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Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 62,933 bioRxiv papers from 279,142 authors.

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in category neuroscience

10,909 results found. For more information, click each entry to expand.

10481: Operant self-stimulation of thalamic terminals in the dorsomedial striatum is constrained by metabotropic glutamate receptor 2
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Posted to bioRxiv 18 Sep 2019

Operant self-stimulation of thalamic terminals in the dorsomedial striatum is constrained by metabotropic glutamate receptor 2
77 downloads neuroscience

Kari A Johnson, Lucas Voyvodic, Yolanda Mateo, David M. Lovinger

Dorsal striatal manipulations including stimulation of dopamine release and activation of medium spiny neurons (MSNs) are sufficient to drive reinforcement-based learning. Glutamatergic innervation of the dorsal striatum by both the cortex and thalamus is a critical determinant of both MSN activity and local regulation of dopamine release. However, the relationship between glutamatergic inputs to the striatum and behavioral reinforcement is not well understood. We sought to evaluate the reinforcing properties of optogenetic stimulation of thalamostriatal terminals, which are associated with vesicular glutamate transporter 2 (Vglut2) expression, in the dorsomedial striatum (DMS), a region implicated in goal-directed operant behaviors. In mice expressing channelrhodopsin-2 (ChR2) under control of the Vglut2 promoter, brief optical stimulation of the DMS reinforces operant lever-pressing behavior. Mice also acquire operant self-stimulation of thalamic terminals in the DMS when ChR2 expression is virally targeted to the intralaminar thalamus. Because the presynaptic G protein-coupled receptor metabotropic glutamate receptor 2 (mGlu2) robustly inhibits glutamate and dopamine release induced by activation of thalamostriatal afferents, we examined the regulation of thalamostriatal self-stimulation by mGlu2. We find that administration of an mGlu2/3 agonist or an mGlu2-selective positive allosteric modulator reduces self-stimulation. In contrast, blockade of these receptors increases thalamostriatal self-stimulation, suggesting that endogenous activation of these receptors negatively modulates the reinforcing properties of thalamostriatal activity. These findings demonstrate that stimulation of thalamic terminals in the DMS is sufficient to reinforce a self-initiated action, and that thalamostriatal reinforcement is constrained by mGlu2 activation.

10482: Spatiotemporal Feature Selection Improves Prediction Accuracy of Multi-Voxel Pattern Classification
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Posted to bioRxiv 28 Aug 2019

Spatiotemporal Feature Selection Improves Prediction Accuracy of Multi-Voxel Pattern Classification
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Jeiran Choupan, Yaniv Gal, Pamela K Douglas, Mark S Cohen, David C. Reutens, Zhengyi Yang

The importance of spatiotemporal feature selection in fMRI decoding studies has not been studied exhaustively. Temporal embedding of features allows the incorporation of brain activity dynamics into multivariate pattern classification, and may provide enriched information about stimulus-specific response patterns and potentially improve prediction accuracy. This study investigates the possibility of enhancing the classification performance by exploring spatial and temporal (spatiotemporal) domain, to identify the optimum combination of the spatiotemporal features based on the classification performance. We investigated the importance of spatiotemporal feature selection using a slow event-related design adapted from the classic Haxby et al. (2001) study. Data were collected using a multiband fMRI sequence with temporal resolution of 0.568 seconds. A wide range of spatiotemporal observations was created as various combinations of spatiotemporal features. Using both random forest, and support vector machine, classifiers, prediction accuracies for these combinations were then compared with the single time-point spatial multivariate pattern approach that uses only a single temporal observation. The results showed that on average spatiotemporal feature selection improved prediction accuracy. Moreover, the random forest algorithm outperformed the support vector machine and benefitted from temporal information to a greater extent. As expected, the most influential temporal durations were found to be around the peak of the hemodynamic response function, a few seconds after the stimuli onset until ~4 seconds after the peak of the hemodynamic response function. The superiority of spatiotemporal feature selection over single time-point spatial approaches invites future work to design systematic and optimal approaches to the incorporation of spatiotemporal dependencies into feature selection for decoding.

10483: Computational modelling of the long-term effects of brain stimulation on the local and global structural connectivity of epileptic patients
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Posted to bioRxiv 07 Aug 2019

Computational modelling of the long-term effects of brain stimulation on the local and global structural connectivity of epileptic patients
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Emmanouil Giannakakis, Frances Hutchings, Christoforos A Papasavvas, Cheol Han, Bernd Weber, Chencheng Zhang, Marcus Kaiser

In patients with drug resistant focal epilepsy, targeted weak stimulation of the affected brain regions has been proposed as an alternative to surgery. However, the effectiveness of stimulation as a treatment presents great variation from patient to patient. In this study, brain activity is simulated for a period of one day using a network of Wilson-Cowan oscillators coupled according to diffusion imaging based structural connectivity. We use this computational model to examine the potential long-term effects of stimulation on brain connectivity. Our findings indicate that the overall simulated effect of stimulation is heavily dependent on the excitability of the stimulated regions. Additionally, stimulation seems to lead to long-term effects in the connectivity of secondary (non-stimulated) regions in epileptic patients. These effects are correlated with a worse surgery outcome in some patients, which suggests that long-term simulations could be used as a tool to determine suitability for surgery/stimulation.

10484: Exploring the prediction of emotional valence and pharmacologic effect across fMRI studies of antidepressants.
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Posted to bioRxiv 01 Aug 2018

Exploring the prediction of emotional valence and pharmacologic effect across fMRI studies of antidepressants.
77 downloads neuroscience

Daniel S. Barron, Mehraveh Salehi, M. Browning, Catherine Harmer, R Todd Constable, Eugene Duff

Clinically approved antidepressants modulate the brain's emotional valence circuits, suggesting that the response of these circuits could serve as a biomarker for screening candidate antidepressant drugs. However, it is necessary that these modulations can be reliably detected. Here, we apply a cross-validated predictive model to classify emotional valence and pharmacologic effect across eleven task-based fMRI datasets (n=306) exploring the effect of antidepressant administration on emotional face processing. We created subject-level contrast of parameter estimates of the emotional faces task and used the Shen whole-brain parcellation scheme to define 268 subject-level features that trained a cross-validated gradient- boosting machine protocol to classify emotional valence (fearful vs happy face visual conditions) and pharmacologic effect (drug vs placebo administration) within and across studies. We found patterns of brain activity that classify emotional valence with a statistically significant level of accuracy (70% across-all-subjects; range from 50-87% across-study). Our classifier failed to consistently discriminate drug from placebo. Subject population (healthy or unhealthy), treatment group (drug or placebo), and drug administration protocol (dose and duration) affected this accuracy with similar populations better predicting one another. We found limited evidence that antidepressants modulated brain response in a consistent manner, however found a consistent signature for emotional valence. Variable functional patterns across studies suggest that predictive modeling can inform biomarker development in mental health and in pharmacotherapy development. Our results suggest that case-controlled designs and more standardized protocols are required for functional imaging to provide robust biomarkers for drug development.

10485: Deep Learning-Based Analysis of Macaque Corneal Sub-Basal Nerve Fibers in Confocal Microscopy Images
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Posted to bioRxiv 05 Sep 2019

Deep Learning-Based Analysis of Macaque Corneal Sub-Basal Nerve Fibers in Confocal Microscopy Images
77 downloads neuroscience

Jonathan D Oakley, Daniel B Russakoff, Rachel L Weinberg, Megan E McCarron, Jessica M Izzi, Joseph L Mankowski

The automated assessment of corneal nerve fiber length (CNFL) in in vivo confocal microscopy (IVCM) images is of increasing clinical interest. These measurements are important biomarkers in a number of diseases including diabetes mellitus, human immunodeficiency virus, Parkinson's disease and multiple sclerosis. Animal models of these and other diseases play an important role in understanding the disease processes as efforts toward developing new and effective therapeutics are made. And while automated methods exist for nerve fiber analysis in clinical data, differences in anatomy and image quality make the macaque data more challenging and has motivated the work reported here. Toward this goal, nerves in macaque corneal IVCM images were manually labelled using an ImageJ plugin (NeuronJ). Different deep convolutional neural network (CNN) architectures were evaluated for accuracy relative to the ground truth manual tracings. The best performing model was used on separately acquired macaque ICVM images to additionally compare inter-reader variability. Results show deep learning-based segmentation of sub-basal nerves in IVCM images to have excellent correlation to manual segmentations in macaque data. The technique is indistinguishable across readers and paves the way for more widespread adoption of objective automated analysis of sub-basal nerves in IVCM.

10486: Title: Risk factors for postoperative meningitis after microsurgery for vestibular schwannoma
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Posted to bioRxiv 09 May 2019

Title: Risk factors for postoperative meningitis after microsurgery for vestibular schwannoma
77 downloads neuroscience

Bowen Huang, Yanming Ren, Chenghong Wang, Zhigang Lan, Xuhui Hui, Wenke Liu, Yuekang Zhang

OBJECTIVE: Meningitis after microsurgery for vestibular schwannoma (VS) is a severe complication and result in high morbidity. But few studies have focused on meningitis after VS surgery alone. The purpose of this study was to identify the risk factors for meningitis after VS surgery. METHODS: We undertook a retrospective analysis of all VS patients, who underwent microsurgery of VS and at least live for 7 days after surgery, between 1st June 2015 and 30st November 2018 at West China Hospital of Sichuan University. Univariate and multivariate analyses were performed to identify the risk factors for postoperative meningitis (POM). RESULTS: We collected 410 patients, 27 of whom had POM. Through univariate analysis, hydrocephalus (p=0. 018), Koos grade IV?p=0.04?, The operative duration (> 3 hours p=0.03) and intraoperative bleeding volume (≥400ml p=0. 02) were significantly correlated to POM. Multivariate analysis showed that Koos grade IV (p=0.04; OR=3.19; 95% CI 1.032-3.190), operation duration (> 3 hours p=0.03 OR= 7.927; 95% CI 1.043-60.265), and intraoperative bleeding volume (≥ 400ml p=0.02; OR=2.551; 95% CI 1.112-5.850) are the independent influencing factors of POM. CONCLUSIONS: Koos grade IV, the duration of operation, and the amount of bleeding were identified as independent risk factors for POM after microsurgery of VS. POM caused a prolonged hospital stay.

10487: A History of Chronic Repeated Predation Stress Reduces Aversion to Ethanol Adulteration in Male, but not Female, C57Bl/6J Mice
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Posted to bioRxiv 20 Jun 2019

A History of Chronic Repeated Predation Stress Reduces Aversion to Ethanol Adulteration in Male, but not Female, C57Bl/6J Mice
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Gladys A. Shaw, Maria Alexis M. Bent, Kimaya R. Council, A. Christian Pais, Ananda Amstadter, Jennifer T. Wolstenholme, Michael F. Miles, Gretchen Neigh

Background: Trauma related psychiatric disorders, such as posttraumatic stress disorder (PTSD), and alcohol use disorder (AUD) are highly comorbid illnesses that separately present an opposing, sex-specific pattern, with increased prevalence of PTSD in females and increased prevalence of AUD diagnoses in males. Likewise, PTSD is a risk factor in the development of AUD, with conflicting data on the impact of sex in the comorbid development of both disorders. Because the likelihood of experiencing more than one traumatic event is high, we aim to utilize chronic exposure to adolescent and early adult predator stress to query the extent to which sex interacts with chronic stress to influence alcohol consumption, or cessation of consumption. Methods: Male (n=16) and female (n=15) C57BL/6J mice underwent chronic repeated predatory stress (CRPS) or daily handling for two weeks during adolescence (P35-P49) and two weeks during adulthood (P65-P79). All mice were subject to open field testing and marble burying analysis as metrics of anxiety-like behavior. Mice subsequently underwent a two-bottle choice intermittent ethanol access (IEA) phase (P90-131) with the options of 20% ethanol or water. After establishing drinking behavior, increasing concentrations of quinine were added to the ethanol to assess ethanol seeking behavior in the presence of an aversive stimuli, as a metric of compulsive-like drinking. Results: CRPS increased baseline corticosterone and anxiety-like behaviors in the open field in both male and female mice as compared to control mice that had not been exposed to CRPS. Consistent with previous reports, we observed a sex difference in alcohol consumption such that females consumed more ethanol per gram of body mass than males. In addition, CRPS increased both alcohol intake by weight and preference, suggesting compulsive-like drinking behavior in male mice during quinine adulteration. Conclusion: Collectively, we demonstrate that CRPS during late adolescence and early adulthood can induce anxiety-like behavior in both sexes but selectively influences ethanol intake in males. Male mice with a history of CRPS continue to engage in ethanol seeking behaviors despite being paired with an aversive gustatory stimulus, suggesting dependence-like drinking behavior. Our results suggest that stress may play a role in the development of anxiety-like behaviors and also drive a sex-specific alteration in drinking behavior.

10488: Mapping effective connectivity between the frontal and contralateral primary motor cortex using dual-coil transcranial magnetic stimulation
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Posted to bioRxiv 22 Aug 2019

Mapping effective connectivity between the frontal and contralateral primary motor cortex using dual-coil transcranial magnetic stimulation
77 downloads neuroscience

Karen Louise Bunday, Sonia Betti, James Bonaiuto, Guy A Orban, Marco Davare

Background: Cytoarchitectonic, anatomical and electrophysiological studies have divided the frontal cortex into distinct anatomical and functional subdivisions. Many of these subdivisions have functional connections with the contralateral primary motor cortex (M1); however, effective neurophysiological connectivity between these regions is not well defined in humans. Objective: We aimed to use dual-coil transcranial magnetic stimulation (TMS) to map, with high spatial resolution, the effective connectivity between different frontal regions of the right hemisphere and contralateral M1 (cM1). Methods: TMS was applied over the left M1 alone (test pulse) or after a conditioning pulse that was applied to different targets over the right frontal cortex, while subjects sat at rest, or during the preparation of index finger abduction or a precision grip. Results: We found four clusters in the precentral gyrus and premotor regions, namely area 6d/FEF, area 43, area 6v, and area 44, which showed significant differential modulations of contralateral MEPs at rest compared to during preparation of index finger abduction and precision grip. Moreover, two clusters in the dorsal lateral prefrontal cortex (8C and 8Av-46-8C) showed differential modulation of contralateral MEPs during preparation of index finger abduction compared to precision grip. Conclusion: We show a gradient of task-related connectivity whereby interactions between caudal premotor regions and cM1 differentiate between rest and movement preparation, but more rostrally, interactions between dorsolateral prefrontal regions and cM1 differentiate between preparation of different types of hand movements. These results thus demonstrate the utility of dual-coil TMS to define fine-grained sub-regions in the human frontal cortex, which are functional and causally involved in hand movements.

10489: Influence of prior beliefs on perception in early psychosis: effects of illness stage and hierarchical level of belief
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Posted to bioRxiv 23 Sep 2018

Influence of prior beliefs on perception in early psychosis: effects of illness stage and hierarchical level of belief
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J. Haarsma, F Knolle, J.D. Griffin, H. Taverne, M. Mada, I.M. Goodyer, the NSPN Consortium, P.C. Fletcher, G.K Murray

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. General scientific summary What 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.

10490: The effect of overnight consolidation in the perceptual learning of non-native tonal contrasts
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Posted to bioRxiv 09 Aug 2019

The effect of overnight consolidation in the perceptual learning of non-native tonal contrasts
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Zhen Qin, Caicai Zhang

Sleep-mediated overnight consolidation was found to facilitate perceptual learning by promoting learners' generalization across talkers in their perception of novel segmental categories. Lexical tone differs from most segmental contrasts in that it is highly variable across talkers, and displays dynamic change over time. It remains unclear whether a similar (or a larger) effect of overnight consolidation would be found for perceptual learning of novel tonal contrasts. Thus, this study aims to examine whether overnight consolidation facilitates generalization across talkers in the discrimination and identification of novel Cantonese level tones by Mandarin listeners. Two groups of Mandarin listeners were perceptually trained either in the morning or in the evening. Listeners were trained in a tone identification (ID) task using stimuli produced by a trained talker. Their development was then tested in the ID and AX discrimination tasks using stimuli produced by trained and untrained talkers in three posttests following training: immediately after training, 12-hour delay, and 24-hour delay. While the evening group slept between the first and second posttests, the morning group did not. The results of accuracy rates in the ID task showed that while Mandarin listeners trained in the evening showed an improved trend, predicted by their individual sleep time, in identifying the level tones produced by both the trained and untrained talkers, Mandarin listeners trained in the morning showed a declining trend. In contrast, the results of d-prime scores in the AX discrimination task did not show different developmental patterns between the two groups. Consistent with previous studies on segmental learning, the finding suggests that overnight consolidation might have assisted the evening trainees' formation of a more abstract (talker-independent) representation of novel tone categories in memory traces. The results are discussed regarding the features of lexical tones to shed light on the mechanism of phonetic learning.

10491: Effects of Transcranial Direct Current Stimulation on GABA and Glutamate in Children: A Pilot Study
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Posted to bioRxiv 05 Sep 2019

Effects of Transcranial Direct Current Stimulation on GABA and Glutamate in Children: A Pilot Study
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Chidera Nwaroh, Adrianna Giuffre, Lauran Cole, Tiffany Bell, Helen Carlson, Frank P MacMaster, Adam Kirton, Ashley D Harris

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain excitability and has therapeutic potential for many conditions. Several studies have shown that anodal tDCS of the primary motor cortex (M1) facilitates motor learning and plasticity, but there is little information about the underlying mechanisms. Using magnetic resonance spectroscopy (MRS) it has been shown that tDCS can affect local levels of g-aminobutyric acid (GABA) and Glx (a measure of glutamate and glutamine combined) in adults, both of which are known to be associated with skill acquisition and plasticity; however this has yet to be studied in children and adolescents. This study examined GABA and Glx in response to conventional anodal tDCS (a-tDCS) and high definition tDCS (HD-tDCS) targeting the M1 in a pediatric population. Twenty-four typically developing, right handed children ages 12–18 years participated in five consecutive days of tDCS intervention (sham, a-tDCS or HD-tDCS) targeting the right M1 while training in a fine motor task (Purdue Pegboard Task) with their left hand. Glutamate and GABA were measured before and after the protocol (at day 5 and 6 weeks) using conventional MRS and GABA-edited MRS in the sensorimotor cortices. Glutamate measured in the left sensorimotor cortex was higher in the HD-tDCS group compared to a-tDCS and sham at 6 weeks (p = 0.001). No changes in GABA were observed in either sensorimotor cortex at any time. These results suggest that the developing brain may demonstrate different responses to tDCD as compared to adults.

10492: Endogenous activity modulates stimulus and circuit-specific neural tuning and perception
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Posted to bioRxiv 02 Jul 2019

Endogenous activity modulates stimulus and circuit-specific neural tuning and perception
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Yuanning Li, Michael J. Ward, R. Mark Richardson, Max G’Sell, Avniel Singh Ghuman

Perception reflects not only input from the sensory periphery, but also the endogenous neural state when sensory inputs enter the brain. Whether endogenous neural states influence perception only through global mechanisms, such as arousal, or can also perception in a neural circuit and stimulus specific manner remains largely unknown. Intracranial recordings from 30 pre-surgical epilepsy patients showed that endogenous activity independently modulated the strength of trial-by-trial neural tuning of different visual category-selective neural circuits. Furthermore, the same aspect of the endogenous activity that influenced tuning in a particular neural circuit also correlated with reaction time only for trials with the category of image that circuit was selective for. These results suggest that endogenous activity may influence neural tuning and perception through circuit-specific predictive coding processes.

10493: Temporary anosmia in mice following nasal lavage with dilute detergent solution
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Posted to bioRxiv 02 Apr 2019

Temporary anosmia in mice following nasal lavage with dilute detergent solution
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Thomas Gerald Mast, Kelsey Zuk, Andrew Rinke, Khaleel Quasem, Bradley Savard, Charles Brobbey, Jacob Reiss, Michael Dryden

Olfactory sensory deprivation induces anosmia and reduces tyrosine hydroxylase and dopamine levels in the olfactory bulb. The behavioral consequences specific to the loss of olfactory bulb dopamine are difficult to determine because sensory deprivation protocols are either confounded by side effects or leave the animal anosmic. A new method to both induce sensory deprivation and to measure the behavioral and circuit consequences is needed. We developed a novel, recoverable anosmia protocol utilizing nasal lavage with a dilute detergent solution. Detergent treatment did not damage the olfactory epithelium as measured by scanning electron microscopy, alcian blue histology, and acetylated tubulin immunohistochemistry. One treatment induced anosmia that lasted 24-48 hours. Lastly, five days of treatment reduced both olfactory bulb tyrosine hydroxylase and dopamine levels which indicates that anosmia persists between treatments. This is the first report of a sensory deprivation protocol that induces recoverable anosmia and can be paired with biochemical, histological, and behavioral investigations of olfaction.

10494: Associations between neonatal cry acoustics and visual attention during the first year
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Posted to bioRxiv 03 Jun 2019

Associations between neonatal cry acoustics and visual attention during the first year
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Aicha Kivinummi, Gaurav Naithani, Outi Tammela, Tuomas Virtanen, Enni Kurkela, Miia Alhainen, Dana JH Niehaus, Anusha Lachman, Jukka Leppänen, Mikko Peltola

It has been suggested that early cry parameters are connected to later cognitive abilities. The present study is the first to investigate whether the acoustic features of infant cry are associated with cognitive development already during the first year, as measured by oculomotor orienting and attention disengagement. Cry sounds for acoustic analyses (fundamental frequency; F0) were recorded in two neonatal cohorts at the age of 0-5 days (Tampere, Finland) or at 6 weeks (Cape Town, South-Africa). Eye-tracking was used to measure oculomotor orienting to peripheral visual stimuli and attention disengagement from central stimuli at 8 months (Tampere) or at 6 months (Cape Town) age. In the Tampere cohort, a marginal positive correlation between fundamental frequency of cry (F0) and visual attention disengagement was observed; infants with a higher neonatal F0 were slower to shift gaze away from the central stimulus to the peripheral stimulus. However, a similar correlation was not observed in the Cape Town cohort. No associations between F0 and oculomotor orienting were observed in either cohort. We discuss possible factors influencing the discrepancy in results between the cohorts and suggest directions for future research investigating the potential of early cry analysis in predicting later cognitive development.

10495: Neurocognitive development of inhibitory control and substance use vulnerability
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Posted to bioRxiv 24 Sep 2019

Neurocognitive development of inhibitory control and substance use vulnerability
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Alina Quach, Brenden Tervo-Clemmens, William Foran, Finnegan J. Calabro, Tammy Chung, Duncan B. Clark, Beatriz Luna

Previous research indicates that risk for substance use is associated with poor inhibitory control. However, it remains unclear whether at risk youth use follow divergent patterns of inhibitory control development. As part of the longitudinal National Consortium on Adolescent Neurodevelopment and Alcohol (NCANDA) study, participants ( N = 113, baseline age: 12-21) completed a rewarded antisaccade task during fMRI, with up to three time points. We examined whether substance use risk factors, including dimensional measures of psychopathology (externalizing, internalizing) and family history of substance use disorder, were associated with developmental differences in inhibitory control performance and BOLD activation at both the trial-level and within individual antisaccade epochs (cue, preparation, and response). Among substance use risk factors, only externalizing psychopathology predicted developmental differences in inhibitory control, where high externalizing predicted lower correct response rates and faster latencies were observed in early adolescence, but normalized by late adolescence. Neuroimaging results revealed high externalizing was associated with developmentally-stable hypo-activation in the left middle frontal gyrus (trial-level), but divergent developmental patterns of posterior parietal cortex activation (cue epoch). Developmental differences in inhibitory control associated with externalizing suggest early adolescence may be a unique period of substance use vulnerability via cognitive and phenotypic disinhibition. Highlights 1. Characterized inhibitory control development in adolescents at-risk for substance use. 2. Externalizing psychopathology is associated with lower antisaccade correct response rate and faster latencies in early adolescence. 3. Externalizing performance differences normalize by late adolescence. 4. Externalizing is associated with prefrontal hypo-activation across development. 5. Externalizing moderates age-related increases in posterior parietal cortex activity.

10496: Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine: An in vivo 1H-magnetic resonance spectroscopy study at 14 T
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Posted to bioRxiv 02 Jul 2019

Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine: An in vivo 1H-magnetic resonance spectroscopy study at 14 T
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Antoine Cherix, Thomas Larrieu, Jocelyn Grosse, João Rodrigues, Bruce McEwen, Carla Nasca, Rolf Gruetter, Carmen Sandi

Background Emerging evidence suggests that hierarchical status may provide vulnerability to develop stress-induced depression. Energy metabolism in the nucleus accumbens (NAc) was recently related to hierarchical status and vulnerability to develop depression-like behavior. Acetyl-L-carnitine (LAC), a mitochondria-boosting supplement, has shown promising antidepressant-like effects opening promising therapeutic strategies for restoring energy balance in depressed patients. Here, we investigated the metabolic impact in the NAc of antidepressant LAC treatment in chronically stressed mice. Method Mice were characterized for emotional behaviors and social rank. They were then exposed to chronic restraint stress (CRS) for 21 days and subsequently tested in a social behavior (SB) test. A group of mice was also given LAC supplementation during the 7 last CRS days. Mice were then tested in the SB and forced swim tests (FST) and scanned in vivo using 1H-magnetic resonance spectroscopy (1H-MRS) to quantitatively assess the NAc neurochemical profile. Results Dominant, but not subordinate, mice showed behavioral vulnerability to CRS. In the NAc, dominant mice showed reduced levels of several energy-related metabolites. LAC treatment counteracted stress-induced behavioral changes in dominant mice, and normalized levels of taurine, phosphocreatine, glutamine and phosphocholine in the NAc. No major accumbal metabolic changes were observed in subordinate mice. Conclusion High social rank is confirmed as a vulnerability factor to develop chronic stress-induced depressive-like behaviors. We reveal a metabolic signature in the NAc for the antidepressant-like effects of LAC in vulnerable mice, characterized by restoration of stress-induced alterations in neuroenergetics and lipid function.

10497: Semantic Probing: Feasibility of using sequential probes to decode what is on a user's mind
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Posted to bioRxiv 16 Dec 2018

Semantic Probing: Feasibility of using sequential probes to decode what is on a user's mind
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Karen Dijkstra, Jason Farquhar, Peter Desain

In this paper, we investigate the feasibility of using multiple sequential probe words to decode their relatedness to an active semantic concept on a user's mind from the respective electrophysiological brain responses. If feasible, this relatedness information could be used by a Brain Computer Interface to infer that semantic concept, by integrating the knowledge of the relationship between the multiple probe words and the 'unknown' target. Such a BCI can take advantage of the N400: an event related potential that is sensitive to semantic content of a stimulus in relation to an established semantic context. However, it is unknown whether the N400 is suited for the multiple probing paradigm we propose, as other intervening words might distract from the established context (i.e., the target word). We perform an experiment in which we present up to ten words after an initial target word, and find no attenuation of the strength of the N400 in grand average ERPs and no decrease in classification accuracy for probes occurring later in the sequences. These results lay the groundwork for the development of a BCI that infers the concept on a user's mind through repeated probing.

10498: Regionally diffuse muscle pain-hypersensitivity in humans during acute muscle pain
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Posted to bioRxiv 21 Jan 2019

Regionally diffuse muscle pain-hypersensitivity in humans during acute muscle pain
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J. S. Dunn, S. S. Nagi, D. A. Mahns

Background: We have previously shown that an intramuscular infusion of 5% hypertonic saline (HS) produces a painful response to normally innocuous stimuli applied to overlying and adjacent skin regions. In the current study, we explored whether a similar interaction could be observed between adjacent, contralateral and remote muscles. Indeed, widespread muscle pain-hypersensitivity is a hallmark of chronic pain conditions such as fibromyalgia. Methods: 5% HS was infused into the flexor carpi ulnaris (FCU) muscle to develop a stable baseline pain (n=30). In separate experiments, each of the three test locations (n=10 per site), the adjacent abductor digiti minimi (ADM), contralateral FCU and contralateral tibialis anterior (TA) (part 1-3, respectively), 50uL of 0.9% normal saline (NS) was infused (in triplicate) prior to, during and following HS-induced muscle pain. Results: Under control conditions (no background pain), the infusion of NS was imperceptible by all subjects. In the presence of HS-induced background pain (FCU), in part 1 the NS co-infusion into ADM increased overall pain by 17%. This was replicated in the contralateral FCU (part 2) with a 12% pain increase, and in the TA (part 3) with a 15% pain increase in response to the NS co-infusions. Notably, over 80% of subjects perceived the NS-induced increase in pain at the HS-infusion location (FCU) rather than the NS-infusion location (adjacent, contralateral and remote). Conclusions: Intramuscular infusion of HS results in pain-hypersensitivity to sub-perceptual stimulation of muscle afferents in a somatotopically unrestricted manner, indicating the involvement of a central (likely supra-spinal) mechanism.

10499: Verbal thinking in rhythm: motor-to-sensory transformation network mediates imagined singing
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Posted to bioRxiv 16 Sep 2019

Verbal thinking in rhythm: motor-to-sensory transformation network mediates imagined singing
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Yanzhu Li, Huan Luo, Xing Tian

What enables us to think verbally? We hypothesized that the interaction between motor and sensory systems induced speech representation without external stimulation or overt articulation. This motor-to-sensory transformation formed the neural basis that enabled us to think verbally. Analogous to the frequency tracking of neural responses to auditory stimuli, we asked participants to imagine singing lyrics of famous songs rhythmically while their neural electro-magnetic signals were recorded using magnetoencephalography (MEG). We found that when participants imagined with less temporal variation, the neural oscillation at the delta band (same frequency band as the rhythm in the songs) showed more consistent phase coherence across trials. This neural phase tracking of imagined singing was observed in a frontal-parietal-temporal network – the proposed motor-to-sensory transformation pathway, including inferior frontal gyrus (IFG), insula, premotor, intra-parietal sulcus (IPS), temporal-parietal junction (TPJ), primary auditory cortex, and superior temporal gyrus and sulcus (STG & STS). These results suggest that neural oscillations can entrain the rhythm of our mental activity. The coherent activation in the motor-to-sensory transformation neural network mediates the internal construction of perceptual representation and forms the neural computation foundation for inner speech during verbal thinking.

10500: Electrophysiological network alterations in adults with copy number variants associated with high neurodevelopmental risk
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Posted to bioRxiv 09 Sep 2019

Electrophysiological network alterations in adults with copy number variants associated with high neurodevelopmental risk
76 downloads neuroscience

Diana C Dima, Rachael Adams, Stefanie C Linden, Alister Baird, Jacqueline Smith, Sonya Foley, Gavin Perry, Bethany C Routley, Lorenzo Magazzini, Mark Drakesmith, Nigel Williams, Joanne Doherty, Marianne Van Den Bree, Michael J Owen, Jeremy Hall, David E.J. Linden, Krish D Singh

Rare copy number variants associated with increased risk for neurodevelopmental and psychiatric disorders (referred to as ND-CNVs) are characterized by heterogeneous phenotypes thought to share a considerable degree of overlap. Altered neural integration has often been linked to psychopathology and is a candidate marker for potential convergent mechanisms through which ND-CNVs modify risk; however, the rarity of ND-CNVs means that few studies have assessed their neural correlates. Here, we used magnetoencephalography (MEG) to investigate resting-state oscillatory connectivity in a cohort of 42 adults with ND-CNVs, including deletions or duplications at 22q11.2, 15q11.2, 15q13.3, 16p11.2, 17q12, 1q21.1, 3q29, and 2p16.3, and 42 controls. We observed decreased connectivity between occipital, temporal and parietal areas in participants with ND-CNVs. This pattern was common across genotypes and not exclusively characteristic of 22q11.2 deletions, which were present in a third of our cohort. Furthermore, a data-driven graph theory framework enabled us to successfully distinguish participants with ND-CNVs from unaffected controls using differences in node centrality and network segregation. Together, our results point to alterations in electrophysiological connectivity as a putative common mechanism through which genetic factors confer increased risk for neurodevelopmental and psychiatric disorders.

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