Another test of the passive facial feedback hypothesis: when your face smiles, you feel happy.

88 undergraduates (44 men, 44 women) participated in an experiment to examine whether the cutaneous sensation of having the cheeks lifted would cause a feeling of happiness. Two types of paired adhesive bandages connected with rubber bands were prepared and used either to raise or lower the cheeks. While the bandages were applied, the participants rated their feelings. The results showed that 50 participants felt happiness when their cheeks were lifted, statistically significant compared to the 27 who felt sadness. They confirmed the hypothesis that people may feel happy when their cheeks are lifted upward.

Variable practice versus constant practice in the acquisition of wheelchair propulsive speeds.

Previous studies have demonstrated that varied practice (involving several versions of a skill) has advantage over constant practice (involving only one version of a skill) in learning a motor skill. However, the support for variable practice mainly came from studies using discrete motor skills. Therefore, the purpose of the study was to assess if variable practice was more effective than constant practice for the purpose of learning a continuous and real-life motor skill: wheelchair propulsion. A total of 36 able-bodied undergraduate students participated in this study. There were two constant-practice groups. One group practiced wheelchair propulsion on a roller system with a single speed, 30% of the maximum speed (30%-only group), and one group practiced using 55% of the maximum speed (55%-only group). One variable-practice group (variable group) practiced the propulsion with two different speeds, 30 and 55% of the maximum speed. In addition to retention tests, two transfer tests (i.e., tests on 40 and 70% of the maximum speeds) were performed by the three groups after the 10 weeks of training. The results were mixed. The variable-practice group produced significantly fewer absolute errors on both transfer tests than the 30%-only group. However, when compared to the 55%-only group, the variable-practice group only produced significantly fewer absolute errors on the transfer test at 70% speed, but not at 40% speed.

Predicting the unpredictable: weighted averaging of past stimulus timing facilitates ocular pursuit of randomly timed stimuli.

In motor control, prediction of future events is vital for overcoming sensory-motor processing delays and facilitating rapid and accurate responses in a dynamic environment. In human ocular pursuit this is so pervasive that prediction of future target motion cannot easily be eliminated by randomizing stimulus parameters. We investigated the prediction of temporally randomized events during pursuit of alternating constant-velocity (ramp) stimuli in which the timing of direction changes varied unpredictably over a given range. Responses were not reactive; instead, smooth eye velocity began to decelerate in anticipation of each target reversal. In the first experiment, using a continuous-motion stimulus, we found that the time at which this occurred was relatively constant regardless of ramp duration, but increased as mean ramp duration of the range increased. Regression analysis revealed a quantitative association between deceleration timing and the previous two or three ramp durations in a trial, suggesting that recent stimulus history was used to create a running average of anticipatory timing. In the second experiment, we used discrete motion stimuli, with intervening periods of fixation, which allowed both target velocity and reversal timing to be varied, thereby decoupling ramp duration and displacement. This enabled us to confirm that the timing of anticipatory deceleration was based on the history of timing, rather than displacement, within the stimulus. We conclude that this strategy is used to minimize error amid temporal uncertainty, while simultaneously overcoming inherent delays in visuomotor processing.

Control of a brain-computer interface without spike sorting.

Two rhesus monkeys were trained to move a cursor using neural activity recorded with silicon arrays of 96 microelectrodes implanted in the primary motor cortex. We have developed a method to extract movement information from the recorded single and multi-unit activity in the absence of spike sorting. By setting a single threshold across all channels and fitting the resultant events with a spline tuning function, a control signal was extracted from this population using a Bayesian particle-filter extraction algorithm. The animals achieved high-quality control comparable to the performance of decoding schemes based on sorted spikes. Our results suggest that even the simplest signal processing is sufficient for high-quality neuroprosthetic control.

Enhanced Stat3 activation in POMC neurons provokes negative feedback inhibition of leptin and insulin signaling in obesity.

Leptin-stimulated Stat3 activation in proopiomelanocortin (POMC)-expressing neurons of the hypothalamus plays an important role in maintenance of energy homeostasis. While Stat3 activation in POMC neurons is required for POMC expression, the role of elevated basal Stat3 activation as present in the development of obesity has not been directly addressed. Here, we have generated and characterized mice expressing a constitutively active version of Stat3 (Stat3-C) in POMC neurons (Stat3-C(POMC) mice). On normal chow diet, these animals develop obesity as a result of hyperphagia and decreased POMC expression accompanied by central leptin and insulin resistance. This unexpected finding coincides with POMC-cell-specific, Stat3-mediated upregulation of SOCS3 expression inhibiting both leptin and insulin signaling as insulin-stimulated PIP(3) (phosphatidylinositol-3,4,5 triphosphate) formation and protein kinase B (AKT) activation in POMC neurons as well as with the fact that insulin's ability to hyperpolarize POMC neurons is largely reduced in POMC cells of Stat3-C(POMC) mice. These data indicate that constitutive Stat3 activation is not sufficient to promote POMC expression but requires simultaneous PI3K (phosphoinositide 3-kinase)-dependent release of FOXO1 repression. In contrast, upon exposure to a high-fat diet, food intake and body weight were unaltered in Stat3-C(POMC) mice compared with control mice. Taken together, these experiments directly demonstrate that enhanced basal Stat3 activation in POMC neurons as present in control mice upon high-fat feeding contributes to the development of hypothalamic leptin and insulin resistance.

Feedback control of the neuromusculoskeletal system in a forward dynamics simulation of stair locomotion.

The aim of this study is to employ feedback control loops to provide a stable forward dynamics simulation of human movement under repeated position constraint conditions in the environment, particularly during stair climbing. A ten-degrees-of-freedom skeletal model containing 18 Hill-type musculotendon actuators per leg was employed to simulate the model in the sagittal plane. The postural tracking and obstacle avoidance were provided by the proportional-integral-derivative controller according to the modulation of the time rate change of the joint kinematics. The stability of the model was maintained by controlling the velocity of the body's centre of mass according to the desired centre of pressure during locomotion. The parameters of the proposed controller were determined by employing the iterative feedback tuning approach to minimize tracking errors during forward dynamics simulation. Simultaneously, an inverse-dynamics-based optimization was employed to compute a set of desired musculotendon forces in the closed-loop simulation to resolve muscle redundancy. Quantitative comparisons of the simulation results with the experimental measurements and the reference muscles' activities illustrate the accuracy and efficiency of the proposed method during the stable ascending simulation.

Confidence and corrections: how we make and un-make up our minds.

Single neurons in several brain areas intervening between sensation and action signal the accumulation of sensory evidence favoring a particular behavioral response. Two new studies show that these same neurons encode decision confidence and that decision makers continue to process relevant sensory information even after a choice has been made.

Enhanced tubuloglomerular feedback in mice with vascular overexpression of A1 adenosine receptors.

Adenosine 1 receptors (A1AR) in the kidney are expressed in the vasculature and the tubular system. Pharmacological inhibition or global genetic deletion of A1AR causes marked reductions or abolishment of tubuloglomerular feedback (TGF) responses. To assess the function of vascular A1AR in TGF, we generated transgenic mouse lines in which A1AR expression in smooth muscle was augmented by placing A1AR under the control of a 5.38-kb fragment of the rat smooth muscle alpha-actin promoter and first intron (12). Two founder lines with highest expression in the kidney [353 +/- 42 and 575 +/- 43% compared with the wild type (WT)] were used in the experiments. Enhanced expression of A1AR at the expected site in these lines was confirmed by augmented constrictor responses of isolated afferent arterioles to administration of the A1AR agonist N6-cyclohexyladenosine. Maximum TGF responses (0-30 nl/min flow step) were increased from 8.4 +/- 0.9 mmHg in WT (n = 21) to 14.2 +/- 0.7 mmHg in A1AR-transgene (tg) 4 (n = 22; P < 0.0001), and to 12.6 +/- 1.2 mmHg in A1AR-tg7 (n = 12; P < 0.02). Stepwise changes in perfusion flow caused greater numerical TGF responses in A1AR-tg than WT in all flow ranges with differences reaching levels of significance in the intermediate flow ranges of 7.5-10 and 10-15 nl/min. Proximal-distal single-nephron glomerular filtration rate (SNGFR) differences (free-flow micropuncture) were also increased in A1AR-tg, averaging 6.25 +/- 1.5 nl/min compared with 2.6 +/- 0.51 nl/min in WT (P = 0.034). Basal plasma renin concentrations as well as the suppression of renin secretion after volume expansion were similar in A1AR-tg and WT mice, suggesting lack of transgene expression in juxtaglomerular cells. These data indicate that A1AR expression in vascular smooth muscle cells is a critical component for TGF signaling and that changes in renal vascular A1AR expression may determine the magnitude of TGF responses.

[Neurophysiological investigations of information processing in the somato-sensory system]. / Neurophysiologische Untersuchungen zur Informationsverarbeitung im somatosensiblen System.

The ability of the human hand to perform complex sensorimotor tasks such as tactile exploration and grasping is based on 1. exact encoding of somatosensory information by cutaneous mechanoreceptors, 2. elaborated processing of afferent signals in somatosensory relay stations and cortex fields, 3. rapid and effective interaction of sensory feedback with motor programs, and 4. different modes of sensory control, which can be switched over.

Feedback control of regulatory T cell homeostasis by dendritic cells in vivo.

CD4(+)CD25(+)Foxp3(+) natural regulatory T cells (T reg cells) maintain self-tolerance and suppress autoimmune diseases such as type 1 diabetes and inflammatory bowel disease (IBD). In addition to their effects on T cells, T reg cells are essential for maintaining normal numbers of dendritic cells (DCs): when T reg cells are depleted, there is a compensatory Flt3-dependent increase in DCs. However, little is known about how T reg cell homeostasis is maintained in vivo. We demonstrate the existence of a feedback regulatory loop between DCs and T reg cells. We find that loss of DCs leads to a loss of T reg cells, and that the remaining T reg cells exhibit decreased Foxp3 expression. The DC-dependent loss in T reg cells leads to an increase in the number of T cells producing inflammatory cytokines, such as interferon gamma and interleukin 17. Conversely, increasing the number of DCs leads to increased T reg cell division and accumulation by a mechanism that requires major histocompatibility complex II expression on DCs. The increase in T reg cells induced by DC expansion is sufficient to prevent type 1 autoimmune diabetes and IBD, which suggests that interference with this feedback loop will create new opportunities for immune-based therapies.

Generalized neuron: feedforward and recurrent architectures.

Feedforward neural networks such as multilayer perceptrons (MLP) and recurrent neural networks are widely used for pattern classification, nonlinear function approximation, density estimation and time series prediction. A large number of neurons are usually required to perform these tasks accurately, which makes the MLPs less attractive for computational implementations on resource constrained hardware platforms. This paper highlights the benefits of feedforward and recurrent forms of a compact neural architecture called generalized neuron (GN). This paper demonstrates that GN and recurrent GN (RGN) can perform good classification, nonlinear function approximation, density estimation and chaotic time series prediction. Due to two aggregation functions and two activation functions, GN exhibits resilience to the nonlinearities of complex problems. Particle swarm optimization (PSO) is proposed as the training algorithm for GN and RGN. Due to a small number of trainable parameters, GN and RGN require less memory and computational resources. Thus, these structures are attractive choices for fast implementations on resource constrained hardware platforms.

Multiple timescales in postural dynamics associated with vision and a secondary task are revealed by wavelet analysis.

Discrete wavelet analysis is used to resolve the center of pressure time series data into several timescale components, providing new insights into postural control. Healthy young and elderly participants stood quietly with their eyes open or closed and either performed a secondary task or stood quietly. Without vision, both younger and older participants had reduced energy in the long timescales, supporting the concept that vision is used to control low frequency postural sway. Furthermore, energy was increased at timescales corresponding to closed-loop (somatosensory and vestibular) and open-loop mechanisms, consistent with the idea of a shift from visual control to other control mechanisms. However, a relatively greater increase was observed for older adults. With a secondary task a similar pattern was observed-increased energy at the short and moderate timescales, decreased energy at long timescales. The possibility of a common strategy-at the timescale level-in response to postural perturbations is considered.

Multisensory integration in dynamical behaviors: maximum likelihood estimation across bimanual skill learning.

Optimal integration of different sensory modalities weights each modality as a function of its degree of certainty (maximum likelihood). Humans rely on near-optimal integration in decision-making tasks (involving e.g., auditory, visual, and/or tactile afferents), and some support for these processes has also been provided for discrete sensorimotor tasks. Here, we tested optimal integration during the continuous execution of a motor task, using a cyclical bimanual coordination pattern in which feedback was provided by means of proprioception and augmented visual feedback (AVF, the position of both wrists being displayed as the orthogonal coordinates of a single cursor). Assuming maximum likelihood integration, the following predictions were addressed: (1) the coordination variability with both AVF and proprioception available is smaller than with only one of the two modalities, and should reach an optimal level; (2) if the AVF is artificially corrupted by noise, variability should increase but saturate toward the level without AVF; (3) if the AVF is imperceptibly phase shifted, the stabilized pattern should be partly adapted to compensate for this phase shift, whereby the amount of compensation reflects the weight assigned to AVF in the computation of the integrated signal. Whereas performance variability gradually decreased over 5 d of practice, we showed that these model-based predictions were already observed on the first day. This suggests not only that the performer integrated proprioceptive feedback and AVF online during task execution by tending to optimize the signal statistics, but also that this occurred before reaching an asymptotic performance level.

Sensory transformations and the use of multiple reference frames for reach planning.

The sensory signals that drive movement planning arrive in a variety of 'reference frames', and integrating or comparing them requires sensory transformations. We propose a model in which the statistical properties of sensory signals and their transformations determine how these signals are used. This model incorporates the patterns of gaze-dependent errors that we found in our human psychophysics experiment when the sensory signals available for reach planning were varied. These results challenge the widely held ideas that error patterns directly reflect the reference frame of the underlying neural representation and that it is preferable to use a single common reference frame for movement planning. We found that gaze-dependent error patterns, often cited as evidence for retinotopic reach planning, can be explained by a transformation bias and are not exclusively linked to retinotopic representations. Furthermore, the presence of multiple reference frames allows for optimal use of available sensory information and explains task-dependent reweighting of sensory signals.

Better learning with more error: probabilistic feedback increases sensitivity to correlated cues in categorization.

Despite the fact that categories are often composed of correlated features, the evidence that people detect and use these correlations during intentional category learning has been overwhelmingly negative to date. Nonetheless, on other categorization tasks, such as feature prediction, people show evidence of correlational sensitivity. A conventional explanation holds that category learning tasks promote rule use, which discards the correlated-feature information, whereas other types of category learning tasks promote exemplar storage, which preserves correlated-feature information. Contrary to that common belief, the authors report 2 experiments that demonstrate that using probabilistic feedback in an intentional categorization task leads to sensitivity to correlations among nondiagnostic cues. Deterministic feedback eliminates correlational sensitivity by focusing attention on relevant cues. Computational modeling reveals that exemplar storage coupled with selective attention is necessary to explain this effect.

Flexibility and practicality graz brain-computer interface approach.

"Graz brain-computer interface (BCI)" transforms changes in oscillatory electroencephalogram (EEG) activity into control signals for external devices and feedback. Steady-state evoked potentials (SSEPs) and event-related desynchronization (ERD) are employed to encode user messages. User-specific setup and training are important issues for robust and reliable classification. Furthermore, in order to implement small and thus affordable systems, focus is put on the minimization of the number of EEG sensors. The system also supports the self-paced operation mode, that is, users have on-demand access to the system at any time and can autonomously initiate communication. Flexibility, usability, and practicality are essential to increase user acceptance. Here, we illustrate the possibilities offered by now from EEG-based communication. Results of several studies with able-bodied and disabled individuals performed inside the laboratory and in real-world environments are presented; their characteristics are shown and open issues are mentioned. The applications include the control of neuroprostheses and spelling devices, the interaction with Virtual Reality, and the operation of off-the-shelf software such as Google Earth.

Micronutrients and amino acids, main regulators of physiological processes.

Human physiology is supposed to be a complex interaction of regulating processes, in which hormones, genes, their proteins and apoptosis are thought to play a dominant role. We hypothesize that regulation of physiological processes is mainly influenced by amino acids and micronutrients with hormones, proteins, apoptosis and gene modifications being their derivatives. Furthermore, we suppose that the cells power plant, the mitochondrion, is in fact an intracellular bacterium, living in absolute symbiosis. Because of its intracellular existence it depends on the host's micronutrients completely. Within the host these micronutrients regulate their own formation, degradation, uptake and excretion. Known deficiencies, such as iodine and vitamin D, affect billions of people. Many micronutrients neither have been investigated, nor have they been studied in relation to each other and solid data are not available. Optimal levels of many micronutrients and all amino acids are not known. Amino acids, vitamins and minerals are capable of altering gene expression, inducing apoptosis and regulating chemical processes. It makes them highly attractive for creating better health, against low cost, as we have already proven in the case of rickets, cretinism and scurvy in severe deficiencies. By creating optimal living conditions and study mitochondria from a symbiotic point of view we suppose that diseases not only can be prevented, but the course of diseases can be altered as well.