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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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Segregation between the parietal memory network and the default mode network: Effects of spatial smoothing and model order in ICA

A brain network consisting of two key parietal nodes, the precuneus and the posterior cingulate cortex, has emerged from recent fMRI studies. Though it is anatomically adjacent to and spatially overlaps with the default mode network (DMN), its function has been associated with memory processing, and it has been referred to as the parietal memory network (PMN). Independent component analysis (ICA) is the most common data-driven method of extracting PMN and DMN simultaneously. However, the effects of data preprocessing and parameter determination in ICA on PMN-DMN segregation are completely unknown. Here, we employ three typical algorithms of group ICA to assess how spatial smoothing and model order influence the degree of PMN-DMN segregation. Our findings indicate that PMN and DMN can only be stably separated using a combination of low-level spatial smoothing and high-order model across the three ICA algorithms. We thus argue for more considerations on parametric settings for interpreting DMN data.

neuroscience

A mixture of sparse coding models explaining properties of face neurons related to holistic and parts-based processing

Experimental studies have revealed evidence of both parts-based and holistic representations of objects and faces in the primate visual system. However, it is still a mystery how such seemingly contradictory types of processing can coexist within a single system. Here, we propose a novel theory called mixture of sparse coding models, inspired by the formation of category-specific subregions in the inferotemporal (IT) cortex. We developed a hierarchical network that constructed a mixture of two sparse coding submodels on top of a simple Gabor analysis. The submodels were each trained with face or non-face object images, which resulted in separate representations of facial parts and object parts. Importantly, evoked neural activities were modeled by Bayesian inference, which had a top-down explaining-away effect that enabled recognition of an individual part to depend strongly on the category of the whole input. We show that this explaining-away effect was indeed crucial for the units in the face submodel to exhibit significant selectivity to face images over object images in a similar way to actual face-selective neurons in the macaque IT cortex. Furthermore, the model explained, qualitatively and quantitatively, several tuning properties to facial features found in the middle patch of face processing in IT as documented by Freiwald, Tsao, and Livingstone (2009). These included, in particular, tuning to only a small number of facial features that were often related to geometrically large parts like face outline and hair, preference and anti-preference of extreme facial features (e.g., very large/small inter-eye distance), and reduction of the gain of feature tuning for partial face stimuli compared to whole face stimuli. Thus, we hypothesize that the coding principle of facial features in the middle patch of face processing in the macaque IT cortex may be closely related to mixture of sparse coding models.

neuroscience

A TOPOLOGICAL/ECOLOGICAL APPROACH TO PERCEPTION

During the exploration of the surrounding environment, the brain links together external inputs, giving rise to perception of a persisting object. During imaginative processes, the same object can be recalled in mind even if it is out of sight. In this proof of concept study, Borsuks theory of shape and the Borsuk-Ulam theorem provide a mathematical foundation for Gibsons notion of persistence perception. Gibsons ecological theory of perception accounts for our knowledge of world objects by borrowing a concept of invariance in topology. A series of transformations can be gradually applied to a pattern, in particular to the shape of an object, without affecting its invariant properties, such as boundedness of parts of a visual scene. High-level representations of objects in our environment are mapped to simplified views (our interpretations) of the objects, in order to construct a symbolic representation of the environment. The representations can be projected continuously to an ecological object that we have seen and continue to see, thanks to the mapping from shapes in our memory to shapes in Euclidean space.

neuroscience

Spatial tuning shifts increase the discriminability and fidelity of population codes in visual cortex

AcknowledgementsMany thanks to the lab and particularly to Rosanne Rademaker and Edward Vul for comments on analyses and on the manuscript. This work was supported by National Science Foundation Graduate Research Fellowships to V.A.V. and T.C.S., a grant from the National Eye Institute (R01-EY025872) and a Scholar Award from the James S. McDonnell Foundation to J.T.S.\n\nABSTRACTSelective visual attention enables organisms to enhance the representation of behaviorally relevant stimuli by altering the encoding properties of single receptive fields (RFs). Yet we know little about how the attentional modulations of single RFs contribute to the encoding of an entire visual scene. Addressing this issue requires (1) measuring a group of RFs that tile a continuous portion of visual space, (2) constructing a population-level measurement of spatial representations based on these RFs, and (3) linking how different types of RF attentional modulations change the population-level representation. To accomplish these aims, we used fMRI to characterize the responses of thousands of voxels in retinotopically organized human cortex. First, we found that the response modulations of voxel RFs (vRFs) depend on the spatial relationship between the RF center and the visual location of the attended target. Second, we used two analyses to assess the spatial encoding quality of a population of voxels. We found that attention increased fine spatial discriminability and representational fidelity near the attended target. Third, we linked these findings by manipulating the observed vRF attentional modulations and recomputing our population measures. Surprisingly, we discovered that attentional enhancements of population-level representations largely depend on position shifts of vRFs, rather than changes in size or gain. Our data suggest that position shifts of single RFs are a principal mechanism by which attention enhances population-level representations in visual cortex.

neuroscience

Spike interval coding of translatory optic flow and depth from motion in the fly visual system

Many animals use the visual motion generated by travelling in a line, the translatory optic flow, to successfully navigate obstacles: near objects appear larger and to move more quickly than distant ones. Flies are experts at navigating cluttered environments, and while their visual processing of rotatory optic flow is understood in exquisite detail, how they process translatory optic flow remains a mystery. Here, we present novel cell types that have motion receptive fields matched to translation self-motion, the vertical translation (VT) cells. One of these, the VT1 cell, encodes forwards sideslip self-motion, and fires action potentials in clusters of spikes, spike bursts. We show that the spike burst coding is size and speed-tuned, and is selectively modulated by parallax motion, the relative motion experienced during translation. These properties are spatially organized, so that the cell is most excited by clutter rather than isolated objects. When the fly is presented with a simulation of flying past an elevated object, the spike burst activity is modulated by the height of the object, and the single spike rate is unaffected. When the moving object alone is experienced, the cell is weakly driven. Meanwhile, the VT2-3 cells have motion receptive fields matched to the lift axis. In conjunction with previously described horizontal cells, the VT cells have the properties required for the fly to successfully navigate clutter and encode its movements along near cardinal axes of thrust, lift and forward sideslip.

neuroscience

Recent progress in multi-electrode spike sorting methods

In recent years, arrays of extracellular electrodes have been developed and manufactured to record simultaneously from hundreds of electrodes packed with a high density. These recordings should allow neuroscientists to reconstruct the individual activity of the neurons spiking in the vicinity of these electrodes, with the help of signal processing algorithms. Algorithms need to solve a source separation problem, also known as spike sorting. However, these new devices challenge the classical way to do spike sorting. Here we review different methods that have been developed to sort spikes from these large-scale recordings. We describe the common properties of these algorithms, as well as their main differences. Finally, we outline the issues that remain to be solved by future spike sorting algorithms.

neuroscience

Genetic overlap between in-scanner head motion and the default network connectivity

The association between in-scanner head motion and intrinsic functional connectivity (iFC) may confound explanations for individual differences in functional connectomics. However, the etiology of the correlation between head motion and iFC has not been established. This study aimed to investigate genetic and environmental contributions on the association between head motion and iFC using a twin dataset (175 same-sex twin pairs, aged 14-23 years, 48% females). After establishing that both head motion and default network iFC are moderately heritable, we found large genetic correlations (-0.52 to -0.73) between head motion and the default network iFCs. Common genes can explain 48% - 61% of the negative phenotypic correlation between the two phenotypes. These results advance our understanding of the relationship between head motion and iFC, and may have profound implications for interpreting individual differences in default network connectivity in clinical research and brain-behavior association.

neuroscience

Response variability and population coupling of cortical synaptic inputs are strongly influenced by network properties

The highly variable spiking of a cortical neuron is \"coupled\" to that of other neurons in the network. This has implications for sensory coding, and appears to represent a fundamental property of cortical sensory processing. To date, most studies of population coupling have focused on recorded spiking activity, an approach that suffers from several confounding issues. Moreover, the contributions of various network properties to population coupling are largely unexplored. To this end, we recorded the membrane potential (V) and the nearby LFP in the visual cortex of the turtle ex vivo wholebrain preparation during ongoing and visually-evoked activity. We used an algorithm to infer the excitatory conductance (g) from V, and calculated the g-LFP coupling. We found that g-LFP coupling was highly variable across neurons, and increased following visual stimulation before relaxing to intermediate values. To investigate the role of the network, we implemented a driven small-world network of leaky integrate-and-fire neurons. This model reproduces the large across-trial response variability and g-LFP coupling dynamic, and suggests crucial roles for anatomical and emergent network properties.

neuroscience

Adaptation modulates correlated response variability in visual cortex

Cortical sensory responses are highly variable across stimulus presentations. This variability can be correlated across neurons (due to some combination of dense intracortical connectivity, cortical activity level, and cortical state), with fundamental implications for population coding. Yet the interpretation of correlated response variability (or \"noise correlation\") has remained fraught with difficulty, in part because of the restriction to extracellular neuronal spike recordings. Here, we measured response variability and its correlation at the most microscopic level of electrical neural activity, the membrane potential, by obtaining dual whole-cell recordings from pairs of cortical pyramidal neurons during visual processing. We found that during visual stimulation, correlated variability adapts towards an intermediate level and that this correlation dynamic is mediated by intracortical mechanisms. A model network with external inputs, synaptic depression, and structure reproduced the observed dynamics of correlated variability. These results establish that intracortical adaptation self-organizes cortical circuits towards a balanced regime at which network coordination maintains an intermediate level.

neuroscience

Learning enhances sensory processing in mouse V1 before improving behavior

A fundamental property of visual cortex is to enhance the representation of those stimuli that are relevant for behavior, but it remains poorly understood how such enhanced representations arise during learning. Using classical conditioning in mice, we show that orientation discrimination is learned in a sequence of distinct behavioral stages, in which animals first rely on stimulus appearance before exploiting its orientation to guide behavior. After confirming that orientation discrimination under classical conditioning requires primary visual cortex (V1), we measured, during learning, response properties of V1 neurons. Learning improved neural discriminability, sharpened orientation tuning and led to higher contrast sensitivity. Remarkably, these learning-related improvements in the V1 representation were fully expressed before successful orientation discrimination was evident in the animals behavior. We propose that V1 plays a key role early in discrimination learning to enhance behaviorally relevant sensory information.

neuroscience

Anterior cingulate is a source of valence-specificinformation about value and uncertainty

Expectations of rewards and punishments can promote similar behavioral states, such as vigilance, as well as distinct behavioral states, such as approach or avoidance. However, the cortical circuits that underlie this behavioral diversity are poorly understood. In a Pavlovian procedure in which monkeys displayed a diverse repertoire of reward, punishment, and uncertainty related behaviors not mandated by the task, I show that many anterior-cingulate (ACC) neurons represent expected value and uncertainty in a valence-specific manner, for example about either rewards or punishments. This flexibility may facilitate the top-down control of many reward- and punishment-related actions and behavioral states.

neuroscience

A first-principle for the nervous system

Higher brain functions such as perception and memory are first-person internal sensations whose mechanisms can have options to concurrently activate motor neurons for behavioral action. By setting up all the required constraints using available information from different levels, a theoretical examination from a first-person frame of reference led to the derivation of a first-principle of the structure-function units. These units operate in synchrony with the synaptically-connected neural circuitry. These units are capable of explaining and interconnecting findings from various levels and enable triangulation of a large number of observations from both the normal and \"loss of function\" states of the system. Indirect evidence for the presence of a comparable circuitry in a remote species - Drosophila - suggests the universal presence of these units across the animal kingdom. The key features of the basic unit meet the expectations of the K-lines proposed for the development of artificial intelligence.

neuroscience

T-SNE visualization of large-scale neural recordings.

Electrophysiology is entering the era of Big Data. Multiple probes, each with hundreds to thousands of individual electrodes, are now capable of simultaneously recording from many brain regions. The major challenge confronting these new technologies is transforming the raw data into physiologically meaningful signals, i.e. single unit spikes. Sorting the spike events of individual neurons from a spatiotemporally dense sampling of the extracellular electric field is a problem that has attracted much attention [22, 23], but is still far from solved. Current methods still rely on human input and thus become unfeasible as the size of the data sets grow exponentially.\n\nHere we introduce the t-student stochastic neighbor embedding (t-sne) dimensionality reduction method [27] as a visualization tool in the spike sorting process. T-sne embeds the n-dimensional extracellular spikes (n = number of features by which each spike is decomposed) into a low (usually two) dimensional space. We show that such embeddings, even starting from different feature spaces, form obvious clusters of spikes that can be easily visualized and manually delineated with a high degree of precision. We propose that these clusters represent single units and test this assertion by applying our algorithm on labeled data sets both from hybrid [23] and paired juxtacellular/extracellular recordings [15]. We have released a graphical user interface (gui) written in python as a tool for the manual clustering of the t-sne embedded spikes and as a tool for an informed overview and fast manual curration of results from other clustering algorithms. Furthermore, the generated visualizations offer evidence in favor of the use of probes with higher density and smaller electrodes. They also graphically demonstrate the diverse nature of the sorting problem when spikes are recorded with different methods and arise from regions with different background spiking statistics.

neuroscience

Interneuronal mechanisms of hippocampal theta oscillation in a full-scale model of the rodent CA1 circuit

The hippocampal theta rhythm plays important roles in information processing; however, the mechanisms of its generation are not well understood. We developed a data-driven, supercomputer-based, full-scale (1:1) model of the CA1 area and studied its interneurons during theta oscillations. Theta rhythm with phase-locked gamma oscillations and phase-preferential discharges of distinct in terneuronal types spontaneously emerged from the isolated CA1 circuit without rhythmic inputs. Perturbation experiments identified parvalbumin-expressing interneurons and neurogliaform cells, as well as interneuronal diversity itself, as important factors in theta generation. These simulations reveal new insights into the spatiotemporal organization of the CA1 circuit during theta oscillations.

neuroscience

Striatal Action-Value Neurons Reconsidered

It is generally believed that during economic decisions, striatal neurons represent the values associated with different actions. This hypothesis is based on a large number of studies, in which the neural activity of striatal neurons was measured while the subject was learning to prefer the more rewarding action. Here we show that these publications are subject to at least one of two critical confounds and that most are subject to both. First, we show that even weak temporal correlations in the neuronal data may result in an erroneous identification of action-value representations. We demonstrate this by erroneously identifying action-value representations, both in simulations and in the neural activity recorded in unrelated experiments. Second, we show that the experiments and analyses designed to dissociate action-value representation from the representation of other decision variables cannot do so. Specifically, we show that neurons representing policy may be erroneous identified as representing action-values. We suggest different solutions to identifying action-value representation that are not subject to these confounds. Applying one of these solutions to previously identified action-value neurons in the basal ganglia we fail to detect action-value representations there. Thus, we conclude that the claim that striatal neurons encode action-values must await new experiments and analyses.

neuroscience

Metrics for comparing Neuronal Tree Shapes based on Persistent Homology

The geometrical tree structures of axonal and dendritic processes play important roles in determining the architecture and capabilities of neuronal circuitry. Morphological features based on this tree structure have played a central role in classifying neurons for over a century. Yet geometrical trees are not automatically adapted to the basic mathematical tool used widely in data analysis, namely vector spaces and linear algebra, since tree geometries cannot be naturally added and subtracted. Current methods for analysis reduce trees to feature vectors in more or less ad hoc ways. A more natural mathematical object suited to characterizing neuronal tree geometries, is a metric space, where only distances between objects need be defined. In recent years, there have been significant developments in the fields of computational topology and geometry that promise to be useful for the analysis of neuronal geometries. In this paper, we adapt these tools to the problem of characterizing and analyzing neuronal morphology.\n\nAs more and more neuroanatomical data are made available through efforts such as NeuroMorpho.org and FlyCircuit.org, the need to develop computational tools to facilitate automatic knowledge discovery from such large datasets becomes more urgent. One fundamental question is how best to compare neuron structures, for instance to organize and classify large collection of neurons. We aim to develop a flexible yet powerful framework to support comparison and classification of large collection of neuron structures efficiently. Specifically we propose to use a topological persistence-based feature vectorization framework. Existing methods to vectorize a neuron (i.e, convert a neuron to a feature vector so as to support efficient comparison and/or searching) typically rely on statistics or summaries of morphometric information, such as the average or maximum local torque angle or partition asymmetry. These simple summaries have limited power in encoding global tree structures. Leveraging recent development in topological data analysis, we vectorize each neuron structure into a simple yet informative summary via the use of topological persistence. In particular, each type of information of interest can be represented as a descriptor function defined on the neuron tree, which is then mapped to a simple persistence-signature. Our framework can encode both local and global tree structure, as well as other information of interest (electrophysiological or dynamical measures), by considering multiple descriptor functions on the neuron. The resulting persistence-based signature is potentially more informative than simple statistical summaries (such as average/mean/max) of morphometric quantities - Indeed, we show that using a certain descriptor function will give a persistence-based signature containing strictly more information than the classical Sholl analysis. At the same time, our framework retains the efficiency associated with treating neurons as points in a simple Euclidean feature space, which would be important for constructing efficient searching or indexing structures over them. We present preliminary experimental results to demonstrate the effectiveness of our persistence-based neuronal feature vectorization framework.

neuroscience

Optical-flow analysis toolbox for characterization of spatiotemporal dynamics in mesoscale optical imaging of brain activity

Wide-field optical imaging techniques constitute powerful tools to sample and study mesoscale neuronal activity. The sampled data constitutes a sequence of image frames in which one can perceive the flow of brain activity starting and terminating at source and sink locations respectively. The most common data analyses include qualitative assessment to identify sources and sinks of activity as well as their trajectories. The quantitative analyses is mostly based on computing the temporal variation of the intensity of pixels while a few studies have also reported estimates of wave motion using optical-flow techniques from computer vision. A comprehensive toolbox for the quantitative analyses of mesoscale brain activity data however is still missing. We present a graphical-user-interface based Matlab(R) toolbox for investigating the spatiotemporal dynamics of mesoscale brain activity using optical-flow analyses. The toolbox includes the implementation of three optical-flow methods namely Horn-Schunck, Combined Local-Global, and Temporospatial algorithms for estimating velocity vector fields of perceived flow in mesoscale brain activity. From the velocity vector fields we determine the locations of sources and sinks as well as the trajectories and temporal velocities of activity flow. Using our toolbox, we compare the efficacy of the three optical-flow methods for determining spatiotemporal dynamics by using simulated data. We also demonstrate the application of optical-flow methods onto sensory-evoked calcium and voltage imaging data. Our results indicate that the combined local-global method we employ, yields results that correlate with the manual assessment. The automated approach permits rapid and effective quantification of mesoscale brain dynamics and may facilitate the study of brain function in response to new experiences or pathology.\n\nConflicts of Interestnone\n\nAuthor contribution statementMHM, MM, NV, and SI designed the study. NA and SI wrote Matlab(R) code for the toolbox and designed the simulated data. MHM, and NA performed the experiments. NA and SI analyzed the data. SI, NA, and MHM wrote the manuscript.

neuroscience

Modulation of Body Mass Composition using Vestibular Nerve Stimulation.

There is increasing evidence of a \"set-point\" for body weight in the brain, that is regulated by the hypothalamus. This system modifies feeding behavior and metabolic rate, to keep body fat within predetermined parameters. It is also known that animals subjected to chronic centrifugation show a reduction in body fat. Experiments with mutant mice found that this loss of fat appears to be mediated by a vestibulo-hypothalamic pathway. Vestibular nerve stimulation (VeNS), also known as galvanic vestibular stimulation, involves non-invasively stimulating the vestibular system by applying a small electrical current between two electrodes placed over the mastoid processes. We suggest that any means of repeatedly stimulating the otolith organs in humans would cause a reduction in total body fat, and that VeNS would be a useful technique to use in this regard. Below we provide pilot data to support this idea.

neuroscience