The Impact of Strategic Trajectory Optimization on Illusory Target Biases During Goal-Directed Aiming

During rapid aiming, movements are planned and executed to avoid worst-case outcomes that require time and energy to correct. As such, downward movements initially undershoot the target to avoid corrections against gravity. Illusory target context can also impact aiming bias. Here, the authors sought to determine how strategic biases mediate illusory biases. Participants aimed to Müller-Lyer figures in different directions (forward, backward, up, down). Downward biases emerged late in the movement and illusory biases emerged from peak velocity. The illusory effects were greater for downward movements at terminal endpoint. These results indicate that strategic biases interact with the limb-target control processes associated with illusory biases. Thus, multiple control processes during rapid aiming may combine and later affect endpoint accuracy (D. Elliott et al., 2010)

The Influence of Visual Feedback and Prior Knowledge About Feedback on Vertical Aiming Strategies

Two experiments were conducted to examine time and energy optimization strategies for movements made with and against gravity. In Experiment 1, we manipulated concurrent visual feedback, and knowledge about feedback. When vision was eliminated upon movement initiation, participants exhibited greater undershooting, both with their primary submovement and their final endpoint, than when vision was available. When aiming downward, participants were more likely to terminate their aiming following the primary submovement or complete a lower amplitude corrective submovement. This strategy reduced the frequency of energy-consuming corrections against gravity. In Experiment 2, we eliminated vision of the hand and the target at the end of the movement. This procedure was expected to have its greatest impact under no vision conditions where no visual feedback was available for subsequent planning. As anticipated, direction and concurrent visual feedback had a profound impact on endpoint bias. Participants exhibited pronounced undershooting when aiming downward and without vision. Differences in undershooting between vision and no vision were greater under blocked feedback conditions. When performers were uncertain about the impending feedback, they planned their movements for the worst-case scenario. Thus movement planning considers the variability in execution, and avoids outcomes that require time and energy to correct

Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed

The Multiple Process Model of Goal-directed Reaching Revisited

Recently our group forwarded a model of speed-accuracy relations in goal-directed reaching. A fundamental feature of our multiple process model was the distinction between two types of online regulation: impulse control and limb-target control. Impulse control begins during the initial stages of the movement trajectory and involves a comparison of actual limb velocity and direction to an internal representation of expectations about the limb trajectory. Limb-target control involves discrete error-reduction based on the relative positions of the limb and the target late in the movement. Our model also considers the role of eye movements, practice, energy optimization and strategic behavior in limb control. Here, we review recent work conducted to test specific aspects of our model. As well, we consider research not fully incorporated into our earlier contribution. We conclude that a slightly modified and expanded version of our model, that includes crosstalk between the two forms of online regulation, does an excellent job of explaining speed, accuracy, and energy optimization in goal-directed reaching

Dual coding with STDP in a spiking recurrent neural network model of the hippocampus.

The firing rate of single neurons in the mammalian hippocampus has been demonstrated to encode for a range of spatial and non-spatial stimuli. It has also been demonstrated that phase of firing, with respect to the theta oscillation that dominates the hippocampal EEG during stereotype learning behaviour, correlates with an animal's spatial location. These findings have led to the hypothesis that the hippocampus operates using a dual (rate and temporal) coding system. To investigate the phenomenon of dual coding in the hippocampus, we examine a spiking recurrent network model with theta coded neural dynamics and an STDP rule that mediates rate-coded Hebbian learning when pre- and post-synaptic firing is stochastic. We demonstrate that this plasticity rule can generate both symmetric and asymmetric connections between neurons that fire at concurrent or successive theta phase, respectively, and subsequently produce both pattern completion and sequence prediction from partial cues. This unifies previously disparate auto- and hetero-associative network models of hippocampal function and provides them with a firmer basis in modern neurobiology. Furthermore, the encoding and reactivation of activity in mutually exciting Hebbian cell assemblies demonstrated here is believed to represent a fundamental mechanism of cognitive processing in the brain

Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation

<p>Abstract</p> <p>Background</p> <p>Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF) function in a von Hippel-Lindau (VHL) independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC) progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC.</p> <p>Methods</p> <p>Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589.</p> <p>Results</p> <p>The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays.</p> <p>Conclusions</p> <p>We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression.</p

25th Annual Computational Neuroscience Meeting: CNS-2016

Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201

The type 1 submovement conundrum: an investigation into the function of velocity zero-crossings within two-component aiming movements

In rapid manual aiming, traditional wisdom would have it that two components manifest from feedback-based processes, where error accumulated within the primary submovement can be corrected within the secondary submovement courtesy of online sensory feedback. In some aiming contexts, there are more type 1 submovements (overshooting) compared to types 2 and 3 submovements (undershooting); particularly for more rapid movements. These particular submovements have also been attributed to a mechanical artefact involving movement termination and stabilization. Hence, the goal of our study was to more closely examine the function of type 1 submovements by revisiting some of our previous datasets. We categorised these submovements according to whether the secondary submovement moved the limb closer (functional), or not (non-functional), to the target. Overall, there were both functional and non-functional submovements with a significantly higher proportion for the former. The displacement at the primary and secondary submovements, and negative velocity peak were significantly greater in the functional compared to non-functional. The influence of submovement type on other movement characteristics, including movement time, was somewhat less clear. These findings indicate that the majority of type 1 submovements are related to intended feedforward- and/or feedback-based processes, although there are a portion that can be attributed an indirect manifestation of a mechanical artefact. As a result, we suggest that submovements should be further categorised by their error-reducing function

The multiple process model of goal-directed aiming/reaching: insights on limb control from various special populations

Several years ago, our research group forwarded a model of goal-directed reaching and aiming that describes the processes involved in the optimization of speed, accuracy, and energy expenditure Elliott et al. (Psychol Bull 136:1023–1044, 2010). One of the main features of the model is the distinction between early impulse control, which is based on a comparison of expected to perceived sensory consequences, and late limb-target control that involves a spatial comparison of limb and target position. Our model also emphasizes the importance of strategic behaviors that limit the opportunity for worst-case or inefficient outcomes. In the 2010 paper, we included a section on how our model can be used to understand atypical aiming/reaching movements in a number of special populations. In light of a recent empirical and theoretical update of our model Elliott et al. (Neurosci Biobehav Rev 72:95-110, 2017), here we consider contemporary motor control work involving typical aging, Down syndrome, autism spectrum disorder, and tetraplegia with tendon-transfer surgery. We outline how atypical limb control can be viewed within the context of the multiple-process model of goal-directed reaching and aiming, and discuss the underlying perceptual-motor impairment that results in the adaptive solution developed by the specific group