77 research outputs found
Autism as a disorder of neural information processing: directions for research and targets for therapy
The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself
Neurobiology of social behavior abnormalities in autism and Williams syndrome
Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities
Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets
Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen’s d = −0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD
Cortisol, cognition and the ageing prefrontal cortex
The structural and functional decline of the ageing human brain varies by brain
region, cognitive function and individual. The underlying biological mechanisms are
poorly understood. One potentially important mechanism is exposure to
glucocorticoids (GCs; cortisol in humans); GC production is increasingly varied with
age in humans, and chronic exposure to high levels is hypothesised to result in
cognitive decline via cerebral remodelling. However, studies of GC exposure in
humans are scarce and methodological differences confound cross-study comparison.
Furthermore, there has been little focus on the effects of GCs on the frontal lobes and
key white matter tracts in the ageing brain. This thesis therefore examines
relationships among cortisol levels, structural brain measures and cognitive
performance in 90 healthy, elderly community-dwelling males from the Lothian
Birth Cohort 1936. Salivary cortisol samples characterised diurnal (morning and
evening) and reactive profiles (before and after a cognitive test battery). Structural
variables comprised Diffusion Tensor Imaging measures of major brain tracts and a
novel manual parcellation method for the frontal lobes. The latter was based on a
systematic review of current manual methods in the context of putative function and
cytoarchitecture. Manual frontal lobe brain parcellation conferred greater spatial and
volumetric accuracy when compared to both single- and multi-atlas parcellation at
the lobar level. Cognitive ability was assessed via tests of general cognitive ability,
and neuropsychological tests thought to show differential sensitivity to the integrity
of frontal lobe sub-regions. The majority of, but not all frontal lobe test scores shared
considerable overlap with general cognitive ability, and cognitive scores correlated
most consistently with the volumes of the anterior cingulate. This is discussed in
light of the diverse connective profile of the cingulate and a need to integrate
information over more diffuse cognitive networks according to proposed de-differentiation
or compensation in ageing. Individuals with higher morning, evening
or pre-test cortisol levels showed consistently negative relationships with specific
regional volumes and tract integrity. Participants whose cortisol levels increased
between the start and end of cognitive testing showed selectively larger regional
volumes and lower tract diffusivity (correlation magnitudes <.44). The significant
relationships between cortisol levels and cognition indicated that flatter diurnal
slopes or higher pre-test levels related to poorer test performance. In contrast, higher
levels in the morning generally correlated with better scores (correlation magnitudes
<.25). Interpretation of all findings was moderated by sensitivity to type I error,
given the large number of comparisons conducted. Though there were limited
candidates for mediation analysis, cortisol-function relationships were partially
mediated by tract integrity (but not sub-regional frontal volumes) for memory and
post-error slowing. This thesis offers a novel perspective on the complex interplay
among glucocorticoids, cognition and the structure of the ageing brain. The findings
suggest some role for cortisol exposure in determining age-related decline in
complex cognition, mediated via brain structure
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