NYC Photo
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 (February-December 2018): 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.

Phase II (January-December 2019):

Summary of Report II:
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. Our group in this consortium will mainly deal with modelling and network analysis of data sets provided by experimental groups.

Phase I

Task. 1.1 Developing the algorithms for detection of the ”Minimum Spanning Tree” (MST) - Part 1

Task. 1.2 Comparing functional and structural networks using conditional Granger Causality - Part 1

Phase II

Task 2.1 Comparing network with MST analysis - testing on experimental data

Task 2.2 Developing a novel community detection method that works on weighted, directed and dense networks

Task 2.3 Testing the methods for the calculation of conditional Granger causality on experimental data

ISI Journal articles published during the project:

1. B Molnár, F. Molnár, M Varga, Z Toroczkai, M Ercsey-Ravasz, A continuous-time max-SAT solver with high analog performance, Nature Communications 9, 2864, 2018, doi:10.1038/s41467-018-07327-2

2. Z.I. Lázár, D.J. Dijk, A.A. Lázár, Infraslow oscillations in human sleep spindle activity, Journal of Neuroscience Methods, 316, 22-24, 2018, doi: 101016/j.jneumeth.2018.12.002

3. P. Hantz, Z.I. Lázár, Procession Intuitively Explained, Frontiers in Physics, vol. 7, art. 5, 2019, doi: 10.3389/fphy.2019.00005

Conferences, Workshops, Invited seminars:

L. Varga, B. Molnár, V.V. Moca, L. Perez-Cervera, A. Diaz-Parra, D. Moratal, S. Canals, R.C. Muresan, M. Ercsey-Ravasz, Stable probability distribution of brain network properties in resting state fMRI, oral presentation at the Conference on Complex Systems, NTU, Singapore, 2019, October

M. Ercsey-Ravasz, Modelling the inter-areal cortical network based on a distance rule: from the mouse to the macaque, invited talk at the CBG Postdoc Retreat of the Max Planck Institute, Dresden, 2019 June

S. Pfarr, M. Wandres, B. Molnár, M Ercsey-Ravasz, C. Korber, W. Sommer, cFos based network analysis reveals profound differences in the representation of memories for alcohol and sweet reward, poster at European Behavioural Pharmacology Society Biennial Meeting 2019, Braga, Portugal, 2019, August

M. Ercsey-Ravasz, Analyzing anatomical and functional brain networks, invited talk at a Workshop at Eotvos Lorand University for Bilateral Collaboration, ELTE, Budapest, Hungary, 2019 September

Z.I. Lazar, Exploring EEG rhythms: applications in neurodegeneration and circadian research, oral presentation at a Workshop at Eotvos Lorand University for Bilateral Collaboration, ELTE, Budapest, Hungary, 2019 September

Z.I. Lazar, Infraslow oscillations in the human sleep EEG: Effects of age, sex, sleep history and circadian phase, oral presentation at the Symposium on Sleep, Aging and Brain Health, Sleep and Brain Research Unit, University of East Anglia, 2019, May

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

Other dissemination activities:

M. Ercsey-Ravasz, Interview at Radio Cluj, 2019 May. Project director was invited to talk about her research and results

M. Ercsey-Ravasz, Interview in the FIRKA magazine, 2019, July. FIRKA is a scientific magazine written for high-school students. The project director was talking about her career, main research areas and important achievements

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