Mapping Early Brain Development in Autism

Department of Neurosciences, School of Medicine, University of California-San Diego, La Jolla, CA 92093, USA.
Neuron (Impact Factor: 15.05). 11/2007; 56(2):399-413. DOI: 10.1016/j.neuron.2007.10.016
Source: PubMed


Although the neurobiology of autism has been studied for more than two decades, the majority of these studies have examined brain structure 10, 20, or more years after the onset of clinical symptoms. The pathological biology that causes autism remains unknown, but its signature is likely to be most evident during the first years of life when clinical symptoms are emerging. This review highlights neurobiological findings during the first years of life and emphasizes early brain overgrowth as a key factor in the pathobiology of autism. We speculate that excess neuron numbers may be one possible cause of early brain overgrowth and produce defects in neural patterning and wiring, with exuberant local and short-distance cortical interactions impeding the function of large-scale, long-distance interactions between brain regions. Because large-scale networks underlie socio-emotional and communication functions, such alterations in brain architecture could relate to the early clinical manifestations of autism. As such, autism may additionally provide unique insight into genetic and developmental processes that shape early neural wiring patterns and make possible higher-order social, emotional, and communication functions.

30 Reads
  • Source
    • "Buspirone exerts anxiolytic effects by acting as a partial agonist at serotonin 5-HT1A receptors (Ohlsen and Pilowsky, 2005), and it also interacts to a lesser degree with other receptors, such as the dopamine D2 receptor (Dhavalshankh et al., 2007). The antipsychotic drug risperidone belongs to the benzisoxazole chemical class (Kumar et al., 2008; Courchesne et al., 2007) and has been reported to act therapeutically by blocking serotonin and dopamine receptors (Grant, 2007); thus, it is useful for studying increases in serotonin neurotransmission . Ethanol also has acute anxiolytic effects that are most likely mediated by GABA A receptors (Radcliffe et al., 1999; Kumar et al., 2009), with depressant effects on the central nervous system at higher doses. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Psychotropic medications are widely used, and their prescription has increased worldwide, consequently increasing their presence in aquatic environments. Therefore, aquatic organisms can be exposed to psychotropic drugs that may be potentially dangerous, raising the question of whether these drugs are attractive or aversive to fish. To answer this question, adult zebrafish were tested in a chamber that allows the fish to escape or seek a lane of contaminated water. These attraction and aversion paradigms were evaluated by exposing the zebrafish to the presence of acute contamination with these compounds. The zebrafish were attracted by certain concentrations of diazepam, fluoxetine, risperidone and buspirone, which were most likely detected by olfaction, because this behavior was absent in anosmic fish. These findings suggest that despite their deleterious effects, certain psychoactive drugs attract fish. Copyright © 2015. Published by Elsevier Inc.
    Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 08/2015; 179. DOI:10.1016/j.cbpc.2015.08.009 · 2.30 Impact Factor
  • Source
    • "However, these hypothesized altered developmental trajectories are rarely thought of as reflecting processes of early compensation in response to an environment that is processed with low fidelity due to increased or decreased levels of neural noise. For example, atypical trajectories of brain overgrowth have been widely noted in autism (e.g., Courchesne et al., 2007; Shen et al., 2013); however, few have considered that this might relate to the prediction that a slowed trajectory of development (a common compensatory response to an inconsistent experience of the environment ) will lead to increases in the volume of higher cortical structures during both phylogeny and ontogeny (Clancy et al., 2000). Specifically, we propose that in some cases that lead to autism, synaptic dysfunction leads to the early environment being sampled with poor fidelity, with a particular cost to the most dynamic and least easily predictable elements of the external environment. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Resilience and adaptation in the face of early genetic or environmental risk has become a major interest in child psychiatry over recent years. However, we still remain far from an understanding of how developing human brains as a whole adapt to the diffuse and widespread atypical synaptic function that may be characteristic of some common developmental disorders. The first part of this paper discusses four types of whole-brain adaptation in the face of early risk: redundancy, reorganization, niche construction, and adjustment of developmental rate. The second part of the paper applies these adaptation processes specifically to autism. We speculate that key features of autism may be the end result of processes of early brain adaptation, rather than the direct consequences of ongoing neural pathology.
    Development and Psychopathology 05/2015; 27(02):425-442. DOI:10.1017/S0954579415000073 · 4.89 Impact Factor
  • Source
    • "This may suggest a developmental shift from hyperconnectivity to hypoconnectivity as individuals with ASD mature into adulthood. In addition, the underconnectivity account emphasizes weaker connectivity of long-range cortical connections in favor of local connectivity [e.g., Just et al., 2004; Muller et al., 2011; Courchesne et al., 2007]. This is consistent with what we observed in our study, with hyperconnectivity in ASD between Broca's and spacially adjacent frontal regions, and between Wernicke's and calcarine regions, when compared to TD controls. "
    [Show abstract] [Hide abstract]
    ABSTRACT: While task-based neuroimaging studies have identified alterations in neural circuitry underlying language processing in children with autism spectrum disorders [ASD], resting state functional magnetic resonance imaging [rsfMRI] is a promising alternative to the constraints posed by task-based fMRI. This study used rsfMRI, in a longitudinal design, to study the impact of a reading intervention on connectivity of the brain regions involved in reading comprehension in children with ASD. Functional connectivity was examined using group independent component analysis (GICA) and seed-based correlation analysis of Broca's and Wernicke's areas, in three groups of participants: an experimental group of ASD children (ASD-EXP), a wait list control group of ASD children (ASD-WLC), and a group of typically developing (TD) control children. Both GICA and seed-based analyses revealed stronger functional connectivity of Broca's and Wernicke's areas in the ASD-EXP group postintervention. Additionally, improvement in reading comprehension in the ASD-EXP group was correlated with greater connectivity in both Broca's and Wernicke's area in the GICA identified reading network component. In addition, increased connectivity between the Broca's area and right postcentral and right STG, and the Wernicke's area and LIFG, were also correlated with greater improvement in reading comprehension. Overall, this study revealed widespread changes in functional connectivity of the brain's reading network as a result of intervention in children with ASD. These novel findings provide valuable insights into the neuroplasticity of brain areas underlying reading and the impact of intensive intervention in modifying them in children with ASD. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 04/2015; DOI:10.1002/hbm.22821 · 5.97 Impact Factor
Show more

Preview (2 Sources)

30 Reads
Available from