Representations of uncertainty in sensorimotor control.

Uncertainty is ubiquitous in our sensorimotor interactions, arising from factors such as sensory and motor noise and ambiguity about the environment. Setting it apart from previous theories, a quintessential property of the Bayesian framework for making inference about the state of world so as to select actions, is the requirement to represent the uncertainty associated with inferences in the form of probability distributions. In the context of sensorimotor control and learning, the Bayesian framework suggests that to respond optimally to environmental stimuli the central nervous system needs to construct estimates of the sensorimotor transformations, in the form of internal models, as well as represent the structure of the uncertainty in the inputs, outputs and in the transformations themselves. Here we review Bayesian inference and learning models that have been successful in demonstrating the sensitivity of the sensorimotor system to different forms of uncertainty as well as recent studies aimed at characterizing the representation of the uncertainty at different computational levels.

Binding of the molecular chaperone αB-crystallin to Aβ amyloid fibrils inhibits fibril elongation.

The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ amyloid fibrils in the extracellular plaques that are characteristic of Alzheimer's disease. We investigated whether this archetypical small heat-shock protein has the ability to interact with Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ(42) fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Aβ(42). Immunoelectron microscopy confirms that binding occurs along the entire length and ends of the fibrils. Investigations into the effect of αB-crystallin on the seeded growth of Aβ fibrils, both in solution and on the surface of a quartz crystal microbalance biosensor, reveal that the binding of αB-crystallin to seed fibrils strongly inhibits their elongation. Because the lag phase in sigmoidal fibril assembly kinetics is dominated by elongation and fragmentation rates, the chaperone mechanism identified here represents a highly effective means to inhibit fibril proliferation. Together with previous observations of αB-crystallin interaction with α-synuclein and insulin fibrils, the results suggest that this mechanism is a generic means of providing molecular chaperone protection against amyloid fibril formation.

Dynamic modulation of detection window in conducting polymer based biosensors.

Here we demonstrate a novel application that employs the ion exchange properties of conducting polymers (CP) to modulate the detection window of a CP based biosensor under electrical stimuli. The detection window can be modulated by electrochemically controlling the degree of swelling of the CP associated with ion transport in and out of the polymer. We show that the modulation in the detection window of a caffeine imprinted polypyrrole biosensor, and by extension other CP based biosensors, can be achieved with this mechanism. Such dynamic modulation in the detection window has great potential for the development of smart biosensors, where the sensitivity of the sensor can be dynamically optimized for a specific test solution.

Rhythm generation in monkey motor cortex explored using pyramidal tract stimulation.

We investigated whether stimulation of the pyramidal tract (PT) could reset the phase of 15-30 Hz beta oscillations observed in the macaque motor cortex. We recorded local field potentials (LFPs) and multiple single-unit activity from two conscious macaque monkeys performing a precision grip task. EMG activity was also recorded from the second animal. Single PT stimuli were delivered during the hold period of the task, when oscillations in the LFP were most prominent. Stimulus-triggered averaging of the LFP showed a phase-locked oscillatory response to PT stimulation. Frequency domain analysis revealed two components within the response: a 15-30 Hz component, which represented resetting of on-going beta rhythms, and a lower frequency 10 Hz response. Only the higher frequency could be observed in the EMG activity, at stronger stimulus intensities than were required for resetting the cortical rhythm. Stimulation of the PT during movement elicited a greatly reduced oscillatory response. Analysis of single-unit discharge confirmed that PT stimulation was capable of resetting periodic activity in motor cortex. The firing patterns of pyramidal tract neurones (PTNs) and unidentified neurones exhibited successive cycles of suppression and facilitation, time locked to the stimulus. We conclude that PTN activity directly influences the generation of the 15-30 Hz rhythm. These PTNs facilitate EMG activity in upper limb muscles, contributing to corticomuscular coherence at this same frequency. Since the earliest oscillatory effect observed following stimulation was a suppression of firing, we speculate that inhibitory feedback may be the key mechanism generating such oscillations in the motor cortex.

Mechanobiology of bone remodelling

Bone as most of living tissues is able, during its entire lifetime, to adapt its internal microstructure and subsequently its associated mechanical properties to the specific mechanical and physiological environment in a process commonly known as bone remodelling. Bone is therefore continuously renewed and microdamage removed minimizing the risk of fracture. Bone remodelling is controlled by mechanical and metabolical stimuli. In this paper, we introduce a new model of bone remodelling that takes into account both types of influences. The predicted results show a good correspondence with experimental and clinical data. For example, in disuse, bone porosity increases until an equilibrium situation, while, in overloading, decreases unless the damage rate is so high that causes resorption and "stress fracture". This model has been employed to predict bone adaptation in the proximal femur after total hip replacement proving its consistence and good correspondence with well-known clinical experiences.

Paradoxical evidence integration in rapid decision processes

Decisions about noisy stimuli require evidence integration over time. Traditionally, evidence integration and decision making are described as a one-stage process: a decision is made when evidence for the presence of a stimulus crosses a threshold. Here, we show that one-stage models cannot explain psychophysical experiments on feature fusion, where two visual stimuli are presented in rapid succession. Paradoxically, the second stimulus biases decisions more strongly than the first one, contrary to predictions of one-stage models and intuition. We present a two-stage model where sensory information is integrated and buffered before it is fed into a drift diffusion process. The model is tested in a series of psychophysical experiments and explains both accuracy and reaction time distributions. © 2012 Rüter et al.

The effect of remodelling and contractility of the actin cytoskeleton on the shear resistance of single cells: a computational and experimental investigation.

The biomechanisms that govern the response of chondrocytes to mechanical stimuli are poorly understood. In this study, a series of in vitro tests are performed, in which single chondrocytes are subjected to shear deformation by a horizontally moving probe. Dramatically different probe force-indentation curves are obtained for untreated cells and for cells in which the actin cytoskeleton has been disrupted. Untreated cells exhibit a rapid increase in force upon probe contact followed by yielding behaviour. Cells in which the contractile actin cytoskeleton was removed exhibit a linear force-indentation response. In order to investigate the mechanisms underlying this behaviour, a three-dimensional active modelling framework incorporating stress fibre (SF) remodelling and contractility is used to simulate the in vitro tests. Simulations reveal that the characteristic force-indentation curve observed for untreated chondrocytes occurs as a result of two factors: (i) yielding of SFs due to stretching of the cytoplasm near the probe and (ii) dissociation of SFs due to reduced cytoplasm tension at the front of the cell. In contrast, a passive hyperelastic model predicts a linear force-indentation curve similar to that observed for cells in which the actin cytoskeleton has been disrupted. This combined modelling-experimental study offers a novel insight into the role of the active contractility and remodelling of the actin cytoskeleton in the response of chondrocytes to mechanical loading.

Neural representations of courtship song in the Drosophila brain.

Acoustic communication in drosophilid flies is based on the production and perception of courtship songs, which facilitate mating. Despite decades of research on courtship songs and behavior in Drosophila, central auditory responses have remained uncharacterized. In this study, we report on intracellular recordings from central neurons that innervate the Drosophila antennal mechanosensory and motor center (AMMC), the first relay for auditory information in the fly brain. These neurons produce graded-potential (nonspiking) responses to sound; we compare recordings from AMMC neurons to extracellular recordings of the receptor neuron population [Johnston's organ neurons (JONs)]. We discover that, while steady-state response profiles for tonal and broadband stimuli are significantly transformed between the JON population in the antenna and AMMC neurons in the brain, transient responses to pulses present in natural stimuli (courtship song) are not. For pulse stimuli in particular, AMMC neurons simply low-pass filter the receptor population response, thus preserving low-frequency temporal features (such as the spacing of song pulses) for analysis by postsynaptic neurons. We also compare responses in two closely related Drosophila species, Drosophila melanogaster and Drosophila simulans, and find that pulse song responses are largely similar, despite differences in the spectral content of their songs. Our recordings inform how downstream circuits may read out behaviorally relevant information from central neurons in the AMMC.

Probabilistic computation in human perception under variability in encoding precision.

A key function of the brain is to interpret noisy sensory information. To do so optimally, observers must, in many tasks, take into account knowledge of the precision with which stimuli are encoded. In an orientation change detection task, we find that encoding precision does not only depend on an experimentally controlled reliability parameter (shape), but also exhibits additional variability. In spite of variability in precision, human subjects seem to take into account precision near-optimally on a trial-to-trial and item-to-item basis. Our results offer a new conceptualization of the encoding of sensory information and highlight the brain's remarkable ability to incorporate knowledge of uncertainty during complex perceptual decision-making.

Does precision decrease with set size?

The brain encodes visual information with limited precision. Contradictory evidence exists as to whether the precision with which an item is encoded depends on the number of stimuli in a display (set size). Some studies have found evidence that precision decreases with set size, but others have reported constant precision. These groups of studies differed in two ways. The studies that reported a decrease used displays with heterogeneous stimuli and tasks with a short-term memory component, while the ones that reported constancy used homogeneous stimuli and tasks that did not require short-term memory. To disentangle the effects of heterogeneity and short-memory involvement, we conducted two main experiments. In Experiment 1, stimuli were heterogeneous, and we compared a condition in which target identity was revealed before the stimulus display with one in which it was revealed afterward. In Experiment 2, target identity was fixed, and we compared heterogeneous and homogeneous distractor conditions. In both experiments, we compared an optimal-observer model in which precision is constant with set size with one in which it depends on set size. We found that precision decreases with set size when the distractors are heterogeneous, regardless of whether short-term memory is involved, but not when it is homogeneous. This suggests that heterogeneity, not short-term memory, is the critical factor. In addition, we found that precision exhibits variability across items and trials, which may partly be caused by attentional fluctuations.

A neurophysiologically plausible population code model for feature integration explains visual crowding.

An object in the peripheral visual field is more difficult to recognize when surrounded by other objects. This phenomenon is called "crowding". Crowding places a fundamental constraint on human vision that limits performance on numerous tasks. It has been suggested that crowding results from spatial feature integration necessary for object recognition. However, in the absence of convincing models, this theory has remained controversial. Here, we present a quantitative and physiologically plausible model for spatial integration of orientation signals, based on the principles of population coding. Using simulations, we demonstrate that this model coherently accounts for fundamental properties of crowding, including critical spacing, "compulsory averaging", and a foveal-peripheral anisotropy. Moreover, we show that the model predicts increased responses to correlated visual stimuli. Altogether, these results suggest that crowding has little immediate bearing on object recognition but is a by-product of a general, elementary integration mechanism in early vision aimed at improving signal quality.

The Silent Period of Evidence Integration in Fast Decision Making

In a typical experiment on decision making, one out of two possible stimuli is displayed and observers decide which one was presented. Recently, Stanford and colleagues (2010) introduced a new variant of this classical one-stimulus presentation paradigm to investigate the speed of decision making. They found evidence for "perceptual decision making in less than 30 ms". Here, we extended this one-stimulus compelled-response paradigm to a two-stimulus compelled-response paradigm in which a vernier was followed immediately by a second vernier with opposite offset direction. The two verniers and their offsets fuse. Only one vernier is perceived. When observers are asked to indicate the offset direction of the fused vernier, the offset of the second vernier dominates perception. Even for long vernier durations, the second vernier dominates decisions indicating that decision making can take substantial time. In accordance with previous studies, we suggest that our results are best explained with a two-stage model of decision making where a leaky evidence integration stage precedes a race-to-threshold process. © 2013 Rüter et al.