The Neural Basis of Perceptual Learning Gilbert, Charles D.; Sigman, Mariano; Crist, Roy E.
Neuron,
09/2001, Volume:
31, Issue:
5
Book Review, Journal Article
Peer reviewed
Open access
Perceptual learning is a lifelong process. We begin by encoding information about the basic structure of the natural world and continue to assimilate information about specific patterns with which we ...become familiar. The specificity of the learning suggests that all areas of the cerebral cortex are plastic and can represent various aspects of learned information. The neural substrate of perceptual learning relates to the nature of the neural code itself, including changes in cortical maps, in the temporal characteristics of neuronal responses, and in modulation of contextual influences. Top-down control of these representations suggests that learning involves an interaction between multiple cortical areas.
Learning in shape identification led to global changes in activation across the entire visual pathway, as revealed with whole-brain fMRI. Following extensive training in a shape identification task, ...brain activity associated with trained shapes relative to the untrained shapes showed: (1) an increased level of activity in retinotopic cortex (RC), (2) a decrease in activation of the lateral occipital cortex (LO), and (3) a decrease in the dorsal attentional network. In addition, RC activations became more correlated (and LO activation, less correlated) with performance. When comparing target-present and target-absent trials within the trained condition, we observed a similar decrease in the dorsal attentional network but not in the visual cortices. These findings indicate a large-scale reorganization of activity in the visual pathway as a result of learning, with the RC becoming more involved (and the LO, less involved) and that these changes are triggered in a top-down manner depending on the perceptual task performed.
Thyroid hormone is essential for normal brain development, although the degree to which the developing brain is sensitive to small perturbations in serum thyroxin is not clear. An important concept ...related to this is that the developing brain possesses potent mechanisms to compensate for low serum thyroid hormone, and this concept is routinely employed in discussions concerning clinical treatments or public health. However, experimental studies have not directly tested whether (or the degree to which) putative compensatory mechanisms can ameliorate the consequences of small reductions in serum thyroxin (T4). To formally test this concept, we employed a model of graded T4 reductions using doses of propylthiouracil (PTU) that were 200‐ to 67‐fold lower than the dose traditionally used to produce hypothyroidism in rats. PTU produced a stepwise decrease in serum total T4, and a stepwise increase in serum thyroid‐stimulating hormone (TSH), in type 2 deiodinase mRNA expression and enzyme activity in the brain, and in the expression of the mRNA encoding the tri‐iodothyronine (T3) transporter MCT8 in the postnatal day (P) 15 cortex. However, the mRNA encoding RC3/neurogranin, a direct target of T3 action, exhibited a strong negative linear correlation with serum total T4 despite these adaptive responses. In addition, single‐cell analysis of RC3 mRNA levels in cortical neurones demonstrated that the co‐expression of MCT8 did not alter the relationship between RC3 mRNA and serum T4. These findings do not support the currently envisioned concept of the developing brain being capable of compensating for low T4.
Clinical trials provide the data that underpin evidence-based oncological practice. Over and above their primary outcome measures, collected and analysed by the clinical trials unit, trials provide ...an opportunity to generate a wide range of additional information over a prolonged period of time. Nationally held data have potential to facilitate longer term follow-up and explore associated toxicities and downstream consequences and in the UK include data from secondary care, including hospital episode statistics, national chemotherapy and radiotherapy datasets and primary care records. Specific to use in oncological practice, the National Cancer Data Repository contains linked data from a variety of sources for patients with a diagnosis of cancer, both cancer and non-cancer related. The challenge of using these data in clinical trials relates to the need to extract identifiable patient data, with the associated ethical and legal issues. The data access processes are time consuming and require evidence of information governance compliance.
This overview article reviews the current data available, the current and potential uses both within and outside clinical trials and the challenges encountered in the process of acquiring data. We focus specifically on the use of nationally held data for non-cancer outcomes, including toxicity and associated conditions.
Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. ...The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.
BackgroundA vaccine is needed to prevent human immunodeficiency virus type 1 (HIV-1) infection MethodsA double-blind, randomized trial of a recombinant HIV-1 envelope glycoprotein subunit (rgp120) ...vaccine was conducted among men who have sex with men and among women at high risk for heterosexual transmission of HIV-1. Volunteers received 7 injections of either vaccine or placebo (ratio, 2:1) over 30 months. The primary end point was HIV-1 seroconversion over 36 months ResultsA total of 5403 volunteers (5095 men and 308 women) were evaluated. The vaccine did not prevent HIV-1 acquisition: infection rates were 6.7% in 3598 vaccinees and 7.0% in 1805 placebo recipients; vaccine efficacy (VE) was estimated as 6% (95% confidence interval, −17% to 24%). There were no significant differences in viral loads, rates of antiretroviral-therapy initiation, or the genetic characteristics of the infecting HIV-1 strains between treatment arms. Exploratory subgroup analyses showed nonsignificant trends toward efficacy in preventing infection in the highest risk (VE, 43%; n=247) and nonwhite (VE, 47%; n=914) volunteers (P=.10, adjusted for multiple subgroup comparisons) ConclusionsThere was no overall protective effect. The efficacy trends in subgroups may provide clues for the development of effective immunization approaches
•The transcriptome of the mangrove oyster Crassostrea brasiliana was sequenced.•The sequencing effort dramatically expanded the existing cDNA sequences available for the species.•Global analysis for ...transcription in the oyster treated with phenanthrene, diesel and domestic sewage was performed.•The pollutants altered mRNAs for genes in biotransformation, antioxidant and stress response pathways.
The Brazilian oyster Crassostrea brasiliana was challenged to three common environmental contaminants: phenanthrene, diesel fuel water-accommodated fraction (WAF) and domestic sewage. Total RNA was extracted from the gill and digestive gland, and cDNA libraries were sequenced using the 454 FLX platform. The assembled transcriptome resulted in ̃20,000 contigs, which were annotated to produce the first de novo transcriptome for C. brasiliana. Sequences were screened to identify genes potentially involved in the biotransformation of xenobiotics and associated antioxidant defence mechanisms. These gene families included those of the cytochrome P450 (CYP450), 70kDa heat shock, antioxidants, such as glutathione S-transferase, superoxide dismutase, catalase and also multi-drug resistance proteins. Analysis showed that the massive expansion of the CYP450 and HSP70 family due to gene duplication identified in the Crassostrea gigas genome also occurred in C. brasiliana, suggesting these processes form the base of the Crassostrea lineage. Preliminary expression analyses revealed several candidates biomarker genes that were up-regulated during each of the three treatments, suggesting the potential for environmental monitoring.
PDF
