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    Assessment of stress responses in rhesus macaques (Macaca mulatta) to daily routine procedures in system neuroscience based on salivary cortisol concentrations 

    Pfefferle, Dana; Plümer, Sina; Burchardt, Leonore; Treue, Stefan; Gail, Alexander
    PLOS ONE 2018; 13(1): Art. e0190190
    Non-human primates participating in neurophysiological research are exposed to potentially stressful experimental procedures, such as dietary control protocols, surgical implants and their maintenance, or social separation during training and experimental session. Here, we investigated the effect of controlled access to fluid, surgical implants, implant-related cleaning of skin margins, and behavioral training sessions on salivary cortisol levels of adult male rhesus macaques participating in neurophysiological research. The animals were trained to chew flavored cotton swabs to non-invasively collect saliva samples. Our data show no differences in cortisol levels between animals with and without implants, but both, controlled access to fluid and cleaning of implants individually increased salivary cortisol concentrations, while both together did not further increase the concentration. Specifically, before cleaning, individuals with controlled access to fluid had 55% higher cortisol concentrations than individuals with free access to fluid. Under free access to fluid, cortisol concentrations were 27% higher after cleaning while no effect of cleaning was found for individuals under controlled fluid access. Training sessions under controlled access to fluid also did not affect salivary cortisol concentrations. The observed changes in cortisol concentrations represent mild stress responses, as they are only a fraction of the range of the regular circadian changes in cortisol levels in rhesus monkeys. They also indicate that combinations of procedures do not necessarily lead to cumulative stress responses. Our results indicate that salivary cortisol levels of rhesus monkeys respond to neurophysiological experimental procedures and, hence, may be used to assess further refinements of such experimental methods.
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    Correlated microtiming deviations in jazz and rock music 

    Sogorski, Mathias; Geisel, Theo; Priesemann, Viola
    PLOS ONE 2018; 13(1): Art. e0186361
    Musical rhythms performed by humans typically show temporal fluctuations. While they have been characterized in simple rhythmic tasks, it is an open question what is the nature of temporal fluctuations, when several musicians perform music jointly in all its natural complexity. To study such fluctuations in over 100 original jazz and rock/pop recordings played with and without metronome we developed a semi-automated workflow allowing the extraction of cymbal beat onsets with millisecond precision. Analyzing the inter-beat interval (IBI) time series revealed evidence for two long-range correlated processes characterized by power laws in the IBI power spectral densities. One process dominates on short timescales (t < 8 beats) and reflects microtiming variability in the generation of single beats. The other dominates on longer timescales and reflects slow tempo variations. Whereas the latter did not show differences between musical genres (jazz vs. rock/pop), the process on short timescales showed higher variability for jazz recordings, indicating that jazz makes stronger use of microtiming fluctuations within a measure than rock/pop. Our results elucidate principles of rhythmic performance and can inspire algorithms for artificial music generation. By studying microtiming fluctuations in original music recordings, we bridge the gap between minimalistic tapping paradigms and expressive rhythmic performances.
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    Model-free inference of direct network interactions from nonlinear collective dynamics. 

    Casadiego, Jose; Nitzan, Mor; Hallerberg, Sarah; Timme, Marc
    Nature Communications 2017; 8(1): Art. 2192
    The topology of interactions in network dynamical systems fundamentally underlies their function. Accelerating technological progress creates massively available data about collective nonlinear dynamics in physical, biological, and technological systems. Detecting direct interaction patterns from those dynamics still constitutes a major open problem. In particular, current nonlinear dynamics approaches mostly require to know a priori a model of the (often high dimensional) system dynamics. Here we develop a model-independent framework for inferring direct interactions solely from recording the nonlinear collective dynamics generated. Introducing an explicit dependency matrix in combination with a block-orthogonal regression algorithm, the approach works reliably across many dynamical regimes, including transient dynamics toward steady states, periodic and non-periodic dynamics, and chaos. Together with its capabilities to reveal network (two point) as well as hypernetwork (e.g., three point) interactions, this framework may thus open up nonlinear dynamics options of inferring direct interaction patterns across systems where no model is known.
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    Neural and Response Correlations to Complex Natural Sounds in the Auditory Midbrain. 

    Lyzwa, Dominika; Wörgötter, Florentin
    Frontiers in neural circuits 2016; 10: Art. 89
    How natural communication sounds are spatially represented across the inferior colliculus, the main center of convergence for auditory information in the midbrain, is not known. The neural representation of the acoustic stimuli results from the interplay of locally differing input and the organization of spectral and temporal neural preferences that change gradually across the nucleus. This raises the question of how similar the neural representation of the communication sounds is across these gradients of neural preferences, and whether it also changes gradually. Analyzed neural recordings were multi-unit cluster spike trains from guinea pigs presented with a spectrotemporally rich set of eleven species-specific communication sounds. Using cross-correlation, we analyzed the response similarity of spiking activity across a broad frequency range for neurons of similar and different frequency tuning. Furthermore, we separated the contribution of the stimulus to the correlations to investigate whether similarity is only attributable to the stimulus, or, whether interactions exist between the multi-unit clusters that lead to neural correlations and whether these follow the same representation as the response correlations. We found that similarity of responses is dependent on the neurons' spatial distance for similarly and differently frequency-tuned neurons, and that similarity decreases gradually with spatial distance. Significant neural correlations exist, and contribute to the total response similarity. Our findings suggest that for multi-unit clusters in the mammalian inferior colliculus, the gradual response similarity with spatial distance to natural complex sounds is shaped by neural interactions and the gradual organization of neural preferences.
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    A Neurocomputational Model of Goal-Directed Navigation in Insect-Inspired Artificial Agents. 

    Goldschmidt, Dennis; Manoonpong, Poramate; Dasgupta, Sakyasingha
    Frontiers in neurorobotics 2017; 11: Art. 20
    Despite their small size, insect brains are able to produce robust and efficient navigation in complex environments. Specifically in social insects, such as ants and bees, these navigational capabilities are guided by orientation directing vectors generated by a process called path integration. During this process, they integrate compass and odometric cues to estimate their current location as a vector, called the home vector for guiding them back home on a straight path. They further acquire and retrieve path integration-based vector memories globally to the nest or based on visual landmarks. Although existing computational models reproduced similar behaviors, a neurocomputational model of vector navigation including the acquisition of vector representations has not been described before. Here we present a model of neural mechanisms in a modular closed-loop control-enabling vector navigation in artificial agents. The model consists of a path integration mechanism, reward-modulated global learning, random search, and action selection. The path integration mechanism integrates compass and odometric cues to compute a vectorial representation of the agent's current location as neural activity patterns in circular arrays. A reward-modulated learning rule enables the acquisition of vector memories by associating the local food reward with the path integration state. A motor output is computed based on the combination of vector memories and random exploration. In simulation, we show that the neural mechanisms enable robust homing and localization, even in the presence of external sensory noise. The proposed learning rules lead to goal-directed navigation and route formation performed under realistic conditions. Consequently, we provide a novel approach for vector learning and navigation in a simulated, situated agent linking behavioral observations to their possible underlying neural substrates.
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    Differential Effects of HCN Channel Block on On and Off Pathways in the Retina as a Potential Cause for Medication-Induced Phosphene Perception. 

    Bemme, Sebastian; Weick, Michael; Gollisch, Tim
    Investigative ophthalmology & visual science 2017-09-01; 58(11) p.4754-4767
    Purpose: Phosphene perception is a characteristic side effect of heart rate-reducing medication that acts on hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels. It is hypothesized that these phosphenes are caused by blocking HCN channels in photoreceptors and neurons of the retina, yet the underlying changes in visual signal processing in the retina caused by the HCN channel block are still unknown. Methods: We examined the effects of pharmacologic HCN channel block on the encoding of visual signals in retinal ganglion cells by recording ganglion cell spiking activity from isolated mouse retinas mounted on multielectrode arrays. Spontaneous activity and responses to various visual stimuli were measured before, during, and after administration of 3 μM ivabradine. Results: Retinal ganglion cells generally showed slower response kinetics and reduced sensitivity to high temporal frequencies under ivabradine. Moreover, ivabradine differentially affected the sensitivity of On and Off ganglion cells. On cells showed reduced response gain, whereas Off cells experienced an increase in response threshold. In line with these differential effects, Off cells, in contrast to On cells, also showed reduced baseline activity during visual stimulation and reduced spontaneous activity. Furthermore, Off cells, but not On cells, showed increased burst-like spiking activity in the presence of ivabradine. Conclusions: Our data suggest that pharmacologic HCN channel block in the retina leads to a shift in the relative activity of the On and Off pathways of the retina. We hypothesize that this imbalance may underlie the medication-induced perception of phosphenes.
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    Environmental enrichment accelerates ocular dominance plasticity in mouse visual cortex whereas transfer to standard cages resulted in a rapid loss of increased plasticity. 

    Kalogeraki, Evgenia; Pielecka-Fortuna, Justyna; Löwel, Siegrid
    PloS one 2017; 12(10): Art. e0186999
    In standard cage (SC) raised mice, experience-dependent ocular dominance (OD) plasticity in the primary visual cortex (V1) rapidly declines with age: in postnatal day 25-35 (critical period) mice, 4 days of monocular deprivation (MD) are sufficient to induce OD-shifts towards the open eye; thereafter, 7 days of MD are needed. Beyond postnatal day 110, even 14 days of MD failed to induce OD-plasticity in mouse V1. In contrast, mice raised in a so-called "enriched environment" (EE), exhibit lifelong OD-plasticity. EE-mice have more voluntary physical exercise (running wheels), and experience more social interactions (bigger housing groups) and more cognitive stimulation (regularly changed labyrinths or toys). Whether experience-dependent shifts of V1-activation happen faster in EE-mice and how long the plasticity promoting effect would persist after transferring EE-mice back to SCs has not yet been investigated. To this end, we used intrinsic signal optical imaging to visualize V1-activation i) before and after MD in EE-mice of different age groups (from 1-9 months), and ii) after transferring mice back to SCs after postnatal day 130. Already after 2 days of MD, and thus much faster than in SC-mice, EE-mice of all tested age groups displayed a significant OD-shift towards the open eye. Transfer of EE-mice to SCs immediately abolished OD-plasticity: already after 1 week of SC-housing and MD, OD-shifts could no longer be visualized. In an attempt to rescue abolished OD-plasticity of these mice, we either administered the anti-depressant fluoxetine (in drinking water) or supplied a running wheel in the SCs. OD-plasticity was only rescued for the running wheel- mice. Altogether our results show that raising mice in less deprived environments like large EE-cages strongly accelerates experience-dependent changes in V1-activation compared to the impoverished SC-raising. Furthermore, preventing voluntary physical exercise of EE-mice in adulthood immediately precludes OD-shifts in V1.
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    Compromised neuroplasticity in cigarette smokers under nicotine withdrawal is restituted by the nicotinic α4β2-receptor partial agonist varenicline 

    Batsikadze, G.; Paulus, W.; Hasan, A.; Grundey, J.; Kuo, M.-F.; Nitsche, M. A.
    Scientific Reports 2017; 7(1): Art. 1387
    Nicotine modulates neuroplasticity and improves cognitive functions in animals and humans. In the brain of smoking individuals, calcium-dependent plasticity induced by non-invasive brain stimulation methods such as transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS) is impaired by nicotine withdrawal, but partially re-established after nicotine re-administration. In order to investigate the underlying mechanism further, we tested the impact of the α4β2-nicotinic receptor partial agonist varenicline on focal and non-focal plasticity in smokers during nicotine withdrawal, induced by PAS and tDCS, respectively. We administered low (0.3 mg) and high (1.0 mg) single doses of varenicline or placebo medication before stimulation over the left motor cortex of 20 healthy smokers under nicotine withdrawal. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor evoked potential amplitudes for 36 hours after plasticity induction. Stimulation-induced plasticity was absent under placebo medication, whereas it was present in all conditions under high dose. Low dose restituted only tDCS-induced non-focal plasticity, producing no significant impact on focal plasticity. High dose varenicline also prolonged inhibitory plasticity. These results are comparable to the impact of nicotine on withdrawal-related impaired plasticity in smokers and suggest that α4β2 nicotinic receptors are relevantly involved in plasticity deficits and restitution in smokers.
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    EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons 

    Burk, Katja; Murdoch, John D.; Freytag, Siona; Koenig, Melanie; Bharat, Vinita; Markworth, Ronja; Burkhardt, Susanne; Fischer, Andre; Dean, Camin
    Scientific Reports 2017; 7(1): Art. 2149
    The sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs in sorting of activated BDNF-TrkB receptors into late endosomal compartments. Mice lacking all three EndophilinAs accumulate Rab7-positive late endosomes. Moreover, EndophilinAs are differentially localized to, co-traffic with, and tubulate, distinct endosomal compartments: In response to BDNF, EndophilinA2 is recruited to both early and late endosomes, EndophilinA3 is recruited to Lamp1-positive late endosomes, and co-trafficks with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalizes at lower levels with endosomes. The absence of all three EndophilinAs caused TrkB to accumulate in EEA1 and Rab7-positive endosomes, and impaired BDNF-TrkB-dependent survival signaling cascades. In addition, EndophilinA triple knockout neurons exhibited increased cell death which could not be rescued by exogenous BDNF, in a neurotrophin-dependent survival assay. Thus, EndophilinAs differentially regulate activated receptor sorting via distinct endosomal compartments to promote BDNF-dependent cell survival.
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    Breakdown of local information processing may underlie isoflurane anesthesia effects. 

    Wollstadt, Patricia; Sellers, Kristin K; Rudelt, Lucas; Priesemann, Viola; Hutt, Axel; Fröhlich, Flavio; Wibral, Michael
    PLoS computational biology 2017-06; 13(6): Art. e1005511
    The disruption of coupling between brain areas has been suggested as the mechanism underlying loss of consciousness in anesthesia. This hypothesis has been tested previously by measuring the information transfer between brain areas, and by taking reduced information transfer as a proxy for decoupling. Yet, information transfer is a function of the amount of information available in the information source-such that transfer decreases even for unchanged coupling when less source information is available. Therefore, we reconsidered past interpretations of reduced information transfer as a sign of decoupling, and asked whether impaired local information processing leads to a loss of information transfer. An important prediction of this alternative hypothesis is that changes in locally available information (signal entropy) should be at least as pronounced as changes in information transfer. We tested this prediction by recording local field potentials in two ferrets after administration of isoflurane in concentrations of 0.0%, 0.5%, and 1.0%. We found strong decreases in the source entropy under isoflurane in area V1 and the prefrontal cortex (PFC)-as predicted by our alternative hypothesis. The decrease in source entropy was stronger in PFC compared to V1. Information transfer between V1 and PFC was reduced bidirectionally, but with a stronger decrease from PFC to V1. This links the stronger decrease in information transfer to the stronger decrease in source entropy-suggesting reduced source entropy reduces information transfer. This conclusion fits the observation that the synaptic targets of isoflurane are located in local cortical circuits rather than on the synapses formed by interareal axonal projections. Thus, changes in information transfer under isoflurane seem to be a consequence of changes in local processing more than of decoupling between brain areas. We suggest that source entropy changes must be considered whenever interpreting changes in information transfer as decoupling.
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    What makes a reach movement effortful? Physical effort discounting supports common minimization principles in decision making and motor control. 

    Morel, Pierre; Ulbrich, Philipp; Gail, Alexander
    PLoS biology 2017-06; 15(6): Art. e2001323
    When deciding between alternative options, a rational agent chooses on the basis of the desirability of each outcome, including associated costs. As different options typically result in different actions, the effort associated with each action is an essential cost parameter. How do humans discount physical effort when deciding between movements? We used an action-selection task to characterize how subjective effort depends on the parameters of arm transport movements and controlled for potential confounding factors such as delay discounting and performance. First, by repeatedly asking subjects to choose between 2 arm movements of different amplitudes or durations, performed against different levels of force, we identified parameter combinations that subjects experienced as identical in effort (isoeffort curves). Movements with a long duration were judged more effortful than short-duration movements against the same force, while movement amplitudes did not influence effort. Biomechanics of the movements also affected effort, as movements towards the body midline were preferred to movements away from it. Second, by introducing movement repetitions, we further determined that the cost function for choosing between effortful movements had a quadratic relationship with force, while choices were made on the basis of the logarithm of these costs. Our results show that effort-based action selection during reaching cannot easily be explained by metabolic costs. Instead, force-loaded reaches, a widely occurring natural behavior, imposed an effort cost for decision making similar to cost functions in motor control. Our results thereby support the idea that motor control and economic choice are governed by partly overlapping optimization principles.
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    Working Memory Requires a Combination of Transient and Attractor-Dominated Dynamics to Process Unreliably Timed Inputs. 

    Nachstedt, Timo; Tetzlaff, Christian
    Scientific reports 2017-05-30; 7(1): Art. 2473
    Working memory stores and processes information received as a stream of continuously incoming stimuli. This requires accurate sequencing and it remains puzzling how this can be reliably achieved by the neuronal system as our perceptual inputs show a high degree of temporal variability. One hypothesis is that accurate timing is achieved by purely transient neuronal dynamics; by contrast a second hypothesis states that the underlying network dynamics are dominated by attractor states. In this study, we resolve this contradiction by theoretically investigating the performance of the system using stimuli with differently accurate timing. Interestingly, only the combination of attractor and transient dynamics enables the network to perform with a low error rate. Further analysis reveals that the transient dynamics of the system are used to process information, while the attractor states store it. The interaction between both types of dynamics yields experimentally testable predictions and we show that this way the system can reliably interact with a timing-unreliable Hebbian-network representing long-term memory. Thus, this study provides a potential solution to the long-standing problem of the basic neuronal dynamics underlying working memory.
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    Subsampling scaling 

    Levina, A.; Priesemann, V.
    Nature Communications 2017; 8: Art. 15140
    In real-world applications, observations are often constrained to a small fraction of a system. Such spatial subsampling can be caused by the inaccessibility or the sheer size of the system, and cannot be overcome by longer sampling. Spatial subsampling can strongly bias inferences about a system’s aggregated properties. To overcome the bias, we derive analytically a subsampling scaling framework that is applicable to different observables, including distributions of neuronal avalanches, of number of people infected during an epidemic outbreak, and of node degrees. We demonstrate how to infer the correct distributions of the underlying full system, how to apply it to distinguish critical from subcritical systems, and how to disentangle subsampling and finite size effects. Lastly, we apply subsampling scaling to neuronal avalanche models and to recordings from developing neural networks. We show that only mature, but not young networks follow power-law scaling, indicating self-organization to criticality during development.
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    Fast Dynamical Coupling Enhances Frequency Adaptation of Oscillators for Robotic Locomotion Control 

    Nachstedt, Timo; Tetzlaff, Christian; Manoonpong, Poramate
    Frontiers in Neurorobotics 2017; 11: Art. 14
    Rhythmic neural signals serve as basis of many brain processes, in particular of locomotion control and generation of rhythmic movements. It has been found that specific neural circuits, named central pattern generators (CPGs), are able to autonomously produce such rhythmic activities. In order to tune, shape and coordinate the produced rhythmic activity, CPGs require sensory feedback, i.e., external signals. Nonlinear oscillators are a standard model of CPGs and are used in various robotic applications. A special class of nonlinear oscillators are adaptive frequency oscillators (AFOs). AFOs are able to adapt their frequency toward the frequency of an external periodic signal and to keep this learned frequency once the external signal vanishes. AFOs have been successfully used, for instance, for resonant tuning of robotic locomotion control. However, the choice of parameters for a standard AFO is characterized by a trade-off between the speed of the adaptation and its precision and, additionally, is strongly dependent on the range of frequencies the AFO is confronted with. As a result, AFOs are typically tuned such that they require a comparably long time for their adaptation. To overcome the problem, here, we improve the standard AFO by introducing a novel adaptation mechanism based on dynamical coupling strengths. The dynamical adaptation mechanism enhances both the speed and precision of the frequency adaptation. In contrast to standard AFOs, in this system, the interplay of dynamics on short and long time scales enables fast as well as precise adaptation of the oscillator for a wide range of frequencies. Amongst others, a very natural implementation of this mechanism is in terms of neural networks. The proposed system enables robotic applications which require fast retuning of locomotion control in order to react to environmental changes or conditions.
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    Gender bias in scholarly peer review 

    Helmer, Markus; Schottdorf, Manuel; Neef, Andreas; Battaglia, Demian
    eLife 2017; 6: Art. 21718
    Peer review is the cornerstone of scholarly publishing and it is essential that peer reviewers are appointed on the basis of their expertise alone. However, it is difficult to check for any bias in the peer-review process because the identity of peer reviewers generally remains confidential. Here, using public information about the identities of 9000 editors and 43000 reviewers from the Frontiers series of journals, we show that women are underrepresented in the peer-review process, that editors of both genders operate with substantial same-gender preference (homophily), and that the mechanisms of this homophily are gender-dependent. We also show that homophily will persist even if numerical parity between genders is reached, highlighting the need for increased efforts to combat subtler forms of gender bias in scholarly publishing.
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    Enhanced Locomotion Efficiency of a Bio-inspired Walking Robot using Contact Surfaces with Frictional Anisotropy 

    Manoonpong, Poramate; Petersen, Dennis; Kovalev, Alexander; Wörgötter, Florentin; Gorb, Stanislav N.; Spinner, Marlene; Heepe, Lars
    Scientific Reports 2016; 6: Art. 39455
    Based on the principles of morphological computation, we propose a novel approach that exploits the interaction between a passive anisotropic scale-like material (e.g., shark skin) and a non-smooth substrate to enhance locomotion efficiency of a robot walking on inclines. Real robot experiments show that passive tribologically-enhanced surfaces of the robot belly or foot allow the robot to grip on specific surfaces and move effectively with reduced energy consumption. Supplementing the robot experiments, we investigated tribological properties of the shark skin as well as its mechanical stability. It shows high frictional anisotropy due to an array of sloped denticles. The orientation of the denticles to the underlying collagenous material also strongly influences their mechanical interlocking with the substrate. This study not only opens up a new way of achieving energy-efficient legged robot locomotion but also provides a better understanding of the functionalities and mechanical properties of anisotropic surfaces. That understanding will assist developing new types of material for other realworld applications.
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    Neurons in Primate Visual Cortex Alternate between Responses to Multiple Stimuli in Their Receptive Field 

    Li, Kang; Kozyrev, Vladislav; Kyllingsbæk, Søren; Treue, Stefan; Ditlevsen, Susanne; Bundesen, Claus
    Frontiers in Computational Neuroscience 2016; 10: Art. 141
    A fundamental question concerning representation of the visual world in our brain is how a cortical cell responds when presented with more than a single stimulus. We find supportive evidence that most cells presented with a pair of stimuli respond predominantly to one stimulus at a time, rather than a weighted average response. Traditionally, the firing rate is assumed to be a weighted average of the firing rates to the individual stimuli (response-averaging model) (Bundesen et al., 2005). Here, we also evaluate a probability-mixing model (Bundesen et al., 2005), where neurons temporally multiplex the responses to the individual stimuli. This provides a mechanism by which the representational identity of multiple stimuli in complex visual scenes can be maintained despite the large receptive fields in higher extrastriate visual cortex in primates. We compare the two models through analysis of data from single cells in the middle temporal visual area (MT) of rhesus monkeys when presented with two separate stimuli inside their receptive field with attention directed to one of the two stimuli or outside the receptive field. The spike trains were modeled by stochastic point processes, including memory effects of past spikes and attentional effects, and statistical model selection between the two models was performed by information theoretic measures as well as the predictive accuracy of the models. As an auxiliary measure, we also tested for uni- or multimodality in interspike interval distributions, and performed a correlation analysis of simultaneously recorded pairs of neurons, to evaluate population behavior.
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    Long-term decoding of movement force and direction with a wireless myoelectric implant 

    Morel, Pierre; Ferrea, Enrico; Taghizadeh-Sarshouri, Bahareh; Audí, Josep Marcel Cardona; Ruff, Roman; Hoffmann, Klaus-Peter; Lewis, Sören; Russold, Michael; Dietl, Hans; Abu-Saleh, Lait; et al.
    Schroeder, DietmarKrautschneider, WolfgangMeiners, ThomasGail, Alexander
    Journal of Neural Engineering 2015; 13(1)
    Objective. The ease of use and number of degrees of freedom of current myoelectric hand prostheses is limited by the information content and reliability of the surface electromyography (sEMG) signals used to control them. For example, cross-talk limits the capacity to pick up signals from small or deep muscles, such as the forearm muscles for distal arm amputations, or sites of targeted muscle reinnervation (TMR) for proximal amputations. Here we test if signals recorded from the fully implanted, induction-powered wireless Myoplant system allow longterm decoding of continuous as well as discrete movement parameters with better reliability than equivalent sEMG recordings. The Myoplant system uses a centralized implant to transmit broadband EMG activity from four distributed bipolar epimysial electrodes. Approach. Two Rhesus macaques received implants in their backs, while electrodes were placed in their upper arm. One of the monkeys was trained to do a cursor task via a haptic robot, allowing us to control the forces exerted by the animal during arm movements. The second animal was trained to perform a center-out reaching task on a touchscreen. We compared the implanted system with concurrent sEMG recordings by evaluating our ability to decode time-varying force in one animal and discrete reach directions in the other from multiple features extracted from the raw EMG signals. Main results. In both cases, data from the implant allowed a decoder trained with data from a single day to maintain an accurate decoding performance during the following months, which was not the case for concurrent surface EMG recordings conducted simultaneously over the same muscles. Significance. These results show that a fully implantable,centralized wireless EMG system is particularly suited for long-term stable decoding of dynamic movements in demanding applications such as advanced forelimb prosthetics in a wide range of configurations (distal amputations, TMR).
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    Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit 

    Zampini, Valeria; Liu, Jian K.; Diana, Marco A.; Maldonado, Paloma P.; Brunel, Nicolas; Dieudonné, Stéphane
    eLife 2016; 5
    Synaptic currents display a large degree of heterogeneity of their temporal characteristics, but the functional role of such heterogeneities remains unknown. We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells (UBCs), which generate intrinsic mossy fibers relaying vestibular inputs to the cerebellar cortex. We show that UBCs respond to sinusoidal modulations of their sensory input with heterogeneous amplitudes and phase shifts. Experiments and modeling indicate that this variability results both from the kinetics of synaptic glutamate transients and from the diversity of postsynaptic receptors. While phase inversion is produced by an mGluR2-activated outward conductance in OFF-UBCs, the phase delay of ON UBCs is caused by a late rebound current resulting from AMPAR recovery from desensitization. Granular layer network modeling indicates that phase dispersion of UBC responses generates diverse phase coding in the granule cell population, allowing climbing-fiber-driven Purkinje cell learning at arbitrary phases of the vestibular input.
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    Visual attention is available at a task-relevant location rapidly after a saccade 

    Yao, Tao; Ketkar, Madhura; Treue, Stefan; Krishna, B. Suresh
    eLife 2016; 5: Art. e18009
    Maintaining attention at a task-relevant spatial location while making eye-movements necessitates a rapid, saccade-synchronized shift of attentional modulation from the neuronal population representing the task-relevant location before the saccade to the one representing it after the saccade. Currently, the precise time at which spatial attention becomes fully allocated to the task-relevant location after the saccade remains unclear. Using a fine-grained temporal analysis of human peri-saccadic detection performance in an attention task, we show that spatial attention is fully available at the task-relevant location within 30 milliseconds after the saccade. Subjects tracked the attentional target veridically throughout our task: i.e. they almost never responded to non-target stimuli. Spatial attention and saccadic processing therefore co-ordinate well to ensure that relevant locations are attentionally enhanced soon after the beginning of each eye fixation.
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