. One hypothesis posits that this female protective effect arises from genetic load for autism spectrum disorder differentially impacting male and female brains. To test this hypothesis, we investigated the impact of cumulative genetic risk for autism spectrum disorder on functional brain connectivity in a balanced sample of boys and girls with autism spectrum disorder and typically developing boys and girls (127 youth, ages 8-17). Brain connectivity analyses focused on the salience network, a core intrinsic functional connectivity network which has previously been implicated in autism spectrum disorder. The effects of polygenic risk on salience network functional connectivity were significantly modulated by participant sex, with genetic load for autism spectrum disorder influencing functional connectivity in boys with and without autism spectrum disorder but not girls. These findings support the hypothesis that autism spectrum disorder risk genes interact with sex differential processes, thereby contributing to the male bias in autism prevalence and proposing an underlying neurobiological mechanism for the female protective effect.

Effects of sensory distraction and salience priming on emotion identification in autism: an fMRI study.

BACKGROUND: Social interaction often occurs in noisy environments with many extraneous sensory stimuli. This is especially relevant for youth with autism spectrum disorders (ASD) who commonly experience sensory over-responsivity (SOR) in addition to social challenges. However, the relationship between SOR and social difficulties is still poorly understood and thus rarely addressed in interventions. This study investigated the effect of auditory sensory distracters on neural processing of emotion identification in youth with ASD and the effects of increasing attention to social cues by priming participants with their own emotional faces. METHODS: While undergoing functional magnetic resonance imaging (fMRI), 30 youth with ASD and 24 typically developing (TD) age-matched controls (ages 8-17 years) identified faces as happy or angry with and without simultaneously hearing aversive environmental noises. Halfway through the task, participants also viewed videos of their own emotional faces. The relationship between parent-rated auditory SOR and brain responses during the task was also examined. RESULTS: Despite showing comparable behavioral performance on the task, ASD and TD youth demonstrated distinct patterns of neural activity. Compared to TD, ASD youth showed greater increases in amygdala, insula, and primary sensory regions when identifying emotions with noises compared to no sounds. After viewing videos of their own emotion faces, ASD youth showed greater increases in medial prefrontal cortex activation compared to TD youth. Within ASD youth, lower SOR was associated with reduced increased activity in subcortical regions after the prime and greater increased activity in the ventromedial prefrontal cortex after the prime, particularly in trials with noises. CONCLUSIONS: The results suggest that the sensory environment plays an important role in how ASD youth process social information. Additionally, we demonstrated that increasing attention to relevant social cues helps ASD youth engage frontal regions involved in higher-order social cognition, a mechanism that could be targeted in interventions. Importantly, the effect of the intervention may depend on individual differences in SOR, supporting the importance of pre-screening youth for sensory challenges prior to social interventions.

Sensory over-responsivity is related to GABAergic inhibition in thalamocortical circuits.

Sensory over-responsivity (SOR), extreme sensitivity to or avoidance of sensory stimuli (e.g., scratchy fabrics, loud sounds), is a highly prevalent and impairing feature of neurodevelopmental disorders such as autism spectrum disorders (ASD), anxiety, and ADHD. Previous studies have found overactive brain responses and reduced modulation of thalamocortical connectivity in response to mildly aversive sensory stimulation in ASD. These findings suggest altered thalamic sensory gating which could be associated with an excitatory/inhibitory neurochemical imbalance, but such thalamic neurochemistry has never been examined in relation to SOR. Here we utilized magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to examine the relationship between thalamic and somatosensory cortex inhibitory (gamma-aminobutyric acid, GABA) and excitatory (glutamate) neurochemicals with the intrinsic functional connectivity of those regions in 35 ASD and 35 typically developing pediatric subjects. Although there were no diagnostic group differences in neurochemical concentrations in either region, within the ASD group, SOR severity correlated negatively with thalamic GABA (r = -0.48, p < 0.05) and positively with somatosensory glutamate (r = 0.68, p < 0.01). Further, in the ASD group, thalamic GABA concentration predicted altered connectivity with regions previously implicated in SOR. These variations in GABA and associated network connectivity in the ASD group highlight the potential role of GABA as a mechanism underlying individual differences in SOR, a major source of phenotypic heterogeneity in ASD. In ASD, abnormalities of the thalamic neurochemical balance could interfere with the thalamic role in integrating, relaying, and inhibiting attention to sensory information. These results have implications for future research and GABA-modulating pharmacologic interventions.

Emerging atypicalities in functional connectivity of language-related networks in young infants at high familial risk for ASD.

Prior studies have demonstrated that infants and toddlers who later go on to develop autism spectrum disorder (ASD) show atypical functional connectivity as well as altered neural processing of language and other auditory stimuli, but the timeline underlying the emergence of these altered developmental trajectories is still unclear. Here we used resting-state fMRI (rsfMRI) during natural sleep to examine the longitudinal development of functional connectivity in language-related networks from 1.5 to 9 months of age. We found that functional connectivity of networks that underlie the integration of sensory and motor representations, which is crucial for language development, is disrupted in infants at high familial risk (HR) for developing ASD as early as 1.5 months of age. By 9 months of age, HR infants showed hyperconnectivity between auditory and somatosensory regions whereas low risk (LR) infants displayed greater intrahemispheric connectivity between auditory cortex and higher-order temporal regions as well as the hippocampus. Furthermore, while LR infants showed robust changes in functional connectivity during the first year of life with increasing long-range connectivity accompanied by decreasing short-range connectivity over time, HR infants displayed limited developmental changes. Our findings demonstrate that early disruptions in the development of language-related network connectivity may provide an early marker for the later emergence of ASD symptomatology.

Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models.

Hearing loss is a major risk factor for tinnitus, hyperacusis, and central auditory processing disorder. Although recent studies indicate that hearing loss causes neuroinflammation in the auditory pathway, the mechanisms underlying hearing loss-related pathologies are still poorly understood. We examined neuroinflammation in the auditory cortex following noise-induced hearing loss (NIHL) and its role in tinnitus in rodent models. Our results indicate that NIHL is associated with elevated expression of proinflammatory cytokines and microglial activation-two defining features of neuroinflammatory responses-in the primary auditory cortex (AI). Genetic knockout of tumor necrosis factor alpha (TNF-α) or pharmacologically blocking TNF-α expression prevented neuroinflammation and ameliorated the behavioral phenotype associated with tinnitus in mice with NIHL. Conversely, infusion of TNF-α into AI resulted in behavioral signs of tinnitus in both wild-type and TNF-α knockout mice with normal hearing. Pharmacological depletion of microglia also prevented tinnitus in mice with NIHL. At the synaptic level, the frequency of miniature excitatory synaptic currents (mEPSCs) increased and that of miniature inhibitory synaptic currents (mIPSCs) decreased in AI pyramidal neurons in animals with NIHL. This excitatory-to-inhibitory synaptic imbalance was completely prevented by pharmacological blockade of TNF-α expression. These results implicate neuroinflammation as a therapeutic target for treating tinnitus and other hearing loss-related disorders.

RNNbow: Visualizing Learning Via Backpropagation Gradients in RNNs.

We present RNNbow, an interactive tool for visualizing the gradient flow during backpropagation in training of recurrent neural networks. By visualizing the gradient, as opposed to activations, RNNbow offers insight into how the network is learning. We show how it illustrates the vanishing gradient and the training process.

Basic level scene understanding: categories, attributes and structures.

A longstanding goal of computer vision is to build a system that can automatically understand a 3D scene from a single image. This requires extracting semantic concepts and 3D information from 2D images which can depict an enormous variety of environments that comprise our visual world. This paper summarizes our recent efforts toward these goals. First, we describe the richly annotated SUN database which is a collection of annotated images spanning 908 different scene categories with object, attribute, and geometric labels for many scenes. This database allows us to systematically study the space of scenes and to establish a benchmark for scene and object recognition. We augment the categorical SUN database with 102 scene attributes for every image and explore attribute recognition. Finally, we present an integrated system to extract the 3D structure of the scene and objects depicted in an image.