The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism.

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

Evidence for mirror systems in emotions.

Why do we feel tears well up when we see a loved one cry? Why do we wince when we see other people hurt themselves? This review addresses these questions from the perspective of embodied simulation: observing the actions and tactile sensations of others activates premotor, posterior parietal and somatosensory regions in the brain of the observer which are also active when performing similar movements and feeling similar sensations. We will show that seeing the emotions of others also recruits regions involved in experiencing similar emotions, although there does not seem to be a reliable mapping of particular emotions onto particular brain regions. Instead, emotion simulation seems to involve a mosaic of affective, motor and somatosensory components. The relative contributions of these components to a particular emotion and their interrelationship are largely unknown, although recent experimental evidence suggests that motor simulation may be a trigger for the simulation of associated feeling states. This mosaic of simulations may be necessary for generating the compelling insights we have into the feelings of others. Through their integration with, and modulation by, higher cognitive functions, they could be at the core of important social functions, including empathy, mind reading and social learning.

Functional imaging of visual semantic processing in the human brain.

Previous neuroimaging studies have identified a large network of cortical areas involved in semantic processing in the human brain, which includes left occipito-temporal and inferofrontal areas. Most studies, however, investigated exclusively the associative/functional semantic knowledge by using mainly words and/or language related tasks, and this factor may have contributed to the large left hemisphere superiority found in semantic processing and to the controversial involvement of left prefrontal structures. The present study investigates the neural basis of visual objects knowledge, accessed exclusively through pictorial information. Regional cerebral blood flow (rCBF) was assessed using positron emission tomography (PET) during 3 conditions in right-handed normal volunteers: resting with eyes closed, retrieval of semantic information related to visual properties of objects (real size), and visual categorization based on physical properties of the image. Confirming previous experiments and neuropsychological findings, most activations were found in left occipito-temporal areas during retrieval of visual semantic knowledge. The absence of any activation in the left prefrontal inferior cortex for visual semantic processing confirms recent observations which suggest that this region would not be involved in retrieval of visual semantic knowledge from living entities. Rather, such knowledge about visual properties of objects, situated closely to cortical regions mediating perception of the visual attributes, can be retrieved directly from these regions when visual images are used as entry level stimuli.

Neuroanatomical substrates of arabic number processing, numerical comparison, and simple addition: a PET study.

Positron emission tomography was used to localize the cerebral networks specifically involved in three basic numerical processes: arabic numeral processing, numerical magnitude comparison, and retrieval of simple addition facts. Relative cerebral blood flow changes were measured while normal volunteers were resting with eyes closed, making physical judgment on nonnumerical characters or arabic digits, comparing, or adding the same digits. Processing arabic digits bilaterally produced a large nonspecific activation of occipito-parietal areas, as well as a specific activation of the right anterior insula. Comparison and simple addition fact retrieval revealed a fronto-parietal network involving mainly the left intraparietal sulcus, the superior parietal lobule and the precentral gyrus. Comparison also activated, but to a lesser extent, the right superior parietal lobe, whereas addition also activated the orbito-frontal areas and the anterior insula in the right hemisphere. Implications for current anatomo-functional models of numerical cognition are drawn.

Number processing and calculation in a case of visual agnosia.

We describe the performance of a brain-damaged subject who suffered from visual agnosia leading to major difficulties in generating and exploiting visual representations from long-term memory. His performance in a physical judgement task in which he was required to answer questions about the visual shapes of Arabic numerals reflected his agnosic problems. However, he showed no impairment in usual number processing and calculation tasks. This case shows that, despite some commonalities in number and object processing, actual numerical processes are not affected by visual agnosia and can be preserved even when fine visual processes are impaired.

Molecular analysis of chromosome arm 17q gain in neuroblastoma.

Complete or partial gain of the long arm of chromosome 17 (17q) has been shown recently by molecular cytogenetic techniques to be the most frequent chromosomal change in neuroblastoma and to be associated with adverse prognosis. Few reports, however, have focused on the precise mapping of the commonly overrepresented region. We have investigated 17q gain by the analysis of allelic imbalances at microsatellite loci dispersed along chromosome 17 in a series of 69 neuroblastomas. Allelic imbalances for at least two consecutive loci were observed in 39/59 informative cases, that is in agreement with previously reported frequencies of 17q gain. In a subset of the cases, comparative genomic hybridization analysis established the relationship between these allelic imbalances and the gain of 17q material. A partial 17q gain was observed in 9 cases, delineating a common region of 17q gain between the marker D17S787 (75 cM, 360 cR) and the telomere. In most cases, molecular results were suggestive of partial tri- or tetrasomy, whereas in 4 cases a higher copy number was documented. Our results also confirm that the presence of additional 17q material is closely associated with 1p36 deletion, MYCN amplification, and diploid or tetraploid chromosomal content. Genes Chromosomes Cancer 28:276-284, 2000.

Polymerase chain reaction compared with dot blotting for the determination of N-myc gene amplification in neuroblastoma.

The magnitude of N-myc amplification (NMA) influences the treatment strategy of localized neuroblastomas. Reliable assays are therefore needed for all types of tumor samples. The aim of this comparative study of 119 tumor samples was to determine whether a polymerase chain reaction (PCR)-based assay could replace the current dot blot assay as a routine and reliable means of determining NMA. The 2 assays exhibited comparable sensitivity and were completely concordant for samples containing at least 20% neuroblastoma cells. In their present state, both assays remain semi-quantitative since an absolute quantification of the N-myc copy number in clinical samples is limited by uncertainty about the amplification level of reference cell lines and by the estimation of the proportion of malignant cells. However, PCR offers several advantages over dot blotting, such as feasibility on minute samples, simplicity, standardization, rapidity and cost effectiveness.