Understanding brain circuit dysfunction in amblyopia using large-scale multimodal recordings in a new visuomotor task applied to animal models and patients
Funding: project code ERANET-NEURON-2-UnscrAMBLY, contract 282/2022 from the State Budget of Romania:
National Program III for Research, Development and Innovation, administered by the Ministry for Research and Innovation through the
Executive Agency for Higher Education, Research, Development and Inovation Funding
(UEFISCDI).
Abstract
We aim to establish the role of predictive processing in neurodevelopmental disorders, specifically in one of the most studied contexts, amblyopia. We use a new visuomotor feedback task across high-visual-acuity preclinical species - cats -, rodents, and humans during large-scale activity readout via best-available methods (functional ultrasound imaging reaching 4 cm depth, mesoscale two-photon imaging, hdEEG) to 1) identify brain regions involved in visuomotor prediction in normal subjects, 2) determine the effect of amblyopia on prediction-related activity patterns, 3) develop functional network models to infer which brain regions and associated brain functions are restored or remain perturbed after amblyopia treatment, 4) validate results via optogenetic perturbation experiments in mice, 5) provide an EEG-based biomarker with high discriminative power across normal vision and different stages of amblyopia, 6) contribute the community with the comparative etiology of one of the best modelled neurodevelopmental disorders. Our results may demonstrate the discriminative power of a prediction feedback probing visuomotor task between amblyopic subjects who exhibit disrupted visuomotor function after having their acuity fully restored and controls. To elucidate the causes of this unmet medical need, we link large-scale functional network activity to neurodevelopment in a behaving animal model that faithfully recapitulates human visual functions.
Research team
Dr. Mária M. Ercsey-Ravasz, principal investigator. |
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Dr. Eng. Raul C. Mureșan, senior researcher. [Curriculum Vitae] |
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Dr. Eng. Vlad V. Moca, senior researcher. |
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Dr. Eng. Levente Varga, postdoc researcher. |
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Dr. Botond Molnár, researcher. |
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Dr. Eng. Adriana Nagy-Dăbâcan, postdoc researcher. |
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Harald Bârzan, PhD researcher. |
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Andrei Ciuparu, PhD researcher. |
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Ana Maria Ichim, PhD researcher. |
Objectives
The primary objective of the project is to provide a network view of the neuronal origins of amblyopia by leveraging the discriminative power of a visuomotor prediction test in a joint clinical and basic science proof-of-concept study covering mice, cats and humans. The secondary objective is to provide a clinically applicable biomarker with high discriminative power across normal vision and different stages of amblyopia.
Expected results
The project will develop a visuomotor testing platform for control subjects and amblyopic patients.
We will develop new methods for functional network analysis applied to ultrasound and 2 photon imaging, and also EEG datasets.
The data analysis will also allow the development of biomarkers for amblyopia.
Members of the UnscrAMBLY consortium at the consortium meeting in Budapest, January 2023.
TINS team installing the virtual reality setup for cats, at TTK in Budapest, January 2023.
Discussions about project progress and next tasks, January 2023.
Testing the virtual reality setup for human subjects at TINS.
Preparatio of an adult subject for the test session using EEG and virtual reality, November 2023.
Setting up the virtual reality setup in combination with EEG recording, November 2023.
Testing the virtual reality setup in combination with EEG recording, November 2023.
TTK workshop on the occasion of the instalation of the virtual reality sistem for humans, November 2023.
Scientific reports
Testimonial
Overview of testimonial (in Romanian).
[pdf]
Testimonial (in Romanian):
Ambliopia, sau „ochiul leneș”, este o dereglare a neurodezvoltării sistemului vizual care se manifestă timpuriu dar care, de obicei, este diagnosticată prea târziu când opțiunile de tratament sunt deseori limitate și ineficiente. Estimările arată că, până în anul 2040, aproximativ 200 de milioane de oameni vor suferi de ambliopie. de aceea înțelegerea mecanismelor neuronale implicate este esențială și promite dezvoltarea unor noi tratamente eficiente cu impact mare în societate. Proiectul ERA-NET UnscrAMBLY a reunit echipe de cercetători din Belgia, Norvegia și Ungaria, împreună cu echipa de la Transylvanian Institute of Neuroscience (TINS) din Cluj-Napoca. Scopul principal al proiectului a fost de înțelege disfuncțiile cerebrale din ambliopie utilizând o abordare inovativă care împletește înregistrări multimodale (imagistică cu ultrasunete, cu doi fotoni și EEG) cu o sarcină vizuomotorie nouă. Investigațiile au fost efectuate în copii cu ambliopie și subiecți sănătoși și în modele animale (șoareci și pisici - cu bună acuitate vizuală). Pe parcursul implementării proiectului, rolul echipei TINS a fost acela de a dezvolta tehnici de analiză și echipamente experimentale inovatoare (hardware și software) care să permită investigații complexe asupra mecanismelor neuronale de predicție. Astfel am dezvoltat un tunel de realitate virtuală (VR) pentru pisici și oameni în timp real și infrastructură de eye-tracking pentru pisici care permite mișcarea liberă a capului, ambele esențiale pentru investigațiile propuse. Mai mult, am dezvoltat metode de analiză pentru EEG și rețelele funcționale cu largă aplicabilitate. Aceste metode au fost distribuite partenerilor iar echipamentele experimentale dezvoltate la TINS au fost predate partenerului din Budapesta care desfășoară activitatea experimentală. Echipele implicate au făcut schimb de experiență în ceea ce privește instrumentarea, achiziția și analiza datelor electrofiziologice și de imagistică. Aceste schimburi au contribuit în mod substanțial la finalizarea stagiului doctoral pentru trei membrii ai echipei, având astfel un impact semnificativ asupra carierei lor. Proiectul a consolidat colaborarea pe termen lung cu partenerii externi, vizibilă prin publicații comune și a condus la aplicații pentru noi proiecte comune de cercetare, consolidând astfel colaborările de lungă durată cu parteneri externi.
Dissemination
Scientific articles:
Grosu G.F., Hopp A.V., Moca V.V., Barzan H., Ciuparu A., Ercsey-Ravasz M., Winkel M., Linde H., Muresan R.C. (2022), The fractal brain: scale-invariance in structure and dynamics. Cerebral Cortex, bhac363.
https://doi.org/10.1093/cercor/bhac363
[pdf] [Open access link]Barzan H., Ichim A.M., Moca V.V., Muresan R.C. (2022), Time-Frequency Representations of Brain Oscillations: Which One Is Better? Frontiers in Neuroinformatics 16:871904.
https://doi.org/10.3389/fninf.2022.871904
[pdf] [Open access link]Dumitru D.A., Ceuta E.B., Moca V.V., Muresan R.C., Dinsoreanu M. (2022), Extraction of Functional Brain Networks from EEG Signals in the Context of Visual Perception. Automation, Quality and Testing, Robotics (AQTR), 2022 IEEE International Conference on, pp. 1-6.
https://doi.org/10.1109/AQTR55203.2022.9801941
[pdf] [IEEE Xplore link]Muresan D.B., Ciure R.D., Ardelean E.R., Moca V.V., Muresan R.C., Dinsoreanu M. (2022), Spike sorting using Superlets: Evaluation of a novel feature space for the discrimination of neuronal spikes. Intelligent Computer Communication and Processing (ICCP), 2022 18th IEEE International Conference on, pp. 229-235.
https://doi.org/10.1109/ICCP56966.2022.10053955
[pdf]Salagean A., Pasc A.M., Ardelean E.R., Muresan R.C., Moca V.V., Dinsoreanu M., Potolea R., Lemnaru C. (2022), Local Field Potential Microstate Analysis. Intelligent Computer Communication and Processing (ICCP), 2022 18th IEEE International Conference on, pp. 221-227.
https://doi.org/10.1109/ICCP56966.2022.10053960
[pdf]Ardelean E.R., Ichim A.M., Dinsoreanu M., Muresan R.C. (2023), Improved space breakdown method – A robust clustering technique for spike sorting. Frontiers in Computational Neuroscience 17:1019637.
https://doi.org/10.3389/fncom.2023.1019637
[pdf] [Open access link]Molnar F., Horvat S., Ribeiro-Gomes A.R., Armas J.M., Molnar B., Ercsey-Ravasz M., Knoblauch K., Kennedy H., Toroczkai Z. (2023), Predictability of cortico-cortical connections in the mammalian brain. Network Neuroscience 2024; 8 (1): 138–157.
https://doi.org/10.1162/netn_a_00345
[Open access link]Ardelean E.R., Coporiie A., Ichim A.M., Dinsoreanu M., Muresan R.C. (2023), A study of autoencoders as a feature extraction technique for spike sorting. PLoS One 18(3):e0282810.
https://doi.org/10.1371/journal.pone.0282810
[pdf] [Open access link]Ardelean E.R., Bârzan H., Ichim A.M., Mureșan R.C., Moca V.V. (2023), Sharp Detection of Oscillation Packets in Rich Time-Frequency Representations of Neural Signals. Frontiers in Human Neurocience 17:1112415.
https://doi.org/10.3389/fnhum.2023.1112415
[Open access link]Ardelean A.I., Dinsoreanu M., Ardelean E.R., Moca V.V., Muresan R.C. (2023), Burst detection in neuronal activity. Intelligent Computer Communication and Processing (ICCP), 2023 19th IEEE International Conference on, pp. 349-356.
https://doi.org/10.1109/ICCP60212.2023.10398703
[pdf]Ardelean E.R., Terec R.D., Maries C.M., Moca V.V., Muresan R.C., Dinsoreanu M. (2023), Spike sorting using Superlets: Identifying feature importance through perturbation. Intelligent Computer Communication and Processing (ICCP), 2023 19th IEEE International Conference on, pp. 357-362.
https://doi.org/10.1109/ICCP60212.2023.10398655
[pdf]Moisa O.M., Pop I., Dinsoreanu M., Ardelean E.R., Moca V.V., Muresan R.C. (2023), Symbolic Analysis Based Pipeline For EEG Data. Intelligent Computer Communication and Processing (ICCP), 2023 19th IEEE International Conference on, pp. 371-378.
https://doi.org/10.1109/ICCP60212.2023.10398607
[pdf]L. Varga, V.V. Moca, B. Molnar, L. Perez-Cervera, M. Kotb Selim, A. Díaz-Parra, D. Moratal, B. Péntek, W. H. Sommer, R. C. Mureșan*, S. Canals*, M. Ercsey-Ravasz*, „Brain dynamics supported by a hierarchy of complex correlation patterns defining a robust functional architecture”, Cell Systems, 15 ,1-17, 2024.
https://doi.org/10.1016/j.cels.2024.07.003
[Open access link]M. Botond, M. Ildiko-Beata, H. Szabolcs, M. Ercsey-Ravasz, „Community detection in directed weighted networks using Voronoi partitioning”, Scientific Reports, 14, 8124 (1-19), 2024.
https://doi.org/10.1038/s41598-024-58624-4
[Open access link]M. Jozsa, M. Ercsey-Ravasz, Zs. Lazar, „Coarse-graining model reveals universal exponential scaling in axonal length distributions”, Journal of Physics: Complexity, 5, 035012 (1-13), 2024.
https://doi.org/10.1088/2632-072X/ad66a6
[Open access link]Ciuparu A., Garvert A.C., Vervaeke K., Muresan R.C. (2024), Adapting supervised machine learning for analysis of neurobiological signals. IEEE International Conference on Automation, Quality and Testing, Robotics (AQTR), Cluj-Napoca, Romania, 2024, pp. 1-6.
https://doi.org/10.1109/AQTR61889.2024.10554180
[Open access link]Gal C., Tincas I., Moca V.V., Ciuparu A., Dan E.L., Smith M.L., Gliga T., Muresan R.C. (2024), Randomness impacts the building of specific priors, visual exploration, and perception in object recognition. Scientific Reports 14, 8527.
https://doi.org/10.1038/s41598-024-59089-1
[Open access link]Ichim A.M., Bârzan H., Moca V.V., Nagy-Dăbâcan A., Ciuparu A., Hapca A., Vervaeke K., Mureșan R.C. (2024) The gamma rhythm as a guardian of brain health. eLife, 13, e100238.
https://doi.org/10.7554/eLife.100238
[Open access link]
Presentations at international conferences:
Dan E.L., Moca V.V., Dinsoreanu M., Muresan R.C. (2022), Gaze lateralization bias during free visual exploration of faces. 31st Annual Computational Neuroscience Meeting, CNS*2022, Melbourne, Australia. In press.
[pdf]Ichim A.M., Barzan H., Moca V.V., Vervaeke K., Muresan R.C. (2022), Blue flicker stimulation enhances gamma rhythms in mouse visual cortex. 31st Annual Computational Neuroscience Meeting, CNS*2022, Melbourne, Australia. In press.
[pdf]L Varga, B Molnar, VV Moca, L Perez-Cervera, A Diaz-Parra, D Moratal, WH Sommer, RC Muresan, S Canals, M Ercsey-Ravasz. The brain's functional connectivity backbone and the impact of AUD. Oral presentation at ISBRA & ESBRA 2nd World Congress on Alcohol and Alcoholism, 2022 September 17-20, Cracow, Poland. Abstract in: ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH. 111 RIVER ST, HOBOKEN 07030-5774, NJ USA: WILEY, 2022. Vol. 46, p. 62-63.
B. Molnár: Optimal Community Detection in Weighted Directed Networks using Voronoi Diagrams, APS March Meeting 2022, Chicago, IL, USA, 14-18 March 2022, oral presentation
Mate Jozsa, Maria Ercsey-Ravasz, Zsolt I. Lazar, Investigating brain wiring by simple statistical models, MECO 47, Erice, Sicily, June 12-16 2022, poster
Ercsey-Ravasz M. (2023), „Modeling the inter-areal cortical network based on a distance rule: from the mouse to the macaque”, International School and Conference on Network Science, NetSci2023, Vienna, Austria, 2023, July 10-14.
Ercsey-Ravasz M. (2023), „Modelling the inter-areal cortical network based on a distance rule”, Computational Neuroscience Academy 2023, Krakow, Poland, 19 July 2023.
Ercsey-Ravasz M. (2023), „Physical networks in the brain”, 6th Grandmaster Early-Career Workshop in Physics GEWP 2023, Cluj-Napoca, Romania, 2023, September 4-9.
Ercsey-Ravasz M., Varga L., Molnar B., Moca V.V., Perez-Cervera L., Díaz-Parra A., Moratal D., Péntek B., Sommer W.H., Mureșan R.C., Canals S. (2023), "Dynamic fMRI unveils a robust functional network architecture in the brain: a hierarchy of strong positive and weak bimodal correlations", poster, International School and Conference on Network Science, NetSci2023, Vienna, Austria, 2023, July 10-14.
Molnar B., Marton I.B., Horvat S., Ercsey-Ravasz M. (2023), "Community detection in directed weighted networks using Voronoi partitioning", contributed talk, International School and Conference on Network Science, NetSci2023, Vienna, Austria, 2023, July 10-14.
Media dissemination, presentations for the general public, etc.:
Maria Ercsey-Ravasz, prezentare invitată la Zilele Maghiare Digitale din Transilvania (Erdelyi Magyar Digitalis Napok), Hálózatkutatás és adatfeldolgozási módszerek az idegtudományokban (Știința rețelelor și metode de procesare a datelor în neuroștiințe), 23 Martie, 2022, Targu Mures.
Maria Ercsey-Ravasz, Interviu la TVR Cluj - limba maghiară, emisiunea Summa.
https://www.facebook.com/534716723271172/videos/1201329150720553/Raul Muresan, prezentare în cadrul programului Studium Generale al Institutlui STAR-UBB, 15.12.2022, Hunting for brain oscillations: functional role and estimation techniques.
„Transylvanian Institute of Neuroscience” (2023), Interview for neurosci.ro about the institute.
https://www.youtube.com/watch?v=07btnKn90dw„Creierul fractal. Ep. 1: De la blestemul complexității la coasta Marii Britanii (Grosu et al., 2023)” (2023), Podcast with neurosci.ro about the „Fractal Brain” article published in Cerebral Cortex.
https://www.youtube.com/watch?v=1PcdJRJVNas„Creierul fractal. Ep. 2: De la micro la macro-scală și mai departe (Grosu et al., 2023)” (2023), Podcast with neurosci.ro about the „Fractal Brain” article published in Cerebral Cortex.
https://www.youtube.com/watch?v=QVkLJsEMU5QComunicat de presă cu privire la articolul publicat în Cell System lansat de TINS și UBB:
https://news.ubbcluj.ro/metoda-revolutionara-dezvoltata-de-cercetatori-clujeni-de-la-tins-si-ubb-pentru-intelegerea-activitatii-creierului/
Preluat de următoarele publicații: cluj24, monitorulcj, adevarul, cotidinaul, agerpres, digi24, edupedu, g4media etc... din România și de Szabadsag din Ungaria.TVR Cluj: interviu cu Maria Ercsey-Ravasz și Vlad Moca.
Kolozsvari TV, Erdelyi Figyelo: interviu cu Maria Ercsey-Ravasz și Levente Varga.
Medical Reports TV: interviu cu Maria Ercsey-Ravasz.