Model Constrained by Visual Hierarchy Improves Prediction of Neural Responses to Natural Scenes.

Accurate estimation of neuronal receptive fields is essential for understanding sensory processing in the early visual system. Yet a full characterization of receptive fields is still incomplete, especially with regard to natural visual stimuli and in complete populations of cortical neurons. While previous work has incorporated known structural properties of the early visual system, such as lateral connectivity, or imposing simple-cell-like receptive field structure, no study has exploited the fact that nearby V1 neurons share common feed-forward input from thalamus and other upstream cortical neurons. We introduce a new method for estimating receptive fields simultaneously for a population of V1 neurons, using a model-based analysis incorporating knowledge of the feed-forward visual hierarchy. We assume that a population of V1 neurons shares a common pool of thalamic inputs, and consists of two layers of simple and complex-like V1 neurons. When fit to recordings of a local population of mouse layer 2/3 V1 neurons, our model offers an accurate description of their response to natural images and significant improvement of prediction power over the current state-of-the-art methods. We show that the responses of a large local population of V1 neurons with locally diverse receptive fields can be described with surprisingly limited number of thalamic inputs, consistent with recent experimental findings. Our structural model not only offers an improved functional characterization of V1 neurons, but also provides a framework for studying the relationship between connectivity and function in visual cortical areas.

Mechanisms for stable, robust, and adaptive development of orientation maps in the primary visual cortex.

Development of orientation maps in ferret and cat primary visual cortex (V1) has been shown to be stable, in that the earliest measurable maps are similar in form to the eventual adult map, robust, in that similar maps develop in both dark rearing and in a variety of normal visual environments, and yet adaptive, in that the final map pattern reflects the statistics of the specific visual environment. How can these three properties be reconciled? Using mechanistic models of the development of neural connectivity in V1, we show for the first time that realistic stable, robust, and adaptive map development can be achieved by including two low-level mechanisms originally motivated from single-neuron results. Specifically, contrast-gain control in the retinal ganglion cells and the lateral geniculate nucleus reduces variation in the presynaptic drive due to differences in input patterns, while homeostatic plasticity of V1 neuron excitability reduces the postsynaptic variability in firing rates. Together these two mechanisms, thought to be applicable across sensory systems in general, lead to biological maps that develop stably and robustly, yet adapt to the visual environment. The modeling results suggest that topographic map stability is a natural outcome of low-level processes of adaptation and normalization. The resulting model is more realistic, simpler, and far more robust, and is thus a good starting point for future studies of cortical map development.

Neural computation via neural geometry: a place code for inter-whisker timing in the barrel cortex?

The place theory proposed by Jeffress (1948) is still the dominant model of how the brain represents the movement of sensory stimuli between sensory receptors. According to the place theory, delays in signalling between neurons, dependent on the distances between them, compensate for time differences in the stimulation of sensory receptors. Hence the location of neurons, activated by the coincident arrival of multiple signals, reports the stimulus movement velocity. Despite its generality, most evidence for the place theory has been provided by studies of the auditory system of auditory specialists like the barn owl, but in the study of mammalian auditory systems the evidence is inconclusive. We ask to what extent the somatosensory systems of tactile specialists like rats and mice use distance dependent delays between neurons to compute the motion of tactile stimuli between the facial whiskers (or 'vibrissae'). We present a model in which synaptic inputs evoked by whisker deflections arrive at neurons in layer 2/3 (L2/3) somatosensory 'barrel' cortex at different times. The timing of synaptic inputs to each neuron depends on its location relative to sources of input in layer 4 (L4) that represent stimulation of each whisker. Constrained by the geometry and timing of projections from L4 to L2/3, the model can account for a range of experimentally measured responses to two-whisker stimuli. Consistent with that data, responses of model neurons located between the barrels to paired stimulation of two whiskers are greater than the sum of the responses to either whisker input alone. The model predicts that for neurons located closer to either barrel these supralinear responses are tuned for longer inter-whisker stimulation intervals, yielding a topographic map for the inter-whisker deflection interval across the surface of L2/3. This map constitutes a neural place code for the relative timing of sensory stimuli.

Creating, documenting and sharing network models.

As computational neuroscience matures, many simulation environments are available that are useful for neuronal network modeling. However, methods for successfully documenting models for publication and for exchanging models and model components among these projects are still under development. Here we briefly review existing software and applications for network model creation, documentation and exchange. Then we discuss a few of the larger issues facing the field of computational neuroscience regarding network modeling and suggest solutions to some of these problems, concentrating in particular on standardized network model terminology, notation, and descriptions and explicit documentation of model scaling. We hope this will enable and encourage computational neuroscientists to share their models more systematically in the future.

From phonemes to articulatory codes: an fMRI study of the role of Broca's area in speech production.

We used event-related functional magnetic resonance imaging to investigate the neuroanatomical substrates of phonetic encoding and the generation of articulatory codes from phonological representations. Our focus was on the role of the left inferior frontal gyrus (LIFG) and in particular whether the LIFG plays a role in sublexical phonological processing such as syllabification or whether it is directly involved in phonetic encoding and the generation of articulatory codes. To answer this question, we contrasted the brain activation patterns elicited by pseudowords with high- or low-sublexical frequency components, which we expected would reveal areas related to the generation of articulatory codes but not areas related to phonological encoding. We found significant activation of a premotor network consisting of the dorsal precentral gyrus, the inferior frontal gyrus bilaterally, and the supplementary motor area for low- versus high-sublexical frequency pseudowords. Based on our hypothesis, we concluded that these areas and in particular the LIFG are involved in phonetic and not phonological encoding. We further discuss our findings with respect to the mechanisms of phonetic encoding and provide evidence in support of a functional segregation of the posterior part of Broca's area, the pars opercularis.

Computational Modeling of Contrast Sensitivity and Orientation Tuning in First-Episode and Chronic Schizophrenia.

Computational modeling is a useful method for generating hypotheses about the contributions of impaired neurobiological mechanisms, and their interactions, to psychopathology. Modeling is being increasingly used to further our understanding of schizophrenia, but to date, it has not been applied to questions regarding the common perceptual disturbances in the disorder. In this article, we model aspects of low-level visual processing and demonstrate how this can lead to testable hypotheses about both the nature of visual abnormalities in schizophrenia and the relationships between the mechanisms underlying these disturbances and psychotic symptoms. Using a model that incorporates retinal, lateral geniculate nucleus (LGN), and V1 activity, as well as gain control in the LGN, homeostatic adaptation in V1, lateral excitation and inhibition in V1, and self-organization of synaptic weights based on Hebbian learning and divisive normalization, we show that (a) prior data indicating increased contrast sensitivity for low-spatial-frequency stimuli in first-episode schizophrenia can be successfully modeled as a function of reduced retinal and LGN efferent activity, leading to overamplification at the cortical level, and (b) prior data on reduced contrast sensitivity and broadened orientation tuning in chronic schizophrenia can be successfully modeled by a combination of reduced V1 lateral inhibition and an increase in the Hebbian learning rate at V1 synapses for LGN input. These models are consistent with many current findings, and they predict several relationships that have not yet been demonstrated. They also have implications for understanding changes in brain and visual function from the first psychotic episode to the chronic stage of illness.

Cortical Maps.

In this article, we review functional organization in sensory cortical regions-how the cortex represents the world. We consider four interrelated aspects of cortical organization: (1) the set of receptive fields of individual cortical sensory neurons, (2) how lateral interaction between cortical neurons reflects the similarity of their receptive fields, (3) the spatial distribution of receptive-field properties across the horizontal extent of the cortical tissue, and (4) how the spatial distributions of different receptive-field properties interact with one another. We show how these data are generally well explained by the theory of input-driven self-organization, with a family of computational models of cortical maps offering a parsimonious account for a wide range of map-related phenomena. We then discuss important challenges to this explanation, with respect to the maps present at birth, maps present under activity blockade, the limits of adult plasticity, and the lack of some maps in rodents. Because there is not at present another credible general theory for cortical map development, we conclude by proposing key experiments to help uncover other mechanisms that might also be operating during map development.

Edge co-occurrences can account for rapid categorization of natural versus animal images.

Making a judgment about the semantic category of a visual scene, such as whether it contains an animal, is typically assumed to involve high-level associative brain areas. Previous explanations require progressively analyzing the scene hierarchically at increasing levels of abstraction, from edge extraction to mid-level object recognition and then object categorization. Here we show that the statistics of edge co-occurrences alone are sufficient to perform a rough yet robust (translation, scale, and rotation invariant) scene categorization. We first extracted the edges from images using a scale-space analysis coupled with a sparse coding algorithm. We then computed the "association field" for different categories (natural, man-made, or containing an animal) by computing the statistics of edge co-occurrences. These differed strongly, with animal images having more curved configurations. We show that this geometry alone is sufficient for categorization, and that the pattern of errors made by humans is consistent with this procedure. Because these statistics could be measured as early as the primary visual cortex, the results challenge widely held assumptions about the flow of computations in the visual system. The results also suggest new algorithms for image classification and signal processing that exploit correlations between low-level structure and the underlying semantic category.

What, if anything, are topological maps for?

What, if anything, is the functional significance of spatial patterning in cortical feature maps? We ask this question of four major theories of cortical map formation: self-organizing maps, wiring optimization, place coding, and reaction-diffusion. We argue that (i) self-organizing maps yield spatial patterning only as a by-product of efficient mechanisms for developing environmentally appropriate distributions of feature preferences, (ii) wiring optimization assumes rather than explains a map-like organization, (iii) place-coding mechanisms can at best explain only a subset of maps in functional terms, and (iv) reaction-diffusion models suggest two factors in the evolution of maps, the first based on efficient development of feature distributions, and the second based on generating feature-specific long-range recurrent cortical circuitry. None of these explanations for the existence of topological maps requires spatial patterning in maps to be useful. Thus despite these useful frameworks for understanding how maps form and how they are wired, the possibility that patterns are merely epiphenomena in the evolution of mammalian neocortex cannot be rejected. The article is intended as a nontechnical introduction to the assumptions and predictions of these four important classes of models, along with other possible functional explanations for maps.

Scaling self-organizing maps to model large cortical networks.

Self-organizing computational models with specific intracortical connections can explain many functional features of visual cortex, such as topographic orientation and ocular dominance maps. However, due to their computational requirements, it is difficult to use such detailed models to study large-scale phenomenal like object segmentation and binding, object recognition, tilt illusions, optic flow, and fovea-periphery differences. This article introduces two techniques that make large simulations practical. First, we show how parameter scaling equations can be derived for laterally connected self-organizing models. These equations result in quantitatively equivalent maps over a wide range of simulation sizes, making it possible to debug small simulations and then scale them up only when needed. Parameter scaling also allows detailed comparison of biological maps and parameters between individuals and species with different brain region sizes. Second, we use parameter scaling to implement a new growing map method called GLISSOM, which dramatically reduces the memory and computational requirements of large self-organizing networks. With GLISSOM, it should be possible to simulate all of human V1 at the single-column level using current desktop workstations. We are using these techniques to develop a new simulator Topographica, which will help make it practical to perform detailed studies of large-scale phenomena in topographic maps.

An automated and reproducible workflow for running and analyzing neural simulations using Lancet and IPython Notebook.

Lancet is a new, simulator-independent Python utility for succinctly specifying, launching, and collating results from large batches of interrelated computationally demanding program runs. This paper demonstrates how to combine Lancet with IPython Notebook to provide a flexible, lightweight, and agile workflow for fully reproducible scientific research. This informal and pragmatic approach uses IPython Notebook to capture the steps in a scientific computation as it is gradually automated and made ready for publication, without mandating the use of any separate application that can constrain scientific exploration and innovation. The resulting notebook concisely records each step involved in even very complex computational processes that led to a particular figure or numerical result, allowing the complete chain of events to be replicated automatically. Lancet was originally designed to help solve problems in computational neuroscience, such as analyzing the sensitivity of a complex simulation to various parameters, or collecting the results from multiple runs with different random starting points. However, because it is never possible to know in advance what tools might be required in future tasks, Lancet has been designed to be completely general, supporting any type of program as long as it can be launched as a process and can return output in the form of files. For instance, Lancet is also heavily used by one of the authors in a separate research group for launching batches of microprocessor simulations. This general design will allow Lancet to continue supporting a given research project even as the underlying approaches and tools change.

Building a mechanistic model of the development and function of the primary visual cortex.

Researchers have used a very wide range of different experimental and theoretical approaches to help understand mammalian visual systems. These approaches tend to have quite different assumptions, strengths, and weaknesses. Computational models of the visual cortex, in particular, have typically implemented either a proposed circuit for part of the visual cortex of the adult, assuming a very specific wiring pattern based on findings from adults, or else attempted to explain the long-term development of a visual cortex region from an initially undifferentiated starting point. Previous models of adult V1 have been able to account for many of the measured properties of V1 neurons, while not explaining how these properties arise or why neurons have those properties in particular. Previous developmental models have been able to reproduce the overall organization of specific feature maps in V1, such as orientation maps, but are generally formulated at an abstract level that does not allow testing with real images or analysis of detailed neural properties relevant for visual function. In this review of results from a large set of new, integrative models developed from shared principles and a set of shared software components, I show how these models now represent a single, consistent explanation for a wide body of experimental evidence, and form a compact hypothesis for much of the development and behavior of neurons in the visual cortex. The models are the first developmental models with wiring consistent with V1, the first to have realistic behavior with respect to visual contrast, and the first to include all of the demonstrated visual feature dimensions. The goal is to have a comprehensive explanation for why V1 is wired as it is in the adult, and how that circuitry leads to the observed behavior of the neurons during visual tasks.

Development of maps of simple and complex cells in the primary visual cortex.

Hubel and Wiesel (1962) classified primary visual cortex (V1) neurons as either simple, with responses modulated by the spatial phase of a sine grating, or complex, i.e., largely phase invariant. Much progress has been made in understanding how simple-cells develop, and there are now detailed computational models establishing how they can form topographic maps ordered by orientation preference. There are also models of how complex cells can develop using outputs from simple cells with different phase preferences, but no model of how a topographic orientation map of complex cells could be formed based on the actual connectivity patterns found in V1. Addressing this question is important, because the majority of existing developmental models of simple-cell maps group neurons selective to similar spatial phases together, which is contrary to experimental evidence, and makes it difficult to construct complex cells. Overcoming this limitation is not trivial, because mechanisms responsible for map development drive receptive fields (RF) of nearby neurons to be highly correlated, while co-oriented RFs of opposite phases are anti-correlated. In this work, we model V1 as two topographically organized sheets representing cortical layer 4 and 2/3. Only layer 4 receives direct thalamic input. Both sheets are connected with narrow feed-forward and feedback connectivity. Only layer 2/3 contains strong long-range lateral connectivity, in line with current anatomical findings. Initially all weights in the model are random, and each is modified via a Hebbian learning rule. The model develops smooth, matching, orientation preference maps in both sheets. Layer 4 units become simple cells, with phase preference arranged randomly, while those in layer 2/3 are primarily complex cells. To our knowledge this model is the first explaining how simple cells can develop with random phase preference, and how maps of complex cells can develop, using only realistic patterns of connectivity.

Similar neural adaptation mechanisms underlying face gender and tilt aftereffects.

Visual aftereffects have been found for a wide variety of stimuli, ranging from oriented lines to human faces, but previous results suggested that face aftereffects were qualitatively different from orientation (tilt) aftereffects. Using computational models, we predicted that these differences were due to the limited range of faces used in previous studies. Here we report psychophysical results verifying this prediction. We used the same paradigm to test tilt aftereffects (TAE) and face gender aftereffects (FAE) and found that they exhibited qualitatively similar aftereffect curves, when a sufficiently large range of test faces was used. Overall, the results suggest that similar adaptation mechanisms may underlie both high-level and low-level visual processing.

Modeling the emergence of whisker direction maps in rat barrel cortex.

Based on measuring responses to rat whiskers as they are mechanically stimulated, one recent study suggests that barrel-related areas in layer 2/3 rat primary somatosensory cortex (S1) contain a pinwheel map of whisker motion directions. Because this map is reminiscent of topographic organization for visual direction in primary visual cortex (V1) of higher mammals, we asked whether the S1 pinwheels could be explained by an input-driven developmental process as is often suggested for V1. We developed a computational model to capture how whisker stimuli are conveyed to supragranular S1, and simulate lateral cortical interactions using an established self-organizing algorithm. Inputs to the model each represent the deflection of a subset of 25 whiskers as they are contacted by a moving stimulus object. The subset of deflected whiskers corresponds with the shape of the stimulus, and the deflection direction corresponds with the movement direction of the stimulus. If these two features of the inputs are correlated during the training of the model, a somatotopically aligned map of direction emerges for each whisker in S1. Predictions of the model that are immediately testable include (1) that somatotopic pinwheel maps of whisker direction exist in adult layer 2/3 barrel cortex for every large whisker on the rat's face, even peripheral whiskers; and (2) in the adult, neurons with similar directional tuning are interconnected by a network of horizontal connections, spanning distances of many whisker representations. We also propose specific experiments for testing the predictions of the model by manipulating patterns of whisker inputs experienced during early development. The results suggest that similar intracortical mechanisms guide the development of primate V1 and rat S1.

Topographica: Building and Analyzing Map-Level Simulations from Python, C/C++, MATLAB, NEST, or NEURON Components.

Many neural regions are arranged into two-dimensional topographic maps, such as the retinotopic maps in mammalian visual cortex. Computational simulations have led to valuable insights about how cortical topography develops and functions, but further progress has been hindered by the lack of appropriate tools. It has been particularly difficult to bridge across levels of detail, because simulators are typically geared to a specific level, while interfacing between simulators has been a major technical challenge. In this paper, we show that the Python-based Topographica simulator makes it straightforward to build systems that cross levels of analysis, as well as providing a common framework for evaluating and comparing models implemented in other simulators. These results rely on the general-purpose abstractions around which Topographica is designed, along with the Python interfaces becoming available for many simulators. In particular, we present a detailed, general-purpose example of how to wrap an external spiking PyNN/NEST simulation as a Topographica component using only a dozen lines of Python code, making it possible to use any of the extensive input presentation, analysis, and plotting tools of Topographica. Additional examples show how to interface easily with models in other types of simulators. Researchers simulating topographic maps externally should consider using Topographica's analysis tools (such as preference map, receptive field, or tuning curve measurement) to compare results consistently, and for connecting models at different levels. This seamless interoperability will help neuroscientists and computational scientists to work together to understand how neurons in topographic maps organize and operate.

Learning innate face preferences.

Newborn humans preferentially orient to facelike patterns at birth, but months of experience with faces are required for full face processing abilities to develop. Several models have been proposed for how the interaction of genetic and environmental influences can explain these data. These models generally assume that the brain areas responsible for newborn orienting responses are not capable of learning and are physically separate from those that later learn from real faces. However, it has been difficult to reconcile these models with recent discoveries of face learning in newborns and young infants. We propose a general mechanism by which genetically specified and environment-driven preferences can coexist in the same visual areas. In particular, newborn face orienting may be the result of prenatal exposure of a learning system to internally generated input patterns, such as those found in PGO waves during REM sleep. Simulating this process with the HLISSOM biological model of the visual system, we demonstrate that the combination of learning and internal patterns is an efficient way to specify and develop circuitry for face perception. This prenatal learning can account for the newborn preferences for schematic and photographic images of faces, providing a computational explanation for how genetic influences interact with experience to construct a complex adaptive system.