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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 118,539 papers from 511,325 authors.

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in category neuroscience

18,154 results found. For more information, click each entry to expand.

17581: Supracategorical fear information revealed by aversively conditioning multiple categories
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Posted 25 May 2020

Supracategorical fear information revealed by aversively conditioning multiple categories
73 downloads bioRxiv neuroscience

Seth M. Levine, Miriam Kumpf, Rainer Rupprecht, Jens V. Schwarzbach

Fear-generalization is a critical function for survival, in which an organism extracts information from a specific instantiation of a threat (e.g., the western diamondback rattlesnake in my front yard on Sunday) and learns to fear—and accordingly respond to—pertinent higher-order information (e.g., snakes live in my yard). Previous work investigating fear-conditioning in humans has used functional magnetic resonance imaging (fMRI) to demonstrate that activity-patterns of stimuli from an aversively-conditioned category (CS+) are more similar to each other than those of a neutral category (CS-). Here we designed a three-phase (i.e., baseline, conditioned, extinction) experiment using fMRI and multiple aversively-conditioned categories to ask whether we would find only similarity increases within the CS+ categories or also an increase in similarity between the CS+ categories. Using representational similarity analysis, we correlated a set of models to activity-patterns underlying several regions of interest and found that, following fear-conditioning, between-category and within-category similarity increased for the CS+ categories in the superior frontal gyrus (SFG) and the right temporal pole (rTP). Activity patterns in the object-selective lateral occipital cortex tended to prefer the semantic model, regardless of the experimental phase. These results advance prior pattern-based neuroimaging work by exploring the effect of aversively-conditioning multiple categories and indicate an extended role for the SFG and rTP in potentially linking discrete information or abstractly representing supracategorical information during fear-learning for the purpose of proper generalization. ### Competing Interest Statement The authors have declared no competing interest.

17582: Delayed maturation of the structural brain connectome in neonates with congenital heart disease
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Posted 21 Sep 2020

Delayed maturation of the structural brain connectome in neonates with congenital heart disease
73 downloads bioRxiv neuroscience

Maria Feldmann, Ting Guo, Steven P. Miller, Walter Knirsch, Raimund Kottke, Cornelia Hagmann, Beatrice Latal, Andras Jakab

There is emerging evidence for delayed brain development in neonates with congenital heart disease (CHD). We hypothesize that the perioperative development of the structural brain connectome is a proxy to such delays. Therefore, we set out to quantify the alterations and longitudinal pre- to postoperative changes in the connectome in CHD neonates and assess risk factors for disturbed perioperative network development relative to healthy term newborns. In this prospective cohort study, 114 term neonates with CHD underwent cardiac surgery at the University Children’s Hospital Zurich. Forty-six healthy term newborns were included as controls. Pre- and postoperative structural connectomes were derived from mean fractional anisotropy values of fibre pathways traced using diffusion tractography. Graph theory parameters calculated across a range of proportional cost thresholds were compared between groups by multi-threshold permutation correction adjusting for con-founders. Network based statistic was calculated for edgewise network comparison. White matter injury (WMI) volume was quantified on 3D T1-weighted images. Random coefficient mixed models with interaction terms of (i) CHD subtype and (ii) WMI volume with postmenstrual age at MRI respectively were built to assess modifying effects on network development. Pre- and postoperatively, at the global level, efficiency, indicative of network integration, was higher in controls compared to CHD neonates. In contrast, local efficiency and transitivity, indicative of network segregation, were higher in CHD neonates compared to controls (all p<0.025 for one-sided t-tests). Preoperatively these group differences were also found across multiple widespread nodes (all p<0.025, accounting for multiple comparison), whereas postoperatively nodal differences were not evident. At the edge-level, the majority of weaker connections in CHD neonates compared to controls involved interhemispheric connections (66.7% preoperatively; 54.5% postoperatively). A trend showing a more rapid pre- to postoperative decrease in local efficiency was found in class I CHD neonates compared to controls. In CHD neonates, larger WMI volume was associated with lower strength (p=0.0026) and global efficiency (p=0.0097). The maturation of the structural connectome is delayed in neonates with CHD, with a pattern of lower structural integration and higher segregation compared to healthy controls. Trend-level evidence indicated that normalized postoperative cardiac physiology in class I CHD neonates might improve structural network topology. In contrast, the degree of WMI burden negatively impacts network strength and integration. Further research is needed to elucidate how aberrant structural network development in CHD represents neural correlates of later neurodevelopmental impairments. ### Competing Interest Statement The authors have declared no competing interest.

17583: Disordered phasic relationships between hippocampal place cells, theta, and gamma rhythms in the Ts65Dn mouse model of Down Syndrome
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Posted 17 Sep 2020

Disordered phasic relationships between hippocampal place cells, theta, and gamma rhythms in the Ts65Dn mouse model of Down Syndrome
73 downloads bioRxiv neuroscience

H.C. Heller, A. Freeburn, D.P. Finn, R.G.K Munn

Down Syndrome (DS) in humans is caused by trisomy of chromosome 21 and is marked by prominent difficulties in learning and memory. Decades of research have demonstrated that the hippocampus is a key structure in learning and memory, and recent work with mouse models of DS have shown changes in spectral coherence in the field potentials of hippocampus and regions important for executive function such as prefrontal cortex. One of the primary functional differences in DS is thought to be an excess of GABAergic innervation from Medial Septum (MS) to regions such as hippocampus. In these experiments, we probe in detail the activity of region CA1 of the hippocampus using in vivo electrophysiology in the Ts65Dn mouse model of DS in comparison to their non-trisomic 2N littermates. We find changes in hippocampal phenomenology that suggest that MS output, which drives theta rhythm in the hippocampus, is strongly altered. Moreover, we find that this change affects the phasic relationship of both CA1 place cells and gamma rhythms to theta. Since the phasic relationship of both of these aspects of hippocampal phenomenology to theta are thought to be critical for the segregation of encoding and retrieval epochs within hippocampus, it is likely that these changes are the neural substrates of the learning and memory deficits seen both in human DS and animal models such as Ts65Dn. ### Competing Interest Statement The authors have declared no competing interest.

17584: Implantable Electrical Connector for Reconnecting Injured Neurons, Approach and Design
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Posted 31 May 2020

Implantable Electrical Connector for Reconnecting Injured Neurons, Approach and Design
73 downloads bioRxiv neuroscience

Soheil Hashemi, Ali Abdolali

In contrast to normal injuries, damages of the nervous system are very difficult to repair. In this paper, a connector is designed to reconnect injured nerve to healthy cells. This cord was designed and tested by the full wave and three dimensional electromagnetic modeling. The connector is comprised of three parts, including the conductor, dielectric coating, and second coating with high conductivity. Electromagnetic characteristics need to be unique to work fine, each part is obtained with regard to the distance between two neurons. The combination of materials with conductivity lower than 100 S/m and relative permittivity lower than 8 creates the connection of two neurons up to 35 cm. The connector is realizable by biocompatible polymers. ### Competing Interest Statement The authors have declared no competing interest.

17585: Sex differences in lifespan trajectories and variability of human sulcal and gyral morphology
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Posted 02 Oct 2020

Sex differences in lifespan trajectories and variability of human sulcal and gyral morphology
73 downloads bioRxiv neuroscience

Covadonga M. Díaz-Caneja, Clara Alloza, Pedro M. Gordaliza, Alberto Fernández Pena, Lucía de Hoyos, Javier Santonja, Elizabeth EL Buimer, Neeltje E.M. van Haren, Wiepke Cahn, Celso Arango, Rene S Kahn, Hilleke E Hulshoff Pol, Hugo G Schnack, Joost Janssen

Sex differences in development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants two scans, 104 three scans, age range: 16-70 years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40 years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. While hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and thickness and lower variability for sulcal width. Across sexes, variability decreased with age for all measures except for cortical volume and thickness. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions. ### Competing Interest Statement The authors have declared no competing interest.

17586: Association between COMT gene Val158Met heterozygote polymorphism and enhanced brain predicting processes
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Posted 26 Sep 2020

Association between COMT gene Val158Met heterozygote polymorphism and enhanced brain predicting processes
73 downloads bioRxiv neuroscience

L. Bonetti, N.A. Sedghi, S.E.P. Bruzzone, N.T. Haumann, T. Paunio, K. Kantojärvi, M. Kliuchko, P. Vuust, E. Brattico

Predicting events in the ever-changing environment is a fundamental survival function intrinsic to the physiology of sensory systems, whose efficiency varies among the population. Even though it is established that a major source of such variations is genetic heritage, there are no studies tracking down auditory predicting processes to genetic mutations. Thus, we examined the neurophysiological responses to deviant stimuli recorded with magnetoencephalography (MEG) in 108 healthy participants carrying different variants of the Val158Met single-nucleotide polymorphism (SNP) within the catechol-O-methyltransferase (COMT) gene, which is responsible for the majority of catecholamines degradation in the prefrontal cortex. Our results showed significant amplitude enhancement of neural responses localized within inferior frontal gyrus, superior and middle temporal cortices to deviant auditory stimuli in heterozygote genotype carriers (Val/Met) vs homozygote (Val/Val and Met/Met) carriers. Integrating neurophysiology and genetics, this study provided new and broader insights into the brain mechanisms underlying optimal deviant detection. ### Competing Interest Statement The authors have declared no competing interest.

17587: Epitomic analysis of the specificity of conformation-dependent, anti-aβ amyloid monoclonal antibodies
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Posted 05 Aug 2020

Epitomic analysis of the specificity of conformation-dependent, anti-aβ amyloid monoclonal antibodies
73 downloads bioRxiv neuroscience

Jorge Mauricio Reyes-Ruiz, Rie Nakajima, Ibtisam Baghallab, Luki Goldschmidt, Jutyna Sosna, Phuong Nguyen Mai Ho, Taha Kumosani, Philip L Felgner, Charles G Glabe

Antibodies against A{beta} amyloid are indispensable research tools and potential therapeutics for Alzheimers Disease, but display unusual properties, such as specificity for aggregated forms of the peptide, ability to distinguish several polymorphic aggregate structures and ability to recognize generic aggregation-related epitopes formed by unrelated amyloid sequences. Understanding the mechanisms underlying these unusual properties of anti-amyloid antibodies and the structures of their corresponding epitopes is crucial for the understanding why they display different therapeutic activities and for the development of more effective therapeutic agents. Here we employed a novel epitomic approach to map the fine structure of the epitopes of 28 monoclonal antibodies against amyloid-beta using immunoselection of random sequences from a phage display, deep sequencing and pattern analysis to define the critical sequence elements recognized by the antibodies. Although most of the antibodies map to linear epitopes in the amino terminal 1-14 residues of A{beta}, the antibodies display differences in the target sequence residues that are critical for binding and in their individual preferences for non-target residues, indicating that the antibodies bind to alternative conformations of the sequence by different mechanisms. Epitomic analysis identifies more non-overlapping sequence A{beta} segments than peptide array approaches that may constitute the conformational epitopes that underly the aggregation specificity of antibodies. Aggregation specific antibodies also recognize sequences that display a significantly higher predicted propensity for forming amyloid than antibodies that recognize A{beta} monomer, indicating that the ability of the random sequences to aggregate into amyloid structures is a critical element of their binding mechanism.

17588: Influence of E/I balance and pruning in peri-personal space differences in schizophrenia: a computational approach
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Posted 07 Nov 2020

Influence of E/I balance and pruning in peri-personal space differences in schizophrenia: a computational approach
73 downloads bioRxiv neuroscience

Renato Paredes, Francesca Ferri, Peggy Series

The encoding of the space close to the body, named peri-personal space (PPS), is thought to play a crucial role in the unusual experiences of the self observed in schizophrenia (SCZ). However, it is unclear why SCZ patients and high schizotypal (H-SPQ) individuals present a narrower PPS and why the boundaries of the PPS are more sharply defined in patients. We hypothesise that the unusual PPS representation observed in SCZ is caused by an imbalance of excitation and inhibition (E/I) in recurrent synapses of unisensory neurons or an impairment of bottom-up and top-down connectivity between unisensory and multisensory neurons. These hypotheses were tested computationally by manipulating the effects of E/I imbalance, feedback weights and synaptic density in the network. Using simulations we explored the effects of such impairments in the PPS representation generated by the network and fitted the model to behavioural data. We found that increased excitation of sensory neurons could account for the smaller PPS observed in SCZ and H-SPQ, whereas a decrease of synaptic density caused the sharp definition of the PPS observed in SCZ. We propose a novel conceptual model of PPS representation in the SCZ spectrum that can account for alterations in self-world demarcation, failures in tactile discrimination and symptoms observed in patients. ### Competing Interest Statement The authors have declared no competing interest.

17589: Idiosyncratic Tower of Babel: Individual differences in word meaning representation increase along abstractness
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Posted 31 Aug 2020

Idiosyncratic Tower of Babel: Individual differences in word meaning representation increase along abstractness
73 downloads bioRxiv neuroscience

Xiaosha Wang, Yanchao Bi

Humans primarily rely on language to communicate, based on a shared understanding of the basic building blocks of communication: words. However, words also have idiosyncratic aspects of meaning. Do we mean the same things when we use the same words? Classical philosophers disagreed on this point, speculating that words have more similar meanings across individuals if they are either more experiential (John Locke) or more abstract (Bertrand Russell). Here, we empirically characterize the individual variation pattern of 90 words using both behavioral and neuroimaging measures. We show that the magnitude of individual meaning disagreement is a function of how much language or sensory experience a word associates with, and this variation increases with abstractness of a word. Uncovering the cognitive and neural origins of word meaning disagreements across individuals has implications for potential mechanisms to modulate such disagreements. ### Competing Interest Statement The authors have declared no competing interest.

17590: Protective mutation A673T as a potential gene therapy for most forms of APP Familial Alzheimer's Disease
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Posted 22 Jul 2020

Protective mutation A673T as a potential gene therapy for most forms of APP Familial Alzheimer's Disease
73 downloads bioRxiv neuroscience

Antoine Guyon, Joël Rousseau, Gabriel Lamothe, Jacques P. Tremblay

The accumulation of plaque in the brain leads to the onset and development of Alzheimer’s disease. The Amyloid precursor protein (APP) is usually cut by a-secretase, however an abnormal cleavage profile by β-secretase (BACE1) leads to the accumulation of Aβ peptides, which forms these plaques. Numerous APP gene mutations favor plaque accumulation, causing Familial Alzheimer Disease (FAD). However, a variant of the APP gene (A673T) in Icelanders reduces BACE1 cleavage by 40 %. A library of plasmids containing APP genes with 29 FAD mutations with or without the additional A673T mutation was generated and transfected in neuroblastomas to assess the effect of this mutation on Aβ peptide production. In most cases the production of Aβ peptides was decreased by the co-dominant A673T mutation. The reduction of Aβ peptide concentrations for the London mutation (V717I) even reached the same level as A673T carriers. These results suggest that the insertion of A673T in the APP gene of genetically susceptible FAD patients may prevent the onset of, slow down, or stop the progression of the disease.

17591: A Microglial Subset at the Tumor-Stroma Interface of Glioma
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Posted 28 Oct 2020

A Microglial Subset at the Tumor-Stroma Interface of Glioma
73 downloads bioRxiv neuroscience

Michael Dominick Caponegro, Ki Oh, Miguel Madeira, Daniel Radin, Nicholas Sterge, Richard A Moffitt, Stella E Tsirka

Background: Myeloid involvement in High Grade Gliomas, such as Glioblastoma, has become apparent and detrimental to disease outcomes. There is great interest in characterizing the HGG tumor microenvironment to understand how neoplastic lesions are supported, and to devise novel therapeutic targets. The tumor microenvironment of the central nervous system is unique as it contains neural and specialized glial cells, including the resident myeloid cells, microglia. Glioma‐associated microglia and peripherally infiltrating monocytes/macrophages (GAM) accumulate within the neoplastic lesion where they facilitate tumor growth and drive immunosuppression. A longstanding limitation has been the ability to accurately differentiate microglia and macrophage roles in pathology, and identify the consequences of the spatial organization of these cells. Results: Here we characterize the tumor‐stroma border and identify peripheral glioma-associated microglia (PGAM) at the tumor leading edge as a unique subpopulation of GAM. Using data mining and analyses of samples derived from both murine and human sources, we show that PGAM exhibit a pro‐inflammatory and chemotactic phenotype that is associated with peripheral monocyte recruitment, poorly enhancing radiomic features, and decreased overall survival. Conclusions: PGAM act as a unique subset of GAM, at the tumor-stroma interface, corresponding to disease outcomes. We propose the application of a novel gene signature to identify these cells, and suggest that PGAM constitute a cellular target of the TME. ### Competing Interest Statement The authors have declared no competing interest.

17592: Morphometrical brain markers of sex difference
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Posted 03 Aug 2020

Morphometrical brain markers of sex difference
73 downloads bioRxiv neuroscience

Daniel Brennan, Tingting Wu, Jin Fan

Many major neuropsychiatric pathologies, some of which appear in adolescence, show differentiated prevalence, onset, and symptomatology across the biological sexes. Therefore, mapping differences in brain structure between males and females during this critical developmental period may provide information about the neural mechanisms underlying the dimorphism of these pathologies. Utilizing a large dataset collected through the Adolescent Brain Cognitive Development study, we investigated the differences of adolescent (9-10 years old) male and female brains (n = 8325) by using a linear Support-Vector Machine Classifier to predict sex based on morphometry and image intensity values of structural brain imaging data. The classifier correctly classified the sex of 86% individuals with the insula, the precentral and postcentral gyri, and the pericallosal sulcus as the most discernable features. The role of these significant dimorphic features in psychopathology was explored by testing them as mediators between sex and clinical symptomology. The results demonstrate the existence of morphometrical brain markers of sex difference. ### Competing Interest Statement The authors have declared no competing interest.

17593: Patient-specific optimization of automated detection improves seizure onset zone localization based on high frequency oscillations
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Posted 15 Sep 2020

Patient-specific optimization of automated detection improves seizure onset zone localization based on high frequency oscillations
73 downloads bioRxiv neuroscience

Casey L. Trevino, Jack J. Lin, Indranil Sen-Gupta, Beth A Lopour

High frequency oscillations (HFOs) are a promising biomarker of epileptogenicity, and automated algorithms are critical tools for their detection. However, previously validated algorithms often exhibit decreased HFO detection accuracy when applied to a new data set, if the parameters are not optimized. This likely contributes to decreased seizure localization accuracy, but this has never been tested. Therefore, we evaluated the impact of parameter selection on seizure onset zone (SOZ) localization using automatically detected HFOs. We detected HFOs in intracranial EEG from twenty medically refractory epilepsy patients with seizure free surgical outcomes using an automated algorithm. For each patient, we assessed classification accuracy of channels inside/outside the SOZ using a wide range of detection parameters and identified the parameters associated with maximum classification accuracy. We found that only three out of twenty patients achieved maximal localization accuracy using conventional HFO detection parameters, and optimal parameter ranges varied significantly across patients. The parameters for amplitude threshold and root-mean-square window had the greatest impact on SOZ localization accuracy; minimum event duration and rejection of false positive events did not significantly affect the results. Using individualized optimal parameters led to substantial improvements in localization accuracy, particularly in reducing false positives from non-SOZ channels. We conclude that optimal HFO detection parameters are patient-specific, often differ from conventional parameters, and have a significant impact on SOZ localization. This suggests that individual variability should be considered when implementing automatic HFO detection as a tool for surgical planning. ### Competing Interest Statement The authors have declared no competing interest.

17594: FMRP sustains presynaptic function via control of activity-dependent bulk endocytosis
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Posted 10 Sep 2020

FMRP sustains presynaptic function via control of activity-dependent bulk endocytosis
73 downloads bioRxiv neuroscience

Katherine Bonnycastle, Peter C. Kind, Michael A. Cousin

Synaptic vesicle (SV) recycling is essential for the maintenance of neurotransmission, with a number of neurodevelopmental disorders linked to defects in this process. Fragile X syndrome (FXS) results from a loss of fragile X mental retardation protein (FMRP) encoded by the FMR1 gene. FMRP is an established translation repressor, however it also has translation-independent presynaptic roles, including regulation of the trafficking and function of specific ion channels. Since defects in SV recycling are exacerbated during intense neuronal activity, we investigated whether these events were disproportionately affected by the absence of FMRP. We revealed that primary neuronal cultures from a Fmr1 knockout rat model display a specific defect in activity-dependent bulk endocytosis (ADBE). ADBE is dominant during intense neuronal activity, and this defect resulted in an inability of Fmr1 knockout neurons to sustain SV recycling during trains of high frequency stimulation. Using a molecular replacement strategy, we revealed that a human FMRP interaction mutant failed to correct ADBE dysfunction in knockout neurons. Therefore, FMRP performs a key role in sustaining neurotransmitter release via selective control of the endocytosis mode, ADBE. SIGNIFICANCE STATEMENT Loss of fragile X mental retardation protein (FMRP) results in fragile X syndrome (FXS), however whether its loss has a direct role in neurotransmitter release remains a matter of debate. We demonstrate that neurons lacking FMRP display a specific defect in a mechanism that sustains neurotransmitter release during intense neuronal firing, called activity-dependent bulk endocytosis (ADBE). This discovery provides key insights into mechanisms of brain communication that occur due to loss of FMRP function. Importantly it also reveals ADBE as a potential therapeutic target to correct the circuit hyperexcitabilty observed in FXS. ### Competing Interest Statement The authors have declared no competing interest.

17595: Impulsivity and Thought Suppression in Behavioral Addiction: Associated Neural Connectivity and Neural Networks
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Posted 15 Oct 2020

Impulsivity and Thought Suppression in Behavioral Addiction: Associated Neural Connectivity and Neural Networks
72 downloads bioRxiv neuroscience

Li Wan, Rujing Zha, Jiecheng Ren, Ying Li, Qian Zhao, Huilin Zuo, Xiaochu Zhang

Impulsivity and thought suppression are two psychological traits that have great variation in healthy population. In extreme cases, both are closely related to mental illness and play an important role in behavioral addiction. We have known the role of the top-down mechanism in impulsivity and thought suppression, but we do not know how the related neural nuclei are functionally connected and interact with each other. In the study, we selected excessive internet users (EIU) as our target population and investigated the relationship between thought suppression and impulsivity in the following aspects: their correlations to psychological symptoms; the associated neural networks; and the associated brain morphometric changes. We acquired data from 131 excessive internet users, with their psychological, resting-state fMRI and T1-MRI data collected. With the whole brain analysis, graph theory analysis, replication with additional brain atlas, replication with additional MRI data, and analysis of brain structure, we found that: (i) implusivity and thought suppression shared common neural connections in the top-down mechanism; (ii) thought suppression was associated with the neural network that connected to the occipital lobe in the resting-state brain but not the morphometric change of the occipital lobe. The study confirmed the overlap between impulsivity and thought suppression in terms of neural connectivity and suggested the role of thought suppression and the occipital network in behavioral addiction. Studying thought suppression provided a new insight into behavioral addiction research. The neural network study helped further understanding of behavioral addiction in terms of information interaction in the brain. ### Competing Interest Statement The authors have declared no competing interest.

17596: Physiological synaptic activity and recognition memory are fueled by astroglial glutamine
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Posted 08 Oct 2020

Physiological synaptic activity and recognition memory are fueled by astroglial glutamine
72 downloads bioRxiv neuroscience

Giselle Cheung, Danijela Bataveljic, Naresh Kumar, Julien Moulard, Glenn Dallérac, Josien Visser, Astrid Rollenhagen, Cédric Mongin, Oana Chever, Alexis-Pierre Bemelmans, Joachim Lübke, Isabelle Leray, Nathalie Rouach

Presynaptic glutamate replenishment is fundamental to brain function. In high activity regimes, such as epileptic episodes, this process is thought to rely on the glutamate-glutamine cycle between neurons and astrocytes. However the presence of an astroglial glutamine supply, as well as its functional relevance in vivo in the healthy brain remain controversial, partly due to a lack of tools that can directly examine glutamine transfer. Here, we generated a novel fluorescent probe that tracks glutamine in live cells, which provided direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein with both gap junction and hemichannel functions, and is essential for synaptic transmission and object recognition memory. Our findings uncover an indispensable recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes. ### Competing Interest Statement The authors have declared no competing interest.

17597: Chronic Exposure to Glucocorticoids Induces Suboptimal Decision-Making in Mice
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Posted 14 Sep 2020

Chronic Exposure to Glucocorticoids Induces Suboptimal Decision-Making in Mice
72 downloads bioRxiv neuroscience

Lidia Cabeza, Bahrie Ramadan, Julie Giustiniani, Christophe Houdayer, Yann Pellequer, Damien Gabriel, Sylvie Fauconnet, Emmanuel Haffen, Pierre-Yves Risold, Dominique Fellmann, David Belin, Yvan Peterschmitt

Anxio-depressive symptoms as well as severe cognitive dysfunction including aberrant decision-making (DM) are documented in neuropsychiatric patients with hypercortisolaemia. Yet, the influence of the hypothalamo-pituitary-adrenal (HPA) axis on DM processes remains poorly understood. As a tractable mean to approach this human condition, adult male C57BL/6JRj mice were chronically treated with corticosterone (CORT) prior to behavioural, physiological and neurobiological evaluation. The behavioural data indicate that chronic CORT delays the acquisition of contingencies required to orient responding towards optimal DM performance in a mouse Gambling Task (mGT). Specifically, CORT-treated animals show a longer exploration and a delayed onset of the optimal DM performance. Remarkably, the proportion of individuals performing suboptimally in the mGT is increased in the CORT condition. This variability seems to be better accounted for by variations in sensitivity to negative rather than to positive outcome. Besides, CORT-treated animals perform worse than control animals in a spatial working memory (WM) paradigm and in a motor learning task. Finally, Western blotting neurobiological analyses show that chronic CORT downregulates glucocorticoid receptor expression in the medial Prefrontal Cortex (mPFC). Besides, corticotropin-releasing factor signalling in the mPFC of CORT individuals negatively correlates with their DM performance. Collectively, this study describes how chronic exposure to glucocorticoids induces suboptimal DM under uncertainty in a mGT, hampers WM and motor learning processes, thus affecting specific emotional, motor, cognitive and neurobiological endophenotypic dimensions relevant for precision medicine in biological psychiatry. ### Competing Interest Statement The authors have declared no competing interest.

17598: Characterising the hippocampal response to perception, construction and complexity
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Posted 27 Jul 2020

Characterising the hippocampal response to perception, construction and complexity
72 downloads bioRxiv neuroscience

Cornelia McCormick, Marshall A. Dalton, Peter Zeidman, Eleanor A Maguire

The precise role played by the hippocampus in supporting cognitive functions such as episodic memory and future thinking is debated, but there is general agreement that it involves constructing representations comprised of numerous elements. Visual scenes have been deployed extensively in cognitive neuroscience because they are paradigmatic multi-element stimuli. However, questions remain about the specificity and nature of the hippocampal response to scenes. Here, we devised a paradigm in which we had participants search pairs of images for either colour or layout differences, thought to be associated with perceptual or spatial constructive processes respectively. Importantly, images depicted either naturalistic scenes or phase-scrambled versions of the same scenes, and were either simple or complex. Using this paradigm during functional MRI scanning, we addressed three questions: 1. Is the hippocampus recruited specifically during scene processing? 2. If the hippocampus is more active in response to scenes, does searching for colour or layout differences influence its activation? 3. Does the complexity of the scenes affect its response? We found that, compared to phase-scrambled versions of the scenes, the hippocampus was more responsive to scene stimuli. Moreover, a clear anatomical distinction was evident, with colour detection in scenes engaging the posterior hippocampus whereas layout detection in scenes recruited the anterior hippocampus. The complexity of the scenes did not influence hippocampal activity. These findings seem to align with perspectives that propose the hippocampus is especially attuned to scenes, and its involvement occurs irrespective of the cognitive process or the complexity of the scenes.

17599: Causality Mapping Using Resting-State fMRI reveals Suppressed Functional Connectivity in Schizophrenia Patients
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Posted 14 Sep 2020

Causality Mapping Using Resting-State fMRI reveals Suppressed Functional Connectivity in Schizophrenia Patients
72 downloads bioRxiv neuroscience

Fayyaz Ahmed, Zunira Saghir, Namra Aamir, Turki Abualait, Safee Ullah Chaudhary, Shahid Bashir

Schizophrenia is a psychotic brain disorder in which patients exhibit aberrant connectivity between different regions of the brain. Neuroimaging is a state-of-the-art technique that is now increasingly been employed in clinical investigation of Schizophrenia. In the present study, we have used resting-state functional magnetic resonance neuroimaging (rsfMRI) to elucidate the cause-and-effect relationships among four regions of the brain including occipital, temporal, and frontal lobes and hippocampus in Schizophrenia. For that, we have employed independent component analysis, a seed-based temporal correlation analysis, and Granger causality analysis for measuring causal relationships amongst four regions of the brain in schizophrenia patients. Eighteen subjects with nine patients and nine controls were evaluated in the study. Our results show that Schizophrenia patients exhibit significantly different activation patterns across the selected regions of the brain in comparison with the control. In addition to that, we also observed an aberrant causal relationship between these four regions of the brain. In particular, the temporal and frontal lobes of patients with schizophrenia had a significantly lowered causal relationship with the other areas of the brain. Taken together, the study elucidates the dysregulated brain activity in Schizophrenia patients, decodes its causal mapping and provides novel insights towards employment in clinical evaluation of Schizophrenia. ### Competing Interest Statement The authors have declared no competing interest.

17600: ATP-sensitive K+ channels control the spontaneous firing of a glycinergic interneuron in the auditory brainstem.
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Posted 18 Jun 2020

ATP-sensitive K+ channels control the spontaneous firing of a glycinergic interneuron in the auditory brainstem.
72 downloads bioRxiv neuroscience

Paulo S. Strazza, Daniela V.F. de Siqueira, Nikollas M. Benites, RM Leão

Cartwheel neurons from the dorsal cochlear nucleus (DCN) are glycinergic interneurons and the primary source of inhibition on the fusiform neurons, the principal excitatory neuron in the DCN. Most cartwheel neurons present spontaneous firing (active neurons), producing a steady inhibitory tone on fusiform neurons. In contrast, a smaller fraction does not fire spontaneously (quiet neurons). Additionally, hyperactivity of fusiform neurons is seen in animals with behavioral evidence of tinnitus. Due to its relevance in controlling the excitability of fusiform neurons, we investigated the ion channels responsible for the spontaneous firing of cartwheel neurons. We found that quiet neurons express an outward conductance not seen in active neurons, which generates a stable resting potential. This current was sensitive to tolbutamide, an ATP-sensitive potassium channel (KATP) antagonist. After its inhibition, quiet neurons start to fire spontaneously, while the behavior of active neurons was not affected. On the other hand, in active neurons, KATP agonist diazoxide activated a conductance similar to the KATP conductance of quiet neurons and stopped spontaneous firing. According to the effect of KATP channels on CW neuron firing, glycinergic neurotransmission in DCN was increased by tolbutamide and decreased by diazoxide. Finally, slices incubated with the tinnitus-inducing agent sodium salicylate presented more quiet neurons expressing the KATP conductance, which increased the proportion of quiet neurons. Our results reveal an unexpected role of KATP channels in controlling the spontaneous firing of neurons. Additionally, changes in KATP channel activity of cartwheel neurons can be related to the DCN hyperactivity seen in tinnitus. ### Competing Interest Statement The authors have declared no competing interest.

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