WatanabeBMML20133MWatanabeABartelsJHMackeYMurayamaNKLogothetis2013-11-0021232146–2150fMRI, one of the most important noninvasive brain imaging methods, relies on the blood oxygen level-dependent (BOLD) signal, whose precise underpinnings are still not fully understood [1]. It is a widespread assumption that the components of the hemodynamic response function (HRF) are fixed relative to each other in time, leading most studies as well as analysis tools to focus on trial-averaged responses, thus using or estimating a condition- or location-specific “canonical HRF” [2, 3 and 4]. In the current study, we examined the nature of the variability of the BOLD response and asked in particular whether the positive BOLD peak is subject to trial-to-trial temporal jitter. Our results show that the positive peak of the stimulus-evoked BOLD signal exhibits a trial-to-trial temporal jitter on the order of seconds. Moreover, the trial-to-trial variability can be exploited to uncover the initial dip in the majority of voxels by pooling trial responses with large peak latencies. Initial dips exposed by this procedure possess higher spatial resolution compared to the positive BOLD signal in the human visual cortex. These findings allow for the reliable observation of fMRI signals that are physiologically closer to neural activity, leading to improvements in both temporal and spatial resolution.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-2146Temporal Jitter of the BOLD Signal Reveals a Reliable Initial Dip and Improved Spatial Resolution150171542115017MackeML2013_23JHMackeIMurrayPELatham2013-08-0081531093219Maximum entropy models have become popular statistical models in neuroscience and other areas in biology and can be useful tools for obtaining estimates of mutual information in biological systems. However, maximum entropy models fit to small data sets can be subject to sampling bias; i.e., the true entropy of the data can be severely underestimated. Here, we study the sampling properties of estimates of the entropy obtained from maximum entropy models. We focus on pairwise binary models, which are used extensively to model neural population activity. We show that if the data is well described by a pairwise model, the bias is equal to the number of parameters divided by twice the number of observations. If, however, the higher order correlations in the data deviate from those predicted by the model, the bias can be larger. Using a phenomenological model of neural population recordings, we find that this additional bias is highest for small firing probabilities, strong correlations and large population sizes—for the parameters we tested, a factor of about four higher. We derive guidelines for how long a neurophysiological experiment needs to be in order to ensure that the bias is less than a specified criterion. Finally, we show how a modified plug-in estimate of the entropy can be used for bias correction.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published110Estimation bias in maximum entropy models15017HaefnerGMB20133RMHaefnerSGerwinnJHMackeMBethge2013-02-00216235–242The activity of cortical neurons in sensory areas covaries with perceptual decisions, a relationship that is often quantified by choice probabilities. Although choice probabilities have been measured extensively, their interpretation has remained fraught with difficulty. We derive the mathematical relationship between choice probabilities, read-out weights and correlated variability in the standard neural decision-making model. Our solution allowed us to prove and generalize earlier observations on the basis of numerical simulations and to derive new predictions. Notably, our results indicate how the read-out weight profile, or decoding strategy, can be inferred from experimentally measurable quantities. Furthermore, we developed a test to decide whether the decoding weights of individual neurons are optimal for the task, even without knowing the underlying correlations. We confirmed the practicality of our approach using simulated data from a realistic population model. Thus, our findings provide a theoretical foundation for a growing body of experimental results on choice probabilities and correlations.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-235Inferring decoding strategies from choice probabilities in the presence of correlated variability1501715017188231501715420SchwartzMATB20123GSchwartzJMackeDAmodeiHTangMJBerry2012-08-00410810691088We explored the manner in which spatial information is encoded by retinal ganglion cell populations. We flashed a set of 36 shape stimuli onto the tiger salamander retina and used different decoding algorithms to read out information from a population of 162 ganglion cells. We compared the discrimination performance of linear decoders, which ignore correlation induced by common stimulation, against nonlinear decoders, which can accurately model these correlations. Similar to previous studies, decoders that ignored correlation suffered only a modest drop in discrimination performance for groups of up to ∼30 cells. However, for more realistic groups of 100+ cells, we found order-of-magnitude differences in the error rate. We also compared decoders that used only the presence of a single spike from each cell against more complex decoders that included information from multiple spike counts and multiple time bins. More complex decoders substantially outperformed simpler decoders, showing the importance of spike timing information. Particularly effective was the first spike latency representation, which allowed zero discrimination errors for the majority of shape stimuli. Furthermore, the performance of nonlinear decoders showed even greater enhancement compared to linear decoders for these complex representations. Finally, decoders that approximated the correlation structure in the population by matching all pairwise correlations with a maximum entropy model fit to all 162 neurons were quite successful, especially for the spike latency representation. Together, these results suggest a picture in which linear decoders allow a coarse categorization of shape stimuli, while nonlinear decoders, which take advantage of both correlation and spike timing, are needed to achieve high-fidelity discrimination.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published19Low Error Discrimination using a Correlated Population Code15017BuesingMS20123LBuesingJHMackeMSahani2012-03-001-2232447Ongoing advances in experimental technique are making commonplace simultaneous recordings of the activity of tens to hundreds of cortical neurons at high temporal resolution. Latent population models, including Gaussian-process factor analysis and hidden linear dynamical system (LDS) models, have proven effective at capturing the statistical structure of such data sets. They can be estimated efficiently, yield useful visualisations of population activity, and are also integral building-blocks of decoding algorithms for brain-machine interfaces (BMI). One practical challenge, particularly to LDS models, is that when parameters are learned using realistic volumes of data the resulting models often fail to reflect the true temporal continuity of the dynamics; and indeed may describe a biologically-implausible unstable population dynamic that is, it may predict neural activity that grows without bound. We propose a method for learning LDS models based on expectation maximisation that constrains parameters to yield stable systems and at the same time promotes capture of temporal structure by appropriate regularisation. We show that when only little training data is available our method yields LDS parameter estimates which provide a substantially better statistical description of the data than alternatives, whilst guaranteeing stable dynamics. We demonstrate our methods using both synthetic data and extracellular multi-electrode recordings from motor cortex.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published23Learning stable, regularised latent models of neural population dynamicsMackeBb20113JMackePBerensMBethge2011-07-0035512Modern recording techniques such as multi-electrode arrays and two-photon imaging methods are capable of simultaneously monitoring the activity of large neuronal ensembles at single cell resolution. These methods finally give us the means to address some of the most crucial questions in systems neuroscience: what are the dynamics of neural population activity? How do populations of neurons perform computations? What is the functional organization of neural ensembles?
While the wealth of new experimental data generated by these techniques provides exciting opportunities to test ideas about how neural ensembles operate, it also provides major challenges: multi-cell recordings necessarily yield data which is high-dimensional in nature. Understanding this kind of data requires powerful statistical techniques for capturing the structure of the neural population responses, as well as their relationship with external stimuli or behavioral observations. Furthermore, linking recorded neural population activity to the predictions of theoretical models of population coding has turned out not to be straightforward.
These challenges motivated us to organize a workshop at the 2009 Computational Neuroscience Meeting in Berlin to discuss these issues. In order to collect some of the recent progress in this field, and to foster discussion on the most important directions and most pressing questions, we issued a call for papers for this Research Topic. We asked authors to address the following four questions:
1. What classes of statistical methods are most useful for modeling population activity?
2. What are the main limitations of current approaches, and what can be done to overcome them?
3. How can statistical methods be used to empirically test existing models of (probabilistic) population coding?
4. What role can statistical methods play in formulating novel hypotheses about the principles of information processing in neural populations?
A total of 15 papers addressing questions related to these themes are now collected in this Research Topic. Three of these articles have resulted in “Focused reviews” in Frontiers in Neuroscience (Crumiller et al., 2011; Rosenbaum et al., 2011; Tchumatchenko et al., 2011), illustrating the great interest in the topic. Many of the articles are devoted to a better understanding of how correlations arise in neural circuits, and how they can be detected, modeled, and interpreted. For example, by modeling how pairwise correlations are transformed by spiking non-linearities in simple neural circuits, Tchumatchenko et al. (2010) show that pairwise correlation coefficients have to be interpreted with care, since their magnitude can depend strongly on the temporal statistics of their input-correlations. In a similar spirit, Rosenbaum et al. (2010) study how correlations can arise and accumulate in feed-forward circuits as a result of pooling of correlated inputs.
Lyamzin et al. (2010) and Krumin et al. (2010) present methods for simulating correlated population activity and extend previous work to more general settings. The method of Lyamzin et al. (2010) allows one to generate synthetic spike trains which match commonly reported statistical properties, such as time varying firing rates as well signal and noise correlations. The Hawkes framework presented by Krumin et al. (2010) allows one to fit models of recurrent population activity to the correlation-structure of experimental data. Louis et al. (2010) present a novel method for generating surrogate spike trains which can be useful when trying to assess the significance and time-scale of correlations in neural spike trains. Finally, Pipa and Munk (2011) study spike synchronization in prefrontal cortex during working memory.
A number of studies are also devoted to advancing our methodological toolkit for analyzing various aspects of population activity (Gerwinn et al., 2010; Machens, 2010; Staude et al., 2010; Yu et al., 2010). For example, Gerwinn et al. (2010) explain how full probabilistic inference can be performed in the popular model class of generalized linear models (GLMs), and study the effect of using prior distributions on the parameters of the stimulus and coupling filters. Staude et al. (2010) extend a method for detecting higher-order correlations between neurons via population spike counts to non-stationary settings. Yu et al. (2010) describe a new technique for estimating the information rate of a population of neurons using frequency-domain methods. Machens (2010) introduces a novel extension of principal component analysis for separating the variability of a neural response into different sources.
Focusing less on the spike responses of neural populations but on aggregate signals of population activity, Boatman-Reich et al. (2010) and Hoerzer et al. (2010) describe methods for a quantitative analysis of field potential recordings. While Boatman-Reich et al. (2010) discuss a number of existing techniques in a unified framework and highlight the potential pitfalls associated with such approaches, Hoerzer et al. (2010) demonstrate how multivariate autoregressive models and the concept of Granger causality can be used to infer local functional connectivity in area V4 of behaving macaques.
A final group of studies is devoted to understanding experimental data in light of computational models (Galán et al., 2010; Pandarinath et al., 2010; Shteingart et al., 2010). Pandarinath et al. (2010) present a novel mechanism that may explain how neural networks in the retina switch from one state to another by a change in gap junction coupling, and conjecture that this mechanism might also be found in other neural circuits. Galán et al. (2010) present a model of how hypoxia may change the network structure in the respiratory networks in the brainstem, and analyze neural correlations in multi-electrode recordings in light of this model. Finally, Shteingart et al. (2010) show that the spontaneous activation sequences they find in cultured networks cannot be explained by Zipf’s law, but rather require a wrestling model.
The papers of this Research Topic thus span a wide range of topics in the statistical modeling of multi-cell recordings. Together with other recent advances, they provide us with a useful toolkit to tackle the challenges presented by the vast amount of data collected with modern recording techniques. The impact of novel statistical methods on the field and their potential to generate scientific progress, however, depends critically on how readily they can be adopted and applied by laboratories and researchers working with experimental data. An important step toward this goal is to also publish computer code along with the articles (Barnes, 2010) as a successful implementation of advanced methods also relies on many details which are hard to communicate in the article itself. In this way it becomes much more likely that other researchers can actually use the methods, and unnecessary re-implementations can be avoided. Some of the papers in this Research Topic already follow this goal (Gerwinn et al., 2010; Louis et al., 2010; Lyamzin et al., 2010). We hope that this practice becomes more and more common in the future and encourage authors and editors of Research Topics to make as much code available as possible, ideally in a format that can be easily integrated with existing software sharing initiatives (Herz et al., 2008; Goldberg et al., 2009).nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published1Statistical analysis of multi-cell recordings: linking population coding models to experimental data1501718823MackeOb20113JHMackeMOpperMBethge2011-05-002010614Simultaneously recorded neurons exhibit correlations whose underlying causes are not known. Here, we use a population of threshold neurons receiving correlated inputs to model neural population recordings. We show analytically that small changes in second-order correlations can lead to large changes in higher-order redundancies, and that the resulting interactions have a strong impact on the entropy, sparsity, and statistical heat capacity of the population. Our findings for this simple model may explain some surprising effects recently observed in neural population recordings.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published3Common Input Explains Higher-Order Correlations and Entropy in a Simple Model of Neural Population Activity150171882365163JHMackeSGerwinnLWWhiteMKaschubeMBethge2011-05-00256570581A striking feature of cortical organization is that the encoding of many stimulus features, for example orientation or direction selectivity, is arranged into topographic maps. Functional imaging methods such as optical imaging of intrinsic signals, voltage sensitive dye imaging or functional magnetic resonance imaging are important tools for studying the structure of cortical maps. As functional imaging measurements are usually noisy, statistical processing of the data is necessary to extract maps from the imaging data. We here present a probabilistic model of functional imaging data based on Gaussian processes. In comparison to conventional approaches, our model yields superior estimates of cortical maps from smaller amounts of data. In addition, we obtain quantitative uncertainty estimates, i.e. error bars on properties of the estimated map. We use our probabilistic model to study the coding properties of the map and the role of noise-correlations by decoding the stimulus from single trials of an imaging experiment.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published11Gaussian process methods for estimating cortical maps150171882370403SGerwinnJHMackeMBethge2011-02-0015116Reconstructing stimuli from the spike trains of neurons is an important approach for understanding the neural code. One of the difficulties associated with this task is that signals which are varying continuously in time are encoded into sequences of discrete events or spikes. An important problem is to determine how much information about the continuously varying stimulus can be extracted from the time-points at which spikes were observed, especially if these time-points are subject to some sort of randomness. For the special case of spike trains generated by leaky integrate and fire neurons, noise can be introduced by allowing variations in the threshold every time a spike is released. A simple decoding algorithm previously derived for the noiseless case can be extended to the stochastic case, but turns out to be biased. Here, we review a solution to this problem, by presenting a simple yet efficient algorithm which greatly reduces the bias, and therefore leads to better decoding performance in the stochastic case.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published15Reconstructing stimuli from the spike-times of leaky integrate and fire neurons1501718823LyamzinML20103DRLyamzinJHMackeNALesica2010-10-001444111As multi-electrode and imaging technology begin to provide us with simultaneous recordings of large neuronal populations, new methods for modeling such data must also be developed. Here, we present a model for the type of data commonly recorded in early sensory pathways: responses to repeated trials of a sensory stimulus in which each neuron has it own time-varying spike rate (as described by its PSTH) and the dependencies between cells are characterized by both signal and noise correlations. This model is an extension of previous attempts to model population spike trains designed to control only the total correlation between cells. In our model, the response of each cell is represented as a binary vector given by the dichotomized sum of a deterministic “signal” that is repeated on each trial and a Gaussian random “noise” that is different on each trial. This model allows the simulation of population spike trains with PSTHs, trial-to-trial variability, and pairwise correlations that match those measured experimentally. Furthermore, the model also allows the noise correlations in the spike trains to be manipulated independently of the signal correlations and single-cell properties. To demonstrate the utility of the model, we use it to simulate and manipulate experimental responses from the mammalian auditory and visual systems. We also present a general form of the model in which both the signal and noise are Gaussian random processes, allowing the mean spike rate, trial-to-trial variability, and pairwise signal and noise correlations to be specified independently. Together, these methods for modeling spike trains comprise a potentially powerful set of tools for both theorists and experimentalists studying population responses in sensory systems.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published10Modeling population spike trains with specified time-varying spike rates, trial-to-trial variability, and pairwise signal and noise correlations150171882365153JHMackeFAWichmann2010-05-005:2210124One major challenge in the sensory sciences is to identify the stimulus features on which sensory systems base their computations, and which are predictive of a behavioral decision: they are a prerequisite for computational models of perception. We describe a technique (decision images) for extracting predictive stimulus features using logistic regression. A decision image not only defines a region of interest within a stimulus but is a quantitative template which defines a direction in stimulus space. Decision images thus enable the development of predictive models, as well as the generation of optimized stimuli for subsequent psychophysical investigations. Here we describe our method and apply it to data from a human face classification experiment. We show that decision images are able to predict human responses not only in terms of overall percent correct but also in terms of the probabilities with which individual faces are (mis-) classified by individual observers. We show that the most predictive dimension for gender categorization is neither aligned with the axis defined by the two class-means, nor with the first principal component of all faces-two hypotheses frequently entertained in the literature. Our method can be applied to a wide range of binary classification tasks in vision or other psychophysical contexts.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published23Estimating predictive stimulus features from psychophysical data: The decision image technique applied to human faces150171882365023SGerwinnJMackeMBethge2010-04-00124142Generalized Linear Models (GLMs) are commonly used statistical methods for modelling the relationship between neural population activity and presented stimuli. When the dimension of the parameter space is large, strong regularization has to be used in order to fit GLMs to datasets of realistic size without overfitting. By imposing properly chosen priors over parameters, Bayesian inference provides an effective and principled approach for achieving regularization. Here we show how the posterior distribution over model parameters of GLMs can be approximated by a Gaussian using the Expectation Propagation algorithm. In this way, we obtain an estimate of the posterior mean and posterior covariance, allowing us to calculate Bayesian confidence intervals that characterize the uncertainty about the optimal solution. From the posterior we also obtain a different point estimate, namely the posterior mean as opposed to the commonly used maximum a posteriori estimate. We systematically compare the different inference techniques on simulated as well as on multi-electrode recordings of retinal ganglion cells, and explore the effects of the chosen prior and the performance measure used. We find that good performance can be achieved by choosing an Laplace prior together with the posterior mean estimate.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published41Bayesian inference for generalized linear models for spiking neurons150171882361023SGerwinnJHMackeMBethge2009-10-00213128The timing of action potentials in spiking neurons depends on the temporal dynamics of their inputs and contains information about temporal fluctuations in the stimulus. Leaky integrate-and-fire neurons constitute a popular class of encoding models, in which spike times depend directly on the temporal structure of the inputs. However, optimal decoding rules for these models have only been studied explicitly in the noiseless case. Here, we study decoding rules for probabilistic inference of a continuous stimulus from the spike times of a population of leaky integrate-and-fire neurons with threshold noise. We derive three algorithms for approximating the posterior distribution over stimuli as a function of the observed spike trains. In addition to a reconstruction of the stimulus we thus obtain an estimate of the uncertainty as well. Furthermore, we derive a `spike-by-spike‘ online decoding scheme that recursively updates the posterior with the arrival of each new spike. We use these decoding rules to reconstruct time-varying stimuli represented by a Gaussian process from spike trains of single neurons as well as neural populations.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published27Bayesian population decoding of spiking neurons150171882351573JHMackePBerensASEckerASToliasMBethge2009-02-00221397423Spike trains recorded from populations of neurons can exhibit substantial pairwise correlations between neurons and rich temporal structure. Thus, for the realistic simulation and analysis of neural systems, it is essential to have efficient methods for generating artificial spike trains with specified correlation structure. Here we show how correlated binary spike trains can be simulated by means of a latent multivariate gaussian model. Sampling from the model is computationally very efficient and, in particular, feasible even for large populations of neurons. The entropy of the model is close to the theoretical maximum for a wide range of parameters. In addition, this framework naturally extends to correlations over time and offers an elegant way to model correlated neural spike counts with arbitrary marginal distributions.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/macke2009_5157[0].pdfpublished26Generating Spike Trains with Specified Correlation Coefficients1501715420150171882348773S-PKuAGrettonJMackeNKLogothetis2008-09-0072610071014Pattern recognition methods have shown that functional magnetic resonance imaging (fMRI) data can reveal significant information about brain activity. For example, in the debate of how object categories are represented in the brain, multivariate analysis has been used to provide evidence of a distributed encoding scheme [Science 293:5539 (2001) 24252430]. Many follow-up studies have employed different methods to analyze human fMRI data with varying degrees of success [Nature reviews 7:7 (2006) 523534]. In this study, we compare four popular pattern recognition methods: correlation analysis, support-vector machines (SVM), linear discriminant analysis (LDA) and Gaussian naïve Bayes (GNB), using data collected at high field (7 Tesla) with higher resolution than usual fMRI studies. We investigate prediction performance on single trials and for averages across varying numbers of stimulus presentations. The performance of the various algorithms depends on the nature of the brain activity being categorized: for
several tasks, many of the methods work well, whereas for others, no method performs above chance level. An important factor in overall classification performance is careful preprocessing of the data, including dimensionality reduction, voxel selection and outlier elimination.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/sdarticle_4877[0].pdfpublished7Comparison of Pattern Recognition Methods in Classifying High-resolution BOLD Signals Obtained at High Magnetic Field in Monkeys15017154201501715421150171882346673JHMackeNMaackRGuptaWDenkBSchölkopfABorst2008-01-002167349357A new technique, Serial Block Face Scanning Electron Microscopy (SBFSEM), allows for automatic
sectioning and imaging of biological tissue with a scanning electron microscope. Image
stacks generated with this technology have a resolution sufficient to distinguish different cellular
compartments, including synaptic structures, which should make it possible to obtain detailed
anatomical knowledge of complete neuronal circuits. Such an image stack contains several thousands
of images and is recorded with a minimal voxel size of 10-20nm in the x and y- and 30nm
in z-direction. Consequently, a tissue block of 1mm3 (the approximate volume of the Calliphora
vicina brain) will produce several hundred terabytes of data. Therefore, highly automated 3D
reconstruction algorithms are needed. As a first step in this direction we have developed semiautomated
segmentation algorithms for a precise contour tracing of cell membranes. These
algorithms were embedded into an easy-to-operate user interface, which allows direct 3D observation
of the extracted objects during the segmentation of image stacks. Compared to purely
manual tracing, processing time is greatly accelerated.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/Macke_Maack_07_JNeuMeth_Segmentation_[0].pdfpublished8Contour-propagation Algorithms for Semi-automated Reconstruction of Neural Processes15017154201501718823TuragaBPDPHM20137SCTuragaLBuesingAMPackerHDalgleishNPettitMHausserJHMackeStateline, NV, USA2013-12-00539547Simultaneous recordings of the activity of large neural populations are extremely valuable as they can be used to infer the dynamics and interactions of neurons in a local circuit, shedding light on the computations performed. It is now possible to measure the activity of hundreds of neurons using 2-photon calcium imaging. However, many computations are thought to involve circuits consisting of thousands of neurons, such as cortical barrels in rodent somatosensory cortex. Here we contribute a statistical method for stitching" together sequentially imaged sets of neurons into one model by phrasing the problem as fitting a latent dynamical system with missing observations. This method allows us to substantially expand the population-sizes for which population dynamics can be characterized---beyond the number of simultaneously imaged neurons. In particular, we demonstrate using recordings in mouse somatosensory cortex that this method makes it possible to predict noise correlations between non-simultaneously recorded neuron pairs.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/2013/NIPS-2013-Turaga.pdfpublished8Inferring neural population dynamics from multiple partial recordings of the same neural circuit15017BusingMS20137LBuesingJHMackeMSahaniLake Tahoe, NV, USA2013-04-0016911699Latent linear dynamical systems with generalised-linear observation models arise in a variety of applications, for example when modelling the spiking activity of populations of neurons. Here, we show how spectral learning methods for linear systems with Gaussian observations (usually called subspace identification in this context) can be extended to estimate the parameters of dynamical system models observed through non-Gaussian noise models. We use this approach to obtain estimates of parameters for a dynamical model of neural population data, where the observed spike-counts are Poisson-distributed with log-rates determined by the latent dynamical process, possibly driven by external inputs. We show that the extended system identification algorithm is consistent and accurately recovers the correct parameters on large simulated data sets with much smaller computational cost than approximate expectation-maximisation (EM) due to the non-iterative nature of subspace identification. Even on smaller data sets, it provides an effective initialization for EM, leading to more robust performance and faster convergence. These benefits are shown to extend to real neural data.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/2013/NIPS-2012-Buesing.pdfpublished8Spectral learning of linear dynamics from generalised-linear observations with application to neural population dataMackeBCYSS20127JHMackeLBüsingJPCunninghamBMYuKVShenoyMSahaniGranada, Spain2012-01-0013501358Neurons in the neocortex code and compute as part of a locally interconnected population. Large-scale multi-electrode recording makes it possible to access
these population processes empirically by fitting statistical models to unaveraged data. What statistical structure best describes the concurrent spiking of cells within a local network? We argue that in the cortex, where firing exhibits extensive correlations in both time and space and where a typical sample of neurons still reflects
only a very small fraction of the local population, the most appropriate model captures shared variability by a low-dimensional latent process evolving with smooth
dynamics, rather than by putative direct coupling. We test this claim by comparing a latent dynamical model with realistic spiking observations to coupled generalised
linear spike-response models (GLMs) using cortical recordings. We find that the latent dynamical approach outperforms the GLM in terms of goodness-offit, and reproduces the temporal correlations in the data more accurately. We also compare models whose observations models are either derived from a Gaussian or point-process models, finding that the non-Gaussian model provides slightly better goodness-of-fit and more realistic population spike counts.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/2012/NIPS-2011-Macke.pdfpublished8Empirical models of spiking in neural populationsMackeML20127JHMackeIMurrayPLathamGranada, Spain2012-01-0020342042Maximum entropy models have become popular statistical models in neuroscience and other areas in biology, and can be useful tools for obtaining estimates of mutual
information in biological systems. However, maximum entropy models fit to small data sets can be subject to sampling bias; i.e. the true entropy of the data can be severely underestimated. Here we study the sampling properties of estimates of the entropy obtained from maximum entropy models. We show that if the data is generated by a distribution that lies in the model class, the bias is equal to the number of parameters divided by twice the number of observations. However, in practice, the true distribution is usually outside the model class, and we show here that this misspecification can lead to much larger bias. We provide a perturbative approximation of the maximally expected bias when the true model is out of
model class, and we illustrate our results using numerical simulations of an Ising model; i.e. the second-order maximum entropy distribution on binary data.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/2012/NIPS-2011-Macke-2.pdfpublished8How biased are maximum entropy models?61217JHMackeSGerwinnMKaschubeLEWhiteMBethgeVancouver, BC, Canada2010-04-0011951203Imaging techniques such as optical imaging of intrinsic signals, 2-photon calcium imaging and voltage sensitive dye imaging can be used to measure the functional organization of visual cortex across different spatial and temporal scales. Here, we present Bayesian methods based on Gaussian processes for extracting topographic maps from functional imaging data. In particular, we focus on the estimation of
orientation preference maps (OPMs) from intrinsic signal imaging data. We model the underlying map as a bivariate Gaussian process, with a prior covariance function that reflects known properties of OPMs, and a noise covariance adjusted to the data. The posterior mean can be interpreted as an optimally smoothed estimate of the map, and can be used for model based interpolations of the map from sparse measurements. By sampling from the posterior distribution, we can get error bars on statistical properties such as preferred orientations, pinwheel locations or pinwheel counts. Finally, the use of an explicit probabilistic model facilitates interpretation of parameters and quantitative model comparisons. We demonstrate our model both on simulated data and on intrinsic signaling data from ferret visual cortex.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/NIPS2009-Macke_6121[0].pdfpublished8Bayesian estimation of orientation preference maps150171882347287SGerwinnJMackeMSeegerMBethgeVancouver, BC, Canada2008-09-00529536Generalized linear models are the most commonly used tools to describe the stimulus selectivity of sensory neurons. Here we present a Bayesian treatment of such models. Using the expectation propagation algorithm, we are able to approximate the full posterior distribution over all weights. In addition, we use a Laplacian prior to favor sparse solutions. Therefore, stimulus features that do not critically influence neural activity will be assigned zero weights and thus be effectively excluded by the model. This feature selection mechanism facilitates both the interpretation of the neuron model as well as its predictive abilities. The posterior distribution can be used to obtain confidence intervals which makes it possible to assess the statistical significance of the solution. In neural data analysis, the available amount of experimental measurements is often limited whereas the parameter space is large. In such a situation, both regularization by a sparsity prior and uncertainty estimates for the model parameters are essential.
We apply our method to multi-electrode recordings of retinal ganglion cells and use our uncertainty estimate to test the statistical significance of functional couplings between neurons. Furthermore we used the sparsity of the Laplace prior to select those filters from a spike-triggered covariance analysis that are most informative about the neural response.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/BayesLNP_4728[0].pdfpublished7Bayesian Inference for Spiking Neuron Models with a Sparsity Prior1501715420150171882347387JHMackeGZeckMBethgeVancouver, BC, Canada2008-09-00969976Stimulus selectivity of sensory neurons is often characterized by estimating their receptive field properties such as orientation selectivity. Receptive fields are usually derived from the mean (or covariance) of the spike-triggered stimulus ensemble. This approach treats each spike as an independent message but does not take into account that information might be conveyed through patterns of neural activity that are distributed across space or time. Can we find a concise description for the processing of a whole population of neurons analogous to the receptive field for single neurons? Here, we present a generalization of the linear receptive field which is not bound to be triggered on individual spikes but can be meaningfully
linked to distributed response patterns. More precisely, we seek to identify those stimulus features and the corresponding patterns of neural activity that are most
reliably coupled. We use an extension of reverse-correlation methods based on canonical correlation analysis. The resulting population receptive fields span the
subspace of stimuli that is most informative about the population response. We evaluate our approach using both neuronal models and multi-electrode recordings from rabbit retinal ganglion cells. We show how the model can be extended to capture nonlinear stimulus-response relationships using kernel canonical correlation analysis, which makes it possible to test different coding mechanisms. Our technique can also be used to calculate receptive fields from multi-dimensional neural measurements such as those obtained from dynamic imaging methods.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/NIPS2007-Macke_4738[0].pdfpublished7Receptive Fields without Spike-Triggering1501715420150171882342667JLaubJHMackeK-RMüllerFAWichmannVancouver, BC, Canada2007-09-00777784Attempting to model human categorization and similarity judgements is both a very interesting but also an exceedingly difficult challenge. Some of the difficulty
arises because of conflicting evidence whether human categorization and similarity judgements should or should not be modelled as to operate on a mental representation that is essentially metric. Intuitively, this has a strong appeal as it would allow (dis)similarity to be represented geometrically as distance in some internal space. Here we show how a single stimulus, carefully constructed in a
psychophysical experiment, introduces l2 violations in what used to be an internal similarity space that could be adequately modelled as Euclidean. We term this one
influential data point a conflictual judgement. We present an algorithm of how to analyse such data and how to identify the crucial point. Thus there may not be a
strict dichotomy between either a metric or a non-metric internal space but rather degrees to which potentially large subsets of stimuli are represented metrically
with a small subset causing a global violation of metricity.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/NIPS2006-Laub_4266[0].pdfpublished7Inducing Metric Violations in Human Similarity Judgements1501715420150171882343057MBethgeSGerwinnJHMackeSan Jose, CA, USA2007-02-00112There are two aspects to unsupervised learning of invariant representations of images: First, we can reduce the dimensionality of the representation by finding an optimal trade-off between temporal stability and informativeness. We show that the answer to this optimization problem is generally not unique so that there is still considerable freedom in choosing a suitable basis. Which of the many optimal representations should be selected? Here, we focus on this second aspect, and seek to find representations that are invariant under geometrical transformations occuring in sequences of natural images. We utilize ideas of steerability and Lie groups, which have been developed in the context of filter design. In particular, we show how an anti-symmetric version of canonical correlation analysis can be used to learn a full-rank image basis which is steerable with respect to rotations. We provide a geometric interpretation of this algorithm by showing that it finds the two-dimensional eigensubspaces of the avera
ge bivector. For data which exhibits a variety of transformations, we develop a bivector clustering algorithm, which we use to learn a basis of generalized quadrature pairs (i.e. complex cells) from sequences of natural images.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/SPIE2007-Bethge_4305[0].pdfpublished11Unsupervised learning of a steerable basis for invariant image representations15017154201501718823586546JHMackeMOpperMBethge2009-03-00ArcherPM20147EArcherJWPillowJMackeSalt Lake City, UT, USA2014-03-00162Computational and Systems Neuroscience Meeting (COSYNE 2014)Modern experimental technologies such as multi-electrode arrays and 2-photon population calcium imaging make
it possible to record the responses of large neural populations (up to 100s of neurons) simultaneously. These
high-dimensional data pose a significant challenge for analysis. Recent work has focused on extracting lowdimensional dynamical trajectories that may underlie such responses. These methods enable visualization of
high-dimensional neural activity, and may also provide insight into the function of underlying circuitry. Previous
work, however, has primarily focused on models of a opulation’s intrinsic dynamics, without taking into
account any external stimulus drive. We propose a new technique that integrates linear dimensionality reduction
of stimulus-response functions (analogous to spike-triggered average and covariance analysis) with a latent
dynamical system (LDS) model of neural activity. Under our model, the population response is governed by a
low-dimensional dynamical system with nonlinear (quadratic) stimulus-dependent input. Parameters of the model can be learned by combining standard expectation maximization for linear dynamical system models with a recently proposed algorithms for learning quadratic feature selectivity. Unlike models with all-to-all connectivity, this
framework scales well to large populations since, given fixed latent dimensionality, the number of parameters
grows linearly with population size. Simultaneous modeling of dynamics and stimulus dependence allows our method to model correlations in response variability while also uncovering low-dimensional stimulus selectivity that is shared across a population. Because stimulus selectivity and noise correlations both arise from coupling to the underlying dynamical system, it is particularly well-suited for studying the neural population activity of sensory
cortices, where stimulus inputs received by different neurons are likely to be mediated by local circuitry, giving rise to both shared dynamics and substantial receptive field overlap.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-162Low-dimensional models of neural population recordings with complex stimulus selectivity15017TuragaBPDPHM20147SCTuragaLBuesingAPackerHDalgleishNPettitMHauserJMackeSalt Lake City, UT, USA2014-03-0084Computational and Systems Neuroscience Meeting (COSYNE 2014)Simultaneous recordings of the activity of large neural populations are extremely valuable as they can be used to
infer the dynamics and interactions of neurons in a local circuit, shedding light on the computations performed. It
is now possible to measure the activity of hundreds of neurons using in-vivo 2-photon calcium imaging. However,
many computations are thought to involve circuits consisting of thousands of neurons, such as cortical barrels in rodent somatosensory cortex. Here we contribute a statistical method for “stitching” together sequentially imaged sets of neurons into one model by phrasing the problem as fitting a latent dynamical system with missing observations.
This method allows us to substantially expand the population sizes for which population dynamics can be characterized—beyond the number of simultaneously imaged neurons. We describe conditions for successful stitching and use recordings from mouse somatosensory cortex to demonstrate that this method enables accurate predictions of noise correlations between non-simultaneously recorded neuron pairs.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-84Predicting noise correlations for non-simultaneously measured neuron pairs15017TuragaBPHM20137SCTuragaLBuesingMPackerMHausserJHMackeSan Diego, CA, USA2013-11-1343rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)Understanding the functional connectivity between different cortical cell types and the resulting population dynamics is a challenging and important problem. Progress with in-vivo 2-photon population calcium imaging has made it possible to densely sample neural activity in superficial layers of a local patch of cortex. In principle, such data can be used to infer the functional (statistical) connectivity between different classes of cortical neurons by fitting models such as generalized linear models or latent dynamical systems (LDS). However, this approach faces 3 major challenges which we address: 1) only small populations of neurons (~200) can currently be simultaneously imaged at any given time; 2) the cell types of individual neurons are often unknown; and 3) it is unclear how to pool data across different animals to derive an average model.
First, while it is not possible to simultaneously image all neurons in a cortical column, it is currently possible to image the activity of ~200 neurons at a time and to repeat this procedure at multiple cortical depths (down to layer 3). We present a computational method ("Stitching LDS") which allows us to "stitch" such non-simultaneously imaged populations of neurons into one large virtual population spanning different depths of cortex. Importantly - and surprisingly - this approach allows us to predict couplings and noise correlations even for pairs of neurons that were never imaged simultaneously.
Second, we automatically cluster neurons based on similarities in their functional connectivity (“Clustering LDS”). Under the assumption that such functionally defined clusters can correspond to cell types, this enables us to infer both the cell types and their functional connectivity.
Third, while connection profiles of individual cells in one class can be variable, we expect the ‘average’ influence of one cell class on another to be fairly consistent across animals. We show how our approach can be used to pool measurements across different animals in a principled manner (“Pooling LDS”). The result is a highly accurate average model of the interactions between different cell classes.
We demonstrate the utility of our computational tools by applying them to model the superficial layers of barrel cortex based on in-vivo 2-photon imaging data in awake mice.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0Inferring interactions between cell types from multiple calcium imaging snapshots of the same neural
circuit15017MackeML20137JMackeIMurrayPLathamSalt Lake City, UT, USA2013-03-00Computational and Systems Neuroscience Meeting (COSYNE 2013)nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0How biased are maximum entropy models of neural population activity?15017BuesingMB20137LBuesingJMackeMSahaniSalt Lake City, UT, USA2013-03-00Computational and Systems Neuroscience Meeting (COSYNE 2013)nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0Robust estimation for neural state-space models15017MackeBCYSS2012_27JHMackeLBüsingJPCunninghamBMYuKVShenoyMSahaniAshburn, VA, USA2012-05-00Janelia Farm Conference 2012: Machine Learning, Statistical Inference, and Neurosciencenonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0Empirical models of spiking in neural populationsHaefnerGMB20117RMHaefnerSGerwinnJHMackeMBethgeWashington, DC, USA2011-11-0041st Annual Meeting of the Society for Neuroscience (Neuroscience 2011)When monkeys make a perceptual decision about ambiguous visual stimuli, individual sensory neurons in MT and other areas have been shown to covary with the decision. This observation suggests that the response variability in those very neurons causes the animal to choose one over the other option. However, the fact that sensory neurons are correlated has greatly complicated attempts to link those covariances (and the associated choice probabilities) to a direct involvement of any particular neuron in a decision-making task.
Here we report on an analytical treatment of choice probabilities in a population of correlated sensory neurons read out by a linear decoder. We present a closed-form solution that links choice probabilities, noise correlations and decoding weights for the case of fixed integration time. This allowed us to analytically prove and generalize a prior numerical finding about the choice probabilities being only due to the difference between the correlations within and between decision pools (Nienborg & Cumming 2010) and derive simplified expressions for a range of interesting cases. We investigated the implications for plausible correlation structures like pool-based and limited-range correlations.
We found that the relationship between choice probabilities and decoding weights is in general non-monotonic and highly sensitive to the underlying correlation structure. In fact, given empirical measures of the interneuronal correlations and CPs, our formulas allow to infer the individual neuronal decoding weights. We confirmed the feasibility of this approach using synthetic data. We then applied our analytical results to a published dataset of empirical noise correlations and choice probabilities (Cohen & Newsome 2008 and 2009) recorded during a classic motion discriminating task (Britten et al 1992). We found that the data are compatible with an optimal read-out scheme in which the responses of neurons with the correct direction preference are summed and those with perpendicular preference, but positively correlated noise, are subtracted. While the correlation data of Cohen & Newsome (being based on individual extracellular electrode recordings) do not give access to the full covariance structure of a neural population, our analytical formulas will make it possible to accurately infer individual read-out weights from simultaneous population recordings.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0Relationship between decoding strategy, choice
probabilities and neural correlations in perceptual decision-making task1501718823MackeBCYSS20117JHMackeLBüsingJPCunninghamBMYuKVShenoyMSahaniSalt Lake City, UT, USA2011-02-00Computational and Systems Neuroscience Meeting (COSYNE 2011)Neural population activity reflects not only variations in stimulus drive ( captured by many neural encoding models) but also the rich computational dynamics of recurrent neural circuitry. Identifying this dynamical structure, and relating it to external stimuli and behavioural events, is a crucial step towards understanding neural computation. One data-driven approach is to fit hidden low-dimensional dynamical systems models to the high-dimensional spiking observations collected by microelectrode arrays (Yu et al, 2006, 2009). This approach yields low-dimensional representations of population-activity, allowing analysis and visualization of population dynamics with single trial resolution. Here, we compare two models using latent linear dynamics, with the dependence of spiking observations on the dynamical state being either linear with Gaussian observations (GaussLDS), or generalised linear with Poisson observations and an exponential nonlinearity (PoissonLDS) (Kulkarni & Paninski, 2007). Both models were fit by Expectation-Maximisation to multi-electrode recordings from pre-motor cortex in behaving monkeys during the delay-period of a delayed reach task. We evaluated the accuracy of different approximations for the E-step necessary for PoissonLDS using elliptical slice sampling. We quantified model-performance using a cross-prediction approach (Yu et al). Although only the Poisson noise model takes the discrete nature of spiking into account, we found no consistent improvement of the Poisson-model over GaussLDS: PoissonLDS was generally more accurate for low dimensions, but slightly under-performed GaussLDS in higher dimensions (cf. Lawhern et al. 2010). We also examined the ability of such models to capture conventional population metrics such as pairwise correlations and the distribution of synchronous spikes counts. We found that both models were able to reproduce these quantities with very low dynamical dimension, although the non-positivity of the Gaussian model introduced a bias. Thus, despite its verisimilitude, the Poisson observation model does not always yield more accurate predictions in real data.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0Modelling low-dimensional dynamics in recorded spiking populations1501718823MackeOB2011_27JHMackeMOpperMBethgeSalt Lake City, UT, USA2011-02-00Computational and Systems Neuroscience Meeting (COSYNE 2011)Finding models for capturing the statistical structure of multi-neuron firing patterns is a major challenge in sensory neuroscience. Recently, Maximum Entropy (MaxEnt) models have become popular tools for studying neural population recordings [4, 3]. These studies have found that small populations in retinal, but not in local cortical circuits, are well described by models based on pairwise correlations. It has also been found that entropy in small populations grows sublinearly [4], that sparsity in the population code is related to correlations [3], and it has been conjectured that neural populations might be at a ícritical pointí. While there have been many empirical studies using MaxEnt models, there has arguably been a lack of analytical studies that might explain the diversity of their findings. In particular, theoretical models would be of great importance for investigating their implications for large populations. Here, we study these questions in a simple, tractable population model of neurons receiving Gaussian inputs [1, 2]. Although the Gaussian input has maximal entropy, the spiking-nonlinearities yield non-trivial higher-order correlations (íhocsí). We find that the magnitude of hocs is strongly modulated by pairwise correlations, in a manner which is consistent with neural recordings. In addition, we show that the entropy in this model grows sublinearly for small, but linearly for large populations. We characterize how the magnitude of hocs grows with population size. Finally, we find that the hocs in this model lead to a diverging specific heat, and therefore, that any such model appears to be at a critical point. We conclude that common input might provide a mechanistic explanation for a wide range of recent empirical observations. [1] SI Amari, H Nakahara, S Wu, Y Sakai. Neural Comput, 2003. [2] JH Macke, M Opper, M Bethge. ArXiv, 2010. [3] IE Ohiorhenuan, et. al Nature, 2010. [4] E Schneidman, MJ Berry, R Segev, W Bialek. Nature, 2006.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0The effect of common input on higher-order correlations and
entropy in neural populations150171882370747JHMackeGSebastianLEWhiteMKaschubeMBethgeSan Diego, CA, USA2010-11-0040th Annual Meeting of the Society for Neuroscience (Neuroscience 2010)A striking feature of cortical organization is that the encoding of many stimulus features, such as orientation preference, is arranged into topographic maps. The structure of these maps has been extensively studied using functional imaging methods, for example optical imaging of intrinsic signals, voltage sensitive dye imaging or functional magnetic resonance imaging. As functional imaging measurements are usually noisy, statistical processing of the data is necessary to extract maps from the imaging data. We here present a probabilistic model of functional imaging data based on Gaussian processes. In comparison to conventional approaches, our model yields superior estimates of cortical maps from smaller amounts of data. In addition, we obtain quantitative uncertainty estimates, i.e. error bars on properties of the estimated map. We use our probabilistic model to study the coding properties of the map and the role of noise correlations by decoding the stimulus from single trials of an imaging experiment. In addition, we show how our method can be used to reconstruct maps from sparse measurements, for example multi-electrode recordings. We demonstrate our model both on simulated data and on intrinsic signaling data from ferret visual cortex.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0Estimating cortical maps with Gaussian process models150171882362427JHMackeFAWichmannNaples, FL, USA2009-08-00319th Annual Meeting of the Vision Sciences Society (VSS 2009)One of the main challenges in the sensory sciences is to identify the stimulus features on which the sensory systems base their computations: they are a pre-requisite for computational models of perception. We describe a technique---decision-images--- for extracting critical stimulus features based on logistic regression. Rather than embedding the stimuli in noise, as is done in classification image analysis, we want to infer the important features directly from physically heterogeneous stimuli. A Decision-image not only defines the critical region-of-interest within a stimulus but is a quantitative template which defines a direction in stimulus space. Decision-images thus enable the development of predictive models, as well as the generation of optimized stimuli for subsequent psychophysical investigations. Here we describe our method and apply it to data from a human face discrimination experiment. We show that decision-images are able to predict human responses not only in terms of overall percent correct but are able to predict, for individual observers, the probabilities with which individual faces are (mis-) classified. We then test the predictions of the models using optimized stimuli. Finally, we discuss possible generalizations of the approach and its relationships with other models.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-31Estimating Critical Stimulus Features from Psychophysical Data: The Decision-Image Technique Applied to Human Faces1501715420150171882358457JMackeSGerwinnLWhiteMKaschubeMBethgeSalt Lake City, UT, USA2009-03-00Computational and Systems Neuroscience Meeting (COSYNE 2009)Neurons in the early visual cortex of mammals exhibit a striking organization with respect to their functional properties. A prominent example is the layout of orientation preferences in primary visual cortex, the orientation preference map (OPM). Functional imaging techniques, such as optical imaging of intrinsic signals have been used extensively for the measurement of OPMs. As the signal-to-noise ratio in individual pixels if often low, the signals are usually spatially smoothed with a fixed linear filter to obtain an estimate of the functional map.
Here, we consider the estimation of the map from noisy measurements as a Bayesian inference problem. By combining prior knowledge about the structure of OPMs with experimental measurements, we want to obtain better estimates of the OPM with smaller trial numbers. In addition, the use of an explicit, probabilistic model for the data provides a principled framework for setting parameters and smoothing.
We model the underlying map as a bivariate Gaussian process (GP, a.k.a. Gaussian random field), with a prior covariance function that reflects known properties of OPMs. The posterior mean of the map can be interpreted as an optimally smoothed map. Hyper-parameters of the model can be chosen by optimization of the marginal likelihood. In addition, the GP also returns a predicted map for any location, and can therefore be used for extending the map to pixel at which no, or only unreliable data was obtained.
We also obtain a posterior distribution over maps, from which we can estimate the posterior uncertainty of statistical properties of the maps, such as the pinwheel density. Finally, our probabilistic model of both the signal and the noise can be used for decoding, and for estimating the informational content of the map.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0Bayesian estimation of orientation preference maps150171882358437SGerwinnJMackeMBethgeSalt Lake City, UT, USA,2009-03-00Computational and Systems Neuroscience Meeting (COSYNE 2009)nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0Bayesian Population Decoding of Spiking Neurons150171882358447PBerensJHMackeASEckerRJCottonMBethgeASToliasSalt Lake City, UT, USA2009-03-00Computational and Systems Neuroscience Meeting (COSYNE 2009)Understanding the structure of multi-neuronal firing patterns in ensembles of cortical neurons is a major challenge for systems neuroscience. The dependence of network properties on the statistics of the sensory input can provide important insights into the computations performed by neural ensembles. Here, we study the functional properties of neural populations in the primary visual cortex of awake, behaving macaques by varying visual input statistics in a controlled way. Using arrays of chronically implanted tetrodes, we record simultaneously from up to thirty well-isolated neurons while presenting sets of images with three different correlation structures: spatially uncorrelated white noise (whn), images matching the second-order correlations of natural images (phs) and natural images including higher-order correlations (nat).
We find that groups of six nearby cortical neurons show little redundancy in their firing patterns (represented as binary vectors, 10ms bins) but rather act almost independently (mean multi-information 0.85 bits/s, range 0.16 - 1.90 bits/s, mean fraction of marginal entropy 0.34 %, N=46). Although network correlations are weak, they are statistically significant. While relatively few groups showed significant redundancies under stimulation with white noise (67.4 ± 3.2%; mean fraction of groups ± S.E.M.), many more did so in the other two conditions (phs: 95.7 ± 0.6%; nat: 89.1 ± 1.4%). Additional higher-order correlations in natural images compared to phase scrambled images did not increase but rather decrease the redundancy in the cortical representation: Network correlations are significantly higher in phs than in nat, as is the number of significantly correlated groups.
Multi-information measures the reduction in entropy due to any form of correlation. By using second order maximum entropy modeling, we find that a large fraction of multi-information is accounted for by pairwise correlations (whn: 75.0 ± 3.3%; phs: 82.8 ± 2.1%; nat: 80.8 ± 2.4%; groups with significant redundancy). Importantly, stimulation with natural images containing higher-order correlations only lead to a slight increase in the fraction of redundancy due to higher-order correlations in the cortical representation (mean difference 2.26 %, p=0.054, Sign test).
While our results suggest that population activity in V1 may be modeled well using pairwise correlations only, they leave roughly 20-25 % of the multi-information unexplained. Therefore, choosing a particular form of higher-order interactions may improve model quality. Thus, in addition to the independent model, we evaluated the quality of three different models: (a) The second-order maximum entropy model, which minimizes higher-order correlations, (b) a model which assumes that correlations are a product of common inputs (Dichotomized Gaussian) and (c) a mixture model in which correlations are induced by a discrete number of latent states. We find that an independent model is sufficient for the white noise condition but neither for phs or nat. In contrast, all of the correlation models (a-c) perform similarly well for the conditions with correlated stimuli.
Our results suggest that under natural stimulation redundancies in cortical neurons are relatively weak. Higher-order correlations in natural images do not increase but rather decrease the redundancies in the cortical representation.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0Sensory input statistics and network mechanisms in primate primary visual cortex1501718823MackeBEOTB20087JHMackePBerensASEckerMOpperASToliasMBethgePrinceton, NJ, USA2008-07-00Annual Meeting 2008 of Sloan-Swartz Centers for Theoretical Neurobiologynonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published0Modeling populations of spiking neurons with the Dichotomized Gaussian distribution1501718823150171542158577S-PKuAGrettonJMackeATToliasNKLogothetisSantorini, Greece2008-06-0067AREADNE 2008: Research in Encoding and Decoding of Neural EnsemblesPattern recognition methods have shown that fMRI data can reveal significant information
about brain activity. For example, in the debate of how object-categories are represented in
the brain, multivariate analysis has been used to provide evidence of distributed encoding
schemes. Many follow-up studies have employed different methods to analyze human fMRI
data with varying degrees of success. In this study we compare four popular pattern recognition
methods: correlation analysis, support-vector machines (SVM), linear discriminant analysis
and Gaussian naïve Bayes (GNB), using data collected at high field (7T) with higher resolution
than usual fMRI studies. We investigate prediction performance on single trials and for averages
across varying numbers of stimulus presentations. The performance of the various algorithms
depends on the nature of the brain activity being categorized: for several tasks,
many of the methods work well, whereas for others, no methods perform above chance level.
An important factor in overall classification performance is careful preprocessing of the data,
including dimensionality reduction, voxel selection, and outlier elimination.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-67Analysis of Pattern Recognition Methods in Classifying Bold Signals in Monkeys at 7-Tesla15017154201501715421150171882351017MBethgeJHMackePBerensASEckerASToliasSantorini, Greece2008-06-0048AREADNE 2008: Research in Encoding and Decoding of Neural EnsemblesIn order to understand how neural systems perform computations and process sensory
information, we need to understand the structure of firing patterns in large populations of
neurons. Spike trains recorded from populations of neurons can exhibit substantial pair wise
correlations between neurons and rich temporal structure. Thus, efficient methods for
generating artificial spike trains with specified correlation structure are essential for the
realistic simulation and analysis of neural systems.
Here we show how correlated binary spike trains can be modeled by means of a latent
multivariate Gaussian model. Sampling from our model is computationally very efficient, and
in particular, feasible even for large populations of neurons. We show empirically that the
spike trains generated with this method have entropy close to the theoretical maximum. They
are therefore consistent with specified pair-wise correlations without exhibiting systematic
higher-order correlations. We compare our model to alternative approaches and discuss its
limitations and advantages. In addition, we demonstrate its use for modeling temporal
correlations in a neuron recorded in macaque primary visual cortex.
Neural activity is often summarized by discarding the exact timing of spikes, and only
counting the total number of spikes that a neuron (or population) fires in a given time window.
In modeling studies, these spike counts have often been assumed to be Poisson distributed
and neurons to be independent. However, correlations between spike counts have been
reported in various visual areas. We show how both temporal and inter-neuron correlations
shape the structure of spike counts, and how our model can be used to generate spike counts
with arbitrary marginal distributions and correlation structure. We demonstrate its capabilities
by modeling a population of simultaneously recorded neurons from the primary visual cortex
of a macaque, and we show how a model with correlations accounts for the data far better
than a model that assumes independence.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-48Flexible Models for Population Spike Trains1501715420150171882351007PBerensASEckerMSubramaniyanJHMackePHauckMBethgeASToliasSantorini, Greece2008-06-0046AREADNE 2008: Research in Encoding and Decoding of Neural EnsemblesUnderstanding the structure of multi-neuronal firing patterns has been a central quest and
major challenge for systems neuroscience. In particular, how do pairwise interactions between
neurons shape the firing patterns of neuronal ensembles in the cortex? To study this
question, we recorded simultaneously from multiple single neurons in the primary visual
cortex of an awake, behaving macaque using an array of chronically implanted tetrodes1. High
contrast flashed and moving bars were used for stimulation, while the monkey was required to
maintain fixation.
In a similar vein to recent studies of in vitro preparations2,3,5, we applied maximum entropy
analysis for the first time to the binary spiking patterns of populations of cortical neurons
recorded in vivo from the awake macaque. We employed the Dichotomized Gaussian
distribution, which can be seen as a close approximation to the pairwise maximum-entropy
model for binary data4. Surprisingly, we find that even pairs of neurons with nearby receptive
fields (receptive field center distance < 0.15°) have only weak correlations between their
binary responses computed in bins of 10 ms (median absolute correlation coefficient: 0.014,
0.010-0.019, 95% confidence intervals, N=95 pairs; positive correlations: 0.015, N=59;
negative correlations: -0.013, N=36). Accordingly, the distribution of spiking patterns of
groups of 10 neurons is described well with a model that assumes independence between
individual neurons (Jensen-Shannon-Divergence: 1.06×10-2 independent model, 0.96×10-2
approximate second-order maximum-entropy model4; H/H1=0.992). These results suggest that
the distribution of firing patterns of small cortical networks in the awake animal is
predominantly determined by the mean activity of the participating cells, not by their
interactions.
Meaningful computations, however, are performed by neuronal populations much larger than
10 neurons. Therefore, we investigated how weak pairwise correlations affect the firing
patterns of artificial populations4 of up to 1000 cells with the same correlation structure as
experimentally measured. We find that in neuronal ensembles of this size firing patterns with
many active or silent neurons occur considerably more often than expected from a fully
independent population (e.g. 130 or more out of 1000 neurons are active simultaneously
roughly every 300 ms in the correlated model and only once every 3-4 seconds in the
independent model). These results suggest that the firing patterns of cortical networks
comparable in size to several minicolumns exhibit a rich structure, even if most pairs appear
relatively independent when studying small subgroups thereof.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-46Pairwise Correlations and Multineuronal Firing Patterns in the Primary Visual Cortex of the Awake, Behaving Macaque15017154201501718823MackeSB20087JHMackeGSchwartzMBerrySantorini, Greece2008-06-0073AREADNE 2008: Research in Encoding and Decoding of Neural Ensemblesnonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-73The role of stimulus correlations for population decoding in
the retina150171882349527GSchwartzJMackeMBerrySalt Lake City, UT, USA,2008-03-00172Computational and Systems Neuroscience Meeting (COSYNE 2008)a large number of retinal ganglion cells, one should be able to construct a decoding algorithm to discriminate different visual stimuli. Despite the inherent noise in the response of the ganglion cell population, everyday visual experience is highly deterministic. We have designed an experiment to study the nature of the population code of the retina in the “low error” regime.
We presented 36 different black and white shapes, each with the same number of black pixels, to the retina of a tiger salamander while recording retinal ganglion cell responses using a multi-electrode array.
Each shape was presented over 100 trials for 0.5 s each and trials were randomly interleaved. Spike trains were recorded from 162 ganglion cells in 13 experiments. We removed noise correlations by shuffling trials, as we wanted to focus on the role of correlations induced by the stimulus (signal correlations).
We designed decoding algorithms for this population response in order to detect each target shape against
the distracter set of the 35 other shapes. Binary response vectors were constructed using a 100 ms bin following the presentation of each shape. First, we used a simple decoder that assumes that all neurons are independent. This decoder is a linear classifier. A second decoder, which takes into account correlations between neurons, was constructed by fitting Ising models1 to the population response using up to 162 neurons for each model.
We also constructed the statistically optimal decoder based on a mixture model, which accounts for signal correlations.
Using populations of many neurons, the optimal and Ising
decoders performed considerably better than the “independent” decoder. For certain shapes, the optimal decoder had 100 times fewer false positives than the independent decoder at 99% hit rate, and, in the median across shapes, the performance enhancement was 8-fold. While the decoder using an Ising model fit to the pairwise correlations did not achieve optimality, it was up to 50 times more accurate than the independent decoder, and 3 times more accurate in the median across shapes.
Some shape discriminations were performed at zero error out of 3500 trials using the optimal and Ising decoders on only a subset of the recorded cells while none reached this “low error” level using the independent decoder even on all 162 cells (see figure).
We find that discrimination with very low error using large populations requires a decoder that models signal correlations. Linear classifiers were unable to reach the “low error” regime. The Ising model of the population response is successfully applied to groups of up to 162 cells and offers a biologically feasible mechanism by which downstream neurons could account for correlations in their inputs.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/COSYNE2008-Schwartz_4952[0].pdfpublished-172The role of stimulus correlations for population decoding in the retina150171882343477NMaackCKapferJHMackeBSchölkopfWDenkABorstGöttingen, Germany2007-04-0011957th Meeting of the German Neuroscience Society, 31st Göttingen Neurobiology ConferenceThe neural processing of visual motion is of essential importance for course control. A basic model suggesting
a possible mechanism of how such a computation could be implemented in the fly visual system is the so
called "correlation-type motion detector" proposed by Reichardt and Hassenstein in the 1950s. The basic
requirement to reconstruct the neural circuit underlying this computation is the availability of electron
microscopic 3D data sets of whole ensembles of neurons constituting the fly visual ganglia. We apply a new
technique,"Serial Block Face Scanning Electron Microscopy" (SBFSEM), that allows for an automatic
sectioning and imaging of biological tissue with a scanning electron microscope [Denk, Horstman (2004)
Serial block face scanning electron microscopy to reconstruct three-dimensional tissue nanostructure. PLOS
Biology 2: 1900-1909]. Image Stacks generated with this technology have a resolution sufficient to
distinguish different cellular compartments, especially synaptic structures. Consequently detailed anatomical
knowledge of complete neuronal circuits can be obtained. Such an image stack contains several thousands of
images and is recorded with a minimal voxel size of 25nm in x and y and 30nm in z direction. Consequently a
tissue block of 1mm³ (volume of the Calliphora vicina brain) produces several hundreds terabyte of data.
Therefore new concepts for managing large data sets and for automated 3D reconstruction algorithms need to
be developed. We developed an automated image segmentation and 3D reconstruction software, which allows
a precise contour tracing of cell membranes and simultaneously displays the resulting 3D structure. In detail,
the software contains two stand-alone packages: Neuron2D and Neuron3D, both offer an easy-to-operate
Graphical-User-Interface.
Neuron2D software provides the following image processing functions:
• Image Viewer: Display image stacks in single or movie mode and optional calculates intensity distribution
of each image.
• Image Preprocessing: Filter process of image stacks. Implemented filters are a Gaussian 2D and a
Non-Linear-Diffusion Filter. The filter step enhances the contrast between contour lines and image
background, leading to an enhanced signal to noise ratio which further improves detection of membrane
structures.
• Image Segmentation: The implemented algorithm extracts contour lines from the preceding image and
automatically traces the contour lines in the following images (z-direction), taking into account the previous
image segmentation. In addition, a manual interaction is possible.
To visualize 3D structures of neuronal circuits the additional software Neuron3D was developed. The
reconstruction of neuronal surfaces from contour lines, obtained in Neuron2D, is implemented as a graph
theory approach. The reconstructed anatomical data can further provide a subset for computational models of
neuronal circuits in the fly visual system.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-11953D Reconstruction of Neural Circuits from Serial EM Images1501715420150171882343457MBethgeJHMackeSGerwinnGZeckGöttingen, Germany2007-04-003597th Meeting of the German Neuroscience Society, 31st Göttingen Neurobiology ConferenceRight from the first synapse in the retina, the visual information gets distributed across several parallel
channels with different temporal filtering properties (Wässle, 2004). Yet, the prevalent system identification
tool for characterizing neural responses, the spike-triggered average, only allows one to investigate the
individual neural responses independently of each other. Here, we present a novel data analysis tool for the
identification of temporal population codes based on canonical correlation analysis (Hotelling, 1936).
Canonical correlation analysis allows one to find `population receptive fields' (PRF) which are maximally
correlated with the temporal response of the entire neural population. The method is a convex optimization
technique which essentially solves an eigenvalue problem and is not prone to local minima.
We apply the method to simultaneous recordings from rabbit retinal ganlion cells in a whole mount
preparation (Zeck et al, 2005). The cells respond to a 16 by 16 pixel m-sequence stimulus presented at a frame
rate of 1/(20 msec). The response of 27 ganglion cells is correlated with each input frame in an interval
between zero and 200 msec relative to the stimulus. The 200 msec response period is binned into 14
equal-sized bins. As shown in the figure, we obtain six predictive population receptive fields (left column),
each of which gives rise to a different population response (right column). The x-axis of the color-coded
images used to describe the population response kernels (right column) corresponds to the index of the 27
different neurons, while the y-axis indicates time relative to the stimulus from 0 (top) to 200 msec (bottom).
The six population receptive fields do not only provide a more concise description of the population response
but can also be estimated much more reliably than the receptive fields of individual neurons.
In conclusion, we suggest to characterize retinal ganglion cell responses in terms of population receptive
fields, rather than discussing stimulus-neuron and neuron-neuron dependencies separately.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/TS24-2C_4345[0].pdfpublished-359Identifying temporal population codes in the retina using canonical correlation analysis1501715420150171882342657MOFranzJHMackeASaleemSRSchultzGöttingen, Germany2007-04-0011997th Meeting of the German Neuroscience Society, 31st Göttingen Neurobiology ConferenceThe representation of the nonlinear response properties of a neuron by a Wiener series expansion has enjoyed
a certain popularity in the past, but its application has been limited to rather low-dimensional and weakly
nonlinear systems due to the exponential growth of the number of terms that have to be estimated. A recently
developed estimation method [1] utilizes the kernel techniques widely used in the machine learning
community to implicitly represent the Wiener series as an element of an abstract dot product space. In contrast
to the classical estimation methods for the Wiener series, the estimation complexity of the implicit
representation is linear in the input dimensionality and independent of the degree of nonlinearity.
From the neural system identification point of view, the proposed estimation method has several advantages:
1. Due to the linear dependence of the estimation complexity on input dimensionality, system identification
can be also done for systems acting on high-dimensional inputs such as images or video sequences.
2. Compared to classical cross-correlation techniques (such as spike-triggered average or covariance
estimates), similar accuracies can be achieved with a considerably smaller amount of data.
3. The new technique does not need white noise as input, but works for arbitrary classes of input signals such
as, e.g., natural image patches.
4. Regularisation concepts from machine learning to identify systems with noise-contaminated output signals.
We present an application of the implicit Wiener series to find the low-dimensional stimulus subspace which
accounts for most of the neuron's activity. We approximate the second-order term of a full Wiener series
model with a set of parallel cascades consisting of a linear receptive field and a static nonlinearity. This type
of approximation is known as reduced set technique in machine learning. We compare our results on
simulated and physiological datasets to existing identification techniques in terms of prediction performance
and accuracy of the obtained subspaces.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de/published-1199Implicit Wiener Series for Estimating Nonlinear Receptive Fields1501715420150171882346687JHMackeGZeckMBethgeSalt Lake City, UT, USA2007-02-0044Computational and Systems Neuroscience Meeting (COSYNE 2007)Right from the first synapse in the retina, visual information gets distributed
across several parallel channels with different temporal filtering properties.
Yet, commonly used system identification tools for characterizing
neural responses, such as the spike-triggered average, only allow one to
investigate the individual neural responses independently of each other.
Conversely, many population coding models of neurons and correlations
between neurons concentrate on the encoding of a single-variate stimulus.
We seek to identify the features of the visual stimulus that are encoded in
the temporal response of an ensemble of neurons, and the corresponding
spike-patterns that indicate the presence of these features.
We present a novel data analysis tool for the identification of such temporal
population codes based on canonical correlation analysis (Hotelling,
1936). The “population receptive fields” (PRFs) are defined to be those
dimensions of the stimulus-space that are maximally correlated with the
temporal response of the entire neural population, irrespective of whether
the stimulus features are encoded by the responses of single neurons or by
patterns of spikes across neurons or time. These dimensions are identified
by canonical correlation analysis, a convex optimization technique which essentially solves an eigenvalue
problem and is not prone to local minima.
Each receptive field can be represented by the weighted sum of a small number of functions that are separable
in space-time. Therefore, non-separable receptive fields can be estimated more efficiently than with spiketriggered
techniques, which makes our method advantageous even for the estimation of single-cell receptive
fields.
The method is demonstrated by applying it to data from multi-electrode recordings from rabbit retinal ganglion
cells in a whole mount preparation (Zeck et al, 2005). The figure displays the first 6 PRFs of a population
of 27 cells from one such experiment. The recovered stimulus-features look qualitatively different
to the receptive fields of single retinal ganglion cells. In addition, we show how the model can be extendended
to capture nonlinear stimulus-response relationships and to test different coding-mechanisms by the
use of kernel-canonical correlation analysis. In conclusion, we suggest to characterize responses of ensembles
of neurons in terms of PRFs, rather than discussing stimulus-neuron and neuron-neuron dependencies
separately.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/Cosyne-2007-I-37_[0].pdfpublished-44Estimating Population Receptive Fields in Space and Time1501715420150171882343587WKienzleJHMackeFAWichmannBSchölkopfMOFranzSalt Lake City, UT, USA2007-02-0016Computational and Systems Neuroscience Meeting (COSYNE 2007)Identification of stimulus-response functions is a central problem in systems neuroscience and related areas.
Prominent examples are the estimation of receptive fields and classification images [1]. In most cases, the
relationship between a high-dimensional input and the system output is modeled by a linear (first-order) or
quadratic (second-order) model. Models with third or higher order dependencies are seldom used, since
both parameter estimation and model interpretation can become very difficult.
Recently, Wu and Gallant [3] proposed the use of kernel methods, which have become a standard tool in
machine learning during the past decade [2]. Kernel methods can capture relationships of any order, while
solving the parameter estmation problem efficiently. In short, the stimuli are mapped into a high-dimensional
feature space, where a standard linear method, such as linear regression or Fisher discriminant, is applied.
The kernel function allows for doing this implicitly, with all computations carried out in stimulus space.
As a consequence, the resulting model is nonlinear, but many desirable properties of linear methods are
retained. For example, the estimation problem has no local minima, which is in contrast to other nonlinear
approaches, such as neural networks [4].
Unfortunately, although kernel methods excel at modeling complex functions, the question of how to interpret
the resulting models remains. In particular, it is not clear how receptive fields should be defined in
this context, or how they can be visualized. To remedy this, we propose the following definition: noting
that the model is linear in feature space, we define a nonlinear receptive field as a stimulus whose image in
feature space maximizes the dot-product with the learned model. This can be seen as a generalization of the
receptive field of a linear filter: if the feature map is the identity, the kernel method becomes linear, and our
receptive field definition coincides with that of a linear filter. If it is nonlinear, we numerically invert the
feature space mapping to recover the receptive field in stimulus space.
Experimental results show that receptive fields of simulated visual neurons, using natural stimuli, are correctly
identified. Moreover, we use this technique to compute nonlinear receptive fields of the human fixation
mechanism during free-viewing of natural images.nonotspecifiedhttp://www.kyb.tuebingen.mpg.de//fileadmin/user_upload/files/publications/Cosyne-2007-I-9_4358[0].pdfpublished-16Nonlinear Receptive Field Analysis: Making Kernel Methods Interpretable15017154201501718823Macke201310JMackeHafnerGMB201010RHäfnerSGerwinnJMackeMBethgeMackeOB200810JHMackeMOpperMBethgeKuGML200810S-PKuAGrettonJMackeNKLogothetis540810JHMackeGZeckMBethgeMacke200610JMacke