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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 433 records · Page 24Linked to original sources

bioRxiv2018

Influence of prior beliefs on perception in early psychosis: effects of illness stage and hierarchical level of belief

Alterations in the balance between prior expectations and sensory evidence may account for faulty perceptions and inferences leading to psychosis. However, uncertainties remain about the nature of altered prior expectations and the degree to which they vary with the emergence of psychosis. We explored how expectations arising at two different levels - cognitive and perceptual - influenced processing of sensory information and whether relative influences of higher and lower level priors differed across people with prodromal symptoms and those with psychotic illness. In two complementary auditory perception experiments, 91 participants (30 with first episode psychosis, 29 at clinical risk for psychosis, and 32 controls) were required to decipher a phoneme within ambiguous auditory input. Expectations were generated in two ways: an accompanying visual input of lip movements observed during auditory presentation, or through written presentation of a phoneme provided prior to auditory presentation. We determined how these different types of information shaped auditory perceptual experience, how this was altered across the prodromal and established phases of psychosis, and how this relates to cingulate glutamate levels assessed by magnetic resonance spectroscopy. The psychosis group relied more on high level cognitive priors compared to both healthy controls and those at clinical risk for psychosis, and more on low level perceptual priors than the clinical risk group. The risk group were marginally less reliant on low level perceptual priors than controls. The results are consistent with previous theory that influences of prior expectations in psychosis in perception differ according to level of prior and illness phase.\n\nGeneral scientific summaryWhat we perceive and believe on any given moment will allow us to form expectations about what we will experience in the next. In psychosis, it is believed that the influence of these so-called perceptual and cognitive prior expectations on perception is altered, thereby giving rise to the symptoms seen in psychosis. However, research thus far has found mixed evidence, some suggesting an increase in the influence of priors and some finding a decrease. Here we test the hypothesis that perceptual and cognitive priors are differentially affected in individuals at-risk for psychosis and individuals with a first episode of psychosis, thereby partially explaining the mixed findings in the literature. We indeed found evidence in favour of this hypothesis, finding weaker perceptual priors in individuals at-risk, but stronger cognitive priors in individuals with first episode psychosis.

neuroscience↗

bioRxiv2013

A data repository and analysis framework for spontaneous neural activity recordings in developing retina

BackgroundDuring early development, neural circuits fire spontaneously, generating activity episodes with complex spatiotemporal patterns. Recordings of spontaneous activity have been made in many parts of the nervous system over the last 25 years, reporting developmental changes in activity patterns and the effects of various genetic perturbations.\n\nResultsWe present a curated repository of multielectrode array recordings of spontaneous activity in developing mouse and ferret retina. The data have been annotated with minimal metadata and converted into HDF5. This paper describes the structure of the data, along with examples of reproducible research using these data files. We also demonstrate how these data can be analysed in the CARMEN workflow system. This article is written as a literate programming document; all programs and data described here are freely available.\n\nConclusions1. We hope this repository will lead to novel analysis of spontaneous activity recorded in different laboratories. 2. We encourage published data to be added to the repository. 3. This repository serves as an example of how multielectrode array recordings can be stored for long-term reuse.

Neuroscience↗

bioRxiv2013

Functional connectivity networks with and without global signal correction

In functional connectivity analyses in BOLD (blood oxygenation level dependent) fMRI data, there is an ongoing debate on whether to correct global signals in fMRI time series data. Although the discussion has been ongoing in the fMRI community since the early days of fMRI data analyses, this subject has gained renewed attention in recent years due to the surging popularity of functional connectivity analyses, in particular graph theory-based network analyses. However, the impact of correcting (or not correcting) for global signals has not been systematically characterized in the context of network analyses. Thus, in this work, I examined the effect of global signal correction on an fMRI network analysis. In particular, voxel-based resting-state fMRI networks were constructed with and without global signal correction. The resulting functional connectivity networks were compared. Without global signal correction, the distributions of the correlation coefficients were positively biased. I also found that, without global signal correction, nodes along the interhemisphic fissure were highly connected whereas some nodes and subgraphs around white-matter tracts became disconnected from the rest of the network. These results from this study show differences between the networks with or without global signal correction.

Neuroscience↗

bioRxiv2013

Analysis of the study of the cerebellar pinceau by Korn and Axelrad

The axon initial segment of each cerebellar Purkinje cell is ensheathed by basket cell axons in a structure called the pinceau, which is largely devoid of chemical synapses and gap junctions. These facts and ultrastructural similarities with the axon cap of the teleost Mauthner cell led to the conjecture that the pinceau mediates ephaptic (via the extracellular field) inhibition. Korn and Axelrad published a study in 1980 in which they reported confirmation of this conjecture. We have analysed their results and show that most are likely to be explained by an artefactual signal arising from the massive stimulation of parallel fibres they employed. We reproduce their experiments and confirm that all of their results are consistent with this artefact. Their data therefore provide no evidence regarding the operation of the pinceau.

Neuroscience↗

bioRxiv2013

Influence of walking speed on locomotor time production

The aim of the present study was to determine whether or not walking speed affects temporal perception. It was hypothesized that fast walking would reduce the perceived length of time while slow walking increase production estimates. 16 healthy subjects were included. After a first << calibration >> phase allowing the determination of different walking speeds, the subjects were instructed to demonstrate periods of time or << target times >> of 3s and 7s, by a walking movement. Then, subjects were asked to simulate walking by raising one foot after the other without advancing. Finally, a third condition, Motionless, involved producing the target times while standing without movement. The results of this study suggest that movement does influence the perception of time, causing an overestimation of time. In agreement with the results of Denner et al. (1963) the subjects produced times which were longer than the target times.

Neuroscience↗

bioRxiv2013

Genomic architecture of human neuroanatomical diversity

Human brain anatomy is strikingly diverse and highly inheritable: genetic factors may explain up to 80% of its variability. Prior studies have tried to detect genetic variants with a large effect on neuroanatomical diversity, but those currently identified account for <5% of the variance. Here we show, based on our analyses of neuroimaging and whole-genome genotyping data from 1,765 subjects, that up to 54% of this heritability is captured by large numbers of single nucleotide polymorphisms of small effect spread throughout the genome, especially within genes and close regulatory regions. The genetic bases of neuroanatomical diversity appear to be relatively independent of those of body size (height), but shared with those of verbal intelligence scores. The study of this genomic architecture should help us better understand brain evolution and disease.

Neuroscience↗

bioRxiv2013

Conneconomics: The Economics of Dense, Large-Scale, High-Resolution Neural Connectomics

We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. Three generalized strategies for dense connectivity mapping at the scale of whole mammalian brains are considered: electron microscopic axon tracing, optical imaging of combinatorial molecular markers at synapses, and bulk DNA sequencing of trans-synaptically exchanged nucleic acid barcode pairs. Due to advances in parallel-beam instrumentation, whole mouse brain electron microscopic image acquisition could cost less than $100 million, with total costs presently limited by image analysis to trace axons through large image stacks. Optical microscopy at 50-100 nm isotropic resolution could potentially read combinatorially multiplexed molecular information from individual synapses, which could indicate the identifies of the pre-synaptic and post-synaptic cells without relying on axon tracing. An optical approach to whole mouse brain connectomics may be achievable for less than $10 million and could be enabled by emerging technologies to sequence nucleic acids in-situ in fixed tissue via fluorescent microscopy. Novel strategies relying on bulk DNA sequencing, which would extract the connectome without direct imaging of the tissue, could produce a whole mouse brain connectome for $100k-$1 million or a mouse cortical connectome for $10k-$100k. Anticipated further reductions in the cost of DNA sequencing could lead to a $1000 mouse cortical connectome.

Neuroscience↗

bioRxiv2013

Embodied cognition, embodied regulation, and the Data Rate Theorem

The Data Rate Theorem carries deep implications for theories of embodied cognition, extensions providing a spectrum of necessary conditions dynamic statistical models useful in empirical studies. A large deviations argument, however, implies that the regulation and stabilization of such systems is itself an interpenetrating phenomenon necessarily convoluted with embodied cognition. For humans, the central regulatory role of culture has long been known. Although a ground-state collapse analogous to generalized anxiety appears ubiquitous to such systems, lack of cultural modulation in real-time automatons or distributed cognition man-machine cockpits makes them subject to a pathology under which all possible targets are enemies.

Neuroscience↗

bioRxiv2013

Hippocampal Motifs

Dorsal Hippocampal neurons provide an allocentric map of space1, characterized by three key properties. First, their firing is spatially selective1-3, termed a rate code. Second, as animals traverse through place fields, neurons sustain elevated firing rates for long periods, however this has received little attention. Third the theta-phase of spikes within this sustained activity varies with animals location, termed phase-precession or a temporal code4-10. The precise relationship between these properties and the mechanisms governing them are not understood, although distal visual cues (DVC) are thought to be sufficient to reliably elicit them2,3. Hence, we measured rat CA1 neurons activity during random foraging in two-dimensional VR--where only DVC provide consistent allocentric location information-- and compared it with their activity in real world (RW). Surprisingly, we found little spatial selectivity in VR. This is in sharp contrast to robust spatial selectivity commonly seen in one-dimensional RW and VR7-11, or two-dimensional RW1-3. Despite this, neurons in VR generated approximately two-second long phase precessing spike sequences, termed \"hippocampal motifs\". Motifs, and \"Motif-fields\", an aggregation of all motifs of a neuron, had qualitatively similar properties including theta-scale temporal coding in RW and VR, but the motifs were far less spatially localized in VR. These results suggest that intrinsic, network mechanisms generate temporally coded hippocampal motifs, which can be dissociated from their spatial selectivity. Further, DVC alone are insufficient to localize motifs spatially to generate a robust rate code.

Neuroscience↗

bioRxiv2014

A microRNA profile in Fmr1 knockout mice reveals microRNA expression alterations with possible roles in fragile X syndrome

Fragile X syndrome (FXS), a common form of inherited mental retardation, is caused by a loss of expression of the fragile X mental retardation protein (FMRP). FMRP is involved in brain functions by interacting with mRNAs and microRNAs (miRNAs) that selectively control gene expression at translational level. However, little is known about the role of FMRP in regulating miRNA expression. Here, we found a development-dependant dynamic expression of Fmr1 mRNA (encoding FMRP) in mouse hippocampus with a small peak at postnatal day 7 (P7). MiRNA microarray analysis showed that the levels of 38 miRNAs showed a significant increase with about 15~250 folds and the levels of 26 miRNAs showed a significant decrease with only about 2~4 folds in the hippocampus of P7 Fmr1 KO mice. Q-PCR assay showed that 9 of the most increased miRNAs (>100 folds in microarrays) were increased about 40~70 folds and their pre-miRNAs were increased about 5~10 folds, but no significant difference in their pri-miRNA levels was observed, suggesting a role of FMRP in regulating miRNA processing from pri-miRNA to pre-miRNA. We further demonstrated that a set of protein-coding mRNAs, potentially targeted by the 9 miRNAs were down-regulated in the hippocampus of Fmr1 KO mice. Finally, luciferase assays demonstrated that miR-34b, miR-340, miR-148a could down-regulate the reporter gene expression by interacting with the Met 3' UTR. Taken together these findings suggest that the miRNA expression alterations resulted from the absence of FMRP might contribute to molecular pathology of FXS.

Neuroscience↗

bioRxiv2014

The organization and dynamics of corticostriatal pathways link the medial orbitofrontal cortex to future decisions

Accurately making a decision in the face of incongruent options increases the efficiency of making similar congruency decisions in the future. This adaptive process is modulated by reward, suggesting that ventral corticostriatal circuits may contribute to the process of conflict adaptation. To evaluate this possibility, a group of healthy adults (N = 30) were tested using functional MRI (fMRI) while they performed a color-word Stroop task. In a conflict-related region of the medial orbitofrontal cortex (mOFC), stronger BOLD responses predicted faster response times (RTs) on the next trial. More importantly, the degree of behavioral conflict adaptation on RTs was correlated with the magnitude of mOFC-RT associations on the previous trial, but only after accounting for network-level interactions with prefrontal and striatal regions. This suggests that conflict adaptation may rely on interactions between distributed corticostriatal circuits. The convergence of white matter projections fro ...

Neuroscience↗

bioRxiv2014

Broadly tuned and respiration-independent inhibition in the olfactory bulb of awake mice

Olfactory representations are shaped by both brain state and respiration; however, the interaction and circuit substrates of these influences are poorly understood. Granule cells (GCs) in the main olfactory bulb (MOB) are presumed to sculpt activity that reaches the olfactory cortex via inhibition of mitral/tufted cells (MTs). GCs may potentially sparsen ensemble activity by facilitating lateral inhibition among MTs, and/or they may enforce temporally-precise activity locked to breathing. Yet, the selectivity and temporal structure of GC activity during wakefulness are unknown. We recorded GCs in the MOB of anesthetized and awake mice and reveal pronounced state-dependent features of odor coding and temporal patterning. Under anesthesia, GCs exhibit sparse activity and are strongly and synchronously coupled to the respiratory cycle. Upon waking, GCs desynchronize, broaden their odor responses, and typically fire without regard for the respiratory rhythm. Thus during wakefulness, GCs exhibit stronger odor responses with less temporal structure. Based on these observations, we propose that during wakefulness GCs likely predominantly shape MT odor responses through broadened lateral interactions rather than respiratory synchronization.

Neuroscience↗

bioRxiv2014

Noradrenergic plasticity of olfactory sensory neuron inputs to the main olfactory bulb

Sensory responses are modulated throughout the nervous system by internal factors including attention, experience, and brain state. This is partly due to fluctuations in neuromodulatory input from regions such as the noradrenergic locus coeruleus (LC) in the brainstem. LC activity changes with arousal and modulates sensory processing, cognition and memory. The main olfactory bulb (MOB) is richly targeted by LC fibers and noradrenaline profoundly influences MOB circuitry and odor-guided behavior. Noradrenaline-dependent plasticity affects the output of the MOB. However, it is unclear whether noradrenergic plasticity includes modulation in the glomerular layer, the site of input to the MOB. Noradrenergic terminals are found in the glomerular layer, but noradrenaline receptor activation does not seem to acutely modulate olfactory sensory neuron terminals in vitro. We investigated whether noradrenaline induces plasticity at the glomerulus. We used wide-field optical imaging to measure changes in odor responses following electrical stimulation of locus coeruleus in anesthetized mice. Surprisingly, the odor-evoked intrinsic optical signals at the glomerulus were persistently weakened after LC activation. Calcium imaging selectively from olfactory sensory neurons confirmed that this effect was due to a uniform gain suppression of presynaptic input, and did not require exposure to a stimulus during the LC activation. Finally, noradrenaline antagonists prevented glomerular suppression. We conclude that noradrenaline release from LC has persistent effects on odor processing already at the first synapse of the main olfactory system. This mechanism could contribute to arousal-dependent memories.

Neuroscience↗

bioRxiv2014

Neuroanatomical diversity of corpus callosum and brain volume in the Autism Brain Imaging Data Exchange (Abide) project

The corpus callosum - the main pathway for long-distance inter-hemispheric integration in the human brain - has been frequently reported to be smaller among autistic patients compared with non-autistic controls. We conducted a meta-analysis of the literature which suggested a statistically significant difference. However, the studies included were heavily underpowered: on average only 20% power to detect differences of 0.3 standard deviations, which makes it difficult to establish the reality of such a difference. We therefore studied the size of the corpus callosum among 694 subjects (328 patients, 366 controls) from the Abide cohort. Despite having achieved 99% power to detect statistically significant differences of 0.3 standard deviations, we did not observe any. To better understand the neuroanatomical diversity of the corpus callosum, and the possible reasons for the previous findings, we analysed the relationship between its size, the size of the brain, intracranial volume and intelligence scores. The corpus callosum appeared to scale non-linearly with brain size, with large brains having a proportionally smaller corpus callosum. Additionally, intelligence scores correlated with brain volume among controls but the correlation was significantly weaker among patients. We used simulations to determine to which extent these two effects could lead to artefactual differences in corpus callosum size within populations. We observed that, were there a difference in brain volume between cases and controls, normalising corpus callosum size by brain volume would not eliminate the brain volume effect, but adding brain volume as a covariate in a linear model would. Finally, we observed that because of the weaker correlation of intelligence scores and brain volume among patients, matching populations by intelligence scores could result in a bias towards including more patients with large brain volumes, inducing an artificial difference. Overall, our results highlight the necessity for open data sharing efforts such as Abide to provide a more solid ground for the discovery of neuroimaging biomarkers, within the context of the wide human neuroanatomical diversity.

Neuroscience↗

bioRxiv2014

Spatial Information in Large-Scale Neural Recordings

A central issue in neural recording is that of distinguishing the activities of many neurons. Here, we develop a framework, based on Fisher information, to quantify how separable a neurons activity is from the activities of nearby neurons. We (1) apply this framework to model information flow and spatial distinguishability for several electrical and optical neural recording methods, (2) provide analytic expressions for information content, and (3) demonstrate potential applications of the approach. This method generalizes to many recording devices that resolve objects in space and thus may be useful in the design of next-generation scalable neural recording systems.

Neuroscience↗

bioRxiv2014

Optimizing Real Time fMRI Neurofeedback for Therapeutic Discovery and Development

While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health (BRAIN, 2013), the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain-behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders.

Neuroscience↗

bioRxiv2014

Application of the radial distribution function for quantitative analysis of neuropil microstructure in stratum radiatum of CA1 region in hippocampus.

Various structures in the brain contain many important clues to the brain?s development and function. Among these, the microscopic organization of neural tissue is of particular interest since such organization has direct potential to affect the formation of local synaptic connectivity between axons and dendrites, serving as an important factor affecting the brain?s development. While the organization of the brain at large and intermediate scales had been well studied, the organization of neural tissue at micrometer scales remains largely unknown. In particular, at present it is not known what specific structures exist in neuropil at micrometer scales, what effect such structures have on formation of synaptic connectivity, and what processes shape the micrometer-scale organization of neuropil. In this work, we present an analysis of recent electron microscopy reconstructions of blocks of neuropil tissue from rat s. radiatum of hippocampal CA1 to provide insights into these questions. We propose a new statistical method for systematically analyzing the small-scale organization of neuropil based on an adaptation of the approach of radial distribution functions from statistical physics. Our results show that the micrometer-scale organization of hippocampal CA1 neuropil can be viewed as a disordered arrangement of axonal and dendritic processes without significant small-scale positional coordinations. We observe several deviations from this picture in the distributions of glia and dendritic spines. Finally, we study the relationship between local synaptic connectivity and the small-scale organization of neuropil.

Neuroscience↗

bioRxiv2014

A novel paradigm for auditory discrimination training with social reinforcement in songbirds

Zebra finches are a highly social, gregarious, species and eagerly engage in vocal communication. We have developed a training apparatus that allows training zebra finches to discriminate socially reinforced and aversive vocal stimuli. In our experiments, juvenile male zebra finches were trained to discriminate a song that was followed by a brief air puff (aversive) and a song that allowed them to stay in visual contact with another bird, audience (social song). During training, the birds learned quickly to avoid air puffs by escaping the aversive song within 2 sec. They escaped significantly more aversive songs than socially reinforced ones, and this effect grew stronger with the number of training sessions. Therefore, we propose this training procedure as an effective method to teach zebra finches to discriminate between different auditory stimuli, which may also be used as a broader paradigm for addressing social reinforcement learning. The apparatus can be built from commercially available parts, and we are sharing the controlling software on our website.

Neuroscience↗