Systems Biology of Alcohol Addiction: Modeling and validating disease state networks in human and animal brains for understanding pathophysiolgy, predicting outcomes and improving therapy

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External SyBil-AA website and promotion video

A SyBil-AA website that will include a professional video presentation of SyBil-AA´s scientific goals and activities and many other features will be posted once the project starts and will be used as an important communication platform for all external recipients.

Report of completed integrative analysis of project data

Regression and explorative methods as well as expert analysis will be used to extract relevant features that mediate graph properties and network model performance. Inter-species comparison for relevant overlaps of this information, e.g. differences in functional connectivity between patients and controls during task performance or induced by interventions may be used as “seed” regions for the analysis of connectivity in the animal models and vice versa. Overlapping brain regions responsive to treatment will be identified and compared with available information on brain site-specific intervention for functional validation. In this way high priority brain regions will be identified for testing the effects of novel drugs on functional and anatomical connectivity as potential markers for medication development.

Recommendations for new network based clinical trials in systems medicine of alcoholism

Based on this integrative analysis of the complete data sets from all WPs and the existing literature we will formulate translational recommendations for new therapeutic strategies and targets for proposing new clinical trials and developing respective protocols.

Kick-off Meeting report

In WP1 we will organize a kick-off meeting at the start of the funding period (month 2-3) to define the objectives of each WP in detail, define the contribution of everyone to the overall goals, agree upon milestones and deliverables, and to talk about the next steps.

Targeted Publication in Addiction-related journals

For a wide distribution of information about our Sybil-AA project we decided to prepare a targeted publication with Science Impact Ltd, a leading science communication company that successfully targets wide array of stakeholders ranging from academic institutions, industry, politics, governments and other interest groups. The publication will appear in the September issue of Impact – Healthcare, an issue that specifically focusses on Addiction.

Publications

Neuroimaging reveals functionally distinct neuronal networks associated with high-level alcohol consumption in two genetic rat models

Auteurs: Vicente Pallarés , Mateusz Dudek, Andrea Moreno, Úrsula Pérez-Ramírez, David Moratal, Mia Haaranen, Roberto Ciccocioppo, Wolfgang H Sommer, Santiago Canals, Petri Hyytiä
Publié dans: Behavioral Pharmacology, 2020, ISSN 0955-8810
Éditeur: Lippincott Williams & Wilkins Ltd.
DOI: 10.1097/fbp.0000000000000582

Choice for Drug or Natural Reward Engages Largely Overlapping Neuronal Ensembles in the Infralimbic Prefrontal Cortex

Auteurs: Simone Pfarr, Laura Schaaf, Janine K. Reinert, Elisabeth Paul, Frank Herrmannsdörfer, Martin Roßmanith, Thomas Kuner, Anita C. Hansson, Rainer Spanagel, Christoph Körber, Wolfgang H. Sommer
Publié dans: The Journal of Neuroscience, Numéro 38/14, 2018, Page(s) 3507-3519, ISSN 0270-6474
Éditeur: Society for Neuroscience
DOI: 10.1523/jneurosci.0026-18.2018

The SyBil-AA real-time fMRI neurofeedback study: protocol of a single-blind randomized controlled trial in alcohol use disorder

Auteurs: Martin Fungisai Gerchen, Martina Kirsch, Nathalie Bahs, Patrick Halli, Sarah Gerhardt, Axel Schäfer, Wolfgang H. Sommer, Falk Kiefer, Peter Kirsch
Publié dans: BMC Psychiatry, Numéro 18/1, 2018, ISSN 1471-244X
Éditeur: BioMed Central
DOI: 10.1186/s12888-018-1604-3

Disrupted modular organization of primary sensory brain areas in schizophrenia

Auteurs: Cécile Bordier, Carlo Nicolini, Giulia Forcellini, Angelo Bifone
Publié dans: NeuroImage: Clinical, 2018, ISSN 2213-1582
Éditeur: Elsevier BV
DOI: 10.1016/j.nicl.2018.02.035

Finding influential nodes for integration in brain networks using optimal percolation theory

Auteurs: Gino Del Ferraro, Andrea Moreno, Byungjoon Min, Flaviano Morone, Úrsula Pérez-Ramírez, Laura Pérez-Cervera, Lucas C. Parra, Andrei Holodny, Santiago Canals, Hernán A. Makse
Publié dans: Nature Communications, Numéro 9/1, 2018, ISSN 2041-1723
Éditeur: Nature Publishing Group
DOI: 10.1038/s41467-018-04718-3

Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence

Auteurs: Natalie Hirth, Marcus W. Meinhardt, Hamid R. Noori, Humberto Salgado, Oswaldo Torres-Ramirez, Stefanie Uhrig, Laura Broccoli, Valentina Vengeliene, Martin Roßmanith, Stéphanie Perreau-Lenz, Georg Köhr, Wolfgang H. Sommer, Rainer Spanagel, Anita C. Hansson
Publié dans: Proceedings of the National Academy of Sciences, Numéro 113/11, 2016, Page(s) 3024-3029, ISSN 0027-8424
Éditeur: National Academy of Sciences
DOI: 10.1073/pnas.1506012113

Multi-modal MRI classifiers identify excessive alcohol consumption and treatment effects in the brain

Auteurs: Alejandro Cosa, Andrea Moreno, Jesús Pacheco-Torres, Roberto Ciccocioppo, Petri Hyytiä, Wolfgang H. Sommer, David Moratal, Santiago Canals
Publié dans: Addiction Biology, 2016, ISSN 1355-6215
Éditeur: Taylor & Francis
DOI: 10.1111/adb.12418

Largely overlapping neuronal substrates of reactivity to drug, gambling, food and sexual cues: A comprehensive meta-analysis

Auteurs: Hamid R. Noori, Alejandro Cosa Linan, Rainer Spanagel
Publié dans: European Neuropsychopharmacology, Numéro 26/9, 2016, Page(s) 1419-1430, ISSN 0924-977X
Éditeur: Elsevier BV
DOI: 10.1016/j.euroneuro.2016.06.013

Spatial Embedding and Wiring Cost Constrain the Functional Layout of the Cortical Network of Rodents and Primates

Auteurs: Szabolcs Horvát, Răzvan Gămănuț, Mária Ercsey-Ravasz, Loïc Magrou, Bianca Gămănuț, David C. Van Essen, Andreas Burkhalter, Kenneth Knoblauch, Zoltán Toroczkai, Henry Kennedy
Publié dans: PLOS Biology, Numéro 14/7, 2016, Page(s) e1002512, ISSN 1545-7885
Éditeur: Public Library of Science
DOI: 10.1371/journal.pbio.1002512

Dopamine and opioid systems adaptation in alcoholism revisited: Convergent evidence from positron emission tomography and postmortem studies

Auteurs: Anita C. Hansson, Gerhard Gründer, Natalie Hirth, Hamid R. Noori, Rainer Spanagel, Wolfgang H. Sommer
Publié dans: Neuroscience & Biobehavioral Reviews, 2018, ISSN 0149-7634
Éditeur: Pergamon Press Ltd.
DOI: 10.1016/j.neubiorev.2018.09.010

Tuning noninvasive brain stimulation with MRI to cope with intersubject variability

Auteurs: Annegret Habich, Santiago Canals, Stefan Klöppel
Publié dans: Current Opinion in Neurology, Numéro 29/4, 2016, Page(s) 453-458, ISSN 1350-7540
Éditeur: Lippincott Williams & Wilkins Ltd.
DOI: 10.1097/WCO.0000000000000353

Stochastic graph Voronoi tessellation reveals community structure

Auteurs: Zsolt I. Lázár, István Papp, Levente Varga, Ferenc Járai-Szabó, Dávid Deritei, Mária Ercsey-Ravasz
Publié dans: Physical Review E, Numéro 95/2, 2017, ISSN 2470-0045
Éditeur: Physics and Society
DOI: 10.1103/PhysRevE.95.022306

Graph Analysis and Modularity of Brain Functional Connectivity Networks: Searching for the Optimal Threshold

Auteurs: Cécile Bordier, Carlo Nicolini, Angelo Bifone
Publié dans: Frontiers in Neuroscience, Numéro 11, 2017, Page(s) 441, ISSN 1662-453X
Éditeur: Frontiers Research Foundation
DOI: 10.3389/fnins.2017.00441

Thermodynamics of network model fitting with spectral entropies

Auteurs: Carlo Nicolini, Vladimir Vlasov, Angelo Bifone
Publié dans: Physical Review E, Numéro 98/2, 2018, ISSN 2470-0045
Éditeur: American Physical Society
DOI: 10.1103/PhysRevE.98.022322

Binge drinking is associated with attenuated frontal and parietal activation during successful response inhibition in fearful context

Auteurs: Aleksandra M. Herman, Hugo D. Critchley, Theodora Duka
Publié dans: European Journal of Neuroscience, 2018, ISSN 0953-816X
Éditeur: Blackwell Publishing Inc.
DOI: 10.1111/ejn.14108

Systemic neurotransmitter responses to clinically approved and experimental neuropsychiatric drugs

Auteurs: Hamid R. Noori, Lewis H. Mervin, Vahid Bokharaie, Özlem Durmus, Lisamon Egenrieder, Stefan Fritze, Britta Gruhlke, Giulia Reinhardt, Hans-Hendrik Schabel, Sabine Staudenmaier, Nikos K. Logothetis, Andreas Bender, Rainer Spanagel
Publié dans: Nature Communications, Numéro 9/1, 2018, ISSN 2041-1723
Éditeur: Nature Publishing Group
DOI: 10.1038/s41467-018-07239-1

Radiomicrobiomics: Advancing Along the Gut-brain Axis Through Big Data Analysis

Auteurs: Silvia De Santis, David Moratal, Santiago Canals
Publié dans: Neuroscience, 2017, ISSN 0306-4522
Éditeur: Elsevier BV
DOI: 10.1016/j.neuroscience.2017.11.055

High frequency neurons determine effective connectivity in neuronal networks

Auteurs: Aref Pariz, Zahra G. Esfahani, Shervin S. Parsi, Alireza Valizadeh, Santiago Canals, Claudio R. Mirasso
Publié dans: NeuroImage, Numéro 166, 2018, Page(s) 349-359, ISSN 1053-8119
Éditeur: Academic Press
DOI: 10.1016/j.neuroimage.2017.11.014

Differential Roles for L-Type Calcium Channel Subtypes in Alcohol Dependence

Auteurs: Stefanie Uhrig, David Vandael, Andrea Marcantoni, Nina Dedic, Ainhoa Bilbao, Miriam A Vogt, Natalie Hirth, Laura Broccoli, Rick E Bernardi, Kai Schönig, Peter Gass, Dusan Bartsch, Rainer Spanagel, Jan M Deussing, Wolfgang H Sommer, Emilio Carbone, Anita C Hansson
Publié dans: Neuropsychopharmacology, 2016, ISSN 0893-133X
Éditeur: Nature Publishing Group
DOI: 10.1038/npp.2016.266

Incubation of neural alcohol cue reactivity after withdrawal and its blockade by naltrexone

Auteurs: Patrick Bach, Georg Weil, Enrico Pompili, Sabine Hoffmann, Derik Hermann, Sabine Vollstädt-Klein, Karl Mann, Ursula Perez-Ramirez, David Moratal, Santiago Canals, Serdar M. Dursun, Andrew J. Greenshaw, Peter Kirsch, Falk Kiefer, Wolfgang H. Sommer
Publié dans: Addiction Biology, 2019, ISSN 1355-6215
Éditeur: Taylor & Francis
DOI: 10.1111/adb.12717

Microstructural White Matter Alterations in Men With Alcohol Use Disorder and Rats With Excessive Alcohol Consumption During Early Abstinence

Auteurs: Silvia De Santis, Patrick Bach, Laura Pérez-Cervera, Alejandro Cosa-Linan, Georg Weil, Sabine Vollstädt-Klein, Derik Hermann, Falk Kiefer, Peter Kirsch, Roberto Ciccocioppo, Wolfgang H. Sommer, Santiago Canals
Publié dans: JAMA Psychiatry, 2019, ISSN 2168-622X
Éditeur: American Medical Association
DOI: 10.1001/jamapsychiatry.2019.0318

Aberrant insular cortex connectivity in abstinent alcohol-dependent rats is reversed by dopamine D3 receptor blockade

Auteurs: Giulia Scuppa, Stefano Tambalo, Simone Pfarr, Wolfgang H. Sommer, Angelo Bifone
Publié dans: Addiction Biology, 2019, ISSN 1355-6215
Éditeur: Taylor & Francis
DOI: 10.1111/adb.12744

Hierarchical organization of functional connectivity in the mouse brain: a complex network approach

Auteurs: Giampiero Bardella, Angelo Bifone, Andrea Gabrielli, Alessandro Gozzi, Tiziano Squartini
Publié dans: Scientific Reports, Numéro 6/1, 2016, ISSN 2045-2322
Éditeur: Nature Publishing Group
DOI: 10.1038/srep32060

Community detection in weighted brain connectivity networks beyond the resolution limit

Auteurs: Carlo Nicolini, Cécile Bordier, Angelo Bifone
Publié dans: NeuroImage, Numéro 146, 2017, Page(s) 28-39, ISSN 1053-8119
Éditeur: Academic Press
DOI: 10.1016/j.neuroimage.2016.11.026

Developing neuroscience-based treatments for alcohol addiction: A matter of choice?

Auteurs: Markus Heilig, Eric Augier, Simone Pfarr, Wolfgang H. Sommer
Publié dans: Translational Psychiatry, Numéro 9/1, 2019, ISSN 2158-3188
Éditeur: Nature Publishing Group
DOI: 10.1038/s41398-019-0591-6

Detecting Alcohol-Induced Brain Damage Noninvasively Using Diffusion Tensor Imaging

Auteurs: Silvia De Santis, Wolfgang H. Sommer, Santiago Canals
Publié dans: ACS Chemical Neuroscience, Numéro 10/10, 2019, Page(s) 4187-4189, ISSN 1948-7193
Éditeur: American Chemical Society
DOI: 10.1021/acschemneuro.9b00481

Differential Effects of Brain Disorders on Structural and Functional Connectivity

Auteurs: Sandro Vega-Pons, Emanuele Olivetti, Paolo Avesani, Luca Dodero, Alessandro Gozzi, Angelo Bifone
Publié dans: Frontiers in Neuroscience, Numéro 10, 2017, ISSN 1662-453X
Éditeur: Frontiers in Neuroscience
DOI: 10.3389/fnins.2016.00605

On the role of the entorhinal cortex in the effective connectivity of the hippocampal formation

Auteurs: Víctor J. López-Madrona, Fernanda S. Matias, Ernesto Pereda, Santiago Canals, Claudio R. Mirasso
Publié dans: Chaos: An Interdisciplinary Journal of Nonlinear Science, Numéro 27/4, 2017, Page(s) 047401, ISSN 1054-1500
Éditeur: American Institute of Physics
DOI: 10.1063/1.4979001

Hold Your Methods! How Multineuronal Firing Ensembles Can Be Studied Using Classical Spike-Train Analysis Techniques

Auteurs: Ovidiu F. Jurjuţ, Medorian Gheorghiu, Wolf Singer, Danko Nikolić, Raul C. Mureşan
Publié dans: Frontiers in Systems Neuroscience, Numéro 13, 2019, ISSN 1662-5137
Éditeur: Frontiers Research Foundation
DOI: 10.3389/fnsys.2019.00021

No basal or drug‐induced sex differences in striatal dopaminergic levels: a cluster and meta‐analysis of rat microdialysis studies

Auteurs: Lisamon Egenrieder, Ekaterina Mitricheva, Rainer Spanagel, Hamid R. Noori
Publié dans: Journal of Neurochemistry, 2019, ISSN 0022-3042
Éditeur: Blackwell Publishing Inc.
DOI: 10.1111/jnc.14911

Soft++, a multi-parametric non-saturating non-linearity that improves convergence in deep neural architectures

Auteurs: Ciuparu A., Nagy-Dăbâcan A., Muresan R.C.
Publié dans: Neurocomputing, 2020, ISSN 0925-2312
Éditeur: Elsevier BV

Repetitive transcranial magnetic stimulation targeting the insular cortex for reduction of heavy drinking in treatment-seeking alcohol-dependent subjects: a randomized controlled trial

Auteurs: Irene Perini, Robin Kämpe, Theodor Arlestig, Hanna Karlsson, Andreas Löfberg, Michal Pietrzak, Abraham Zangen, Markus Heilig
Publié dans: Neuropsychopharmacology, 2019, ISSN 0893-133X
Éditeur: Nature Publishing Group
DOI: 10.1038/s41386-019-0565-7

Reconsolidation impairment of reward memory by stimulating stress response

Auteurs: Christina Dinter, Derik Hermann, Judith Heckmann, Holger Hill, Iris Reinhard, Sabine Vollstädt‐Klein, Peter Kirsch, Falk Kiefer
Publié dans: Addiction Biology, Numéro 25/1, 2019, ISSN 1355-6215
Éditeur: Taylor & Francis
DOI: 10.1111/adb.12712

Refined parcellation of the nervous system by algorithmic detection of hidden features within communities

Auteurs: Dongmei Shi, Anna Levina, Hamid R. Noori
Publié dans: Physical Review E, Numéro 100/1, 2019, ISSN 2470-0045
Éditeur: Phys Rev E.
DOI: 10.1103/physreve.100.012301

Neural substrates of sexual arousal are not sex dependent

Auteurs: Ekaterina Mitricheva, Rui Kimura, Nikos K. Logothetis, Hamid R. Noori
Publié dans: Proceedings of the National Academy of Sciences, Numéro 116/31, 2019, Page(s) 15671-15676, ISSN 0027-8424
Éditeur: National Academy of Sciences
DOI: 10.1073/pnas.1904975116

The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles

Auteurs: Răzvan Gămănuţ, Henry Kennedy, Zoltán Toroczkai, Mária Ercsey-Ravasz, David C. Van Essen, Kenneth Knoblauch, Andreas Burkhalter
Publié dans: Neuron, Numéro 97/3, 2018, Page(s) 698-715.e10, ISSN 0896-6273
Éditeur: Cell Press
DOI: 10.1016/j.neuron.2017.12.037

Shifts in the functional topography of frontal cortex‐striatum connectivity in alcohol use disorder

Auteurs: Martin Fungisai Gerchen, Alena Rentsch, Martina Kirsch, Falk Kiefer, Peter Kirsch
Publié dans: Addiction Biology, Numéro 24/6, 2018, Page(s) 1245-1253, ISSN 1355-6215
Éditeur: Taylor & Francis
DOI: 10.1111/adb.12692

Just a very expensive breathing training? Risk of respiratory artefacts in functional connectivity-based real-time fMRI neurofeedback

Auteurs: Franziska Weiss, Vera Zamoscik, Stephanie N.L. Schmidt, Patrick Halli, Peter Kirsch, Martin Fungisai Gerchen
Publié dans: NeuroImage, Numéro 210, 2020, Page(s) 116580, ISSN 1053-8119
Éditeur: Academic Press
DOI: 10.1016/j.neuroimage.2020.116580

Segmented Echo Planar Imaging Improves Detection of Subcortical Functional Connectivity Networks in the Rat Brain

Auteurs: Stefano Tambalo, Giulia Scuppa, Angelo Bifone
Publié dans: Scientific Reports, Numéro 9/1, 2019, ISSN 2045-2322
Éditeur: Nature Publishing Group
DOI: 10.1038/s41598-018-37863-2

Oxytocin attenuates neural response to emotional faces in social drinkers: an fMRI study

Auteurs: Patrick Bach, Anne Koopmann, Jan Malte Bumb, Sina Zimmermann, Sina Bühler, Iris Reinhard, Stephanie H. Witt, Marcella Rietschel, Sabine Vollstädt-Klein, Falk Kiefer
Publié dans: European Archives of Psychiatry and Clinical Neuroscience, 2020, ISSN 0940-1334
Éditeur: Dr. Dietrich Steinkopff Verlag
DOI: 10.1007/s00406-020-01115-0

A multiscale cerebral neurochemical connectome of the rat brain

Auteurs: Hamid R. Noori, Judith Schöttler, Maria Ercsey-Ravasz, Alejandro Cosa-Linan, Melinda Varga, Zoltan Toroczkai, Rainer Spanagel
Publié dans: PLOS Biology, Numéro 15/7, 2017, Page(s) e2002612, ISSN 1545-7885
Éditeur: PLoS Biol
DOI: 10.1371/journal.pbio.2002612

Structural and functional, empirical and modeled connectivity in the cerebral cortex of the rat

Auteurs: Antonio Díaz-Parra, Zachary Osborn, Santiago Canals, David Moratal, Olaf Sporns
Publié dans: NeuroImage, Numéro 159, 2017, Page(s) 170-184, ISSN 1053-8119
Éditeur: Academic Press
DOI: 10.1016/j.neuroimage.2017.07.046

Low μ-Opioid Receptor Status in Alcohol Dependence Identified by Combined Positron Emission Tomography and Post-Mortem Brain Analysis

Auteurs: Derik Hermann, Natalie Hirth, Matthias Reimold, Anil Batra, Michael N Smolka, Sabine Hoffmann, Falk Kiefer, Hamid R Noori, Wolfgang H Sommer, Gerald Reischl, Christian la Fougère, Karl Mann, Rainer Spanagel, Anita C Hansson
Publié dans: Neuropsychopharmacology, Numéro 42/3, 2016, Page(s) 606-614, ISSN 0893-133X
Éditeur: Nature Publishing Group
DOI: 10.1038/npp.2016.145

Hub-driven remote synchronization in brain networks

Auteurs: Vladimir Vlasov, Angelo Bifone
Publié dans: Scientific Reports, Numéro 7/1, 2017, ISSN 2045-2322
Éditeur: Nature Publishing Group
DOI: 10.1038/s41598-017-09887-7

Anterior insula stimulation suppresses appetitive behavior while inducing forebrain activation in alcohol-preferring rats

Auteurs: Mia Haaranen, Giulia Scuppa, Stefano Tambalo, Vilja Järvi, Sine M. Bertozzi, Andrea Armirotti, Wolfgang H. Sommer, Angelo Bifone, Petri Hyytiä
Publié dans: Translational Psychiatry, Numéro 10/1, 2020, ISSN 2158-3188
Éditeur: Nature Publishing Group
DOI: 10.1038/s41398-020-0833-7

Chronic alcohol consumption alters extracellular space geometry and transmitter diffusion in the brain

Auteurs: Silvia De Santis, Alejandro Cosa-Linan, Raquel Garcia-Hernandez, Lesia Dmytrenko, Lydia Vargova, Ivan Vorisek, Serena Stopponi, Patrick Bach, Peter Kirsch, Falk Kiefer, Roberto Ciccocioppo, Eva Sykova, David Moratal, Wolfgang H. Sommer, Santiago Canals
Publié dans: Science Advances, Numéro 6/26, 2020, Page(s) eaba0154, ISSN 2375-2548
Éditeur: SCIENCE ADVANCES
DOI: 10.1126/sciadv.aba0154

TherMouseDuino: An affordable Open-Source temperature control system for functional magnetic resonance imaging experimentation with mice

Auteurs: Darío R Quiñones, Luis Miguel Fernández-Mollá, Jesús Pacheco-Torres, José M Caramés, Santiago Canals, David Moratal
Publié dans: Magnetic Resonance Imaging, 2019, ISSN 0730-725x
Éditeur: Elsevier BV
DOI: 10.1016/j.mri.2019.01.009

Mapping Functional Connectivity in the Rodent Brain Using Electric-Stimulation fMRI

Auteurs: Laura Pérez-Cervera, José María Caramés, Luis Miguel Fernández-Mollá, Andrea Moreno, Begoña Fernández, Elena Pérez-Montoyo, David Moratal, Santiago Canals, Jesús Pacheco-Torres
Publié dans: Preclinical MRI, Numéro 1718, 2018, Page(s) 117-134, ISBN 978-1-4939-7530-3
Éditeur: Springer New York
DOI: 10.1007/978-1-4939-7531-0_8

Signal detection in extracellular neural ensemble recordings using higher criticism

Auteurs: Fathizadeh, F.; Mitricheva, E.; Kimura, R.; Logothetis, N.; Noori, H.
Publié dans: Numéro 5, 2019
Éditeur: arXiv

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