Why Neurons Are Not the Right Level of Abstraction for Implementing Cognition

International audienceThe cortex accounts for 70% of the brain volume. The human cortex is made of micro-columns, arrangements of 110 cortical neurons (Mountcastle), grouped in by the thousand in so-called macro-colums (or columns) which belong to the same functional unit as exemplified by Nobel laureates Hubel and Wiesel with the orientation columns of the primary visual cortex. The cortical column activity does not exhibit the limitations of single neurons: activation can be sustained for very long periods (sec.) instead of been transient and subject to fatigue. Therefore, the cortical column has been proposed as the building block of cognition by several researchers, but to not effect – since explanations about how the cognition works at the column level were missing. Thanks to the Theory of neuronal Cognition, it is no more the case. The cortex functionality is cut into small areas: the cortical maps. Today, about 80 cortical maps are known in the primary and secondary cortex [1]. These maps form a hierarchical organization. A cortical map is a functional structure encompassing several thousands of cortical columns. The function of such maps (also known as Kohonen maps) is to build topographic (i.e., organized and localized) representations of the input stimulii (events). This organization is such that similar inputs activate either the same cortical column or neighboring columns. Also, the more frequent the stimulus, the greater the number of cortical columns involved. Each map acts as a novelty detector and a filter. Events are reported as patterns of activations on various maps, each map specialized in a specific " dimension ". Spatial and temporal coordinates of events are linked to activations within the hippo-campus and define de facto the episodic memory. Learning is achieved at neuronal level using the famous Hebb's law: " Neurons active in the same time frame window reinforce their connections ". This rule does not respect " causality ". This, plus the fact that there is at least as much feedback connections as there are feed-forward ones, explain why a high level cortical activation generates a low level cortical pattern of activations – the same one that would trigger this high level activity. Therefore, our opinion is that the true building block of the cognition is a set of feed-forward and feedback connections between at least two maps, each map a novelty detector

Assimilation of SLA along track observations in the Mediterranean with an oceanographic model forced by atmospheric pressure

A large number of SLA observations at a high along track horizontal resolution are an important ingredient of the data assimilation in the Mediterranean Forecasting System (MFS). Recently, new higher-frequency SLA products have become available, and the atmospheric pressure forcing has been implemented in the numerical model used in the MFS data assimilation system. In a set of numerical experiments, we show that, in order to obtain the most accurate analyses, the ocean model should include the atmospheric pressure forcing and the observations should contain the atmospheric pressure signal. When the model is not forced by the atmospheric pressure, the high-frequency filtering of SLA observations, however, improves the quality of the SLA analyses. It is further shown by comparing the power density spectra of the model fields and observations that the model is able to extract the correct information from noisy observations even without their filtering during the pre-processing

Pathophysiological features of the pulsatile secretion of biologically active luteinizing hormone in man

The development of an in vitro bioassay of high specificity, sensitivity and precision for the measurement of low circulating concentrations of biologically active glycoprotein hormones has offered exciting new insights into the in vivo secretion and metabolic clearance of luteinizing hormone (LH) in various pathophysiological states. Moreover, the most recent combined application of the rat interstitial cell testosterone (RICT) bioassay and a novel multiple-parameter deonvolution model has allowed investigators to dissect plasma concentration profiles of bioactive LH into defined secretory bursts, which have numerically explicit amplitudes, locations in time, and durations, and are acted upon by detenninable subject- and study-specific endogenous metabolic clearance rates. Here, we have: (i) reviewed the ability of the endogenous GnRH pulse signal to regulate the in vivo secretion of biologically active LH molecules as assessed in the RICT and by deconvolution mechanics; (ii) demonstrated that low-dose exogenous GnRH pulses effectively mimic spontaneous bioactive LH pulsatility; (iii) investigated the role of endogenous androgen and estrogen in modulating bioactive gonadotropin secretion in men and women; and (iv) described significant alterations in endogenous LH bioactivity in puberty and healthy aging.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27746/1/0000138.pd

Cellular Angiofibroma of Oral Mucosa: Report of Two Cases

Cellular angiofibroma is a benign vascular neoplasm that typically arises in the vulva, perineal, and paratesticular region. Microscopically the lesions exhibit multiple small, non-dilated capillary channels, many of which contain erythrocytes. The endothelial lining cells are prominent, with monomorphic oval nuclei. Interposed among the vessels are both delicate and mature collagen fibers with fibroblastic hypercellularity that is variable in older lesions where sclerosis is prominent. The lesions usually do not recur following simple excision. Recent evidence indicates that cellular angiofibromas may be cytogenetically related to spindle cell lipoma. This represents the first reported instances of cellular angiofibroma in the oral cavity

Investigation of K14/K5 as a stem cell marker in the limbal region of the bovine cornea

Background: Identification of stem cells from a corneal epithelial cell population by specific molecular markers has been investigated previously. Expressions of P63, ABCG2 and K14/K5 have all been linked to mammalian corneal epithelial stem cells. Here we report on the limitations of K14/K5 as a limbal stem cell marker. Methodology/Principal Findings: K14/K5 expression was measured by immunohistochemistry, Western blotting and Real time PCR and compared between bovine epithelial cells in the limbus and central cornea. A functional study was also included to investigate changes in K5/14 expression within cultured limbal epithelial cells undergoing forced differentiation. K14 expression (or its partner K5) was detected in quiescent epithelial cells from both the limbal area and central cornea. K14 was localized predominantly to basal epithelial cells in the limbus and suprabasal epithelial cells in the central cornea. Western blotting revealed K14 expression in both limbus and central cornea (higher levels in the limbus). Similarly, quantitative real time PCR found K5, partner to K14, to be expressed in both the central cornea and limbus. Following forced differentiation in culture the limbal epithelial cells revealed an increase in K5/14 gene/protein expression levels in concert with a predictable rise in a known differentiation marker. Conclusions/Significance: K14 and its partner K5 are limited not only to the limbus but also to the central bovine cornea epithelial cells suggesting K14/K5 is not limbal specific in situ. Furthermore K14/K5 expression levels were not lowered (in fact they increased) within a limbal epithelial cell culture undergoing forced differentiation suggesting K14/K5 is an unreliable maker for undifferentiated cells ex vivo

Masked suffix priming and morpheme positional constraints

Although masked stem priming (e.g., dealer\u2013DEAL) is one of the most established effects in visual word identification (e.g., Grainger et al., 1991), it is less clear whether primes and targets sharing a suffix (e.g., kindness\u2013WILDNESS) also yield facilitation (Giraudo & Grainger, 2003; Du\uf1abeitia et al., 2008). In a new take on this issue, we show that prime nonwords facilitate lexical decisions to target words ending with the same suffix (sheeter\uac\u2013TEACHER) compared to a condition where the critical suffix was substituted by another one (sheetal\u2013TEACHER) or by an unrelated non\u2013morphological ending (sheetub\u2013 TEACHER). We also show that this effect is genuinely morphological, as no priming emerged in non\u2013complex items with the same orthographic characteristics (sportel\u2013BROTHEL vs. sportic\u2013BROTHEL vs. sportur\u2013BROTHEL). In a further experiment, we took advantage of these results to assess whether suffixes are recognized in a position\u2013specific fashion. Masked suffix priming did not emerge when the relative order of stems and suffixes was reversed in the prime nonwords\u2014ersheet did not yield any time saving in the identification of teacher as compared to either alsheet or obsheet. We take these results to show that \u2013er was not identified as a morpheme in ersheet, thus indicating that suffix identification is position specific. This conclusion is in line with data on interference effects in nonword rejection (Crepaldi, Rastle, & Davis, 2010), and strongly constrains theoretical proposals on how complex words are identified. In particular, because these findings were reported in a masked priming paradigm, they suggest that positional constraints operate early, most likely at a pre\u2013lexical level of morpho\u2013orthographic analysi

Computational Approaches and Analysis for a Spatio-Structural-Temporal Invasive Carcinoma Model

Spatio-temporal models have long been used to describe biological systems of cancer, but it has not been until very recently that increased attention has been paid to structural dynamics of the interaction between cancer populations and the molecular mechanisms associated with local invasion. One system that is of particular interest is that of the urokinase plasminogen activator (uPA) wherein uPA binds uPA receptors on the cancer cell surface, allowing plasminogen to be cleaved into plasmin, which degrades the extracellular matrix and this way leads to enhanced cancer cell migration. In this paper, we develop a novel numerical approach and associated analysis for spatio-structuro-temporal modelling of the uPA system for up to two-spatial and two-structural dimensions. This is accompanied by analytical exploration of the numerical techniques used in simulating this system, with special consideration being given to the proof of stability within numerical regimes encapsulating a central differences approach to approximating numerical gradients. The stability analysis performed here reveals instabilities induced by the coupling of the structural binding and proliferative processes. The numerical results expound how the uPA system aids the tumour in invading the local stroma, whilst the inhibitor to this system may impede this behaviour and encourage a more sporadic pattern of invasion.PostprintPeer reviewe