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

Deliverables

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.

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Publications

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

Author(s): Martin Fungisai Gerchen, Martina Kirsch, Nathalie Bahs, Patrick Halli, Sarah Gerhardt, Axel Schäfer, Wolfgang H. Sommer, Falk Kiefer, Peter Kirsch
Published in: BMC Psychiatry, Issue 18/1, 2018, ISSN 1471-244X
DOI: 10.1186/s12888-018-1604-3

Disrupted modular organization of primary sensory brain areas in schizophrenia

Author(s): Cécile Bordier, Carlo Nicolini, Giulia Forcellini, Angelo Bifone
Published in: NeuroImage: Clinical, 2018, ISSN 2213-1582
DOI: 10.1016/j.nicl.2018.02.035

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

Author(s): 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
Published in: Nature Communications, Issue 9/1, 2018, ISSN 2041-1723
DOI: 10.1038/s41467-018-04718-3

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

Author(s): 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
Published in: Proceedings of the National Academy of Sciences, Issue 113/11, 2016, Page(s) 3024-3029, ISSN 0027-8424
DOI: 10.1073/pnas.1506012113

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

Author(s): Alejandro Cosa, Andrea Moreno, Jesús Pacheco-Torres, Roberto Ciccocioppo, Petri Hyytiä, Wolfgang H. Sommer, David Moratal, Santiago Canals
Published in: Addiction Biology, 2016, ISSN 1355-6215
DOI: 10.1111/adb.12418

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

Author(s): Hamid R. Noori, Alejandro Cosa Linan, Rainer Spanagel
Published in: European Neuropsychopharmacology, Issue 26/9, 2016, Page(s) 1419-1430, ISSN 0924-977X
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

Author(s): Szabolcs Horvát, Răzvan Gămănuț, Mária Ercsey-Ravasz, Loïc Magrou, Bianca Gămănuț, David C. Van Essen, Andreas Burkhalter, Kenneth Knoblauch, Zoltán Toroczkai, Henry Kennedy
Published in: PLOS Biology, Issue 14/7, 2016, Page(s) e1002512, ISSN 1545-7885
DOI: 10.1371/journal.pbio.1002512

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

Author(s): Anita C. Hansson, Gerhard Gründer, Natalie Hirth, Hamid R. Noori, Rainer Spanagel, Wolfgang H. Sommer
Published in: Neuroscience & Biobehavioral Reviews, 2018, ISSN 0149-7634
DOI: 10.1016/j.neubiorev.2018.09.010

Tuning noninvasive brain stimulation with MRI to cope with intersubject variability

Author(s): Annegret Habich, Santiago Canals, Stefan Klöppel
Published in: Current Opinion in Neurology, Issue 29/4, 2016, Page(s) 453-458, ISSN 1350-7540
DOI: 10.1097/WCO.0000000000000353

Stochastic graph Voronoi tessellation reveals community structure

Author(s): Zsolt I. Lázár, István Papp, Levente Varga, Ferenc Járai-Szabó, Dávid Deritei, Mária Ercsey-Ravasz
Published in: Physical Review E, Issue 95/2, 2017, ISSN 2470-0045
DOI: 10.1103/PhysRevE.95.022306

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

Author(s): Cécile Bordier, Carlo Nicolini, Angelo Bifone
Published in: Frontiers in Neuroscience, Issue 11, 2017, Page(s) 441, ISSN 1662-453X
DOI: 10.3389/fnins.2017.00441

Thermodynamics of network model fitting with spectral entropies

Author(s): Carlo Nicolini, Vladimir Vlasov, Angelo Bifone
Published in: Physical Review E, Issue 98/2, 2018, ISSN 2470-0045
DOI: 10.1103/PhysRevE.98.022322

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

Author(s): Aleksandra M. Herman, Hugo D. Critchley, Theodora Duka
Published in: European Journal of Neuroscience, 2018, ISSN 0953-816X
DOI: 10.1111/ejn.14108

Systemic neurotransmitter responses to clinically approved and experimental neuropsychiatric drugs

Author(s): 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
Published in: Nature Communications, Issue 9/1, 2018, ISSN 2041-1723
DOI: 10.1038/s41467-018-07239-1

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

Author(s): Silvia De Santis, David Moratal, Santiago Canals
Published in: Neuroscience, 2017, ISSN 0306-4522
DOI: 10.1016/j.neuroscience.2017.11.055

High frequency neurons determine effective connectivity in neuronal networks

Author(s): Aref Pariz, Zahra G. Esfahani, Shervin S. Parsi, Alireza Valizadeh, Santiago Canals, Claudio R. Mirasso
Published in: NeuroImage, Issue 166, 2018, Page(s) 349-359, ISSN 1053-8119
DOI: 10.1016/j.neuroimage.2017.11.014

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

Author(s): 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
Published in: Neuropsychopharmacology, 2016, ISSN 0893-133X
DOI: 10.1038/npp.2016.266

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

Author(s): 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
Published in: Addiction Biology, 2019, ISSN 1355-6215
DOI: 10.1111/adb.12717

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

Author(s): 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
Published in: JAMA Psychiatry, 2019, ISSN 2168-622X
DOI: 10.1001/jamapsychiatry.2019.0318

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

Author(s): Giulia Scuppa, Stefano Tambalo, Simone Pfarr, Wolfgang H. Sommer, Angelo Bifone
Published in: Addiction Biology, 2019, ISSN 1355-6215
DOI: 10.1111/adb.12744

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

Author(s): Giampiero Bardella, Angelo Bifone, Andrea Gabrielli, Alessandro Gozzi, Tiziano Squartini
Published in: Scientific Reports, Issue 6/1, 2016, ISSN 2045-2322
DOI: 10.1038/srep32060

Community detection in weighted brain connectivity networks beyond the resolution limit

Author(s): Carlo Nicolini, Cécile Bordier, Angelo Bifone
Published in: NeuroImage, Issue 146, 2017, Page(s) 28-39, ISSN 1053-8119
DOI: 10.1016/j.neuroimage.2016.11.026

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

Author(s): Markus Heilig, Eric Augier, Simone Pfarr, Wolfgang H. Sommer
Published in: Translational Psychiatry, Issue 9/1, 2019, ISSN 2158-3188
DOI: 10.1038/s41398-019-0591-6

Detecting Alcohol-Induced Brain Damage Noninvasively Using Diffusion Tensor Imaging

Author(s): Silvia De Santis, Wolfgang H. Sommer, Santiago Canals
Published in: ACS Chemical Neuroscience, Issue 10/10, 2019, Page(s) 4187-4189, ISSN 1948-7193
DOI: 10.1021/acschemneuro.9b00481

Differential Effects of Brain Disorders on Structural and Functional Connectivity

Author(s): Sandro Vega-Pons, Emanuele Olivetti, Paolo Avesani, Luca Dodero, Alessandro Gozzi, Angelo Bifone
Published in: Frontiers in Neuroscience, Issue 10, 2017, ISSN 1662-453X
DOI: 10.3389/fnins.2016.00605

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

Author(s): Víctor J. López-Madrona, Fernanda S. Matias, Ernesto Pereda, Santiago Canals, Claudio R. Mirasso
Published in: Chaos: An Interdisciplinary Journal of Nonlinear Science, Issue 27/4, 2017, Page(s) 047401, ISSN 1054-1500
DOI: 10.1063/1.4979001

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

Author(s): Ovidiu F. Jurjuţ, Medorian Gheorghiu, Wolf Singer, Danko Nikolić, Raul C. Mureşan
Published in: Frontiers in Systems Neuroscience, Issue 13, 2019, ISSN 1662-5137
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

Author(s): Lisamon Egenrieder, Ekaterina Mitricheva, Rainer Spanagel, Hamid R. Noori
Published in: Journal of Neurochemistry, 2019, ISSN 0022-3042
DOI: 10.1111/jnc.14911

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

Author(s): Ciuparu A., Nagy-Dăbâcan A., Muresan R.C.
Published in: Neurocomputing, 2020, ISSN 0925-2312

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

Author(s): Irene Perini, Robin Kämpe, Theodor Arlestig, Hanna Karlsson, Andreas Löfberg, Michal Pietrzak, Abraham Zangen, Markus Heilig
Published in: Neuropsychopharmacology, 2019, ISSN 0893-133X
DOI: 10.1038/s41386-019-0565-7

Reconsolidation impairment of reward memory by stimulating stress response

Author(s): Christina Dinter, Derik Hermann, Judith Heckmann, Holger Hill, Iris Reinhard, Sabine Vollstädt‐Klein, Peter Kirsch, Falk Kiefer
Published in: Addiction Biology, Issue 25/1, 2019, ISSN 1355-6215
DOI: 10.1111/adb.12712

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

Author(s): Dongmei Shi, Anna Levina, Hamid R. Noori
Published in: Physical Review E, Issue 100/1, 2019, ISSN 2470-0045
DOI: 10.1103/physreve.100.012301

Neural substrates of sexual arousal are not sex dependent

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

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

Author(s): Răzvan Gămănuţ, Henry Kennedy, Zoltán Toroczkai, Mária Ercsey-Ravasz, David C. Van Essen, Kenneth Knoblauch, Andreas Burkhalter
Published in: Neuron, Issue 97/3, 2018, Page(s) 698-715.e10, ISSN 0896-6273
DOI: 10.1016/j.neuron.2017.12.037

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

Author(s): Martin Fungisai Gerchen, Alena Rentsch, Martina Kirsch, Falk Kiefer, Peter Kirsch
Published in: Addiction Biology, Issue 24/6, 2018, Page(s) 1245-1253, ISSN 1355-6215
DOI: 10.1111/adb.12692

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

Author(s): Franziska Weiss, Vera Zamoscik, Stephanie N.L. Schmidt, Patrick Halli, Peter Kirsch, Martin Fungisai Gerchen
Published in: NeuroImage, Issue 210, 2020, Page(s) 116580, ISSN 1053-8119
DOI: 10.1016/j.neuroimage.2020.116580

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

Author(s): Stefano Tambalo, Giulia Scuppa, Angelo Bifone
Published in: Scientific Reports, Issue 9/1, 2019, ISSN 2045-2322
DOI: 10.1038/s41598-018-37863-2

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

Author(s): Patrick Bach, Anne Koopmann, Jan Malte Bumb, Sina Zimmermann, Sina Bühler, Iris Reinhard, Stephanie H. Witt, Marcella Rietschel, Sabine Vollstädt-Klein, Falk Kiefer
Published in: European Archives of Psychiatry and Clinical Neuroscience, 2020, ISSN 0940-1334
DOI: 10.1007/s00406-020-01115-0

A multiscale cerebral neurochemical connectome of the rat brain

Author(s): Hamid R. Noori, Judith Schöttler, Maria Ercsey-Ravasz, Alejandro Cosa-Linan, Melinda Varga, Zoltan Toroczkai, Rainer Spanagel
Published in: PLOS Biology, Issue 15/7, 2017, Page(s) e2002612, ISSN 1545-7885
DOI: 10.1371/journal.pbio.2002612

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

Author(s): Antonio Díaz-Parra, Zachary Osborn, Santiago Canals, David Moratal, Olaf Sporns
Published in: NeuroImage, Issue 159, 2017, Page(s) 170-184, ISSN 1053-8119
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

Author(s): 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
Published in: Neuropsychopharmacology, Issue 42/3, 2016, Page(s) 606-614, ISSN 0893-133X
DOI: 10.1038/npp.2016.145

Hub-driven remote synchronization in brain networks

Author(s): Vladimir Vlasov, Angelo Bifone
Published in: Scientific Reports, Issue 7/1, 2017, ISSN 2045-2322
DOI: 10.1038/s41598-017-09887-7

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

Author(s): Mia Haaranen, Giulia Scuppa, Stefano Tambalo, Vilja Järvi, Sine M. Bertozzi, Andrea Armirotti, Wolfgang H. Sommer, Angelo Bifone, Petri Hyytiä
Published in: Translational Psychiatry, Issue 10/1, 2020, ISSN 2158-3188
DOI: 10.1038/s41398-020-0833-7

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

Author(s): 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
Published in: Science Advances, Issue 6/26, 2020, Page(s) eaba0154, ISSN 2375-2548
DOI: 10.1126/sciadv.aba0154

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

Author(s): Laura Pérez-Cervera, José María Caramés, Luis Miguel Fernández-Mollá, Andrea Moreno, Begoña Fernández, Elena Pérez-Montoyo, David Moratal, Santiago Canals, Jesús Pacheco-Torres
Published in: Preclinical MRI, Issue 1718, 2018, Page(s) 117-134
DOI: 10.1007/978-1-4939-7531-0_8

Signal detection in extracellular neural ensemble recordings using higher criticism

Author(s): Fathizadeh, F.; Mitricheva, E.; Kimura, R.; Logothetis, N.; Noori, H.
Published in: Issue 5, 2019