Brain activation modulated by sentence comprehension.

The comprehension of visually presented sentences produces brain activation that increases with the linguistic complexity of the sentence. The volume of neural tissue activated (number of voxels) during sentence comprehension was measured with echoplanar functional magnetic resonance imaging. The modulation of the volume of activation by sentence complexity was observed in a network of four areas: the classical left-hemisphere language areas (the left laterosuperior temporal cortex, or Wernicke's area, and the left inferior frontal gyrus, or Broca's area) and their homologous righthemisphere areas, although the right areas had much smaller volumes of activation than did the left areas. These findings generally indicate that the amount of neural activity that a given cognitive process engenders is dependent on the computational demand that the task imposes. This study examines what it means to be "thinking harder" in the course of sentence comprehension, in terms of functional magnetic resonance imaging (fMRI)-measured brain activation. One of the challenges of brain science is to relate the dynamics of higher level cognition to the equally dynamic activity of brain-level events. A possible meeting ground between these two levels is the modLulation in the amount of neuronal activity (at the brain level) in a given task, measured as a function of the amount of computational demand that the task places on cognitive resources (1). In particular, we examined whether sentences that were more computationally demanding also engender more brain activation (2, 3). At the cognitive level, sentence comprehension requires combining information from a sequence of words and phrases, computing their syntactic and thematic relations, and using world knowledge to construct a representation of the sentence meaning. These processes require the consumption of computational resources to perform the comprehension operations and also to maintain the representations of the component word meanings, propositions, and relational structures in an activated state during the processing (1). At the brain level, sentence comprehension entails activation in a network of cortical areas, most prominent of which are the left laterosuperior temporal cortex (Wernicke's area) (4) and the left inferio

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Peer reviewe

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)