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Comparative Investigation of the Cortical Circuits in Mouse, NHP and Human

COFUND-FLAGERA II-CORTICITY

contract number: 14

Sponsored by the Romanian National Authority for Scientific Research CNCS-UEFISCDI and the European Comission

Project Coordinator: Dr. Ken Knoblauch, INSERM, Lyon

PI at the Babes-Bolyai University: Dr. Mária Ercsey-Ravasz

Period: 02 February 2018- 30 November 2020

E-mail: ercsey.ravasz@phys.ubbcluj.ro

Research topic:

The proposal investigates the differences in physiology, anatomy and organization of the cortex in mouse, non-human primate (NHP) and human. This work requires tight collaborations between physiologists, anatomists and theoreticians. Our capacity to successfully integrate across these approaches is strongly supported by the numerous joint publications linking these disciplines in leading international journals by the PI’s of the consortium.

Anatomy: Tract-tracing will be used to build macaque and mouse inter-areal cortical connectomes. This work will generate large data bases on inter-areal connection weights and quantitative measures of laminar distributions as well as atlases of mouse and macaque. The structural basis of hierarchy and local-global integration will be investigated with viral tracers that will be used to map the long distance and local input to the parent neurons of feedforward and feedback connections in visual cortex of mouse and macaque.

Physiology: Hierarchical processing in the human, NHP and mouse brains will be compared using electrophysiological and imaging approaches and together with tract tracing, will inform embedded large-scale dynamic models of inter-areal processing in the cortex. Differences in the inter-areal matrix density lead to widely different core structures across the three species, which will be explored by weighted network structural analysis, thereby revealing the core-periphery organization, which we hypothesize could be relevant to the Global Neuronal Workspace theory of consciousness. We will manipulate consciousness with anesthetics and stimulation techniques in macaque and mouse thereby by exploring Global Neuronal Workspace function via auditory signatures of consciousness in a predictive coding paradigm.

Modeling: Conditional Granger causality analysis on multi-variate time series recordings will help identify functional subnetwork motifs, in order to explore the links between structural and dynamical features in the networks across the three species. Whole-brain computational modeling will address the functional role of the underlying anatomy by studying in silico theoretical measures of integration and segregation allowing topological hierarchical analyses of effective connectivity as opposed to anatomical or functional connectivity. Altogether, the project aims to provide quantitative metrics of differences in brain organization related to changes in brain size and order, and will demonstrably underpin the relevance of investigations in the mouse and macaque for understanding the human brain.

Consortium

Coordinator: INSERM, Lyon, France, PIs: Ken Knoblauch, Henry Kennedy

Babes-Bolyai University,Physics Department, Romania, PI: Maria Ercsey-Ravasz

University Pompeu Fabra, Center of Brain and Cognition, Spain, PI: Gustavo Deco

CEA Saclay, France, PI: Bechir Jarraya

ESI for Neuroscience, Germany, PIs:Pascal fries, Martin Vinck

University of Notre-Dame, Dept. of Physics, PI: Zoltan Toroczkai

Progress:

Phase I (2018 February-December): Budget: 252,000 RON

Summary of Report I:
In this project we collaborate with experimental neurologists, more specifically researchers from INSERM (Lyon) and ESI (Frankfurt), as well as Prof. Toroczkai, a theoretical scientist with specialty in network science, from the University of Notre Dame. We had a consortium meeting in Frankfurt between July 26 and 27, 2018, where the main topics of the project were discussed in details and also some some preliminary results were presented. The INSERM Group has pledged to release some renewed data about the monkey's structural contectome. This happened in September and we have already begun analysis, see the results below. We also discussed the possibility for ESI to share some data. This is a huge amount of ECoG data and even sharing it is not a trivial problem. We are currently working on this. Meanwhile, we have begun developing our methods for the different types of analysis, especially the minimal spanning tree (MST) analysis. Here are some results. With regard to Granger causality (GC), the ESI group has already extracted the data from the Granger causality network, so for now we have decided that it would be more important to analyze their networks and to postpone the development of the GC conditional measure.

ISI Journal articles published during the project:

1. B Molnár, F. Molnar, M Varga, Z Toroczkai, M Ercsey-Ravasz, „A continuous-time max-SAT solver with high analog performance”, under review in Nature Communications.2018

2. Z.I. Lázár, D.J. Dijk, A.A. Lázár, Infraslow oscillations in human sleep spindle activity, Journal of Neuroscience Methods, under evaluation 2018

Other publications:

- M. Ercsey-Ravasz, "Agyi halozaok modellezese egy tavolsagszabaly alapjan" ("Modeling structural brain networks based on a distance rule"), FIRKA, invited paper 2017-2018 vol. 4 (emt.ro)

Previous publications relevant to the project:

- Răzvan Gămănuţ, Henry Kennedy, Zoltán Toroczkai, Mária Ercsey-Ravasz, David C Van Essen, Kenneth Knoblauch, Andreas Burkhalter, The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles, Neuron 97, 698-715. e10 , 2018.

- Sz. Horvát†, Răzvan Gămănuț†, Mária Ercsey-Ravasz†, Loïc Magrou, Bianca Gămănuț, David C. Van Essen, Andreas Burkhalter, Kenneth Knoblauch, Zoltán Toroczkai, Henry Kennedy,”Spatial embedding and wiring cost constrain the functional layout of cortical networks in rodents and primates”, PLoS Biol., vol. 14, e1002512, 2016. († indicates equal contribution).

- M. Ercsey-Ravasz, N.T. Markov, C. Lamy, D.C. Van Essen, K. Knoblauch, Z. Toroczkai, H. Kennedy, “A predictive network model of cerebral cortical connectivity based on a distance rule.”, Neuron vol. 80, pp. 184-197, 2013

- N.T. Markov, M. Ercsey-Ravasz, D.C. Van Essen, K. Knoblauch, Z. Toroczkai, H. Kennedy, "Cortical High-density Counter-stream Architectures", Science, 342, 1238406, 2013 doi:10.1126/science.1238406

Conferences, Workshops, Invited seminars:

Maria Ercsey-Ravasz, "The new era of network science", invited talk at the "Jozsef Attila Szabadegyetem" (Attila Jozsef Free University), Budapest, Hungary, February, 2018

Maria Ercsey-Ravasz, Levente Varga visited one of the partners, Zoltan Toroczkai at the University of Notre Dame in the USA, in the period of July 1-15, 2018.

Consortium meeting in Frankfurt between all partners. From the BBU group Maria Ercsey-Ravasz and Levente Varga have participated. July 24-25, 2018.

A. Lazar, Zs. I. Lazar, D.-J. Dijk, Sex differences in the circadian and sleep dependent regulation of sleep spindles in humans, 24th Congress of the European Sleep Research Society, 25 – 28 September 2018, Basel, Switzerland

Zs. I. Lazar, Symposium on Sleep, Aging and Brain Health & Inauguration of the Sleep and Brain Research Unit, University of East Anglia, May 1, 2019