Action planning and the timescale of evidence accumulation

Perceptual decisions are based on the temporal integration of sensory evidence for different states of the outside world. The timescale of this integration process varies widely across behavioral contexts and individuals, and it is diagnostic for the underlying neural mechanisms. In many situations, the decision-maker knows the required mapping between perceptual evidence and motor response (henceforth termed “sensory-motor contingency”) before decision formation. Here, the integrated evidence can be directly translated into a motor plan and, indeed, neural signatures of the integration process are evident as build-up activity in premotor brain regions. In other situations, however, the sensory-motor contingencies are unknown at the time of decision formation. We used behavioral psychophysics and computational modeling to test if knowledge about sensory-motor contingencies affects the timescale of perceptual evidence integration. We asked human observers to perform the same motion discrimination task, with or without trial-to-trial variations of the mapping between perceptual choice and motor response. When the mapping varied, it was either instructed before or after the stimulus presentation. We quantified the timescale of evidence integration under these different sensory-motor mapping conditions by means of two approaches. First, we analyzed subjects’ discrimination threshold as a function of stimulus duration. Second, we fitted a dynamical decision-making model to subjects’ choice behavior. The results from both approaches indicated that observers (i) integrated motion information for several hundred ms, (ii) used a shorter than optimal integration timescale, and (iii) used the same integration timescale under all sensory-motor mappings. We conclude that the mechanisms limiting the timescale of perceptual decisions are largely independent from long-term learning (under fixed mapping) or rapid acquisition (under variable mapping) of sensory-motor contingencies. This conclusion has implications for neurophysiological and neuroimaging studies of perceptual decision-making

NICE : A Computational solution to close the gap from colour perception to colour categorization

The segmentation of visible electromagnetic radiation into chromatic categories by the human visual system has been extensively studied from a perceptual point of view, resulting in several colour appearance models. However, there is currently a void when it comes to relate these results to the physiological mechanisms that are known to shape the pre-cortical and cortical visual pathway. This work intends to begin to fill this void by proposing a new physiologically plausible model of colour categorization based on Neural Isoresponsive Colour Ellipsoids (NICE) in the cone-contrast space defined by the main directions of the visual signals entering the visual cortex. The model was adjusted to fit psychophysical measures that concentrate on the categorical boundaries and are consistent with the ellipsoidal isoresponse surfaces of visual cortical neurons. By revealing the shape of such categorical colour regions, our measures allow for a more precise and parsimonious description, connecting well-known early visual processing mechanisms to the less understood phenomenon of colour categorization. To test the feasibility of our method we applied it to exemplary images and a popular ground-truth chart obtaining labelling results that are better than those of current state-of-the-art algorithms

Neurobiological Models of Two-Choice Decision Making Can Be Reduced to a One-Dimensional Nonlinear Diffusion Equation

The response behaviors in many two-alternative choice tasks are well described by so-called sequential sampling models. In these models, the evidence for each one of the two alternatives accumulates over time until it reaches a threshold, at which point a response is made. At the neurophysiological level, single neuron data recorded while monkeys are engaged in two-alternative choice tasks are well described by winner-take-all network models in which the two choices are represented in the firing rates of separate populations of neurons. Here, we show that such nonlinear network models can generally be reduced to a one-dimensional nonlinear diffusion equation, which bears functional resemblance to standard sequential sampling models of behavior. This reduction gives the functional dependence of performance and reaction-times on external inputs in the original system, irrespective of the system details. What is more, the nonlinear diffusion equation can provide excellent fits to behavioral data from two-choice decision making tasks by varying these external inputs. This suggests that changes in behavior under various experimental conditions, e.g. changes in stimulus coherence or response deadline, are driven by internal modulation of afferent inputs to putative decision making circuits in the brain. For certain model systems one can analytically derive the nonlinear diffusion equation, thereby mapping the original system parameters onto the diffusion equation coefficients. Here, we illustrate this with three model systems including coupled rate equations and a network of spiking neurons

Second Order Dimensionality Reduction Using Minimum and Maximum Mutual Information Models

Conventional methods used to characterize multidimensional neural feature selectivity, such as spike-triggered covariance (STC) or maximally informative dimensions (MID), are limited to Gaussian stimuli or are only able to identify a small number of features due to the curse of dimensionality. To overcome these issues, we propose two new dimensionality reduction methods that use minimum and maximum information models. These methods are information theoretic extensions of STC that can be used with non-Gaussian stimulus distributions to find relevant linear subspaces of arbitrary dimensionality. We compare these new methods to the conventional methods in two ways: with biologically-inspired simulated neurons responding to natural images and with recordings from macaque retinal and thalamic cells responding to naturalistic time-varying stimuli. With non-Gaussian stimuli, the minimum and maximum information methods significantly outperform STC in all cases, whereas MID performs best in the regime of low dimensional feature spaces

Does the association of education with breast cancer replicate within twin pairs? A register-based study on Danish female twins

A positive association between socio-economic position and breast cancer has been widely observed, but not hitherto within twin pairs, where shared familial factors were adjusted for

A Motion Illusion Reveals Mechanisms of Perceptual Stabilization

Visual illusions are valuable tools for the scientific examination of the mechanisms underlying perception. In the peripheral drift illusion special drift patterns appear to move although they are static. During fixation small involuntary eye movements generate retinal image slips which need to be suppressed for stable perception. Here we show that the peripheral drift illusion reveals the mechanisms of perceptual stabilization associated with these micromovements. In a series of experiments we found that illusory motion was only observed in the peripheral visual field. The strength of illusory motion varied with the degree of micromovements. However, drift patterns presented in the central (but not the peripheral) visual field modulated the strength of illusory peripheral motion. Moreover, although central drift patterns were not perceived as moving, they elicited illusory motion of neutral peripheral patterns. Central drift patterns modulated illusory peripheral motion even when micromovements remained constant. Interestingly, perceptual stabilization was only affected by static drift patterns, but not by real motion signals. Our findings suggest that perceptual instabilities caused by fixational eye movements are corrected by a mechanism that relies on visual rather than extraretinal (proprioceptive or motor) signals, and that drift patterns systematically bias this compensatory mechanism. These mechanisms may be revealed by utilizing static visual patterns that give rise to the peripheral drift illusion, but remain undetected with other patterns. Accordingly, the peripheral drift illusion is of unique value for examining processes of perceptual stabilization

A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation

Integrin signaling regulates cell migration and plays a pivotal role in developmental processes and cancer metastasis. Integrin signaling has been studied extensively and much data is available on pathway components and interactions. Yet the data is fragmented and an integrated model is missing. We use a rule-based modeling approach to integrate available data and test biological hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. The detailed biochemical characterization of integrin signaling provides us with measured values for most of the kinetics parameters. However, measurements are not fully accurate and the cellular concentrations of signaling proteins are largely unknown and expected to vary substantially across different cellular conditions. By sampling model behaviors over the physiologically realistic parameter range we find that the model exhibits only two different qualitative behaviours and these depend mainly on the relative protein concentrations, which offers a powerful point of control to the cell. Our study highlights the necessity to characterize model behavior not for a single parameter optimum, but to identify parameter sets that characterize different signaling modes

Quantitative trace analysis of a broad range of antiviral drugs in poultry muscle using column-switch liquid chromatography coupled to tandem mass spectrometry

A liquid chromatography–tandem mass spectrometry method for the analysis of seven antiviral drugs, zanamivir, ribavirin, oseltamivir, oseltamivir carboxylate, amantadine, rimantadine and arbidol, in poultry muscle is reported. The antiviral drugs were extracted from the homogenized poultry muscle sample using methanol. The extract was purified using tandem solid-phase extraction combining a cation exchange cartridge and a phenylboronic acid cartridge. To prevent excessive matrix effects, the analytes were separated from the matrix constituents using a column-switch liquid chromatography system combining a reversed-phase and a Hypercarb analytical column. Detection was carried out using tandem mass spectrometry. The method was fully validated according to 2002/657/EC [1] and proved to be adequate for quantification and confirmation of zanamivir and ribavirin at 10 μg kg−1, oseltamivir, oseltamivir carboxylate, amantadine and rimantadine at levels below 1.0 μg kg−1 and for qualitative confirmatory analysis of arbidol at levels below 1 μg kg−1

Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.</p> <p>Methods/Design</p> <p>This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (¹²⁵I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with ¹²⁵I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during ¹²⁵I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.</p> <p>The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.</p> <p>Discussion</p> <p>To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.</p> <p>Trial registration</p> <p>UMIN000003992</p

A Novel Pseudopodial Component of the Dendritic Cell Anti-Fungal Response: The Fungipod

Fungal pathologies are seen in immunocompromised and healthy humans. C-type lectins expressed on immature dendritic cells (DC) recognize fungi. We report a novel dorsal pseudopodial protrusion, the “fungipod”, formed by DC after contact with yeast cell walls. These structures have a convoluted cell-proximal end and a smooth distal end. They persist for hours, exhibit noticeable growth and total 13.7±5.6 µm long and 1.8±0.67 µm wide at the contact. Fungipods contain clathrin and an actin core surrounded by a sheath of cortactin. The actin cytoskeleton, but not microtubules, is required for fungipod integrity and growth. An apparent rearward flow (225±55 nm/second) exists from the zymosan contact site into the distal fungipod. The phagocytic receptor Dectin-1 is not required for fungipod formation, but CD206 (Mannose Receptor) is the generative receptor for these protrusions. The human pathogen Candida parapsilosis induces DC fungipod formation strongly, but the response is species specific since the related fungal pathogens Candida tropicalis and Candida albicans induce very few and no fungipods, respectively. Our findings show that fungipods are dynamic actin-driven cellular structures involved in fungal recognition by DC. They may promote yeast particle phagocytosis by DC and are a specific response to large (i.e., 5 µm) particulate ligands. Our work also highlights the importance of this novel protrusive structure to innate immune recognition of medically significant Candida yeasts in a species specific fashion