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Results for “Neuroscience”

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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.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 955 records · Page 53Linked to original sources

bioRxiv2016

Extending Levelt’s Propositions to perceptual multistability involving interocular grouping

Levelts Propositions have been a touchstone for experimental and modeling studies of perceptual multistability. We asked whether Levelts Propositions extend to perceptual multistability involving interocular grouping. To address this question we used split-grating stimuli withcomplementary halves of the same color. As in previous studies, subjects reported four percepts in alternation: the two stimuli presented to each eye (single-eye percepts), as well as two interocularly grouped, single color percepts (grouped percepts). Most subjects responded to increased color saturation by more frequently reporting a single color image, thus increasingthe predominance of grouped percepts (Levelts Proposition I). In these subjects increased predominance was due to a decrease in the average dominance duration of single-eye percepts, while that of grouped percepts remained largely unaffected. This is in accordance with generalized Levelts Proposition II which posits that the average dominance duration of the stronger (in this case single-eye) percept is primarily affectedbychanges in stimulus strength. In accordance with Proposition III, thealternation rate increased as the difference in the strength of the percepts decreased. To explain the mechanism behind these observations, we introduce a hierarchical model consisting of low-level neural populations, eachresponding to input at a visual hemifield, and higher-level populations representing the percepts. The model exhibits the changes in dominance durationobserved in the data, and conforms to all of Levelts Propositions.

Neuroscience↗

bioRxiv2016

Simulated forward and backward self motion, based on realistic parameters, causes strong motion induced blindness

Motion Induced Blindness (MIB) is a well-established visual phenomenon whereby highly salient targets disappear when viewed against a moving background mask. No research has yet explored whether contracting and expanding optic flow can also trigger target disappearance. We explored MIB using mask speeds corresponding to driving at 35, 50, 65 and 80 km/h in simulated forward (expansion) and backward (contraction) motion as well as 2-D radial movement, random, and static mask motion types. Participants (n = 18) viewed MIB targets against masks with different movement types, speed, and target locations. To understand the relationship between saccades, pupil response and perceptual disappearance, we ran two additional eye-tracking experiments (n = 19). Target disappearance increased significantly with faster mask speeds and upper visual field target presentation. Simulated optic flow and 2-D radial movement caused comparable disappearance, and all moving masks caused significantly more disappearance than a static mask. Saccades could not entirely account for differences between conditions, suggesting that self-motion optic flow does cause MIB in an artificial setting. Pupil analyses implied that MIB disappearance induced by optic flow is not subjectively salient, potentially explaining why MIB is not noticed during driving. Potential implications of MIB for driving safety and Head-Up-Display (HUD) technologies are discussed.

Neuroscience↗

bioRxiv2016

Brain heating induced by near infrared lasers during multi-photon microscopy

Two-photon imaging and optogenetic stimulation rely on high illumination powers, particularly for state-of-the-art applications that target deeper structures, achieve faster measurements, or probe larger brain areas. However, little information is available on heating and resulting damage induced by high-power illumination in the brain. Here we used thermocouple probes and quantum dot nanothermometers to measure temperature changes induced by two-photon microscopy in the neocortex of awake and anaesthetized mice. We characterized heating as a function of wavelength, exposure time, and distance from the center of illumination. Although total power is highest near the surface of the brain, heating was most severe hundreds of microns below the focal plane, due to heat dissipation through the cranial window. Continuous illumination of a 1mm2 area produced a peak temperature increase of approximately 1.8{degrees}C/100mW. Continuous illumination with powers above 250 mW induced lasting damage, detected with immunohistochemistry against Iba1, GFAP, heat shock proteins, and activated Caspase-3. Higher powers were usable in experiments with limited duty ratios, suggesting an approach to mitigate damage in high-power microscopy experiments.

Neuroscience↗

bioRxiv2016

Two distinct scene processing networks connecting vision and memory

A number of regions in the human brain are known to be involved in processing natural scenes, but the field has lacked a unifying framework for understanding how these different regions are organized and interact. We provide evidence from functional connectivity and meta-analyses for a new organizational principle, in which scene processing relies on two distinct networks that split the classically defined Parahippocampal Place Area (PPA). The first network consists of the Occipital Place Area (OPA/TOS) and posterior PPA, which contain retinotopic maps and are related primarily to visual features. The second network consists of the caudal Inferior Parietal Lobule (cIPL), Retrosplenial Cortex (RSC), and anterior PPA, which connect to the hippocampus and are involved in a much broader set of tasks involving episodic memory and navigation. This new framework for understandingthe neural substrates of scene processing bridges results from many lines of research, and makes specific functional predictions.

Neuroscience↗

bioRxiv2016

Enhanced pre-frontal functional-structural networks to support behavioural deficits after traumatic brain injury

Traumatic brain injury (TBI) affects its structural connectivity, triggering the re-organization of structural-functional circuits in a manner that remains poorly understood. We studied the re-organization of brain networks after TBI, taking advantage of a computational method based on magnetic resonance imaging (MRI) including diffusion-weighted imaging in combination with functional resting state data obtained from the blood-oxygenation-level-dependent T2* signal. We enrolled young participants who had suffered moderate to severe TBI (N=14, age 13.14 {+/-} 3.25 years), comparing them to young typically developing control participants (N=27, age 15.04 {+/-} 2.26 years). We found increased functional and structural connectivity within a cortico-subcortical network in TBI patients brains that involved prefrontal cortex, anterior cingulate gyrus, orbital gyrus and caudate nucleus. In comparison to control participants, TBI patients increased functional connectivity from prefrontal regions towards two different networks: 1) a subcortical network including part of the motor network, basal ganglia, cerebellum, hippocampus, amygdala, posterior cingulum and precuneus; and 2) a task-positive network, involving regions of the dorsal attention system together with the dorsolateral and ventrolateral prefrontal regions. We also found the increased prefrontal activation in TBI patients was correlated with some behavioural indices, such as the amount of body sway, whereby patients with worse balance activated frontal regions more strongly. The enhanced prefrontal activation found in TBI patients may provide the structural scaffold for stronger cognitive control of certain behavioural functions, consistent with the observation that various motor tasks are performed less automatically following TBI and that more cognitive control is associated with such actions.

Neuroscience↗

bioRxiv2016

Functional brain segmentation using inter-subject correlation in fMRI

The human brain continuously processes massive amounts of rich sensory information. To better understand such highly complex brain processes, modern neuroimaging studies are increasingly utilizing experimental setups that better mimic daily-life situations. We propose a new exploratory data-analysis approach, functional segmentation intersubject correlation analysis (FuSeISC), to facilitate the analysis of functional magnetic resonance (fMRI) data sets collected in these experiments. The method provides a new type of functional segmentation of brain areas, not only characterizing areas that display similar processing across subjects but also areas in which processing across subjects is highly variable.\n\nWe tested FuSeISC using fMRI data sets collected during traditional block-design stimuli (37 subjects) as well as naturalistic auditory narratives (19 subjects). The method identified spatially local and/or bilaterally symmetric clusters in several cortical areas, many of which are known to be processing the types of stimuli used in the experiments. The method is not only prominent for spatial exploration of large fMRI data sets obtained using naturalistic stimuli, but has other potential applications such as generation of a functional brain atlases including both lower-and higher-order processing areas.\n\nFinally, as a part of FuSeISC, we propose a criterion-based sparsification of the shared nearest-neighbor graph for detecting clusters in noisy data. In our tests with synthetic data, this technique was superior to well-known clustering methods, such as Ward's method, affinity propagation and K-means++.

Neuroscience↗

bioRxiv2016

Magnetic Resonance Imaging Tracking of Distal Inflammatory Changes following Mild Traumatic Brain Injury (mTBI) in rats.

Sensorimotor disturbances continue to represent one of the most debilitating and widely reported complications in patients suffering mild traumatic brain injuries (mTBI). Loss of peripheral neuronal function at sites distal and disconnected to the central nervous control central centers is well documented. Distal muscular atrophy, complex regional pain symptoms, and poor wound healing are just a few of the many complications with often more severe secondary complications such decubitus ulcers and osteomyelitis seen at sites in the body distal to the center of injury. MRI has been widely established as a diagnostic and therapeutic planning tool in patients and animal models with neuronal disease. However, studies investigating the neural correlates of spinal cord changes after TBI are lacking. Here, we used T2 MR imaging to determine the effects of mTBI on the morphology and inflammatory changes of the spinal cord. We hypothesize that rats receiving mTBI utilizing a controlled cortical impact (CCI) contusion will demonstrate T2 signal changes at distal locomotor centers in the spine. Experimental mTBI and sham groups of Sprague-Dawley rats were used (n = 2 sham and 4 experimental). A mild CCI was applied to the right brain cortex. Rats were sacrificed at 60 days post injury and spinal cords harvested for ex vivo MRI T2 analysis. Focal areas/lesions of increased T2 hyperintensity were noted in mTBI injured rats (n = 4). Experimental group of rats also demonstrated secondary spinal cord locomotor and sensation adverse effects clinically. MR imaging showed volumetric reductions and T2 signal changes in the cervical, thoracic, and lumbar segments of the spinal cord at 8 weeks post-injury. T2 intensity values were elevated in all experimental groups in comparison to the sham group within the distal cord, suggesting that remote CCI causes secondary spinal cord inflammation and neurodegeneration at distant sites. These findings also further support the idea that the most peripheral nerves and spinal cord will be most negatively affected by a TBI. While our research is in its preliminary stages, our results further confirm that mTBI has more far reaching effects than previously understood. T2 MRI is an effective tool to assess the extent of spinal cord injury related to antecedent TBI.

Neuroscience↗

bioRxiv2016

Global and local connectivity differences converge with gene expression in a neurodevelopmental disorder of known genetic origin

Knowledge of genetic cause in neurodevelopmental disorders can highlight molecular and cellular processes critical for typical development. Furthermore, the relative homogeneity of neurodevelopmental disorders of known genetic origin allows the researcher to establish the subsequent neurobiological processes that mediate cognitive and behavioural outcomes. The current study investigated white matter structural connectivity in a group of individuals with intellectual disability due to mutations in ZDHHC9. In addition to shared cause of cognitive impairment, these individuals have a shared cognitive profile, involving oro-motor control difficulties and expressive language impairment. Analysis of structural network properties using graph theory measures showed global reductions in mean clustering coefficient and efficiency in the ZDHHC9 group, with maximal differences in frontal and parietal areas. Regional variation in clustering coefficient and local efficiency across cortical regions in cases and controls were significantly associated with known pattern of expression of ZDHHC9 in the normal adult human brain. The results demonstrate that a mutation in a single gene impacts upon white matter organisation across the whole-brain, but also shows regionally specific effects, according to variation in gene expression. Furthermore, these regionally specific patterns may link to specific developmental mechanisms, and correspond to specific cognitive deficits.

Neuroscience↗

bioRxiv2016

Biologically plausible learning in recurrent neural networks for flexible cognitive tasks

Neural activity during cognitive tasks exhibits complex dynamics that flexibly encode task-relevant variables. Chaotic recurrent networks, which spontaneously generate rich dynamics, have been proposed as a model of cortical computation during cognitive tasks. However, existing methods for training these networks are either biologically implausible, and/or require a continuous, real-time error signal to guide learning. Here we show that a biologically plausible learning rule can train such recurrent networks, guided solely by delayed, phasic rewards at the end of each trial. Networks endowed with this learning rule can successfully learn nontrivial tasks requiring flexible (context-dependent) associations, memory maintenance, nonlinear mixed selectivities, and coordination among multiple outputs. The resulting networks replicate complex dynamics previously observed in animal cortex, such as dynamic encoding of task features and selective integration of sensory inputs. We conclude that recurrent neural networks offer a plausible model of cortical dynamics during both learning and performance of flexible behavior.

Neuroscience↗

bioRxiv2016

Initiation of Retina Regeneration By a Conserved Mechanism of Adult Neurogenesis

Retina damage or disease in humans often leads to reactive gliosis, preventing the formation of new cells and resulting in visual impairment or blindness. Current efforts to repair damaged retinas are inefficient and not capable of fully restoring vision. Conversely, the zebrafish retina is capable of spontaneous regeneration upon damage, using Muller glia (MG) derived progenitors. Understanding how zebrafish MG initiate regeneration may help develop new treatments that prompt mammalian retinas to regenerate. Here we show that inhibition of GABA signaling facilitates initiation of MG proliferation. GABA levels decrease following damage, and MG are positioned to detect the decrease. Using pharmacological and genetic approaches we demonstrate that GABAA receptor inhibition stimulates regeneration in undamaged retinas while activation inhibits regeneration in damaged retinas. GABA induced proliferation causes upregulation of regeneration associated genes. This is the first evidence that neurotransmitters control retina regeneration in zebrafish through an evolutionarily conserved mechanism of neurogenesis.

Neuroscience↗

bioRxiv2016

Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density

SynGAP is a Ras/Rap GTPase-activating protein (GAP) present in high concentration in postsynaptic densities (PSDs) from mammalian forebrain where it binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95. We show that phosphorylation of synGAP by Ca2+/calmodulin-dependent protein kinase II (CaMKII) decreases its affinity for the PDZ domains as much as 10-fold, measured by surface plasmon resonance. SynGAP is abundant enough in postsynaptic densities (PSDs) to occupy about one third of the PDZ domains of PSD-95. Therefore, we hypothesize that phosphorylation by CaMKII reduces synGAP's ability to restrict binding of other proteins to the PDZ domains of PSD-95. We support this hypothesis by showing that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present at a higher ratio to PSD-95 in PSDs isolated from synGAP heterozygous mice.

Neuroscience↗

bioRxiv2016

Theta-burst transcranial magnetic stimulation to the prefrontal or parietal cortex does not impair metacognitive visual awareness

Neuroimaging studies commonly associate dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex with conscious perception. However, such studies only investigate correlation, rather than causation. In addition, many studies conflate objective performance with subjective awareness. In an influential recent paper, Rounis and colleagues addressed these issues by showing that theta burst transcranial magnetic stimulation (tbs-TMS) applied to the DLPFC impaired metacognitive (subjective) awareness for a perceptual task, while objective performance was kept constant. We attempted to replicate this finding, with minor modifications, including an active tbs-TMS control site. Using a between-subjects design for both DLPFC and posterior parietal cortices, we found no evidence of a tbs-TMS-induced metacognitive impairment. In a second experiment, we devised a highly rigorous within-subjects tbs-TMS design for DLPFC, but again failed to find any evidence of metacognitive impairment. One crucial difference between our results and the Rounis study is our strict exclusion of data deemed unsuitable for a signal detection theory analysis. Indeed, when we included this unstable data, a significant, though invalid, metacognitive impairment was found. These results cast doubt on previous findings relating metacognitive awareness to DLPFC, and inform the current debate concerning whether or not prefrontal regions are preferentially implicated in conscious perception.

Neuroscience↗

bioRxiv2016

Estimating the efficacy of transcranial magnetic stimulation in small animals

The efficacy of transcranial magnetic stimulation (TMS) is determined by the magnitude and direction of the induced electric field in the cortex. The electric field distribution is influenced by the conductivity structure, in particular, the size of the head and the shapes of conductivity boundaries. We show that neglecting the head size can result in overestimating the stimulus intensity by a factor of 5-8 in the case of the rat brain. In the current modelling literature, the TMS-induced electric field is estimated with detailed computational simulations; however, in many experimental studies, less attention is paid on modelling. We attempt to bridge this gap by suggesting the use of simple simulations, for example with the spherical head model, when studying bioelectromagnetic phenomena.

Neuroscience↗

bioRxiv2016

Vision and locomotion shape the interactions between neuron types in mouse visual cortex

In the mouse primary visual cortex (V1), sensory responses are shaped by behavioral factors such as locomotion. These factors are thought to control a disinhibitory circuit, whereby interneurons expressing vasoactive intestinal peptide (Vip) inhibit those expressing somatostatin (Sst), disinhibiting pyramidal cells (Pyr). We measured the effect of locomotion on these neurons and on interneurons expressing parvalbumin (Pvalb) in layer 2/3 of mouse V1, and found in-consistencies with the disinhibitory model. In the presence of large stimuli, locomotion increased Sst cell responses without suppressing Vip cells. In the presence of small stimuli, locomotion increased Vip cell responses without suppressing Sst cells. A circuit model could reproduce each cell types activity from the measured activity of other cell types, but only if we allowed locomotion to increase feedforward synaptic weights while modulating recurrent weights. These results suggest that locomotion alters cortical function by changing effective synaptic connectivity, rather than only through disinhibition.

Neuroscience↗

bioRxiv2016

Video-rate volumetric functional imaging of the brain at synaptic resolution

Neurons and neural networks often extend hundreds to thousands of micrometers in three dimensions. To capture all the calcium transients associated with their activity, we need volume imaging methods with sub-second temporal resolution. Such speed is challenging for conventional two-photon laser scanning microscopy (2PLSM) to achieve, because of its dependence on serial focal scanning in 3D and the limited brightness of indicators. Here we present an optical module that can be easily integrated into standard 2PLSMs to generate an axially elongated Bessel focus. Scanning the Bessel focus in 2D turned frame rate into volume rate and enabled video-rate volumetric imaging. Using Bessel foci designed to maintain synaptic-level lateral resolution in vivo, we demonstrated the power of this approach in enabling discoveries for neurobiology by imaging the calcium dynamics of volumes of neurons and synapses in fruit flies, zebrafish larvae, mice, and ferrets in vivo.

Neuroscience↗

bioRxiv2016

Familiarity Facilitates Feature-based Face Processing

Recognition of personally familiar faces is remarkably efficient, effortless and robust. We asked if feature-based face processing facilitates detection of familiar faces by testing the effect of face inversion on a visual search task for familiar and unfamiliar faces. Because face inversion disrupts configural and holistic face processing, we hypothesized that inversion would diminish the familiarity advantage to the extent that it is mediated by such processing. Subjects detected personally familiar and stranger target faces in arrays of two, four, or six face images. Subjects showed significant facilitation of personally familiar face detection for both upright and inverted faces. The effect of familiarity on target absent trials, which involved only rejection of unfamiliar face distractors, suggests that familiarity facilitates rejection of unfamiliar distractors as well as detection of familiar targets. The preserved familiarity effect for inverted faces suggests that facilitation of face detection afforded by familiarity reflects mostly feature-based processes.

Neuroscience↗

bioRxiv2016

ICGenealogy: Mapping the function of neuronal ion channels in model and experiment

Ion channel models are the building blocks of computational neuron models. Their biological fidelity is therefore crucial for the interpretability of simulations. However, the number of published models, and the lack of standardization, make the comparison of models with one another and with experimental data difficult. Here, we present a framework for the automated large-scale classification of ion channel models. Using annotated metadata and model responses to a set of voltage-clamp protocols, we assigned 2378 models of voltage- and calcium-gated ion channels coded in NEURON to 211 clusters. The IonChannelGenealogy web interface provides an interactive resource for the categorization of new and existing models and experimental recordings. It enables quantitative comparisons of simulated and/or measured ion channel kinetics, and facilitates field-wide standardization of experimentally-constrained modeling.

Neuroscience↗

bioRxiv2016

Task-specific shaping of feature-based attention in area MT

Non-spatial selective attention is based on the notion that specific features or objects in the visual environment are effectively prioritized in cortical visual processing. Feature-based attention (FBA) in particular, is a well-studied process that dynamically and selectively enhances neurons preferentially processing the attended feature attribute (e.g. leftward motion). In everyday life, however, behavior may require high sensitivity for an entire feature dimension (e.g. motion). Yet, evidence for feature dimension-specific attentional modulation on a cellular level is lacking. We here investigate neuronal activity in macaque motion-selective medio-temporal area (MT) in an experimental setting requiring the monkeys to detect either a motion change or a color change. We hypothesized that neural activity in MT is enhanced if the task requires perceptual sensitivity to motion. Despite identical visual stimulation, we found that mean firing rates were higher in the motion task, and response variability and latency were lower as compared to the color task. This task-specific response modulation in the processing of visual motion was independent from the relation between attended and stimulating motion direction. It emerged already in the absence of visual input, and consisted of a spatially global and tuning-independent shift of the MT baseline activity. The results provide single cell support for the hypothesis of a feature dimension-specific top-down signal emphasizing the processing of an entire feature class.

Neuroscience↗