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The cerebellar granule cell layer has inspired numerous theoretical models of neural representations that support learned behaviors, beginning with the work of Marr and Albus. In these models, granule cells form a sparse, combinatorial encoding of diverse sensorimotor inputs. Such sparse representations are optimal for learning to discriminate random stimuli. However, recent observations of dense, low-dimensional activity across granule cells have called into question the role of sparse coding in these neurons. Here, we generalize theories of cerebellar learning to determine the optimal granule cell representation for tasks beyond random stimulus discrimination, including continuous input-output transformations as required for smooth motor control. We show that for such tasks, the optimal granule cell representation is substantially denser than predicted by classic theories. Our results provide a general theory of learning in cerebellum-like systems and suggest that optimal cerebellar representations are task-dependent.

We present a windowed technique to learn parsimonious time-varying autoregressive models from multivariate timeseries. This unsupervised method uncovers interpretable spatiotemporal structure in data via non-smooth and non-convex optimization. In each time window, we assume the data follow a linear model parameterized by a system matrix, and we model this stack of potentially different system matrices as a low rank tensor. Because of its structure, the model is scalable to high-dimensional data and can easily incorporate priors such as smoothness over time. We find the components of the tensor using alternating minimization and prove that any stationary point of this algorithm is a local minimum. We demonstrate on a synthetic example that our method identifies the true rank of a switching linear system in the presence of noise. We illustrate our model's utility and superior scalability over extant methods when applied to several synthetic and real-world example: two types of time-varying linear systems, worm behavior, sea surface temperature, and monkey brain datasets.

Significance Population histories are encoded by genomic variation among modern individuals. Population genetic inference methods, all theoretically rooted in probabilistic population models, can recover complex demographic histories from genomic variation data. However, the mutation process is treated very simply in these models—usually as a single constant. Recent empirical findings show that the mutation process is complex and dynamic over a range of evolutionary timescales and thus, deserving of richer descriptions in population genetic models. Here, we show that complex mutation spectrum histories can be accommodated by extending classical theoretical tools. We develop mathematical optimization methods and software to infer both demographic history and mutation spectrum history, revealing human mutation signatures varying through time and global divergence of mutational processes., As populations boom and bust, the accumulation of genetic diversity is modulated, encoding histories of living populations in present-day variation. Many methods exist to decode these histories, and all must make strong model assumptions. It is typical to assume that mutations accumulate uniformly across the genome at a constant rate that does not vary between closely related populations. However, recent work shows that mutational processes in human and great ape populations vary across genomic regions and evolve over time. This perturbs the mutation spectrum (relative mutation rates in different local nucleotide contexts). Here, we develop theoretical tools in the framework of Kingman’s coalescent to accommodate mutation spectrum dynamics. We present mutation spectrum history inference (mushi), a method to perform nonparametric inference of demographic and mutation spectrum histories from allele frequency data. We use mushi to reconstruct trajectories of effective population size and mutation spectrum divergence between human populations, identify mutation signatures and their dynamics in different human populations, and calibrate the timing of a previously reported mutational pulse in the ancestors of Europeans. We show that mutation spectrum histories can be placed in a well-studied theoretical setting and rigorously inferred from genomic variation data, like other features of evolutionary history.

Booming and busting populations modulate the accumulation of genetic diversity, encoding histories of living populations in present-day variation. Many methods exist to decode these histories, and all must make strong model assumptions. It is typical to assume that mutations accumulate uniformly across the genome at a constant rate that does not vary between closely related populations. However, recent work shows that mutational processes in human and great ape populations vary across genomic regions and evolve over time. This perturbs themutation spectrum: the relative mutation rates in different local nucleotide contexts. Here, we develop theoretical tools in the framework of Kingman’s coalescent to accommodate mutation spectrum dynamics. We describemushi: a method to perform fast, nonparametric joint inference of demographic and mutation spectrum histories from allele frequency data. We usemushito reconstruct trajectories of effective population size and mutation spectrum divergence between human populations, identify mutation signatures and their dynamics in different human populations, and produce more accurate time calibration for a previously-reported mutational pulse in the ancestors of Europeans. We show that mutation spectrum histories can be productively incorporated in a well-studied theoretical setting, and rigorously inferred from genomic variation data like other features of evolutionary history.

Knowledge of mesoscopic brain connectivity is important for understanding inter- and intraregion information processing. Models of structural connectivity are typically constructed and analyzed with the assumption that regions are homogeneous. We instead use the Allen Mouse Brain Connectivity Atlas to construct a model of whole-brain connectivity at the scale of 100 μm voxels. The data consist of 428 anterograde tracing experiments in wild type C57BL/6J mice, mapping fluorescently labeled neuronal projections brain-wide. Inferring spatial connectivity with this dataset is underdetermined, since the approximately 2 × 105 source voxels outnumber the number of experiments. To address this issue, we assume that connection patterns and strengths vary smoothly across major brain divisions. We model the connectivity at each voxel as a radial basis kernel-weighted average of the projection patterns of nearby injections. The voxel model outperforms a previous regional model in predicting held-out experiments and compared with a human-curated dataset. This voxel-scale model of the mouse connectome permits researchers to extend their previous analyses of structural connectivity to much higher levels of resolution, and it allows for comparison with functional imaging and other datasets., Author Summary Anatomical tracing experiments can provide a wealth of information regarding connectivities originating from the injection sites. However, it is difficult to integrate all this information into a comprehensive connectivity model. In this study we construct a high-resolution model of the mouse brain connectome using the assumption that connectivity patterns vary smoothly within brain regions, and we present several extensions of this model. We believe that this higher resolution connectome will be of great use to the community, enabling comparisons with other data modalities, such as functional imaging and gene expression, as well as for theoretical studies.

Unraveling the interplay of excitation and inhibition within rhythm-generating networks remains a fundamental issue in neuroscience. We use a biophysical model to investigate the different roles of local and long-range inhibition in the respiratory network, a key component of which is the pre-Bötzinger complex inspiratory microcircuit. Increasing inhibition within the microcircuit results in a limited number of out-of-phase neurons before rhythmicity and synchrony degenerate. Thus unstructured local inhibition is destabilizing and cannot support the generation of more than one rhythm. A two-phase rhythm requires restructuring the network into two microcircuits coupled by long-range inhibition in the manner of a half-center. In this context, inhibition leads to greater stability of the two out-of-phase rhythms. We support our computational results with in vitro recordings from mouse pre-Bötzinger complex. Partial excitation block leads to increased rhythmic variability, but this recovers after blockade of inhibition. Our results support the idea that local inhibition in the pre-Bötzinger complex is present to allow for descending control of synchrony or robustness to adverse conditions like hypoxia. We conclude that the balance of inhibition and excitation determines the stability of rhythmogenesis, but with opposite roles within and between areas. These different inhibitory roles may apply to a variety of rhythmic behaviors that emerge in widespread pattern-generating circuits of the nervous system. NEW & NOTEWORTHY The roles of inhibition within the pre-Bötzinger complex (preBötC) are a matter of debate. Using a combination of modeling and experiment, we demonstrate that inhibition affects synchrony, period variability, and overall frequency of the preBötC and coupled rhythmogenic networks. This work expands our understanding of ubiquitous motor and cognitive oscillatory networks.

Recovering brain connectivity from tract tracing data is an important computational problem in the neurosciences. Mesoscopic connectome reconstruction was previously formulated as a structured matrix regression problem (Harris et al. in Neural Information Processing Systems, 2016), but existing techniques do not scale to the whole-brain setting. The corresponding matrix equation is challenging to solve due to large scale, ill-conditioning, and a general form that lacks a convergent splitting. We propose a greedy low-rank algorithm for the connectome reconstruction problem in very high dimensions. The algorithm approximates the solution by a sequence of rank-one updates which exploit the sparse and positive definite problem structure. This algorithm was described previously (Kressner and Sirković in Numer Lin Alg Appl 22(3):564–583, 2015) but never implemented for this connectome problem, leading to a number of challenges. We have had to design judicious stopping criteria and employ efficient solvers for the three main sub-problems of the algorithm, including an efficient GPU implementation that alleviates the main bottleneck for large datasets. The performance of the method is evaluated on three examples: an artificial “toy” dataset and two whole-cortex instances using data from the Allen Mouse Brain Connectivity Atlas. We find that the method is significantly faster than previous methods and that moderate ranks offer a good approximation. This speedup allows for the estimation of increasingly large-scale connectomes across taxa as these data become available from tracing experiments. The data and code are available online. ispartof: Journal Of Mathematical Neuroscience vol:9 issue:1 ispartof: location:Germany status: Published online

We provide a novel analysis of low-rank tensor completion based on hypergraph expanders. As a proxy for rank, we minimize the max-quasinorm of the tensor, which generalizes the max-norm for matrices. Our analysis is deterministic and shows that the number of samples required to approximately recover an order-$t$ tensor with at most $n$ entries per dimension is linear in $n$, under the assumption that the rank and order of the tensor are $O(1)$. As steps in our proof, we find a new expander mixing lemma for a $t$-partite, $t$-uniform regular hypergraph model, and prove several new properties about tensor max-quasinorm. To the best of our knowledge, this is the first deterministic analysis of tensor completion. We develop a practical algorithm that solves a relaxed version of the max-quasinorm minimization problem, and we demonstrate its efficacy with numerical experiments., Comment: 35 pages, 4 figures. To appear in SIAM Journal on Mathematics of Data Science

We prove an analogue of Alon's spectral gap conjecture for random bipartite, biregular graphs. We use the Ihara-Bass formula to connect the non-backtracking spectrum to that of the adjacency matrix, employing the moment method to show there exists a spectral gap for the non-backtracking matrix. A byproduct of our main theorem is that random rectangular zero-one matrices with fixed row and column sums are full-rank with high probability. Finally, we illustrate applications to community detection, coding theory, and deterministic matrix completion., Small changes to the paper

Knowledge of mesoscopic brain connectivity is important for understanding inter- and intra-region information processing. Models of structural connectivity are typically constructed and analyzed with the assumption that regions are homogeneous. We instead use the Allen Mouse Brain Connectivity Atlas to construct a model of whole brain connectivity at the scale of 100 µm voxels. The dataset used consists of 366 anterograde tracing experiments in wild type C7BL/6 mice, mapping fluorescently-labeled neuronal projections brain-wide. Inferring spatial connectivity with this dataset remains underdetermined, since the approximately 2 × 105 source voxels outnumber the number of experiments. To address this, we assume that connection patterns and strengths vary smoothly across major brain divisions. We model the connectivity at each voxel as a radial basis kernel-weighted average of the projection patterns of nearby injections. The voxel model outperforms a previous regional model in predicting held-out experiments and compared to a human-curated dataset. This voxel-scale model of the mouse connectome permits researchers to extend their previous analyses of structural connectivity to unprecedented levels of resolution, and allows for comparison with functional imaging and other datasets.

Using human evaluation of 100,000 words spread across 24 corpora in 10 languages diverse in origin and culture, we present evidence of a deep imprint of human sociality in language, observing that (1) the words of natural human language possess a universal positivity bias; (2) the estimated emotional content of words is consistent between languages under translation; and (3) this positivity bias is strongly independent of frequency of word usage. Alongside these general regularities, we describe inter-language variations in the emotional spectrum of languages which allow us to rank corpora. We also show how our word evaluations can be used to construct physical-like instruments for both real-time and offline measurement of the emotional content of large-scale texts., Manuscript: 7 pages, 4 figures; Supplementary Material: 49 pages, 43 figures, 6 tables. Online appendices available at http://www.uvm.edu/storylab/share/papers/dodds2014a/

We demonstrate that the concerns expressed by Garcia et al. are misplaced, due to (1) a misreading of our findings in [1]; (2) a widespread failure to examine and present words in support of asserted summary quantities based on word usage frequencies; and (3) a range of misconceptions about word usage frequency, word rank, and expert-constructed word lists. In particular, we show that the English component of our study compares well statistically with two related surveys, that no survey design influence is apparent, and that estimates of measurement error do not explain the positivity biases reported in our work and that of others. We further demonstrate that for the frequency dependence of positivity---of which we explored the nuances in great detail in [1]---Garcia et al. did not perform a reanalysis of our data---they instead carried out an analysis of a different, statistically improper data set and introduced a nonlinearity before performing linear regression., 5 pages, 2 figures, 1 table. Expanded version of reply appearing in PNAS 2015

Synaptic connectivity varies widely across neuronal types. Cerebellar granule cells receive five orders of magnitude fewer inputs than the Purkinje cells they innervate, and cerebellum-like circuits, including the insect mushroom body, also exhibit large divergences in connectivity. In contrast, the number of inputs per neuron in cerebral cortex is more uniform and large. We investigate how the dimension of a representation formed by a population of neurons depends on how many inputs each neuron receives and what this implies for learning associations. Our theory predicts that the dimensions of the cerebellar granule-cell and Drosophila Kenyon-cell representations are maximized at degrees of synaptic connectivity that match those observed anatomically, showing that sparse connectivity is sometimes superior to dense connectivity. When input synapses are subject to supervised plasticity, however, dense wiring becomes advantageous, suggesting that the type of plasticity exhibited by a set of synapses is a major determinant of connection density.

We conduct a detailed investigation of correlations between real-time expressions of individuals made across the United States and a wide range of emotional, geographic, demographic, and health characteristics. We do so by combining (1) a massive, geo-tagged data set comprising over 80 million words generated over the course of several recent years on the social network service Twitter and (2) annually-surveyed characteristics of all 50 states and close to 400 urban populations. Among many results, we generate taxonomies of states and cities based on their similarities in word use; estimate the happiness levels of states and cities; correlate highly-resolved demographic characteristics with happiness levels; and connect word choice and message length with urban characteristics such as education levels and obesity rates. Our results show how social media may potentially be used to estimate real-time levels and changes in population-level measures such as obesity rates.

We study a family of binary state, socially-inspired contagion models which incorporate imitation limited by an aversion to complete conformity. We uncover rich behavior in our models whether operating with either probabilistic or deterministic individual response functions on both dynamic and fixed random networks. In particular, we find significant variation in the limiting behavior of a population's infected fraction, ranging from steady-state to chaotic. We show that period doubling arises as we increase the average node degree, and that the universality class of this well known route to chaos depends on the interaction structure of random networks rather than the microscopic behavior of individual nodes. We find that increasing the fixedness of the system tends to stabilize the infected fraction, yet disjoint, multiple equilibria are possible depending solely on the choice of the initially infected node., Comment: 4 pages, 3 figures

Over the last million years, human language has emerged and evolved as a fundamental instrument of social communication and semiotic representation. People use language in part to convey emotional information, leading to the central and contingent questions: (1) What is the emotional spectrum of natural language? and (2) Are natural languages neutrally, positively, or negatively biased? Here, we report that the human-perceived positivity of over 10,000 of the most frequently used English words exhibits a clear positive bias. More deeply, we characterize and quantify distributions of word positivity for four large and distinct corpora, demonstrating that their form is broadly invariant with respect to frequency of word use., Manuscript: 9 pages, 3 tables, 5 figures; Supplementary Information: 12 pages, 3 tables, 8 figures

For a broad range single-seed contagion processes acting on generalized random networks, we derive a unifying analytic expression for the possibility of global spreading events in a straightforward, physically intuitive fashion. Our reasoning lays bare a direct mechanical understanding of an archetypal spreading phenomena that is not evident in circuitous extant mathematical approaches., 4 pages, 1 figure, 1 table

Individual happiness is a fundamental societal metric. Normally measured through self-report, happiness has often been indirectly characterized and overshadowed by more readily quantifiable economic indicators such as gross domestic product. Here, we examine expressions made on the online, global microblog and social networking service Twitter, uncovering and explaining temporal variations in happiness and information levels over timescales ranging from hours to years. Our data set comprises over 46 billion words contained in nearly 4.6 billion expressions posted over a 33 month span by over 63 million unique users. In measuring happiness, we use a real-time, remote-sensing, non-invasive, text-based approach---a kind of hedonometer. In building our metric, made available with this paper, we conducted a survey to obtain happiness evaluations of over 10,000 individual words, representing a tenfold size improvement over similar existing word sets. Rather than being ad hoc, our word list is chosen solely by frequency of usage and we show how a highly robust metric can be constructed and defended., 27 pages, 17 figures, 3 tables. Supplementary Information: 1 table, 52 figures

The advent of social media has provided an extraordinary, if imperfect, 'big data' window into the form and evolution of social networks. Based on nearly 40 million message pairs posted to Twitter between September 2008 and February 2009, we construct and examine the revealed social network structure and dynamics over the time scales of days, weeks, and months. At the level of user behavior, we employ our recently developed hedonometric analysis methods to investigate patterns of sentiment expression. We find users' average happiness scores to be positively and significantly correlated with those of users one, two, and three links away. We strengthen our analysis by proposing and using a null model to test the effect of network topology on the assortativity of happiness. We also find evidence that more well connected users write happier status updates, with a transition occurring around Dunbar's number. More generally, our work provides evidence of a social sub-network structure within Twitter and raises several methodological points of interest with regard to social network reconstructions., Comment: 22 pages, 21 figures, 5 tables, In press at the Journal of Computational Science