Function of the frontal lobe in autistic individuals: a proton magnetic resonance spectroscopic study

Fujii, Emiko; Mori, Koichi; Miyazaki, Masahito; Hashimoto, Toshiaki; Harada, Masafumi; Kubo, Shoji

doi:10.2152/jmi.57.35

Cited by 46 publications

(55 citation statements)

References 37 publications

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“…Thus, the disruption in the diffusion of this tract can have significant consequence in brain connectivity. Our finding of reduced levels of NAA/Cr in dACC is in line with previous reports of lower NAA concentration in adults with autism in the ACC (Fujii et al, 2010), hippocampal-amygdala formation (Suzuki et al, 2010), and frontal, parietal, and occipital cortices (Kleinhans, Schweinsburg, Cohen, Müller, & Courchesne, 2007). Reduction in NAA, a neurochemical representing neuronal and axonal health and density, can be an indication of disease (Fayed et al, 2006; Maddock & Buonocore, 2012; Meyerhoff et al, 1993).…”

Section: Discussionsupporting

confidence: 93%

Multimodal neuroimaging based classification of autism spectrum disorder using anatomical, neurochemical, and white matter correlates

Libero

DeRamus

Lahti

et al. 2015

Cortex

115

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Neuroimaging techniques, such as fMRI, structural MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) have uncovered evidence for widespread functional and anatomical brain abnormalities in autism spectrum disorder (ASD) suggesting it to be a system-wide neural systems disorder. Nevertheless, most previous studies have focused on examining one index of neuropathology through a single neuroimaging modality, and seldom using multiple modalities to examine the same cohort of individuals. The current study aims to bring together multiple brain imaging modalities (structural MRI, DTI, and 1H-MRS) to investigate the neural architecture in the same set of individuals (19 high-functioning adults with ASD and 18 typically developing (TD) peers). Morphometry analysis revealed increased cortical thickness in ASD participants, relative to typical controls, across the left cingulate, left pars opercularis of the inferior frontal gyrus, left inferior temporal cortex, and right precuneus, and reduced cortical thickness in right cuneus and right precentral gyrus. ASD adults also had reduced fractional anisotropy (FA) and increased radial diffusivity (RD) for two clusters on the forceps minor of the corpus callosum, revealed by DTI analyses. 1H-MRS results showed a reduction in the N-acetylaspartate/Creatine ratio in dorsal anterior cingulate cortex (dACC) in ASD participants. A decision tree classification analysis across the three modalities resulted in classification accuracy of 91.9% with FA, RD, and cortical thickness as key predictors. Examining the same cohort of adults with ASD and their TD peers, this study found alterations in cortical thickness, white matter (WM) connectivity, and neurochemical concentration in ASD. These findings underscore the potential for multimodal imaging to better inform on the neural characteristics most relevant to the disorder.

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Section: Discussionsupporting

confidence: 93%

Multimodal neuroimaging based classification of autism spectrum disorder using anatomical, neurochemical, and white matter correlates

Libero

DeRamus

Lahti

et al. 2015

Cortex

115

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“…Anterior cingulate NAA, t-Cho, Cre, and mI signals were also found to be altered in some earlier studies [9, 10, 31, 34–37]. In the left dorsolateral prefrontal cortex (DLPFC), low NAA/Cre levels were found in the study by Fujii and colleagues [36], but no significant differences were found in two other studies [34, 38]. …”

Section: Introductionmentioning

confidence: 78%

Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study

et al. 2017

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BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disease characterized by difficulties in social communication, unusually restricted, repetitive behavior and interests, and specific abnormalities in language and perception. The precise etiology of ASD is still unknown and probably heterogeneous. In a subgroup of patients, toxic environmental exposure might lead to an imbalance between oxidative stress and anti-oxidant systems. Previous serum and postmortem studies measuring levels of glutathione (GSH), the main cellular free radical scavenger in the brain, have supported the hypothesis that this compound might play a role in the pathophysiology of autism.MethodsUsing the method of single-voxel proton magnetic resonance spectroscopy (MRS), we analyzed the GSH signal in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) of 24 ASD patients with normal or above average IQs and 18 matched control subjects. We hypothesized that we would find decreased GSH concentrations in both regions.ResultsWe did not find overall group differences in neurometabolites including GSH, neither in the dorsal ACC (Wilks’ lambda test; p = 0.429) nor in the DLPFC (p = 0.288). In the dACC, we found a trend for decreased GSH signals in ASD patients (p = 0.076).ConclusionsWe were unable to confirm our working hypothesis regarding decreased GSH concentrations in the ASD group. Further studies combining MRS, serum, and cerebrospinal fluid measurements of GSH metabolism including other regions of interest or even whole brain spectroscopy are needed.

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“…Thus, 24 studies were included into the database. 12, 13, 14, 15, 16, 17, 18, 20, 21, 22, 25, 26, 28, 29, 31, 32, 33, 34, 35, 36, 37, 38, 39 From the database, one study was excluded from the meta-analysis because they did not report raw data regarding the metabolite measure 28 and one study was excluded because it did not provide sufficient data to calculate the standardized mean difference 36 (Figure 1). …”

Section: Resultsmentioning

confidence: 99%

Age-related change in brain metabolite abnormalities in autism: a meta-analysis of proton magnetic resonance spectroscopy studies

2012

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Abnormal trajectory of brain development has been suggested by previous structural magnetic resonance imaging and head circumference findings in autism spectrum disorders (ASDs); however, the neurochemical backgrounds remain unclear. To elucidate neurochemical processes underlying aberrant brain growth in ASD, we conducted a comprehensive literature search and a meta-analysis of 1H-magnetic resonance spectroscopy (1H-MRS) studies in ASD. From the 22 articles identified as satisfying the criteria, means and s.d. of measure of N-acetylaspartate (NAA), creatine, choline-containing compounds, myo-Inositol and glutamate+glutamine in frontal, temporal, parietal, amygdala-hippocampus complex, thalamus and cerebellum were extracted. Random effect model analyses showed significantly lower NAA levels in all the examined brain regions but cerebellum in ASD children compared with typically developed children (n=1295 at the maximum in frontal, P<0.05 Bonferroni-corrected), although there was no significant difference in metabolite levels in adulthood. Meta-regression analysis further revealed that the effect size of lower frontal NAA levels linearly declined with older mean age in ASD (n=844, P<0.05 Bonferroni-corrected). The significance of all frontal NAA findings was preserved after considering between-study heterogeneities (P<0.05 Bonferroni-corrected). This first meta-analysis of 1H-MRS studies in ASD demonstrated robust developmental changes in the degree of abnormality in NAA levels, especially in frontal lobes of ASD. Previously reported larger-than-normal brain size in ASD children and the coincident lower-than-normal NAA levels suggest that early transient brain expansion in ASD is mainly caused by an increase in non-neuron tissues, such as glial cell proliferation.

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Function of the frontal lobe in autistic individuals: a proton magnetic resonance spectroscopic study

Abstract: These findings suggest neuronal dysfunction in the ACC and left DLPFC in autism, and also a relationship between social disability and metabolic dysfunction in these regions. Dysfunction in the ACC and the left DLPFC may contribute to the pathogenesis of autism.

Cited by 46 publications

References 37 publications

Multimodal neuroimaging based classification of autism spectrum disorder using anatomical, neurochemical, and white matter correlates

Multimodal neuroimaging based classification of autism spectrum disorder using anatomical, neurochemical, and white matter correlates

Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study

Age-related change in brain metabolite abnormalities in autism: a meta-analysis of proton magnetic resonance spectroscopy studies

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