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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2016

Predictions shape confidence in right inferior frontal gyrus

It is clear that prior expectations shape perceptual decision-making, yet their contribution to the construction of subjective decision confidence remains largely unexplored. We recorded fMRI data while participants made perceptual decisions and confidence judgements, controlling for potential confounds of attention. Results show that subjective confidence increases as perceptual prior expectations increasingly support the decision, and that this relationship is associated with BOLD activity in right inferior frontal gyrus (rIFG). Specifically, rIFG is sensitive to the discrepancy between expectation and decision (mismatch), and, crucially, higher mismatch responses are associated with lower decision confidence. Connectivity analyses revealed the source of the expectancy information to be bilateral orbitofrontal cortex (OFC) and the source of sensory signals to be intracalcarine sulcus. Altogether, our results indicate that predictive information is integrated into subjective confidence in rIFG, and reveal an occipital-frontal network that constructs confidence from top-down and bottom-up signals. This interpretation was further supported by exploratory findings that the white matter density of intracalcarine sulcus and OFC negatively predicted their respective contributions to the construction of confidence. Our findings advance our understanding of the neural basis of subjective perceptual processes by revealing an occipito-frontal functional network that integrates prior beliefs into the construction of confidence.

Neuroscience↗

bioRxiv2016

Language impairment resulting from a de novo deletion of 7q32.1-q33: a case report

Chromosome 7 is a hot spot for cognitive disorders involving language deficits. We report on a girl who presents with a cognitive and speech delay, motor problems, hearing loss, and behavioral disturbances, and a de novo deletion within 7q32.1-q33 (chromosome position: chr7:127109685-132492196, hg 18). Several genes involved in brain development and function are located within the deleted region. Many of them are related to developmental disorders encompassing language deficits (dyslexia, speech-sound disorder, and autism). The probands phenotype may result from a change in the expression level of some of these genes.

Neuroscience↗

bioRxiv2016

Interpretability of Multivariate Brain Maps in Brain Decoding: Definition and Quantification

Brain decoding is a popular multivariate approach for hypothesis testing in neuroimaging. Linear classifiers are widely employed in the brain decoding paradigm to discriminate among experimental conditions. Then, the derived linear weights are visualized in the form of multivariate brain maps to further study the spatio-temporal patterns of underlying neural activities. It is well known that the brain maps derived from weights of linear classifiers are hard to interpret because of high correlations between predictors, low signal to noise ratios, and the high dimensionality of neuroimaging data. Therefore, improving the interpretability of brain decoding approaches is of primary interest in many neuroimaging studies. Despite extensive studies of this type, at present, there is no formal definition for interpretability of multivariate brain maps. As a consequence, there is no quantitative measure for evaluating the interpretability of different brain decoding methods. In this paper, first, we present a theoretical definition of interpretability in brain decoding; we show that the interpretability of multivariate brain maps can be decomposed into their reproducibility and representativeness. Second, as an application of the proposed definition, we formalize a heuristic method for approximating the interpretability of multivariate brain maps in a binary magnetoencephalography (MEG) decoding scenario. Third, we pro pose to combine the approximated interpretability and the performance of the brain decoding into a new multi-objective criterion for model selection. Our results for the MEG data show that optimizing the hyper-parameters of the regularized linear classifier based on the proposed criterion results in more informative multivariate brain maps. More importantly, the presented definition provides the theoretical background for quantitative evaluation of interpretability, and hence, facilitates the development of more effective brain decoding algorithms in the future.

Neuroscience↗

bioRxiv2016

A switching cost for motor planning

Movement planning consists of choosing the endpoint of the movement and selecting the motor program that will bring the effector on the endpoint. It is widely accepted that movement endpoint is updated on a trial-by-trial basis with respect to the observed errors and that the motor program for a given movement follows the rules of optimal feedback control. Here, we show clear limitations of these predictions because of the existence of a switching cost for motor planning. First, this cost prevented participants from tuning their motor program appropriately for each individual trial. This was true even when the participants selected the width of the target that they reached toward or when they had learned the appropriate motor program previously. These data are compatible with the existence of a switching cost such as those found in cognitive studies. Interestingly, this cost of switching shares many features of costs reported in cognitive task switching experiments and, when tested in the same participants, was correlated with it. Second, we found that randomly changing the width of a target over the course of a reaching experiment prevents the motor system from updating the endpoint of movements on the basis of the performance on the previous trial if the width of the target has changed. These results provide new insights into the process of motor planning and how it relates to optimal control theory and to a selection by consequences process rather than to an error-based process for action selection.

Neuroscience↗

bioRxiv2016

The thalamus is a gateway for stimulus-evoked activity in the habenula

The thalamus mediates diverse brain functions including arousal, perception and memory formation, and is characterized by widespread connectivity. One thalamus projection that is evolutionarily conserved is to the habenula, a regulator of broadly acting neuromodulators. The function of this projection is unknown, as the information transmitted has not been identified. By two-photon calcium imaging of larval zebrafish, we show that change in irradiance triggers dynamic responses in the habenula. Neuroanatomical tracing shows that the dorsal left habenula neuropil, which has the most prominent response to irradiance change and influences irradiance-dependent behavior and raphe response, is innervated by retinorecipient nuclei in the thalamus. Optogenetic stimulation of the thalamus triggers habenula activity, while lesion reduces light-evoked habenula activity. These data establish that the thalamus controls habenula activity following irradiance change, thereby suggesting that the thalamo-habenula projection provides a pathway for visual stimuli to affect neuromodulator release and behavior.

Neuroscience↗

bioRxiv2016

Unconscious integration of multisensory bodily inputs in the peripersonal space shapes bodily self-consciousness

Recent studies have highlighted the role of multisensory integration as a key mechanism of self-consciousness. In particular, integration of bodily signals within the peripersonal space (PPS) underlies the experience of the self in a body we own (self-identification) and that is experienced as occupying a specific location in space (self-location), two main components of bodily self-consciousness (BSC). Experiments investigating the effects of multisensory integration on BSC have typically employed supra-threshold sensory stimuli, neglecting the role of unconscious sensory signals in BSC, as tested in other consciousness research. Here, we used psychophysical techniques to test whether multisensory integration of bodily stimuli underlying BSC may also occur for multisensory inputs presented below the threshold of conscious perception. Our results indicate that visual stimuli rendered invisible (through continuous flash suppression) boost processing of tactile stimuli on the body (Exp. 1), and enhance the perception of near-threshold tactile stimuli (Exp. 2), only once they entered peripersonal space. We then employed unconscious multisensory mechanisms to manipulate BSC. Participants were presented with tactile stimulation on their body and with visual stimuli on a virtual body, seen at a distance, which were either visible or rendered invisible. We report that if visuo-tactile stimulation was synchronized, participants self-identified with the virtual body (Exp. 3), and shifted their self-location toward the virtual body (Exp.4), even if visual stimuli were fully invisible. Our results indicate that multisensory inputs, even outside of awareness, are integrated and affect the phenomenological content of self-consciousness, grounding BSC firmly in the field of psychophysical consciousness studies.

Neuroscience↗

bioRxiv2016

Minimal Data Needed for Valid & Accurate Image-Based fMRI Meta-Analysis

Meta-analysis is a powerful statistical tool to combine results from a set of studies. When image data is available for each study, a number of approaches have been proposed to perform such meta-analysis including combination of standardised statistics, just effect estimates or both effects estimates and their sampling variance. While the latter is the preferred approach in the statistical community, often only standardised estimates are shared, reducing the possible meta-analytic approaches. Given the growing interest in data sharing in the neuroimaging community there is a need to identify what is the minimal data to be shared in order to allow for future image-based meta-analysis. In this paper, we compare the validity and the accuracy of eight meta-analytic approaches on simulated and real data. In one-sample tests, combination of contrast estimates into a random-effects General Linear Model or non-parametric statistics provide a good approximation of the reference approach. If only standardised statistical estimates are shared, permutations of z-score is the preferred approach.

Neuroscience↗

bioRxiv2016

Detecting distortions of peripherally-presented letter stimuli under crowded conditions

When visual features in the periphery are close together they become difficult to recognise: something is present but it is unclear what. This is called \"crowding\". Here we investigated sensitivity to features in highly familiar shapes (letters) by applying spatial distortions. In Experiment 1, observers detected which of four peripherally-presented (8 deg of retinal eccentricity) target letters was distorted (spatial 4AFC). The letters were presented either isolated or surrounded by four undistorted flanking letters, and distorted with one of two types of distortion at a range of distortion frequencies and amplitudes. The bandpass noise distortion (\"BPN\") technique causes spatial distortions in cartesian space, whereas radial frequency distortion (\"RF\") causes shifts in polar coordinates. Detecting distortions in target letters was more difficult in the presence of flanking letters, consistent with the effect of crowding. The BPN distortion type showed evidence of tuning, with sensitivity to distortions peaking at approximately 6.5 c/deg for un-flanked letters. The presence of flanking letters causes this peak to rise to approximately 8.5 c/deg. In contrast to the tuning observed for BPN distortions, RF distortion sensitivity increased as the radial frequency of distortion increased. In a series of follow-up experiments we found that sensitivity to distortions is reduced when flanking letters were also distorted, that this held when observers were required to report which target letter was undistorted, and that this held when flanker distortions were always detectable. The perception of geometric distortions in letter stimuli is impaired by visual crowding.

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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↗