Localized enlargement of the frontal cortex in early autism

Center for Autism Research, Children's Hospital Research Center, and Neurosciences Department, University of California at San Diego, San Diego, California, USA.
Biological Psychiatry (Impact Factor: 10.26). 02/2005; 57(2):126-33. DOI: 10.1016/j.biopsych.2004.11.005
Source: PubMed


Evidence from behavioral, imaging, and postmortem studies indicates that the frontal lobe, as well as other brain regions such as the cerebellum and limbic system, develops abnormally in children with autism. It is not yet clear to what extent the frontal lobe is affected; that is, whether all regions of frontal cortex show the same signs of structural maldevelopment.
In the present study, we measured cortical volume in four subregions of the frontal cortex in 2-year-old to 9-year-old boys with autism and normal control boys.
The dorsolateral region showed a reduced age effect in patients when compared with control subjects, with a predicted 10% increase in volume from 2 years of age to 9 years of age compared with a predicted 48% increase for control subjects. In a separate analysis, dorsolateral and medial frontal regions were significantly enlarged in patients aged 2 to 5 years compared with control subjects of the same age, but the precentral gyrus and orbital cortex were not.
These data indicate regional variation in the degree of frontocortical overgrowth with a possible bias toward later developing or association areas. Possible mechanisms for these regional differences are discussed.

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    • "ASD is considered a neurodevelopmental disorder with a brain-based etiology [DiCicco-Bloom et al., 2006]. Evidence from neuroimaging and head circumference studies suggest that there is a unique head growth trajectory in ASD, with a normal or slightly reduced head circumference at birth [Courchesne, Carper, & Akshoomoff, 2003; Dementieva et al., 2005; Gray, Taffe, Sweeney, Forster, & Tonge, 2012; Lainhart From the Murdoch Childrens Research Institute, Melbourne, "
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    ABSTRACT: Very preterm (VP) survivors are at increased risk of autism spectrum disorder (ASD) compared with term-born children. This study explored whether neonatal magnetic resonance (MR) brain features differed in VP children with and without ASD at 7 years. One hundred and seventy-two VP children (<30 weeks' gestation or <1250 g birth weight) underwent structural brain MR scans at term equivalent age (TEA; 40 weeks' gestation ±2 weeks) and were assessed for ASD at 7 years of age. The presence and severity of white matter, cortical gray matter, deep nuclear gray matter, and cerebellar abnormalities were assessed, and total and regional brain volumes were measured. ASD was diagnosed using a standardized parent report diagnostic interview and confirmed via an independent assessment. Eight VP children (4.7%) were diagnosed with ASD. Children with ASD had more cystic lesions in the cortical white matter at TEA compared with those without ASD (odds ratio [OR] 8.7, 95% confidence interval [CI] 1.5, 51.3, P = 0.02). There was also some evidence for smaller cerebellar volumes in children with ASD compared with those without ASD (OR = 0.82, CI = 0.66, 1.00, P = 0.06). Overall, the results suggest that VP children with ASD have different brain structure in the neonatal period compared with those who do not have ASD. Autism Res 2015. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    Autism Research 10/2015; DOI:10.1002/aur.1558 · 4.33 Impact Factor
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    • "We hypothesized that, at resting state, children with ASD would exhibit increased low-and highfrequency brain activities in the frontal and sensorimotor cortices. This hypothesis is based on the observation that the brain generate signals up to 2884 Hz [17] and previous reports children with ASD have aberrant activity and abnormal development in the sensorimotor/ frontal cortices [18] [19] [20], which has been associated with sensory and motor symptoms. A previous study [2] revealed little about temporal resolution with analysis of up to 120 Hz [2]. "
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    ABSTRACT: The abnormality of intrinsic brain activity in autism spectrum disorders (ASDs) is still inconclusive. Contradictory results have been found pointing towards hyper-activity or hypo-activity in various brain regions. The present research aims to investigate the spatial and spectral signatures of aberrant brain activity in an unprecedented frequency range of 1-2884Hz at source levels in ASD using newly developed methods. Seven ASD subjects and age- and gender-matched controls were studied using a high-sampling rate magnetoencephalography (MEG) system. Brain activity in delta (1-4Hz), theta (4-8Hz), alpha (8-12Hz), beta (12-30Hz), low gamma (30-55Hz), high gamma (65-90Hz), ripples (90-200Hz), high-frequency oscillations (HFOs, 200-1000Hz), and very high-frequency oscillations (VHFOs, 1000-2884Hz) was volumetrically localized and measured using wavelet and beamforming. In comparison to controls, ASD subjects had significantly higher odds of alpha activity (8-12Hz) in the sensorimotor cortex (mu rhythm), and generally high-frequency activity (90-2884Hz) in the frontal cortex. The source power of HFOs (200-1000Hz) in the frontal cortex in ASD was significantly elevated as compared with controls. The results suggest that ASD has significantly altered intrinsic brain activity in both low- and high-frequency ranges. Increased intrinsic high-frequency activity in the frontal cortex may play a key role in ASD. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
    Brain and Development 04/2015; DOI:10.1016/j.braindev.2015.04.007 · 1.88 Impact Factor
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    • "Interestingly, morphometric studies in ASD draw an inconclusive picture on hippocampal volume in this disorder [9]. However, the frontal cortex, including the orbitofrontal region, has been shown to be a main target area of early brain overgrowth in ASD [10]. In addition, malformations in the frontal cortex through neuroinflammatory responses or migration defects seem to persist regardless of developmental influences [11]. "
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    ABSTRACT: Please cite this article in press as: Pehrs C, et al. The quartet theory: Implications for autism spectrum disorder. Phys Life Rev (2015), http://dx.
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