Reconceptualizing functional brain connectivity in autism from a developmental perspective

Developmental changes in large-scale network connectivity in autism

Reprint of: Mapping connectivity in the developing brain

Mapping connectivity in the developing brain

Mapping connectivity in the developing brain

In this review article, we summarize recent progress toward understanding disturbances in functional and anatomical brain connectivity in autism. Autism is a neurodevelopmental disorder affecting language, social interaction, and repetitive behaviors. Recent studies have suggested that limitations of frontal–posterior brain connectivity in autism underlie the varied set of deficits associated with this disorder. Specifically, the underconnectivity theory of autism postulates that individuals with autism have a reduced communication bandwidth between frontal and posterior cortical areas, which constrains the psychological processes that rely on the integrated functioning of frontal and posterior brain networks. This review summarizes the recent findings of reduced frontal–posterior functional connectivity (synchronization) in autism in a wide variety of high-level tasks, focusing on data from functional magnetic resonance imaging studies. It also summarizes the findings of disordered anatomical connectivity in autism, as measured by a variety of techniques, including distribution of white matter volumes and diffusion tensor imaging. We conclude with a discussion of the implications of these findings for autism and future directions for this line of research.

Chapter 6 - Brain function and brain connectivity in autism

With the increasing prevalence of autism spectrum disorders (ASD), the pace of research aimed at understanding the neurobiology of this complex neurodevelopmental disorder has accelerated. Neuroimaging and postmortem studies have provided evidence for disruptions in functional and structural connectivity in the brains of individuals with ASD (Vissers et al., 2012). This burgeoning literature continues to struggle with methodological and conceptual issues inherent to discovering relationships between brain and behavior. While there has been considerable progress, many open questions remain. In this special topic, a collection of empirical contributions and reviews from leaders in the field attempt to synthesize and extend prior work investigating brain connectivity in autism. Multiple theoretical perspectives and neuroimaging methods are brought together with the aim of addressing outstanding questions about the nature and extent of brain connectivity aberrations in autism.

It has been proposed that autism spectrum disorder (ASD) may be characterized by an extreme male brain (EMB) pattern of brain development. Here, we performed the first investigation of how age-related changes in functional brain connectivity may be expressed differently in females and males with ASD. We analyzed resting-state functional magnetic resonance imaging data of 107 typically developing (TD) females, 114 TD males, 104 females, and 115 males with ASD (6-26 years) from the autism brain imaging data exchange repository. We explored how interhemispheric homotopic connectivity and its maturational curvatures change across groups. Differences between ASD and TD and between females and males with ASD were observed for the rate of changes in connectivity in the absence of overall differences in connectivity. The largest portion of variance in age-related changes in connectivity was described through similarities between TD males, ASD males, and ASD females, in contrast to TD females. We found that shape of developmental curvature is associated with symptomatology in both males and females with ASD. We demonstrated that females and males with ASD tended to follow the male pattern of developmental changes in interhemispheric connectivity, supporting the EMB theory of ASD.

BackgroundPrevious studies have shown a physically active lifestyle in both midlife and later life to benefit cognition and brain health in older age. However, exploring the influence of physical activity engagement on functional brain connectivity is needed to fully understand the neural mechanism underlying the effect of physical engagement. Additionally, in order to give lifestyle advice to different age groups, it is important to understand the unique contributions of physical activity at different life stages, which has rarely been examined.MethodThe current study investigated the effect of self‐reported midlife and current physical activity engagement on functional connectivity among 105 cognitively high functioning older adults (age = 66.6±4.1). Self‐reported midlife and current moderate‐to‐vigorous physical activity (MVPA) were recorded using the Lifetime Total Physical Activity Questionnaire. We included covariates in all analyses (i.e., age, sex, years of education, socioeconomic status, genetic risk of Alzheimer’s disease (i.e., APOE ε4 carrier status). Five regions of interest (ROIs) were selected based on previous literature on the relationship between exercise and brain health which included: prefrontal (i.e., bilateral superior frontal, middle frontal, and pars opercularis of the inferior frontal gyrus), and bilateral hippocampus.ResultResults showed that people who were active in midlife had greater functional connectivity between middle frontal gyrus and superior parietal region, postcentral gyrus (Voxel p<0.005, Cluster p<0.05 FDR corrected; figure 1a) than people who were relatively inactive in midlife. This effect stayed the same after controlling for current MVPA time. Secondly, the results showed that people who were active currently have greater functional connectivity between hippocampus and frontal pole (Voxel p<0.005, Cluster p<0.05 FDR corrected; figure 1b). Currently active participants also showed greater functional connectivity between pars triangularis of the inferior frontal gyrus, and bilateral middle temporal region, and frontal pole (Voxel p<0.001, Cluster p<0.05 FDR corrected; figure1c) compared to currently inactive participants, which stayed consistent after controlling for midlife MVPA time.ConclusionAs a conclusion, although midlife and current MVPA time were positively associated with each other, they both influence brain functional connectivity in later life independently. The results emphasize the importance of keeping a physically active lifestyle across midlife and into later life.

Distortions and disconnections: Disrupted brain connectivity in autism

State-Dependent Differences in Functional Connectivity in Young Children With Autism Spectrum Disorder

Recent study have shown that electroencephalogram (EEG) is an effective and efficient strategy to analyze the abnormality of children with autism. Much of the work on Autism Spectrum Disorders (ASD) focused on analysing simple features of EEG signals and using them for classification problems. How-ever, there is growing evidence that ASD is a psychiatric disorder in which the brain is abnormally connected functionally and brain areas do not communicate properly with each other. In this paper, we explore the brain functional connectivity of children with autism by comparing the difference between children with ASD and typically developing children (TD). Specifically, we collect EEG data from 62 children (31 ASD, 31 TD) under affection-evoked movie clips, and compute the brain functional connectivity using four commonly-used connectivity models (i.e., Coherence, Phased Lag Index, Weighted Phased Lag Index, Phase Locking Value) in five different frequency bands (theta (4–8 Hz), alpha (8–12 Hz), low beta (12–16 Hz), high beta (16–25 Hz), and gamma (25–45 Hz)). Then we compare the difference by using statistical analysis in each frequency band. The results indicate that difference in brain functional connectivity in children with ASD and TD are existed in all five frequency bands, which shows a potential as the biomarker for diagnosis and classification of ASD.

A basic tenet of biological psychiatry is that psychiatric disorders are driven by abnormalities in brain function, which in turn reflect abnormalities in the underlying brain circuits, i.e., in the wiring of the brain. These circuit abnormalities presumably reflect a complex interplay between genes and environment. Many psychiatric disorders have strong genetic underpinnings: common or rare variants of genes, individually or in combination, elevate the susceptibility to disorders such as autism (1), schizophrenia (2), and many others. Most psychiatric disorders are thought to be neurodevelopmental in nature, either because symptoms typically arise during childhood (e.g., autism) or because the interactions between genes and environment begin early, even if the onset of the disorder becomes evident only in adolescence or adulthood. To better understand, diagnose, and treat psychiatric disorders, it is crucial to obtain deeper insights into brain circuits in health and disease and in humans and animal models. Here, we focus on the relevance of human in vivo neuroimaging, particularly involving magnetic resonance imaging (MRI). We briefly address three major points. First, recent neuroimaging studies have already provided important insights about abnormalities related to brain structure, function, and connectivity in psychopathology. Second, recent advances in neuroimaging of healthy adults, including many driven by the Human Connectome Project, offer exciting prospects for accelerated progress in characterizing disease-related brain connectivity abnormalities. Third, methodological limitations of each neuroimaging method, some of which are inadequately appreciated, require critical assessments and careful interpretation of research findings, especially when placed in the context of the extraordinary complexity of brain circuits revealed by studies of laboratory animals.

Functional connectivity mediates the relationship between cardiorespiratory fitness and stress in midlife.

Cannabis and Brain Health: What Is Next for Developmental Cohort Studies?