Early Category-Specific Cortical Activation Revealed by Visual Stimulus Inversion

Visual categorization may already start within the first 100-ms after stimulus onset, in contrast with the long-held view that during this early stage all complex stimuli are processed equally and that category-specific cortical activation occurs only at later stages. The neural basis of this proposed early stage of high-level analysis is however poorly understood. To address this question we used magnetoencephalography and anatomically-constrained distributed source modeling to monitor brain activity with millisecond-resolution while subjects performed an orientation task on the upright and upside-down presented images of three different stimulus categories: faces, houses and bodies. Significant inversion effects were found for all three stimulus categories between 70–100-ms after picture onset with a highly category-specific cortical distribution. Differential responses between upright and inverted faces were found in well-established face-selective areas of the inferior occipital cortex and right fusiform gyrus. In addition, early category-specific inversion effects were found well beyond visual areas. Our results provide the first direct evidence that category-specific processing in high-level category-sensitive cortical areas already takes place within the first 100-ms of visual processing, significantly earlier than previously thought, and suggests the existence of fast category-specific neocortical routes in the human brain

Neuroanatomical Abnormalities in Violent Individuals with and without a Diagnosis of Schizophrenia

Several structural brain abnormalities have been associated with aggression in patients with schizophrenia. However, little is known about shared and distinct abnormalities underlying aggression in these subjects and non-psychotic violent individuals. We applied a region-of interest volumetric analysis of the amygdala, hippocampus, and thalamus bilaterally, as well as whole brain and ventricular volumes to investigate violent (n = 37) and non-violent chronic patients (n = 26) with schizophrenia, non-psychotic violent (n = 24) as well as healthy control subjects (n = 24). Shared and distinct volumetric abnormalities were probed by analysis of variance with the factors violence (non-violent versus violent) and diagnosis (non-psychotic versus psychotic), adjusted for substance abuse, age, academic achievement and negative psychotic symptoms. Patients showed elevated vCSF volume, smaller left hippocampus and smaller left thalamus volumes. This was particularly the case for non-violent individuals diagnosed with schizophrenia. Furthermore, patients had reduction in right thalamus size. With regard to left amygdala, we found an interaction between violence and diagnosis. More specifically, we report a double dissociation with smaller amygdala size linked to violence in non-psychotic individuals, while for psychotic patients smaller size was linked to non-violence. Importantly, the double dissociation appeared to be mostly driven by substance abuse. Overall, we found widespread morphometric abnormalities in subcortical regions in schizophrenia. No evidence for shared volumetric abnormalities in individuals with a history of violence was found. Finally, left amygdala abnormalities in non-psychotic violent individuals were largely accounted for by substance abuse. This might be an indication that the association between amygdala reduction and violence is mediated by substance abuse. Our results indicate the importance of structural abnormalities in aggressive individuals

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Human impacts on fire occurrence: a case study of hundred years of forest fires in a dry alpine valley in Switzerland

Forest fire regimes are sensitive to alterations of climate, fuel load, and ignition sources. We investigated the impact of human activities and climate on fire occurrence in a dry continental valley of the Swiss Alps (Valais) by relating fire occurrence to population and road density, biomass removal by livestock grazing and wood harvest, temperature and precipitation in two distinct periods (1904–1955 and 1956–2006) using generalized additive modeling. This study provides evidence for the role played by humans and temperature in shaping fire occurrence. The existence of ignition sources promotes fire occurrence to a certain extent only; for example, high road density tends to be related to fewer fires. Changes in forest uses within the study region seem to be particularly important. Fire occurrence appears to have been negatively associated with livestock pasturing in the forest and wood harvesting, in particular during the period 1904–1955. This study illustrates consistently how fire occurrence has been influenced by land use and socioeconomic conditions. It also suggests that there is no straightforward linear relationship between human factors and fire occurrence