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Brain connectivity of the central control of breathing in humans using EEG and fMRI: integration of data and hypothesis driven approaches

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Academic year: 2021

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U N I V E R S I T À D I P I S A

DIPARTIMENTO DI INGEGNERIA DELL’INFORMAZIONE Dottorato di Ricerca in Ingegneria dell’Informazione

Activity Report by the Student Alejandro Luis CALLARA – cycle XXXI

1. Research Activity

The work related to my research activity arises from the interests of Fondazione Toscana "G. Monasterio", and in particular from the clinical demand and research interests in the study of Cheyne-Stokes Respiration in patients with congestive Heart-Failure. In particular, the main interest is that of elucidating brain activity and connectivity related to the central control of breathing.

To this aim, brain networks involved in the physiological and pathological central control of breathing were investigated, exploiting cardiorespiratory signals, electroencephalography (EEG) and functional Magnetic Resonance Imaging (fMRI). Specifically, I integrated hypothesis driven and data driven approaches within different methodological frameworks to perform exploratory analysis of brain connectivity from EEG and fMRI.

Concerning EEG-based studies, I developed a computational framework that addresses challenges arising from the clinical research (i.e. low-density EEG acquisitions and resting-state/block-design paradigms). The framework was applied to both physiological and pathological cases for the study of cortical activity and connectivity under different ventilatory conditions. Differences in brain activity and connectivity related to different ventilatory conditions were identified in terms of directed cortico-cortical interactions in both physiological and pathological cases. Differences between the physiological and pathological case were also observed. Results relative to this research activity were presented and refined through the participation to several conferences [C3], [C7], [O2].

Concerning fMRI-based studies, a second framework integrating i) ICA, ii) independent component classification, iii) temporal and spatial correlation and iv) regression analysis was developed for the study of functional brain connectivity. The framework was applied to healthy subjects under CO2 stimulation for the

study of chemosensitivity of central chemoreceptors to different levels of CO2. In particular, a supra-linear

response of central chemoreceptors to CO2 challenges was identified. Methodologies and results relative to

this research activity were presented to several conferences [C1], [C5], [O3]. I also contributed to the study of a supra-linear relationship between brain activity and CO2 levels, through model-based approaches [C2],

[C4].

Participation to DataBrain Project (funded by the University of Pisa, PRA_2016_56)

My contribution to this project was the optimization of tissue clarification and image acquisition protocols, and the development of algorithms for 3D neuron segmentation and morphometric extraction. The CLARITY protocol for tissue delipidation was optimized for 1mm-thick brain slices in terms of optimum clarification time through a rigorous quantitative approach [J1]. Lipid removal is a crucial step in confocal imaging, since their presence reduces the depth at which light can penetrate through tissues. This work opened an entire subfield of segmentation, since no algorithms are validated for this type of data. To this end, I developed

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both an automatic algorithm for single-neuron segmentation from confocal acquisition representing dense-packed neurons within the brain (SmRG, [S1]) and a tool to facilitate the manual segmentation (ManSegTool, [J2], [S2]), necessary to validate the SmRG performance.

2. Teaching Assistant Activity

October 2017 - December 2017, Graduate Teaching Assistant @ Biomedical Engineering M. Sc. program. Image processing with MATLAB for the course of Meccanobiologia held by prof. Arti Ahluwalia

October 2016 - December 2016, Graduate Teaching Assistant @ Biomedical Engineering Bachelor program. Image processing with MATLAB for the course of Fenomeni di Trasporto held by prof. Arti Ahluwalia

3. Tutoring Activity

During the PhD I assisted prof. Nicola Vanello for the lab-training activity of students @ Bionics Engineering M. Sc.

4. Formation Activity

COURSES/CREDITS:

• Game Theory and Optimization in Communications and Networking, 4 credits. • Signal Processing and mining of Big data: biological data as case study, 5 credits.

• Multi-modal Registration of Visual Data, 4 credits.

• Academic Writing and Academic Presentation skills, 4 credits. • Using E-infrastructures for biodiversity conservation, 5 credits.

• Rapid Prototyping for Engineers, 3 credits.

• Introduction to modeling and simulation of complex and multidisciplinary

dynamical system, 5 credits.

• Academic writing and presentation skills (C1 plus), 5 credits. TOTAL: 35

5. Publications

International Journals

[J1] C. Magliaro, A. Callara, G. Mattei, M. Morcinelli, M. Viaggi, F. Vaglini, A. Ahluwalia: “Clarifying CLARITY: quantitative optimization of the diffusion based delipidation protocol for genetically labeled tissue”, Frontiers in Neuroscience, Vol.10, N.179, 2016

[J2] C. Magliaro, A.L. Callara, N. Vanello, A. Ahluwalia: “A manual segmentation tool for three-dimensional neuron datasets”, Frontiers in Neuroinformatics, Vol.11, N.36, 2017

International Conferences/Workshops with Peer Review

[C1] Callara, A. L., Morelli, M. S., Cauzzo, S., Giannoni, A., Hartwig, V., Montanaro, D., Passino, C., Landini, L., Emdin, M., & Vanello, N. (2019). Exploring the supra-linear relationship between PETCO2 and fMRI signal change with ICA, EMBConference, July 2019, Berlin, Germany.

[C2] Cauzzo, S., Callara, A. L., Morelli, M. S., Hartwig, V., Montanaro D., Passino, C., Emdin, M., Giannoni, A., & Vanello, N. (2019). On the Use of Linear-Modelling based Algorithms for Physiological Noise Correction in fMRI Studies of the Central Breathing Control, EMBConference, July 2019, Berlin, Germany.

[C3] Callara, A. L., Morelli, M. S., Hartwig, V., Giannoni, A., Landini, L., Passino, C., Emdin, M., & Vanello, N. (2019). Effective connectivity in Cheyne-Stokes respiration from low-density EEG: a methodological framework, accepted for OHBM 2019, June 2019, Rome, Italy.

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[C4] Cauzzo, S., Callara, A. L., Morelli, M. S., Hartwig, V., Montanaro D., Passino, C., Emdin, M., Giannoni, A., & Vanello, N. (2019). Breath hold challenges in fMRI: Methodological issues in modelling BOLD signal changes, OHBM, June 2019, Rome, Italy.

[C5] A.L. Callara, M.S. Morelli, S. Cauzzo, A. Giannoni, V. Hartwig, D. Montanaro, C. Passino, L. Landini, M. Emdin, N. Vanello. “Nonlinear Modeling and Complexity Measures of Brain Dynamics: Methodological Issues and Interpretation” 19th World Congress of Psycophysiology, Lucca, October

2018. International Journal of Psychophysiology.

[C6] C. Magliaro, A.L. Callara, N. Arami, C. De Maria, V. Ferrari, N. Vanello, A. Tognetti, M. Mangione, M.C. Viaggi, F. Vaglini, M. Castagna, D. De Rossi, L. Landini, A. Ahluwalia. “Databrain: A web-accessible database for three-dimensional reconstructions and quantitative morphometrics of neurons” IFMBE Proceedings, 65, pp. 767-770, 2017

[C7] A.L. Callara, M. Morelli, A. Giannoni, L. Landini, M. Emdin, N. Vanello: “EEG functional brain connectivity in different respiration phases in Cheyne-Stokes Respiration”, OHBM 2017, June 2017

Others

[O1] Callara, A. L., Magliaro, C., Ahluwalia, A., & Vanello, N. (2018). Smart Region-Growing: a novel algorithm for the segmentation of 3D clarified confocal image stacks. bioRxiv, 287029.

[O2] Callara, A. L., Morelli, M. S., Hartwig, V., Giannoni, A., Landini, L., Emdin, M., & N. Vanello, N. (2018). EEG functional brain connectivity in patients with Cheyne-Stokes respiration. Gruppo Nazionale di Bioingegneria, Milan, Italy, June 2018.

[O3] Callara, A. L., Morelli, M. S., Cauzzo, S., Giannoni, A., Hartwig, V., Montanaro, D., Passino, C., Landini, L., Emdin, M., & Vanello, N. (2018). Models of BOLD signal changes in breath hold studies and CO2 challenges: Methodological issues and interpretation. GIDRM workshop: Advanced hardware, Methods and Applications in NMR/MRI. L’aquila, Italy, June 2018.

6. Software development

[S1] https://github.com/AlejandroCallara/SmRG

[S2] https://github.com/CentroEPiaggio/ManSegTool

Riferimenti

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