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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2016

Concordance Among Indices of Intrinsic Brain Function: Inter-Individual Variation and Temporal Dynamics Perspectives

Various resting-state fMRI (R-fMRI) measures have been developed to characterize intrinsic brain activity. While each of these measures has gained a growing presence in the literature, questions remain regarding the common and unique aspects these indices capture. The present work provided a comprehensive examination of inter-individual variation and intra-individual temporal variation for commonly used measures, including fractional amplitude of low frequency fluctuations, regional homogeneity, voxel-mirrored homotopic connectivity, network centrality and global signal correlation. Regardless of whether examining intra-individual or inter-individual variation, we found that these definitionally distinct R-fMRI indices tend to exhibit a relatively high degree of covariation, which doesnt exist in phase randomized surrogate data. As a measure of intrinsic brain function, concordance for R-fMRI indices was negatively correlated with age across individuals (i.e., concordance among functional indices decreased with age). To understand the functional significance of concordance, we noted that higher concordance was generally associated with higher strengths of R-fMRI indices, regardless of whether looking through the lens of inter-individual (i.e., high vs. low concordance participants) or intra-individual (i.e., high vs. low concordance states identified via temporal dynamic analyses) differences. We also noted a linear increase in functional concordance together with the R-fMRI indices through the scan, which may suggest a decrease in arousal. The current study demonstrated an enriched picture regarding the relationship among the R-fMRI indices, as well as provided new insights in examining dynamic states within and between individuals.

Neuroscience↗

bioRxiv2016

Temperature-dependent changes in neuronal dynamics in a patient with an SCN1A mutation and hyperthermia induced seizures

Dravet syndrome is the prototype of SCN1A-mutation associated epilepsies. It is characterised by prolonged seizures, typically provoked by fever. We describe the evaluation of an SCN1A mutation in a child with early-onset temperature-sensitive seizures.\n\nThe patient carries a heterozygous miss-sense variant (c3818C>T; pAla1273Val) in the NaV1.1 brain sodium channel. We characterised the functional effects of the variant using patch clamp recordings on Chinese Hamster Ovary Cells at different temperatures (32, 37, and 40{degrees}C).\n\nThe variant channels produced a temperature-dependent destabilization of channel activation and fast inactivation. Implementing these empirical abnormalities in a computational model produces a higher threshold for depolarization block in the variant, particularly at 40{degrees}C, suggesting a failure to autoregulate at high-input states.\n\nThese results reveal direct effects of abnormalities in biophysical NaV1.1 channel properties on neuronal dynamics. They illustrate the value of combining cellular measurements with computational models to integrate different scales (gene/channel to patient) of observations.

Neuroscience↗

bioRxiv2016

Posterior inferotemporal cortex cells use multiple visual pathways to complement fine and coarse discriminations

In the macaque monkey brain, posterior inferior temporal cortex (PIT) cells are responsible for visual object recognition. They receive concurrent inputs from visual areas V4, V3 and V2. We asked how these different anatomical pathways contribute to PIT response properties by deactivating them while monitoring PIT activity. Using cortical cooling of areas V2/V3 or V4 and a hierarchical model of visual recognition, we conclude that these distinct pathways do not transmit different classes of visual features, but serve instead to maintain a balance of local-and global-feature selectivity in IT.

Neuroscience↗

bioRxiv2016

Unsupervised spike sorting for large scale, high density multielectrode arrays

A new method for automated spike sorting for recordings with high density, large scale multielectrode arrays is presented. Exploiting the dense sampling of single neurons by multiple electrodes, we obtain an efficient, low-dimensional representation of detected spikes consisting of estimated spatial spike locations and dominant spike shape features, which enables fast and reliable clustering into single units. Millions of events can be sorted in minutes, and the method is parallelized and scales better than quadratically with the number of detected spikes. We demonstrate this method using recordings with a 4,096 channel array, and present validation based on anatomical imaging, optogenetic stimulation and model-based quality control. A comparison with semi-automated, shape-based spike sorting exposes significant limitations of conventional methods. Our analysis shows that it is feasible to reliably isolate the activity of hundreds to thousands of neurons in a single recording, and that dense, multi-channel probes substantially aid reliable spike sorting.

Neuroscience↗

bioRxiv2016

Adaptation-induced blindness is orientation-tuned and monocular

We examined the recently discovered phenomenon of Adaptation-Induced Blindness (AIB), in which highly visible gratings with gradual onset profiles become invisible after exposure to a rapidly flickering grating, even at very high contrasts. Using very similar stimuli to those in the original AIB experiment, we replicated the original effect across multiple contrast levels, with observers at chance in detecting the gradual onset stimuli at all contrasts. Then, using full-contrast target stimuli with either abrupt or gradual onsets, we tested both the orientation tuning and interocular transfer of AIB. If, as the original authors suggested, AIB were a high-level (perhaps parietally mediated) effect resulting from the gating of awareness, we would not expect the effects of AIB to be tuned to the adapting orientation, and the effect should transfer interocularly. Instead, we find that AIB (which was present only for the gradual onset target stimuli) is both tightly orientation-tuned and shows absolutely no interocular transfer, suggesting a very early cortical locus.

Neuroscience↗

bioRxiv2016

Cortical rhythms are modulated by respiration

The brain generates oscillatory neuronal activity at a broad range of frequencies and the presence and amplitude of certain oscillations at specific times and in specific brain regions are highly correlated with states of arousal, sleep, and with a wide range of cognitive processes. The neuronal mechanisms underlying the generation of brain rhythms are poorly understood, particularly for low-frequency oscillations. We recently reported that respiration-locked olfactory bulb activity causes delta band (0.5-4 Hz) oscillatory neuronal activity in the whisker sensory (barrel) cortex in mice. Furthermore, gamma oscillations (30 - 100Hz), which are widely implicated in cognitive processing, were power-modulated in synchrony with the respiratory rhythm. These findings link afferent sensory activity caused by respiration directly to cortical rhythms associated with cognitive functions. Here we review the related literature and present new evidence to propose that respiration has a direct influence on oscillatory cortical activity, including gamma oscillations, and on transitions between synchronous and asynchronous cortical network states (marked by phase transitions). Oscillatory cortical activity, as well as phase transitions, has been implicated in cognitive functions, potentially linking respiratory phase to cognitive processing. We further argue that respiratory influence on cortical activity is present in most, and possibly in all areas of the neocortex in mice and humans. We furthermore suggest that respiration had a role in modulating cortical rhythms from early mammalian evolution. Early mammals relied strongly on their olfactory sense and had proportionately large olfactory bulbs. We propose that to this day the respiratory rhythm remains an integral element of dynamic cortical activity in mammals. We argue that breathing modulates all cortical functions, including cognitive and emotional processes, which could elucidate the well-documented but largely unexplained effects of respiratory exercises on mood and cognitive function.

Neuroscience↗

bioRxiv2016

Nonsinusoidal oscillations underlie pathological phase-amplitude coupling in the motor cortex in Parkinson’s disease

Parkinsons disease (PD) is associated with abnormal beta oscillations (13-30 Hz) in the basal ganglia and motor cortex (M1). Recent reports show that M1 beta-high gamma (50-200 Hz) phase-amplitude coupling (PAC) is exaggerated in PD and is reduced following acute deep brain stimulation (DBS). Here we analyze invasive M1 electrocorticography recordings in PD patients on and off DBS, and in isolated cervical dystonia patients, and show that M1 beta oscillations are nonsinusoidal, having sharp and asymmetric features. These sharp oscillatory beta features underlie the previously reported PAC, providing an alternative to the standard interpretation of PAC as an interaction between two distinct frequency components. Specifically, the ratio between peak and trough sharpness is nearly perfectly correlated with beta-high gamma PAC (r = 0.96) and predicts PD-related motor deficit. Using a simulation of the local field potential, we demonstrate that sharp oscillatory waves can arise from synchronous synaptic activity. We propose that exaggerated beta-high gamma PAC may actually reflect such synchronous synaptic activity, manifesting as sharp beta oscillations that are \"smoothed out\" with DBS. These results support the \"desynchronization\" hypothesis of DBS wherein DBS counteracts pathological synchronization throughout the basal ganglia-thalamocortical loop. We argue that PAC can be influenced by more than one mechanism. In this case synaptic synchrony, rather than the often assumed spike-field coherence, may underlie exaggerated PAC. These often overlooked temporal features of the oscillatory waveform carry critical physiological information about neural processes and dynamics that may lead to better understanding of underlying neuropathology.

Neuroscience↗

bioRxiv2016

Periodic actin structures in neuronal axons are required to maintain microtubules

Axons are the cable-like neuronal processes wiring the nervous system. They contain parallel bundles of microtubules as structural backbones, surrounded by regularly-spaced actin rings termed the periodic membrane skeleton (PMS). Despite being an evolutionarily-conserved, ubiquitous, highly-ordered feature of axons, the function of PMS is unknown. Here we studied PMS abundance, organisation and function, combining versatile Drosophila genetics with super-resolution microscopy and various functional readouts. Analyses with 11 different actin regulators and 3 actin-targeting drugs suggest PMS to contain short actin filaments which are depolymerisation resistant and sensitive to spectrin, adducin and nucleator deficiency - consistent with microscopy-derived models proposing PMS as specialised cortical actin. Upon actin removal we observed gaps in microtubule bundles, reduced microtubule polymerisation and reduced axon numbers suggesting a role of PMS in microtubule organisation. These effects become strongly enhanced when carried out in neurons lacking the microtubule-stabilising protein Short stop (Shot). Combining the aforementioned actin manipulations with Shot deficiency revealed a close correlation between PMS abundance and microtubule regulation, consistent with a model in which PMS-dependent microtubule polymerisation contributes to their maintenance in axons. We discuss potential implications of this novel PMS function along axon shafts for axon maintenance and regeneration.\n\nSignificance statementAxons are cable-like neuronal processes that are up to a meter long in humans. These delicate structures often need to be maintained for an organisms lifetime, i.e. up to a century in humans. Unsurprisingly, we gradually lose about 50% of axons as we age. Bundles of microtubules form the structural backbones and highways for life-sustaining transport within axons, and maintenance of these bundles is essential for axonal longevity. However, the mechanisms which actively maintain axonal microtubules are poorly understood. Here we identify cortical actin as an important factor maintaining microtubule polymerisation in axons. This finding provides potential explanations for the previously identified, but unexplained, links between mutations in genes encoding cortical actin regulators and neurodegeneration.

Neuroscience↗

bioRxiv2016

Local versus global effects of isoflurane anesthesia on visual processing in the fly brain

Introduction Introduction Results Discussion Methods References Volatile general anesthetics such as isoflurane abolish behavioral responsiveness in all animals, but the neural underpinnings of this phenomenon remain unclear (van Swinderen and Kottler, 2014). Although the cellular and molecular mechanisms through which general anesthetics work have been quite well characterized (Franks, 2008, Garcia et al., 2010, Brown et al., 2011), it is unclear what aspect of neural activity is at the core of the profound disconnection from the environment that is induced by all general anesthetics. To some extent, our understanding of the mechanisms of general anesthesia has paralleled our understanding of how the brain works, from neurons and action potentials, to receptor ...

Neuroscience↗

bioRxiv2016

From what we perceive to what we remember: Characterizing representational dynamics of visual memorability

Not all visual memories are equal--some endure in our minds, while others quickly disappear. Recent behavioral work shows we can reliably predict which images will be remembered. This image property is called memorability. Memorability is intrinsic to an image, robust across observers, and unexplainable by low-level visual features. However, its neural bases and relation with perception and memory remain unknown. Here we characterize the representational dynamics of memorability using magnetoencephalography (MEG). We find memorability is indexed by brain responses starting at 218ms for faces and 371ms for scenes--later than classical early face/scene discrimination perceptual signals, yet earlier than the late memory encoding signal observed at ~700ms. The results show memorability is a high-level image property whose spatio-temporal neural dynamics are different from those of memory encoding. Together, this work brings new insights into the underlying neural processes of the transformation from what we perceive to what we remember.

Neuroscience↗

bioRxiv2016

Two frequency bands contain the most stimulus-related information in visual cortex

Sensory cortices represent the world through the activity of diversely tuned cells. How the activity of single cells is coordinated within populations and across sensory hierarchies is largely unknown. Cortical oscillations may coordinate local and distributed neuronal groups. Using datasets from intracortical multi-electrode recordings and from large-scale electrocorticography (ECoG) grids, we investigated how visual features could be extracted from the local field potential (LFP) and how this compared with the information available from multi-unit activity (MUA). MUA recorded from macaque V1 contained comparable amounts of information as simultaneously recorded LFP power in two frequency bands, one in the alpha-beta band and the other in the gamma band. ECoG-LFP contained information in the same bands as microelectrode-LFP, even when identifying natural scenes. The fact that information was contained in the same bands in both intracortical and ECoG recordings suggests that oscillatory activity could play similar roles at both spatial scales.

Neuroscience↗

bioRxiv2016

HDAC inhibition protects degenerating cone photoreceptors in vivo

Retinal diseases caused by cone photoreceptor cell death are devastating as the patients are experiencing loss of accurate and color vision. Understanding the mechanisms of cone cell death and the identification of key players therein could provide new treatment options. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration (cpfl1). We show that HDAC inhibition protects cones in vitro, in retinal explant cultures. More importantly, in vivo a single TSA injection increased cone survival for up to 10 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and diseases associated with impaired cone migration.

Neuroscience↗

bioRxiv2016

Cytokine and Leukocyte Profiling Reveal Pro-Inflammatory and Autoimmune Features in Frontotemporal Dementia Patients

The growing link between systemic environment and brain function opens the possibility that cellular communication and composition in blood are correlated with brain health. We tested this concept in frontotemporal dementia with novel, unbiased tools that measure hundreds of soluble signaling proteins or characterize the vast immune cell repertoire in blood. With these tools we discovered complementary abnormalities indicative of abnormal T cell populations and autoimmunity in frontotemporal dementia.

Neuroscience↗

bioRxiv2016

The hippocampus generalizes across memories that share item and context information

Episodic memory is known to rely on the hippocampus, but how the hippocampus organizes different episodes to permit their subsequent retrieval remains controversial. According to one view, hippocampal coding differentiates between similar events to reduce interference, whereas an alternative view is that the hippocampus assigns similar representations to events that share item and context information. Here, we used multivariate analyses of activity patterns measured with functional magnetic resonance imaging (fMRI) to characterize how the hippocampus distinguishes between memories based on similarity of their item and/or context information. Hippocampal activity patterns discriminated between events that shared either item or context information, but generalized across events that shared similar item-context associations. The current findings provide novel evidence that, whereas the hippocampus can resist mnemonic interference by separating events that generalize along a single attribute dimension, overlapping hippocampal codes may support memory for events with overlapping item-context relations.

Neuroscience↗

bioRxiv2016

Olfactory perception of chemically diverse molecules

Background: Understanding the relationship between a stimulus and how it is perceived reveals fundamental principles about the mechanisms of sensory perception. While this stimulus-percept problem is mostly understood for color vision and tone perception, it is not currently possible to predict how a given molecule smells. While there has been some progress in predicting the pleasantness and intensity of an odor, perceptual data for a larger number of diverse molecules are needed to improve current predictions. Towards this goal, we tested the olfactory perception of 480 structurally and perceptually diverse molecules at two concentrations using a panel of 55 healthy human subjects.\n\nResults: For each stimulus, we collected data on perceived intensity, pleasantness, and familiarity. In addition, subjects were asked to apply 20 semantic odor quality descriptors to these stimuli, and were offered the option to describe the smell in their own words. Using this dataset, we replicated several previous correlations between molecular features of the stimulus and olfactory perception. The number of sulfur atoms in a molecule was highly correlated with the descriptors \"garlic\" \"fish\" \"decayed,\" and large and structurally complex molecules were perceived to be more pleasant. We discovered a number of strong correlations in intensity perception between molecules, which suggests a shared mechanism for perceiving these molecules. We show that familiarity had a strong effect on the ability of subjects to describe a smell. Many subjects used commercial products to describe familiar odors, highlighting the role of prior experience in biasing verbal report of perceived smells. Nonspecific descriptors like \"chemical\" were applied frequently to unfamiliar smells, and unfamiliar odors were generally rated as neither pleasant nor unpleasant.\n\nConclusions: We present a very large psychophysical dataset and use this to correlate molecular features of a stimulus to olfactory percept. Our work reveals robust correlations between molecular features and perceptual qualities, and highlights the dominant role of familiarity and experience in assigning verbal descriptors to smells.

Neuroscience↗

bioRxiv2016

Subcortical source and modulation of the narrowband gamma oscillation in mouse visual cortex

Primary visual cortex (V1) exhibits two types of gamma rhythm: broadband activity in the 30-90 Hz range, and a narrowband oscillation seen in mice at frequencies close to 60 Hz. We investigated the sources of the narrowband gamma oscillation, the factors modulating its strength, and its relationship to broadband gamma activity. Narrowband and broadband gamma power were uncorrelated. Increasing visual contrast had opposite effects on the two rhythms: it increased broadband activity, but suppressed the narrowband oscillation. The narrowband oscillation was strongest in layer 4, and was mediated primarily by excitatory currents entrained by the synchronous, rhythmic firing of neurons in the lateral geniculate nucleus (LGN). The power and peak frequency of the narrowband gamma oscillation increased with light intensity. Silencing the cortex optogenetically did not affect narrowband oscillation in either LGN firing or cortical excitatory currents, suggesting that this oscillation reflects unidirectional flow of signals from thalamus to cortex.\n\nHighlights*Local field potential in mouse primary visual cortex exhibits a pronounced narrowband gamma oscillation close to 60 Hz.\n\n*Narrowband gamma is highest in the thalamorecipient layer 4\n\n*Narrowband gamma increases with light intensity and arousal state, and is suppressed by visual contrast.\n\n*Lateral geniculate nucleus neurons fire synchronously at the narrowband gamma frequency, independent of V1 activity.

Neuroscience↗

bioRxiv2016

Pan-retinal characterisation of Light Responses from Ganglion Cells in the Developing Mouse Retina

We have investigated the ontogeny of light-driven responses in mouse retinal ganglion cells (RGCs). Using a large-scale, high-density multielectrode array, we recorded from hundreds to thousands of RGCs simultaneously at pan-retinal level, including dorsal and ventral locations. Responses to different contrasts not only revealed a complex developmental profile for ON, OFF and ON-OFF RGC types, but also unveiled differences between dorsal and ventral RGCs. At eye-opening, dorsal RGCs of all types were more responsive to light, perhaps indicating an environmental priority to nest viewing for pre-weaning pups. The developmental profile of ON and OFF RGCs exhibited antagonistic behavior, with the strongest ON responses shortly after eye-opening, followed by an increase in the strength of OFF responses later on. Further, we found that with maturation receptive field (RF) center sizes decrease, responses to light get stronger, and centers become more circular while seeing differences in all of them between RGC types. These findings show that retinal functionality is not spatially homogeneous, likely reflecting ecological requirements that favour the early development of dorsal retina, and reflecting different roles in vision in the mature animal.

Neuroscience↗

bioRxiv2016

Alpha Phase Dynamics Predict Age-Related Visual Working Memory Decline

Alpha oscillations are modulated in response to visual temporal and spatial cues, However, the neural response to alerting cues is less explored, as is how this response is affected by healthy aging. Using scalp EEG, we examined how visual cortical alpha activity relates to working memory performance. Younger (20-30 years) and older (60-70 years) participants were presented with a visual alerting cue uninformative of the position or size of a lateralized working memory array. Older adults showed longer response times overall, and reduced accuracy when memory load was high. Older adults had less consistent cue-evoked phase resetting than younger adults, which predicted worse performance. Alpha phase prior to memory array presentation predicted response time, but the relationship between phase and response time was weaker in older adults. These results suggest that changes in alpha phase dynamics, especially prior to presentation of task-relevant stimuli, potentially contribute to age-related cognitive decline.

Neuroscience↗