Minicolumnar pathology in autism

Casanova, Manuel F.; Buxhoeveden, Daniel P.; Switala, Andrew E.; Roy, Emil

doi:10.1212/wnl.58.3.428

Cited by 752 publications

(558 citation statements)

References 30 publications

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“…Instead, the improved tactile spatial localization that accompanies an increase in duration of adapting stimulation most likely would occur as a result of local dynamic corticocortical interactions that operate to improve the contrast of the primary somatosensory cortical response to a repetitive stimulus through lateral inhibition. Based on this perspective, the measures of tactile localization performance described in this paper appear to reflect the deficit in short-range parietal corticocortical connectivity identified in subjects with autism by Casanova and colleagues (Casanova et al, 2002(Casanova et al, , 2003. Such changes in connectivity could lead to the imbalance in excitation and inhibition that others have predicted underlies the neocortical hyperexcitability and unstable activity in cortical networks characteristic of autism (Polleux and Lauder, 2004;Rubenstein and Merzenich, 2003).…”

Section: Discussionmentioning

confidence: 70%

Vibrotactile adaptation fails to enhance spatial localization in adults with autism

et al. 2007

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A recent study (Tannan et al., 2006) showed that pre-exposure of a skin region to a 5 sec 25 Hz flutter stimulus ("adaptation") results in an approximately 2-fold improvement in the ability of neurologically healthy human adults to localize mechanical stimulation delivered to the same skin region that received the adapting stimulation. Tannan et al. (Tannan et al., 2006) proposed that tactile spatial discriminative performance is improved following adaptation because adaptation is accompanied by an increase in the spatial contrast in the response of contralateral primary somatosensory cortex (SI) to mechanical skin stimulation -an effect identified in previous imaging studies of SI cortex in anesthetized non-human primates (e.g., Simons et al., 2005;Tommerdahl et al., 2002;Whitsel et al., 1989).In the experiments described in this report, a paradigm identical to that employed previously by Tannan et al. (2006) was used to study adults with autism. The results demonstrate that although cutaneous localization performance of adults with autism is significantly better than the performance of control subjects when the period of adapting stimulation is short (i.e., 0.5 sec), tactile spatial discriminative capacity remained unaltered in the same subjects when the duration of adapting stimulation was increased (to 5 sec). Both the failure of prior history of tactile stimulation to alter tactile spatial localization in adults with autism, and the better-than-normal tactile localization performance of adults with autism when the period of adaptation is short are concluded to be attributable to the deficient cerebral cortical GABAergic inhibitory neurotransmission characteristic of this disorder.

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Section: Discussionmentioning

confidence: 70%

Vibrotactile adaptation fails to enhance spatial localization in adults with autism

et al. 2007

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“…43 Cell columns are more numerous in the brains of autistic patients, and are smaller and less compact in their cellular configuration in BA9 of the DLPFC. 44 Functional magnetic resonance imaging has shown that these prefrontal structures are associated with impaired executive functioning, relating to working memory and attention in particular. 45,46 Diffusion tensor imaging has demonstrated differences in long-distance frontoparietal connections between autistic subjects and controls.…”

Section: Discussionmentioning

confidence: 99%

SLC25A12 expression is associated with neurite outgrowth and is upregulated in the prefrontal cortex of autistic subjects

Lepagnol-Bestel

Maussion

Boda³

et al. 2008

Mol Psychiatry

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Autism is a neurodevelopmental disorder with a strong genetic component, probably involving several genes. Genome screens have provided evidence of linkage to chromosome 2q31-q33, which includes the SLC25A12 gene. Association between autism and single-nucleotide polymorphisms in SLC25A12 has been reported in various studies. SLC25A12 encodes the mitochondrial aspartate/glutamate carrier functionally important in neurons with highmetabolic activity. Neuropathological findings and functional abnormalities in autism have been reported for Brodmann's area (BA) 46 and the cerebellum. We found that SLC25A12 was expressed more strongly in the post-mortem brain tissues of autistic subjects than in those of controls, in the BA46 prefrontal cortex but not in cerebellar granule cells. SLC25A12 expression was not modified in brain subregions of bipolar and schizophrenic patients. SLC25A12 was expressed in developing human neuronal tissues, including neocortical regions containing excitatory neurons and neocortical progenitors and the ganglionic eminences that generate neocortical inhibitory interneurons. At mid-gestation, when gyri and sulci start to develop, SLC25A12 molecular gradients were identified in the lateral prefrontal and ventral temporal cortex. These fetal structures generate regions with abnormal activity in autism, including the dorsolateral prefrontal cortex (BA46), the pars opercularis of the inferior frontal cortex and the fusiform gyrus. SLC25A12 overexpression or silencing in mouse embryonic cortical neurons also modified dendrite length and the mobility of dendritic mitochondria. Our findings suggest that SLC25A12 overexpression may be involved in the pathophysiology of autism, modifying neuronal networks in specific subregions, such as the dorsolateral prefrontal cortex and fusiform gyrus, at both pre-and postnatal stages.

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“…Casanova et al [21,22] showed that in postmortem brain tissues from individuals with autism, the frontal and temporal cortical minicolumns were smaller, more numerous and less compact than those of non-autistic subjects. Alterations in the size and cellular distribution within cortical minicolumns in autism may reflect disturbances in the processing of thalamic inputs to cortex.…”

Section: Discussionmentioning

confidence: 99%

“…-stereotypical behaviors, impaired verbal and nonverbal communication and blunted social interaction) are accompanied by structural and functional changes in cortex, cerebellum and amygdala [3,4,7,8,[19][20][21][22]37,38,49,55,67,101,125]. Structural and functional changes apparent in early childhood suggest that autism is a disorder of brain development [4,19,20,[37][38][39]111].…”

Section: Introductionmentioning

confidence: 99%

“…Postmortem microscopic evaluation of brain tissue from adults with autism demonstrates abnormalities in cerebral cortical development that include increased cortical thickness and neuronal density, neuronal disorganization related to abnormal migration, poorly differentiated gray-white matter boundaries and an increased number of white matter neurons [4]. In addition, frontal and temporal cortical minicolumns are smaller and more numerous and less compact than those of control subjects [21,22]. Alterations in the size and cellular distribution within cortical minicolumns in autism may reflect disturbances in the processing of thalamic inputs to cortex.…”

Section: Introductionmentioning

confidence: 99%

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Modeling early cortical serotonergic deficits in autism

Boylan

Blue

Höhmann

2007

Behavioural Brain Research

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Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro-and macroscopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas.

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Minicolumnar pathology in autism

Abstract: In autism, there are minicolumnar abnormalities in the frontal and temporal lobes of the brain.

Cited by 752 publications

References 30 publications

Vibrotactile adaptation fails to enhance spatial localization in adults with autism

Vibrotactile adaptation fails to enhance spatial localization in adults with autism

SLC25A12 expression is associated with neurite outgrowth and is upregulated in the prefrontal cortex of autistic subjects

Modeling early cortical serotonergic deficits in autism

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