Setting boundaries: Development of neural and behavioral event cognition in early childhood.

The ongoing stream of sensory experience is so complex and ever-changing that we tend to parse this experience at "event boundaries," which structures and strengthens memory. Memory processes undergo profound change across early childhood. Whether young children also divide their ongoing processing along event boundaries, and if those boundaries relate to memory, could provide important insight into the development of memory systems. In Study 1, 4-7-year-old children and adults segmented a cartoon, and we tested their memory. Children's event boundaries were more variable than adults' and differed in location and consistency of agreement. Older children's event segmentation was more adult-like than younger children's, and children who segmented events more like adults had better memory for those events. In Study 2, we asked whether these developmental differences in event segmentation had their roots in distinct neural representations. A separate group of 4-8-year-old children watched the same cartoon while undergoing an fMRI scan. In the right hippocampus, greater pattern dissimilarity across event boundaries compared to within events was evident for both child and adult behavioral boundaries, suggesting children and adults share similar event cognition. However, the boundaries identified by a data-driven Hidden Markov Model found that a different brain region-the left and right angular gyrus-aligned only with event boundaries defined by children. Overall, these data suggest that children's event cognition is reasonably well-developed by age 4 but continues to become more adult-like across early childhood. RESEARCH HIGHLIGHTS: Adults naturally break their experience into events, which structures and strengthens memory, but less is known about children's event perception and memory. Study 1 had adults and children segment and remember events from an animated show, and Study 2 compared those segmentations to other children's fMRI data. Children show better recognition and temporal order memory and more adult-like event segmentation with age, and children who segment more like adults have better memory. Children's and adults' behavioral boundaries mapped onto pattern similarity differences in hippocampus, and children's behavioral boundaries matched a data-driven model's boundaries in angular gyrus.

Little brain, little minds: The big role of the cerebellum in social development.

Seminal work in the 1990's found alterations in the cerebellum of individuals with social disorders including autism spectrum disorder and schizophrenia. In neurotypical populations, distinct portions of the posterior cerebellum are consistently activated in fMRI studies of social cognition and it has been hypothesized that the cerebellum plays an essential role in social cognition, particularly in theory of mind. Here we review the lesion literature and find that the effect of cerebellar damage on social cognition is strongly linked to the age of insult, with dramatic impairments observed after prenatal insult, strong deficits observed after childhood damage, and mild and inconsistent deficits observed following damage to the adult cerebellum. To explain the developmental gradient, we propose that early in life, the forward model dominates cerebellar computations. The forward model learns and uses errors to help build schemas of our interpersonal worlds. Subsequently, we argue that once these schemas have been built up, the inverse model, which is the foundation of automatic processing, becomes dominant. We provide suggestions for how to test this, and also outline directions for future research.

A missing link in affect regulation: the cerebellum.

The cerebellum is one-third the size of the cerebrum yet holds twice the number of neurons. Historically, its sole function was thought to be in the calibration of smooth movements through the creation and ongoing modification of motor programs. This traditional viewpoint has been challenged by findings showing that cerebellar damage can lead to striking changes in non-motor behavior, including emotional changes. In this manuscript, we review the literature on clinical and subclinical affective disturbances observed in individuals with lesions to the cerebellum. Disorders include pathological laughing and crying, bipolar disorder, depression and mixed mood changes. We propose a theoretical model based on cerebellar connectivity to explain how the cerebellum calibrates affect. We conclude with actionable steps for future researchers to test this model and improve upon the limitations of past literature.

Distinct alterations in cerebellar connectivity with substantia nigra and ventral tegmental area in Parkinson's disease.

In Parkinson's disease (PD), neurodegeneration of dopaminergic neurons occurs in the midbrain, specifically targeting the substantia nigra (SN), while leaving the ventral tegmental area (VTA) relatively spared in early phases of the disease. Although the SN and VTA are known to be functionally dissociable in healthy adults, it remains unclear how this dissociation is altered in PD. To examine this issue, we performed a whole-brain analysis to compare functional connectivity in PD to healthy adults using resting-state functional magnetic resonance imaging (rs-fMRI) data compiled from three independent datasets. Our analysis showed that across the sample, the SN had greater connectivity with the precuneus, anterior cingulate gyrus, and areas of the occipital cortex, partially replicating our previous work in healthy young adults. Notably, we also found that, in PD, VTA-right cerebellum connectivity was higher than SN-right cerebellum connectivity, whereas the opposite trend occurred in healthy controls. This double dissociation may reflect a compensatory role of the cerebellum in PD and could provide a potential target for future study and treatment.

Contingency of semantic generalization on episodic specificity varies across development.

Semantic memory-general knowledge of ideas and concepts-includes generalization processes that support inference. Episodic memory, on the other hand, preserves the specificity of individual events by binding together unique combinations of elements from an episode and relies on pattern separation to distinguish similar experiences. These two memory systems play complementary roles, supporting different mnemonic goals, but the nature and extent of their interdependence is unclear.1,2 Some models suggest that new information is encoded initially as hippocampus-dependent episodic memory and then, either through repetition or gist extraction, becomes semantic over time.3,4 These models also posit a neocortical route to semantic memory acquisition exists that can bypass the hippocampus.3 Both proposed routes are slow learning mechanisms, yet generalization can occur rapidly. Recent models suggest that fast generalization relies, in part, on the retrieval of individual but related episodes.5,6 Such episodic memory gating mechanisms render fast generalization contingent on the memory specificity of instances, a pattern that has been observed in adults.7,8 None of these models take into account the observation that generalization and episodic specificity have asynchronous developmental profiles, with generalization emerging years before episodic memory.9,10 We ask two questions about generalized and specific memory during early childhood: first, is rapid generalization contingent on remembering specific past memories? And second, does the strength or nature of this contingency differ across development? We found that the interdependence of generalization and episodic memory varies across development: generalization success in adults, but not in children, was contingent on context binding.

Multimodal mapping of the face connectome.

Face processing supports our ability to recognize friend from foe, form tribes and understand the emotional implications of changes in facial musculature. This skill relies on a distributed network of brain regions, but how these regions interact is poorly understood. Here we integrate anatomical and functional connectivity measurements with behavioural assays to create a global model of the face connectome. We dissect key features, such as the network topology and fibre composition. We propose a neurocognitive model with three core streams; face processing along these streams occurs in a parallel and reciprocal manner. Although long-range fibre paths are important, the face network is dominated by short-range fibres. Finally, we provide evidence that the well-known right lateralization of face processing arises from imbalanced intra- and interhemispheric connections. In summary, the face network relies on dynamic communication across highly structured fibre tracts, enabling coherent face processing that underpins behaviour and cognition.

Altered functional connectivity of cortical networks in semantic variant Primary Progressive Aphasia.

As their illness progresses, patients with the semantic variant of Primary Progressive Aphasia (svPPA) frequently exhibit peculiar behaviors indicative of altered visual attention or an increased interest in artistic endeavors. In the present study, we examined changes within and between large-scale functional brain networks that may explain this altered visual behavior. We first examined the connectivity of the visual association network, the dorsal attention network, and the default mode network in healthy young adults (n = 89) to understand the typical architecture of these networks in the healthy brain. We then compared the large-scale functional connectivity of these networks in a group of svPPA patients (n = 12) to a group of age-matched cognitively normal controls (n = 30). Our results showed that the between-network connectivity of the dorsal attention and visual association networks was elevated in svPPA patients relative to controls. We further showed that this heightened between-network connectivity was associated with a decrease in the within-network connectivity of the default mode network, possibly due to progressive degeneration of the anterior temporal lobes in svPPA. These results suggest that focal neurodegeneration can lead to the reorganization of large-scale cognitive networks beyond the primarily affected network(s), possibly contributing to cognitive or behavioral changes that are commonly present as part of the clinical phenotype of svPPA.

A Guide to Representational Similarity Analysis for Social Neuroscience.

Representational similarity analysis (RSA) is a computational technique that uses pairwise comparisons of stimuli to reveal their representation in higher-order space. In the context of neuroimaging, mass-univariate analyses and other multivariate analyses can provide information on what and where information is represented but have limitations in their ability to address how information is represented. Social neuroscience is a field that can particularly benefit from incorporating RSA techniques to explore hypotheses regarding the representation of multidimensional data, how representations can predict behavior, how representations differ between groups and how multimodal data can be compared to inform theories. The goal of this paper is to provide a practical as well as theoretical guide to implementing RSA in social neuroscience studies.

Direct modulation of aberrant brain network connectivity through real-time NeuroFeedback.

The existence of abnormal connectivity patterns between resting state networks in neuropsychiatric disorders, including Autism Spectrum Disorder (ASD), has been well established. Traditional treatment methods in ASD are limited, and do not address the aberrant network structure. Using real-time fMRI neurofeedback, we directly trained three brain nodes in participants with ASD, in which the aberrant connectivity has been shown to correlate with symptom severity. Desired network connectivity patterns were reinforced in real-time, without participants' awareness of the training taking place. This training regimen produced large, significant long-term changes in correlations at the network level, and whole brain analysis revealed that the greatest changes were focused on the areas being trained. These changes were not found in the control group. Moreover, changes in ASD resting state connectivity following the training were correlated to changes in behavior, suggesting that neurofeedback can be used to directly alter complex, clinically relevant network connectivity patterns.

The Gap Between Adaptive Behavior and Intelligence in Autism Persists into Young Adulthood and is Linked to Psychiatric Co-morbidities.

For individuals with autism spectrum disorder (ASD), long-term outcomes have been troubling, and intact IQ has not been shown to be protective. Nevertheless, relatively little research into adaptive functioning among adults with ASD has been completed to date. Therefore, both adaptive functioning and comorbid psychopathology were assessed among 52 adults with ASD without intellectual disability (ID). Adaptive functioning was found to substantially lag behind IQ, and socialization was a particular weakness. Comorbid psychopathology was significantly correlated with the size of IQ-adaptive functioning discrepancy. These findings emphasize key intervention targets of both adaptive skill and psychopathology for transition-age youth and young adults with ASD, as well as the need for ongoing monitoring of anxiety and depression symptoms during this developmental window.

Sex differences in parent-reported executive functioning and adaptive behavior in children and young adults with autism spectrum disorder.

This study is the largest to date examining executive function and adaptive skills in females with autism spectrum disorder (ASD). Its primary aim was to utilize parent ratings of real-world executive functioning and adaptive behavior to better understand whether females with ASD differ from males with ASD in these areas of everyday functioning. We compared 79 females with ASD to 158 males with ASD (ages 7-18) who were statistically matched on age, IQ, and level of ADHD or ASD traits. All participants were assessed using the Behavior Rating Inventory of Executive Function (BRIEF) and a subset (56 females and 130 males) also received the Vineland Adaptive Behavior Scales (VABS). Females were rated by parents as having greater problems with executive function on the BRIEF. Parents also rated females as exhibiting more difficulties than males on the Daily Living Skills domain of the VABS. There was a correlation between increased global EF difficulty and decreased adaptive ability in both males and females. Our results indicate relative weaknesses for females compared to males diagnosed with ASD on executive function and daily living skills. These differences occur in the absence of sex differences in our sample in age, IQ, clinician ratings of core ASD symptomatology, parent ratings of ADHD symptoms, and parent-reported social and communication adaptive skills on the VABS. These findings indicate specific liabilities in real world EF and daily living skills for females with ASD and have important implications for targeting their treatments. Autism Res 2017, 10: 1653-1662. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Real-World Executive Functions in Adults with Autism Spectrum Disorder: Profiles of Impairment and Associations with Adaptive Functioning and Co-morbid Anxiety and Depression.

Although executive functioning (EF) difficulties are well documented among children and adolescents with autism spectrum disorder (ASD), little is known about real-world measures of EF among adults with ASD. Therefore, this study examined parent-reported real-world EF problems among 35 adults with ASD without intellectual disability and their correlations with adaptive functioning and co-morbid anxiety and depression symptomatology. A variable EF profile was found with prominent deficits occurring in flexibility and metacognition. Flexibility problems were associated with anxiety-related symptoms while metacognition difficulties were associated with depression symptoms and impaired adaptive functioning (though the metacognition-adaptive functioning relationship was moderated by ADHD symptoms). These persistent EF problems are predictors of broader functioning and therefore remain an important treatment target among adults with ASD.

Replication and Comparison of the Newly Proposed ADOS-2, Module 4 Algorithm in ASD Without ID: A Multi-site Study.

Recent updates have been proposed to the Autism Diagnostic Observation Schedule-2 Module 4 diagnostic algorithm. This new algorithm, however, has not yet been validated in an independent sample without intellectual disability (ID). This multi-site study compared the original and revised algorithms in individuals with ASD without ID. The revised algorithm demonstrated increased sensitivity, but lower specificity in the overall sample. Estimates were highest for females, individuals with a verbal IQ below 85 or above 115, and ages 16 and older. Best practice diagnostic procedures should include the Module 4 in conjunction with other assessment tools. Balancing needs for sensitivity and specificity depending on the purpose of assessment (e.g., clinical vs. research) and demographic characteristics mentioned above will enhance its utility.