The quality and complexity of pairwise maximum entropy models for large cortical populations.

We investigate the ability of the pairwise maximum entropy (PME) model to describe the spiking activity of large populations of neurons recorded from the visual, auditory, motor, and somatosensory cortices. To quantify this performance, we use (1) Kullback-Leibler (KL) divergences, (2) the extent to which the pairwise model predicts third-order correlations, and (3) its ability to predict the probability that multiple neurons are simultaneously active. We compare these with the performance of a model with independent neurons and study the relationship between the different performance measures, while varying the population size, mean firing rate of the chosen population, and the bin size used for binarizing the data. We confirm the previously reported excellent performance of the PME model for small population sizes N < 20. But we also find that larger mean firing rates and bin sizes generally decreases performance. The performance for larger populations were generally not as good. For large populations, pairwise models may be good in terms of predicting third-order correlations and the probability of multiple neurons being active, but still significantly worse than small populations in terms of their improvement over the independent model in KL-divergence. We show that these results are independent of the cortical area and of whether approximate methods or Boltzmann learning are used for inferring the pairwise couplings. We compared the scaling of the inferred couplings with N and find it to be well explained by the Sherrington-Kirkpatrick (SK) model, whose strong coupling regime shows a complex phase with many metastable states. We find that, up to the maximum population size studied here, the fitted PME model remains outside its complex phase. However, the standard deviation of the couplings compared to their mean increases, and the model gets closer to the boundary of the complex phase as the population size grows.

Restricted Boltzmann Machines as Models of Interacting Variables.

We study the type of distributions that restricted Boltzmann machines (RBMs) with different activation functions can express by investigating the effect of the activation function of the hidden nodes on the marginal distribution they impose on observed binary nodes. We report an exact expression for these marginals in the form of a model of interacting binary variables with the explicit form of the interactions depending on the hidden node activation function. We study the properties of these interactions in detail and evaluate how the accuracy with which the RBM approximates distributions over binary variables depends on the hidden node activation function and the number of hidden nodes. When the inferred RBM parameters are weak, an intuitive pattern is found for the expression of the interaction terms, which reduces substantially the differences across activation functions. We show that the weak parameter approximation is a good approximation for different RBMs trained on the MNIST data set. Interestingly, in these cases, the mapping reveals that the inferred models are essentially low order interaction models.

Task-dependent mixed selectivity in the subiculum.

CA1 and subiculum (SUB) connect the hippocampus to numerous output regions. Cells in both areas have place-specific firing fields, although they are more dispersed in SUB. Weak responses to head direction and running speed have been reported in both regions. However, how such information is encoded in CA1 and SUB and the resulting impact on downstream targets are poorly understood. Here, we estimate the tuning of simultaneously recorded CA1 and SUB cells to position, head direction, and speed. Individual neurons respond conjunctively to these covariates in both regions, but the degree of mixed representation is stronger in SUB, and more so during goal-directed spatial navigation than free foraging. Each navigational variable could be decoded with higher precision, from a similar number of neurons, in SUB than CA1. The findings point to a possible contribution of mixed-selective coding in SUB to efficient transmission of hippocampal representations to widespread brain regions.

Efficiency of Local Learning Rules in Threshold-Linear Associative Networks.

We derive the Gardner storage capacity for associative networks of threshold linear units, and show that with Hebbian learning they can operate closer to such Gardner bound than binary networks, and even surpass it. This is largely achieved through a sparsification of the retrieved patterns, which we analyze for theoretical and empirical distributions of activity. As reaching the optimal capacity via nonlocal learning rules like back propagation requires slow and neurally implausible training procedures, our results indicate that one-shot self-organized Hebbian learning can be just as efficient.

Action representation in the mouse parieto-frontal network.

The posterior parietal cortex (PPC) and frontal motor areas comprise a cortical network supporting goal-directed behaviour, with functions including sensorimotor transformations and decision making. In primates, this network links performed and observed actions via mirror neurons, which fire both when individuals perform an action and when they observe the same action performed by a conspecific. Mirror neurons are believed to be important for social learning, but it is not known whether mirror-like neurons occur in similar networks in other social species, such as rodents, or if they can be measured in such models using paradigms where observers passively view a demonstrator. Therefore, we imaged Ca2+ responses in PPC and secondary motor cortex (M2) while mice performed and observed pellet-reaching and wheel-running tasks, and found that cell populations in both areas robustly encoded several naturalistic behaviours. However, neural responses to the same set of observed actions were absent, although we verified that observer mice were attentive to performers and that PPC neurons responded reliably to visual cues. Statistical modelling also indicated that executed actions outperformed observed actions in predicting neural responses. These results raise the possibility that sensorimotor action recognition in rodents could take place outside of the parieto-frontal circuit, and underscore that detecting socially-driven neural coding depends critically on the species and behavioural paradigm used.

Multiscale relevance and informative encoding in neuronal spike trains.

Neuronal responses to complex stimuli and tasks can encompass a wide range of time scales. Understanding these responses requires measures that characterize how the information on these response patterns are represented across multiple temporal resolutions. In this paper we propose a metric - which we call multiscale relevance (MSR) - to capture the dynamical variability of the activity of single neurons across different time scales. The MSR is a non-parametric, fully featureless indicator in that it uses only the time stamps of the firing activity without resorting to any a priori covariate or invoking any specific structure in the tuning curve for neural activity. When applied to neural data from the mEC and from the ADn and PoS regions of freely-behaving rodents, we found that neurons having low MSR tend to have low mutual information and low firing sparsity across the correlates that are believed to be encoded by the region of the brain where the recordings were made. In addition, neurons with high MSR contain significant information on spatial navigation and allow to decode spatial position or head direction as efficiently as those neurons whose firing activity has high mutual information with the covariate to be decoded and significantly better than the set of neurons with high local variations in their interspike intervals. Given these results, we propose that the MSR can be used as a measure to rank and select neurons for their information content without the need to appeal to any a priori covariate.

Hippocampal spike-time correlations and place field overlaps during open field foraging.

Phase precessing place cells encode spatial information on fine timescales via the timing of their spikes. This phase code has been extensively studied on linear tracks and for short runs in the open field. However, less is known about the phase code on unconstrained trajectories lasting tens of minutes, typical of open field foraging. In previous work (Monsalve-Mercado and Leibold, Physical Review Letters, 119, 38101 (2017)), an analytic expression was derived for the spike-time cross-correlation between phase precessing place cells during natural foraging in the open field. This expression makes two predictions on how this phase code differs from the linear track case: cross-correlations are symmetric with respect to time, and they represent the distance between pairs of place fields in that the theta-filtered cross-correlations around zero time lag are positive for cells with nearby fields while they are negative for those with fields further apart. Here we analyze several available open field recordings and show that these predictions hold for pairs of CA1 place cells. We also show that the relationship remains during remapping in CA1, and it is also present in place cells in area CA3. For CA1 place cells of Fmr1-null mice, which exhibit normal place fields but somewhat weaker temporal coordination with respect to theta compared to wild type, the cross-correlations still remain symmetric but the relationship to place field overlap is largely lost. The relationship discussed here describes how spatial information is communicated by place cells to downstream areas in a finer theta-timescale, relevant for learning and memory formation in behavioral tasks lasting tens of minutes in the open field.

On the Complexity of Logistic Regression Models.

We investigate the complexity of logistic regression models, which is defined by counting the number of indistinguishable distributions that the model can represent (Balasubramanian, 1997). We find that the complexity of logistic models with binary inputs depends not only on the number of parameters but also on the distribution of inputs in a nontrivial way that standard treatments of complexity do not address. In particular, we observe that correlations among inputs induce effective dependencies among parameters, thus constraining the model and, consequently, reducing its complexity. We derive simple relations for the upper and lower bounds of the complexity. Furthermore, we show analytically that defining the model parameters on a finite support rather than the entire axis decreases the complexity in a manner that critically depends on the size of the domain. Based on our findings, we propose a novel model selection criterion that takes into account the entropy of the input distribution. We test our proposal on the problem of selecting the input variables of a logistic regression model in a Bayesian model selection framework. In our numerical tests, we find that while the reconstruction errors of standard model selection approaches (AIC, BIC, ℓ1 regularization) strongly depend on the sparsity of the ground truth, the reconstruction error of our method is always close to the minimum in all conditions of sparsity, data size, and strength of input correlations. Finally, we observe that when considering categorical instead of binary inputs, in a simple and mathematically tractable case, the contribution of the alphabet size to the complexity is very small compared to that of parameter space dimension. We further explore the issue by analyzing the data set of the "13 keys to the White House," a method for forecasting the outcomes of US presidential elections.

Phase transitions and asymmetry between signal comprehension and production in biological communication.

We introduce a model for collective information acquisition from the environment, in a biological population. In this model, individuals can make noisy observations of the environment, and communicate their observation by production and comprehension of signals. As the communication noise decreases, the model shows an order-disorder transition from a disordered phase in which no consensus about the environmental state exists to an ordered phase where the population forms a consensus about the environmental state. The ordered phase itself is composed of an informed consensus, in which the correct belief about the environment prevails, and an uninformed consensus phase, in which consensus on a random belief about the environmental state is formed. The probability of reaching informed consensus increases with increasing the observation probability. This phenomenology implies that a maximum noise level, and a minimum observation probability are necessary for informed consensus in a communicating population. Furthermore, we show that the fraction of observant individuals needed for the group to reach informed consensus decreases with increasing population size. This results from a shift in the uninformed-informed transition to smaller observation probabilities by increasing population size. Importantly, we also find that an amount of noise in signal production deteriorates the information flow and the inference capability, more than the same amount of noise in comprehension. This finding implies that there is higher selection pressure to reduce noise in production of signals compared to comprehension. Regarding this asymmetry, we propose an experimental design to separately measure comprehension and production noise in a given population and test the predicted asymmetry.

Minimum Description Length Codes Are Critical.

In the Minimum Description Length (MDL) principle, learning from the data is equivalent to an optimal coding problem. We show that the codes that achieve optimal compression in MDL are critical in a very precise sense. First, when they are taken as generative models of samples, they generate samples with broad empirical distributions and with a high value of the relevance, defined as the entropy of the empirical frequencies. These results are derived for different statistical models (Dirichlet model, independent and pairwise dependent spin models, and restricted Boltzmann machines). Second, MDL codes sit precisely at a second order phase transition point where the symmetry between the sampled outcomes is spontaneously broken. The order parameter controlling the phase transition is the coding cost of the samples. The phase transition is a manifestation of the optimality of MDL codes, and it arises because codes that achieve a higher compression do not exist. These results suggest a clear interpretation of the widespread occurrence of statistical criticality as a characterization of samples which are maximally informative on the underlying generative process.

A Novel Mechanism for the Grid-to-Place Cell Transformation Revealed by Transgenic Depolarization of Medial Entorhinal Cortex Layer II.

The spatial receptive fields of neurons in medial entorhinal cortex layer II (MECII) and in the hippocampus suggest general and environment-specific maps of space, respectively. However, the relationship between these receptive fields remains unclear. We reversibly manipulated the activity of MECII neurons via chemogenetic receptors and compared the changes in downstream hippocampal place cells to those of neurons in MEC. Depolarization of MECII impaired spatial memory and elicited drastic changes in CA1 place cells in a familiar environment, similar to those seen during remapping between distinct environments, while hyperpolarization did not. In contrast, both manipulations altered the firing rate of MEC neurons without changing their firing locations. Interestingly, only depolarization caused significant changes in the relative firing rates of individual grid fields, reconfiguring the spatial input from MEC. This suggests a novel mechanism of hippocampal remapping whereby rate changes in MEC neurons lead to locational changes of hippocampal place fields.

Ten Years of Grid Cells.

The medial entorhinal cortex (MEC) creates a neural representation of space through a set of functionally dedicated cell types: grid cells, border cells, head direction cells, and speed cells. Grid cells, the most abundant functional cell type in the MEC, have hexagonally arranged firing fields that tile the surface of the environment. These cells were discovered only in 2005, but after 10 years of investigation, we are beginning to understand how they are organized in the MEC network, how their periodic firing fields might be generated, how they are shaped by properties of the environment, and how they interact with the rest of the MEC network. The aim of this review is to summarize what we know about grid cells and point out where our knowledge is still incomplete.

Learning with hidden variables.

Learning and inferring features that generate sensory input is a task continuously performed by cortex. In recent years, novel algorithms and learning rules have been proposed that allow neural network models to learn such features from natural images, written text, audio signals, etc. These networks usually involve deep architectures with many layers of hidden neurons. Here we review recent advancements in this area emphasizing, amongst other things, the processing of dynamical inputs by networks with hidden nodes and the role of single neuron models. These points and the questions they arise can provide conceptual advancements in understanding of learning in the cortex and the relationship between machine learning approaches to learning with hidden nodes and those in cortical circuits.

Correlations and functional connections in a population of grid cells.

We study the statistics of spike trains of simultaneously recorded grid cells in freely behaving rats. We evaluate pairwise correlations between these cells and, using a maximum entropy kinetic pairwise model (kinetic Ising model), study their functional connectivity. Even when we account for the covariations in firing rates due to overlapping fields, both the pairwise correlations and functional connections decay as a function of the shortest distance between the vertices of the spatial firing pattern of pairs of grid cells, i.e. their phase difference. They take positive values between cells with nearby phases and approach zero or negative values for larger phase differences. We find similar results also when, in addition to correlations due to overlapping fields, we account for correlations due to theta oscillations and head directional inputs. The inferred connections between neurons in the same module and those from different modules can be both negative and positive, with a mean close to zero, but with the strongest inferred connections found between cells of the same module. Taken together, our results suggest that grid cells in the same module do indeed form a local network of interconnected neurons with a functional connectivity that supports a role for attractor dynamics in the generation of grid pattern.

Multi-neuronal activity and functional connectivity in cell assemblies.

Our ability to collect large amounts of data from many cells has been paralleled by the development of powerful statistical models for extracting information from this data. Here we discuss how the activity of cell assemblies can be analyzed using these models, focusing on the generalized linear models and the maximum entropy models and describing a number of recent studies that employ these tools for analyzing multi-neuronal activity. We show results from simulations comparing inferred functional connectivity, pairwise correlations and the real synaptic connections in simulated networks demonstrating the power of statistical models in inferring functional connectivity. Further development of network reconstruction techniques based on statistical models should lead to more powerful methods of understanding functional anatomy of cell assemblies.

Grid cells and cortical representation.

One of the grand challenges in neuroscience is to comprehend neural computation in the association cortices, the parts of the cortex that have shown the largest expansion and differentiation during mammalian evolution and that are thought to contribute profoundly to the emergence of advanced cognition in humans. In this Review, we use grid cells in the medial entorhinal cortex as a gateway to understand network computation at a stage of cortical processing in which firing patterns are shaped not primarily by incoming sensory signals but to a large extent by the intrinsic properties of the local circuit.

Network mechanisms of grid cells.

One of the major breakthroughs in neuroscience is the emerging understanding of how signals from the external environment are extracted and represented in the primary sensory cortices of the mammalian brain. The operational principles of the rest of the cortex, however, have essentially remained in the dark. The discovery of grid cells, and their functional organization, opens the door to some of the first insights into the workings of the association cortices, at a stage of neural processing where firing properties are shaped not primarily by the nature of incoming sensory signals but rather by internal self-organizing principles. Grid cells are place-modulated neurons whose firing locations define a periodic triangular array overlaid on the entire space available to a moving animal. The unclouded firing pattern of these cells is rare within the association cortices. In this paper, we shall review recent advances in our understanding of the mechanisms of grid-cell formation which suggest that the pattern originates by competitive network interactions, and we shall relate these ideas to new insights regarding the organization of grid cells into functionally segregated modules.

Maximum likelihood reconstruction for Ising models with asynchronous updates.

We describe how the couplings in an asynchronous kinetic Ising model can be inferred. We consider two cases: one in which we know both the spin history and the update times and one in which we know only the spin history. For the first case, we show that one can average over all possible choices of update times to obtain a learning rule that depends only on spin correlations and can also be derived from the equations of motion for the correlations. For the second case, the same rule can be derived within a further decoupling approximation. We study all methods numerically for fully asymmetric Sherrington-Kirkpatrick models, varying the data length, system size, temperature, and external field. Good convergence is observed in accordance with the theoretical expectations.

Learning and inference in a nonequilibrium Ising model with hidden nodes.

We study inference and reconstruction of couplings in a partially observed kinetic Ising model. With hidden spins, calculating the likelihood of a sequence of observed spin configurations requires performing a trace over the configurations of the hidden ones. This, as we show, can be represented as a path integral. Using this representation, we demonstrate that systematic approximate inference and learning rules can be derived using dynamical mean-field theory. Although naive mean-field theory leads to an unstable learning rule, taking into account Gaussian corrections allows learning the couplings involving hidden nodes. It also improves learning of the couplings between the observed nodes compared to when hidden nodes are ignored.