The impact of functional connectivity changes on support vector machines mapping of fMRI data

Functional magnetic resonance imaging (fMRI) is currently one of the most widely used methods for studying human brain function in vivo. Although many different approaches to fMRI analysis are available, the most widely used methods employ so called ""mass-univariate"" modeling of responses in a voxel-by-voxel fashion to construct activation maps. However, it is well known that many brain processes involve networks of interacting regions and for this reason multivariate analyses might seem to be attractive alternatives to univariate approaches. The current paper focuses on one multivariate application of statistical learning theory: the statistical discrimination maps (SDM) based on support vector machine, and seeks to establish some possible interpretations when the results differ from univariate `approaches. In fact, when there are changes not only on the activation level of two conditions but also on functional connectivity, SDM seems more informative. We addressed this question using both simulations and applications to real data. We have shown that the combined use of univariate approaches and SDM yields significant new insights into brain activations not available using univariate methods alone. In the application to a visual working memory fMRI data, we demonstrated that the interaction among brain regions play a role in SDM`s power to detect discriminative voxels. (C) 2008 Elsevier B.V. All rights reserved.

Genetic Susceptibility Loci in Rheumatoid Arthritis Establish Transcriptional Regulatory Networks with Other Genes

Linkage studies have identified the human leukocyte antigen (HLA)-DRB1 as a putative rheumatoid arthritis (RA) susceptibility locus (SL). Nevertheless, it was estimated that its contribution was partial, suggesting that other non-HLA genes may play a role in RA susceptibility. To test this hypothesis, we conducted microarray transcription profiling of peripheral blood mononuclear cells in 15 RA patients and analyzed the data, using bioinformatics programs (significance analysis of microarrays method and GeneNetwork), which allowed us to determine the differentially expressed genes and to reconstruct transcriptional networks. The patients were grouped according to disease features or treatment with tumor necrosis factor blocker. Transcriptional networks that were reconstructed allowed us to identify the interactions occurring between RA SL and other genes, for example, HLA-DRB1 interacting with FNDC3A (fibronectin type III domain containing 3A). Given that fibronectin fragments can stimulate mediators of matrix and cartilage destruction in RA, this interaction is of special interest and may contribute to a clearer understanding of the functional role of HLA-DRB1 in RA pathogenesis.

Puzzling challenges in contemporary neuroscience: Insights from complexity and emergence in epileptogenic circuits

The brain is a complex system that, in the normal condition, has emergent properties like those associated with activity-dependent plasticity in learning and memory, and in pathological situations, manifests abnormal long-term phenomena like the epilepsies. Data from our laboratory and from the literature were classified qualitatively as sources of complexity and emergent properties from behavior to electrophysiological, cellular, molecular, and computational levels. We used such models as brainstem-dependent acute audiogenic seizures and forebrain-dependent kindled audiogenic seizures. Additionally we used chemical OF electrical experimental models of temporal lobe epilepsy that induce status epilepticus with behavioral, anatomical, and molecular sequelae such as spontaneous recurrent seizures and long-term plastic changes. Current Computational neuroscience tools will help the interpretation. storage, and sharing of the exponential growth of information derived from those studies. These strategies are considered solutions to deal with the complexity of brain pathologies such as the epilepsies. (C) 2008 Elsevier Inc. All rights reserved.

Modulation of Mediotemporal and Ventrostriatal Function in Humans by Delta 9-Tetrahydrocannabinol A Neural Basis for the Effects of Cannabis sativa on Learning and Psychosis

Context: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. Objectives: To investigate the effects of 2 main psychoactive constituents of C sativa, Delta 9-tetrahydrocannabinol (Delta 9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. Design: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta 9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. Setting: University research center. Participants: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. Main Outcome Measures: Regional brain activation ( blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. Results: Delta 9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta 9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta 9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect. Conclusion: The modulation of mediotemporal and ventrostriatal function by Delta 9-THC may underlie the effects of C sativa on verbal learning and psychotic symptoms, respectively.

Genes that code for T cell signaling proteins establish transcriptional regulatory networks during thymus ontogeny

Gene expression profiling by cDNA microarrays during murine thymus ontogeny has contributed to dissecting the large-scale molecular genetics of T cell maturation. Gene profiling, although useful for characterizing the thymus developmental phases and identifying the differentially expressed genes, does not permit the determination of possible interactions between genes. In order to reconstruct genetic interactions, on RNA level, within thymocyte differentiation, a pair of microarrays containing a total of 1,576 cDNA sequences derived from the IMAGE MTB library was applied on samples of developing thymuses (14-17 days of gestation). The data were analyzed using the GeneNetwork program. Genes that were previously identified as differentially expressed during thymus ontogeny showed their relationships with several other genes. The present method provided the detection of gene nodes coding for proteins implicated in the calcium signaling pathway, such as Prrg2 and Stxbp3, and in protein transport toward the cell membrane, such as Gosr2. The results demonstrate the feasibility of reconstructing networks based on cDNA microarray gene expression determinations, contributing to a clearer understanding of the complex interactions between genes involved in thymus/thymocyte development.

Characterization of dimethacrylate polymeric networks: A study of the crosslinked structure formed by monomers used in dental composites

The resin phase of dental composites is mainly composed of combinations of dimethacrylate comonomers, with final polymeric network structure defined by monomer type/reactivity and degree of conversion. This fundamental study evaluates how increasing concentrations of the flexible triethylene glycol dimethacrylate (TEGDMA) influences void formation in bisphenol A diglycidyl dimethacrylate (BisGMA) co-polymerizations and correlates this aspect of network structure with reaction kinetic parameters and macroscopic volumetric shrinkage. Photopolymerization kinetics was followed in real-time by a near-infrared (NIR) spectroscopic technique, viscosity was assessed with a viscometer, volumetric shrinkage was followed with a linometer, free volume formation was determined by positron annihilation lifetime spectroscopy (PALS) and the sol-gel composition was determined by extraction with dichloromethane followed by (1)H NMR analysis. Results show that, as expected, volumetric shrinkage increases with TEGDMA concentration and monomer conversion. Extraction/(1)H NMR studies show increasing participation of the more flexible TEGDMA towards the limiting stages of conversion/crosslinking development. As the conversion progresses, either based on longer irradiation times or greater TEGDMA concentrations, the network becomes more dense, which is evidenced by the decrease in free volume and weight loss after extraction in these situations. For the same composition (BisGMA/TEGDMA 60-40 mol%) light-cured for increasing periods of time (from 10 to 600 s), free volume decreased and volumetric shrinkage increased, in a linear relationship with conversion. However, the correlation between free volume and macroscopic volumetric shrinkage was shown to be rather complex for variable compositions exposed for the same time (600 s). The addition of TEGDMA decreases free-volume up to 40 mol% (due to increased conversion), but above that concentration, in spite of the increase in conversion/crosslinking, free volume pore size increases due to the high concentration of the more flexible monomer. In those cases, the increase in volumetric shrinkage was due to higher functional group concentration, in spite of the greater free volume. Therefore, through the application of the PALS model, this study elucidates the network formation in dimethacrylates commonly used in dental materials. (C) 2010 Elsevier Ltd. All rights reserved.

Relational learning in children with deafness and cochlear implants

This four-experiment series sought to evaluate the potential of children with neurosensory deafness and cochlear implants to exhibit auditory-visual and visual-visual stimulus equivalence relations within a matching-to-sample format. Twelve children who became deaf prior to acquiring language (prelingual) and four who became deaf afterwards (postlingual) were studied. All children learned auditory-visual conditional discriminations and nearly all showed emergent equivalence relations. Naming tests, conducted with a subset of the: children, showed no consistent relationship to the equivalence-test outcomes.. This study makes several contributions: to the literature on stimulus equivalence. First; it demonstrates that both pre- and postlingually deaf children-can: acquire auditory-visual equivalence-relations after cochlear implantation, thus demonstrating symbolic functioning. Second, it directs attention to a population that may be especially interesting for researchers seeking to analyze the relationship. between speaker and listener repertoires. Third, it demonstrates the feasibility of conducting experimental studies of stimulus control processes within the limitations of a hospital, which these children must visit routinely for the maintenance of their cochlear implants.