Development of the brainstem and cerebellum in autistic patients

Hashimoto, Toshiaki; Tayama, Masanobu; Murakawa, K; Yoshimoto, Tsutomu; Miyazaki, Masahito; Harada, Masamitsu; Kuroda, Yasuhiro

doi:10.1007/bf02178163

Cited by 327 publications

(192 citation statements)

References 32 publications

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“…Significant group differences in individual regions were limited to the left middle frontal gyrus, although the ASD group average was lower than the control group in all the brain regions assayed (frontal, parietal, occipital, and cerebellar) and when all brain areas were averaged, suggesting the possibility of widespread abnormalities. This study extended prior work in this area by establishing that neural abnormalities, which have been identified using 1 H-MRS predominantly in younger and likely lower functioning autistic individuals (Chugani et al, 1999;Friedman et al, 2003;Friedman et al, 2006;Hashimoto et al, 1997;Hashimoto et al, 1995;Hisaoka et al, 2001;Otsuka et al, 1999), may also be present in a higher functioning broadly inclusive ASD sample. None of the individuals in our sample had IQs in the mentally retarded range and the sample included individuals with diagnoses in the less severe end of the autism spectrum; approximately 43% of the sample was diagnosed as PDD-NOS or Asperger's disorder.…”

Section: Discussionsupporting

confidence: 66%

“…Structural neuroimaging studies of individuals with Autistic Disorder, who among individuals with ASD have the highest level of autistic symptomatology and the lowest level of adaptive functioning (Walker et al, 2004), have reported widespread abnormalities including agedependent increased brain volume (Aylward et al, 2002;Courchesne et al, 2001;Hazlett et al, 2005;Redcay and Courchesne, 2005;Sparks et al, 2002) reduced size of vermal lobules VI and VII (Ciesielski et al, 1997;Courchesne et al, 1994a;Courchesne et al, 1988;Hashimoto et al, 1995;Kaufmann et al, 2003), and reversed patterns of asymmetry (Herbert et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…In the current 1 H MRS study, four a-priori regions of interest (ROI) (frontal lobe, cerebellar hemisphere, cerebellar vermis, and parietal lobe) were selected based on structural and functional abnormalities previously reported in ASD (Allen et al, 2004;Carper and Courchesne, 2005;Ciesielski et al, 1997;Courchesne et al, 1993;Courchesne et al, 1994a;Courchesne et al, 1994b;Courchesne et al, 1988;Hashimoto et al, 1995;Kaufmann et al, 2003;Kleinhans et al, 2005b;Luna et al, 2002;Muller et al, 2003;Townsend et al, 1999). The occipital lobe was also included to serve as a control region, based on reports that the occipital lobes appear to be less affected in ASD (Buxhoeveden et al, 2006;Carper et al, 2002;Hadjikhani et al, 2004;Salmond et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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N-acetyl aspartate in autism spectrum disorders: Regional effects and relationship to fMRI activation

et al. 2007

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Rapid progress in our understanding of macrostructural abnormalities in autism spectrum disorders (ASD) has occurred in recent years. However, the relationship between the integrity of neural tissue and neural function has not been previously investigated. Single-voxel proton magnetic resonance spectroscopy and functional magnetic resonance imaging of an executive functioning task was obtained in 13 high functioning adolescents and adults with ASD and 13 agematched controls. The ASD group showed significant reductions in N-acetyl aspartate (NAA) in all brain regions combined and a specific reduction in left frontal cortex compared to controls. Regression analyses revealed a significant group interaction effect between frontal and cerebellar NAA. In addition, a significant positive semi-partial correlation between left frontal lobe NAA and frontal lobe functional activation was found in the ASD group. These findings suggest that widespread neuronal dysfunction is present in high functioning individuals with ASD. Hypothesized developmental links between frontal and cerebellar vermis neural abnormalities were supported, in that impaired neuronal functioning in the vermis was associated with impaired neuronal functioning in the frontal lobes in the ASD group. Furthermore, this study provided the first direct evidence of the relationship between abnormal functional activation in prefrontal cortex and neuronal dysfunction in ASD.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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N-acetyl aspartate in autism spectrum disorders: Regional effects and relationship to fMRI activation

et al. 2007

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“…Rats exposed to valproic acid on day 12.5 of gestation (VPA rats) exhibit several anatomical abnormalities in the brainstem and cerebellum (Rodier et al, 1996(Rodier et al, , 1997Ingram et al, 2000), resembling those found at autopsy and in brain imaging studies of autistic patients (Bauman and Kemper, 1994;Gaffney et al, 1988;Hashimoto et al, 1995;Courchesne, 1997). We previously presented evidence that administration of VPA on day 12.5 of gestation also has long-term effects on postnatal behaviors in male rats, which include lower sensitivity to pain and higher sensitivity to nonpainful stimuli; diminished acoustic prepulse inhibition; locomotor and repetitive, stereotypic-like hyperactivity combined with lower exploratory activity; decreased number of social behaviors; and increased latency to social behaviors (Schneider et al, 2001;Schneider and Przewlocki, 2005).…”

Section: Introductionmentioning

confidence: 94%

Environmental Enrichment Reverses Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Issues for a Therapeutic Approach in Autism

Schneider

Turczak

Przewłocki

2005

Neuropsychopharmacol

249

155

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Environmental enrichment has been repeatedly shown to affect multiple aspects of brain function, and is known to improve cognitive, behavioral, and histopathological outcome after brain injuries. The purpose of the present experiments was to determine the effect of an enriched environment on behavioral aberrations observed in male rats exposed to valproic acid on day 12.5 of gestation (VPA rats), and proposed on the basis of etiological, anatomical, and behavioral data as an animal model of autism. Environmental enrichment reversed almost all behavioral alterations observed in the model. VPA rats after environmental enrichment (VPA-E) compared to VPA rats reared in standard conditions have higher sensitivity to pain and lower sensitivity to nonpainful stimuli; stronger acoustic prepulse inhibition; lower locomotor, repetitive/stereotypic-like activity, and enhanced exploratory activity; decreased anxiety; increased number of social behaviors; and shorter latency to social explorations. In comparison with control animals (Con), VPA-E rats exhibited increased number of pinnings in adolescence and social explorations in adulthood, and were less anxious in the elevated plus maze. Similar differences in social behavior and anxiety were observed between control rats exposed to environmental enrichment (Con-E) and control group reared in standard conditions. These results suggest that postnatal environmental manipulations can counteract the behavioral alterations in VPA rats. We propose environmental enrichment as an important tool for the treatment of autism spectrum disorders.

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“…Many brain regions of suspected abnormality have been reported (Akshoomoff, 2002), though with little consensus (Brambilla et al, 2003;Rumsey, 2000). Major brain structures implicated include frontal (Damasio, 1978;Zilbovicius, 1995), parietal (Courchesne, 1993), and mediotemporal regions (Bachevalier, 1994), as well as cerebellum, basal ganglia, brain stem, and limbic system (Courchesne, 1997;Hashimoto et al, 1995;Rodier, 2002).…”

Section: Introductionmentioning

confidence: 99%

Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism

et al. 2005

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Some recent evidence has suggested abnormalities of the dorsal stream and possibly the mirror neuron system in autism, which may be responsible for impairments of joint attention, imitation, and secondarily for language delays. The current study investigates functional connectivity along the dorsal stream in autism, examining interregional blood oxygenation level dependent (BOLD) signal cross-correlation during visuomotor coordination. Eight high-functioning autistic men and 8 handedness and age-matched controls were included. Visually prompted button presses were performed with the preferred hand. For each subject, functional connectivity was computed in terms of BOLD signal correlation with the mean time series in bilateral visual area 17. Our hypothesis of reduced dorsal stream connectivity in autism was only in part confirmed. Functional connectivity with superior parietal areas was not significantly reduced. However, the autism group showed significantly reduced connectivity with bilateral inferior frontal area 44, which is compatible with the hypothesis of mirror neuron defects in autism. More generally, our findings suggest that dorsal stream connectivity in autism may not be fully functional.

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Development of the brainstem and cerebellum in autistic patients

Cited by 327 publications

References 32 publications

N-acetyl aspartate in autism spectrum disorders: Regional effects and relationship to fMRI activation

N-acetyl aspartate in autism spectrum disorders: Regional effects and relationship to fMRI activation

Environmental Enrichment Reverses Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Issues for a Therapeutic Approach in Autism

Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism

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