The structural nature of perceptual experiences

Intuitively, we think of perception as providing us with direct cognitive access to physical objects and their properties. But this common sense picture of perception becomes problematic when we notice that perception is not always veridical. In fact, reflection on illusions and hallucinations seems to indicate that perception cannot be what it intuitively appears to be. This clash between intuition and reflection is what generates the puzzle of perception. The task and enterprise of unravelling this puzzle took, and still takes, centre stage in the philosophy of perception. The goal of my dissertation is to make a contribution to this enterprise by formulating and defending a new structural approach to perception and perceptual consciousness. The argument for my structural approach is developed in several steps. Firstly, I develop an empirically inspired causal argument against naïve and direct realist conceptions of perceptual consciousness. Basically, the argument says that perception and hallucination can have the same proximal causes and must thus belong to the same mental kind. I emphasise that this insight gives us good reasons to abandon what we are instinctively driven to believe - namely that perception is directly about the outside physical world. The causal argument essentially highlights that the information that the subject acquires in perceiving a worldly object is always indirect. To put it another way, the argument shows that what we, as perceivers, are immediately aware of, is not an aspect of the world but an aspect of our sensory response to it. A view like this is traditionally known as a Representative Theory of Perception. As a second step, emphasis is put on the task of defending and promoting a new structural version of the Representative Theory of Perception; one that is immune to some major objections that have been standardly levelled at other Representative Theories of Perception. As part of this defence and promotion, I argue that it is only the structural features of perceptual experiences that are fit to represent the empirical world. This line of thought is backed up by a detailed study of the intriguing phenomenon of synaesthesia. More precisely, I concentrate on empirical cases of synaesthetic experiences and argue that some of them provide support for a structural approach to perception. The general picture that emerges in this dissertation is a new perspective on perceptual consciousness that is structural through and through.

Structural joint inversion of time-lapse crosshole ERT and GPR traveltime data

Time-lapse geophysical monitoring and inversion are valuable tools in hydrogeology for monitoring changes in the subsurface due to natural and forced (tracer) dynamics. However, the resulting models may suffer from insufficient resolution, which leads to underestimated variability and poor mass recovery. Structural joint inversion using cross-gradient constraints can provide higher-resolution models compared with individual inversions and we present the first application to time-lapse data. The results from a synthetic and field vadose zone water tracer injection experiment show that joint 3-D time-lapse inversion of crosshole electrical resistance tomography (ERT) and ground penetrating radar (GPR) traveltime data significantly improve the imaged characteristics of the point injected plume, such as lateral spreading and center of mass, as well as the overall consistency between models. The joint inversion method appears to work well for cases when one hydrological state variable (in this case moisture content) controls the time-lapse response of both geophysical methods. Citation: Doetsch, J., N. Linde, and A. Binley (2010), Structural joint inversion of time-lapse crosshole ERT and GPR traveltime data, Geophys. Res. Lett., 37, L24404, doi: 10.1029/2010GL045482.

The acquisition of pronouns by French children: A parallel study of production and comprehension

This study examines syntactic and morphological aspects of the production and comprehension of pronouns by 99 typically developing French-speaking children aged 3 years, 5 months to 6 years, 5 months. A fine structural analysis of subject, object, and reflexive clitics suggests that whereas the object clitic chain crosses the subject chain, the reflexive clitic chain is nested within it. We argue that this structural difference introduces differences in processing complexity, chain crossing being more complex than nesting. In support of this analysis, both production and comprehension experiments show that children have more difficulty with object than with reflexive clitics (with more omissions in production and more erroneous judgments in sentences involving Principle B in comprehension). Concerning the morphological aspect, French subject and object pronouns agree in gender with their referent. We report serious difficulties with pronoun gender both in production and comprehension in children around the age of 4 (with nearly 30% errors in production and chance level judgments in comprehension), which tend to disappear by age 6. The distribution of errors further suggests that the masculine gender is processed as the default value. These findings provide further insights into the relationship between comprehension and production in the acquisition process.

Structural covariance of superficial white matter in mild Alzheimer's disease compared to normal aging.

INTRODUCTION: Interindividual variations in regional structural properties covary across the brain, thus forming networks that change as a result of aging and accompanying neurological conditions. The alterations of superficial white matter (SWM) in Alzheimer's disease (AD) are of special interest, since they follow the AD-specific pattern characterized by the strongest neurodegeneration of the medial temporal lobe and association cortices. METHODS: Here, we present an SWM network analysis in comparison with SWM topography based on the myelin content quantified with magnetization transfer ratio (MTR) for 39 areas in each hemisphere in 15 AD patients and 15 controls. The networks are represented by graphs, in which nodes correspond to the areas, and edges denote statistical associations between them. RESULTS: In both groups, the networks were characterized by asymmetrically distributed edges (predominantly in the left hemisphere). The AD-related differences were also leftward. The edges lost due to AD tended to connect nodes in the temporal lobe to other lobes or nodes within or between the latter lobes. The newly gained edges were mostly confined to the temporal and paralimbic regions, which manifest demyelination of SWM already in mild AD. CONCLUSION: This pattern suggests that the AD pathological process coordinates SWM demyelination in the temporal and paralimbic regions, but not elsewhere. A comparison of the MTR maps with MTR-based networks shows that although, in general, the changes in network architecture in AD recapitulate the topography of (de)myelination, some aspects of structural covariance (including the interhemispheric asymmetry of networks) have no immediate reflection in the myelination pattern.

Cis-trans interactions of cell surface receptors: biological roles and structural basis.

Cell surface receptors bind ligands expressed on other cells (in trans) in order to communicate with neighboring cells. However, an increasing number of cell surface receptors are found to also interact with ligands expressed on the same cell (in cis). These observations raise questions regarding the biological role of such cis interactions. Specifically, it is important to know whether cis and trans binding have distinct functional effects and, if so, how a single cell discriminates between interactions in cis versus trans. Further, what are the structural features that allow certain cell surface receptors to engage ligand both on the same as well as on an apposed cell membrane? Here, we summarize known examples of receptors that display cis-trans binding and discuss the emerging diversity of biological roles played by these unconventional two-way interactions, along with their structural basis.

Identification of optimal structural connectivity using functional connectivity and neural modeling.

The complex network dynamics that arise from the interaction of the brain's structural and functional architectures give rise to mental function. Theoretical models demonstrate that the structure-function relation is maximal when the global network dynamics operate at a critical point of state transition. In the present work, we used a dynamic mean-field neural model to fit empirical structural connectivity (SC) and functional connectivity (FC) data acquired in humans and macaques and developed a new iterative-fitting algorithm to optimize the SC matrix based on the FC matrix. A dramatic improvement of the fitting of the matrices was obtained with the addition of a small number of anatomical links, particularly cross-hemispheric connections, and reweighting of existing connections. We suggest that the notion of a critical working point, where the structure-function interplay is maximal, may provide a new way to link behavior and cognition, and a new perspective to understand recovery of function in clinical conditions.

Statistical learning theory for geospatial data. Case study: Aral sea

In recent years there has been an explosive growth in the development of adaptive and data driven methods. One of the efficient and data-driven approaches is based on statistical learning theory (Vapnik 1998). The theory is based on Structural Risk Minimisation (SRM) principle and has a solid statistical background. When applying SRM we are trying not only to reduce training error ? to fit the available data with a model, but also to reduce the complexity of the model and to reduce generalisation error. Many nonlinear learning procedures recently developed in neural networks and statistics can be understood and interpreted in terms of the structural risk minimisation inductive principle. A recent methodology based on SRM is called Support Vector Machines (SVM). At present SLT is still under intensive development and SVM find new areas of application (www.kernel-machines.org). SVM develop robust and non linear data models with excellent generalisation abilities that is very important both for monitoring and forecasting. SVM are extremely good when input space is high dimensional and training data set i not big enough to develop corresponding nonlinear model. Moreover, SVM use only support vectors to derive decision boundaries. It opens a way to sampling optimization, estimation of noise in data, quantification of data redundancy etc. Presentation of SVM for spatially distributed data is given in (Kanevski and Maignan 2004).

Identification and removal of low-complexity sites in allele-specific analysis of ChIP-seq data.

MOTIVATION: High-throughput sequencing technologies enable the genome-wide analysis of the impact of genetic variation on molecular phenotypes at unprecedented resolution. However, although powerful, these technologies can also introduce unexpected artifacts. Results: We investigated the impact of library amplification bias on the identification of allele-specific (AS) molecular events from high-throughput sequencing data derived from chromatin immunoprecipitation assays (ChIP-seq). Putative AS DNA binding activity for RNA polymerase II was determined using ChIP-seq data derived from lymphoblastoid cell lines of two parent-daughter trios. We found that, at high-sequencing depth, many significant AS binding sites suffered from an amplification bias, as evidenced by a larger number of clonal reads representing one of the two alleles. To alleviate this bias, we devised an amplification bias detection strategy, which filters out sites with low read complexity and sites featuring a significant excess of clonal reads. This method will be useful for AS analyses involving ChIP-seq and other functional sequencing assays.

Crystal structure of yeast peroxisomal multifunctional enzyme: structural basis for substrate specificity of (3R)-hydroxyacyl-CoA dehydrogenase units.

(3R)-hydroxyacyl-CoA dehydrogenase is part of multifunctional enzyme type 2 (MFE-2) of peroxisomal fatty acid beta-oxidation. The MFE-2 protein from yeasts contains in the same polypeptide chain two dehydrogenases (A and B), which possess difference in substrate specificity. The crystal structure of Candida tropicalis (3R)-hydroxyacyl-CoA dehydrogenase AB heterodimer, consisting of dehydrogenase A and B, determined at the resolution of 2.2A, shows overall similarity with the prototypic counterpart from rat, but also important differences that explain the substrate specificity differences observed. Docking studies suggest that dehydrogenase A binds the hydrophobic fatty acyl chain of a medium-chain-length ((3R)-OH-C10) substrate as bent into the binding pocket, whereas the short-chain substrates are dislocated by two mechanisms: (i) a short-chain-length 3-hydroxyacyl group ((3R)-OH-C4) does not reach the hydrophobic contacts needed for anchoring the substrate into the active site; and (ii) Leu44 in the loop above the NAD(+) cofactor attracts short-chain-length substrates away from the active site. Dehydrogenase B, which can use a (3R)-OH-C4 substrate, has a more shallow binding pocket and the substrate is correctly placed for catalysis. Based on the current structure, and together with the structure of the 2-enoyl-CoA hydratase 2 unit of yeast MFE-2 it becomes obvious that in yeast and mammalian MFE-2s, despite basically identical functional domains, the assembly of these domains into a mature, dimeric multifunctional enzyme is very different.

The implications of alternative splicing in the ENCODE protein complement.

Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the ENCODE pilot project. We find that alternative splicing in human genes is more frequent than has commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as functional proteins, and it seems unlikely that the spectrum of conventional enzymatic or structural functions can be substantially extended through alternative splicing.