Project

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Sleep as a model to understand and manipulate cortical activity in order to promote neuroplasticity and functional recovery after stroke

English title Sleep as a model to understand and manipulate cortical activity in order to promote neuroplasticity and functional recovery after stroke
Applicant Bassetti Claudio L.
Number 160803
Funding scheme Sinergia
Research institution Universitätsklinik für Neurologie Inselspital Universität Bern
Institution of higher education University of Berne - BE
Main discipline Neurophysiology and Brain Research
Start/End 01.01.2016 - 30.06.2019
Approved amount 1'830'298.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Neurology, Psychiatry

Keywords (10)

EEG; sleep; TMS; optogenetic; neuroplasticity; stroke recovery; slow wave activity; stroke; cortex; bistability

Lay Summary (German)

Lead
Die verschiedenen Hirnfunktionen entstehen durch ein Zusammenspiel komplexer Netzwerke unterschiedlicher Zelltypen. Dieses Forschungsprojekt untersucht die Mechanismen von Schlaf, welche bei Tieren und Menschen eine positive Auswirkung auf die Hirnaktivität vor und nach einem Hirnschlag haben können. Die verfügbaren Behandlungen zur Rehabilitation nach einem Schlaganfall jedoch basieren meist noch immer ausschliesslich auf Training und Übungen. Die Ergebnisse dieser Studie sollen zu Entwicklung neuer Therapien, verbesserter Rehabilitation und Erhöhung der Lebensqualität von Hirnschlagpatienten beitragen.
Lay summary

Die verschiedenen Hirnfunktionen entstehen durch ein Zusammenspiel komplexer Netzwerke unterschiedlicher Zelltypen. Gestörte Verbindungen zwischen den Zellen können die Gehirnfunktion beinträchtigen. Bei einem Hirnschlag führt der Unterbruch der Blutversorgung zu Schädigung der Zellen und ihren Verbindungen und kann Hirnfunktionsstörungen bis hin zu permanente Behinderungen verursachen. Beobachtungen aus Experimenten deuten darauf hin, dass bestimmte Hirnzustände, wie z. B. Schlaf, das Hirngewebe bei einem Schlaganfall schützen und reparieren können. Dieses Forschungsprojekt untersucht die Mechanismen von Schlaf, welche bei Tieren und Menschen eine positive Auswirkung auf die Hirnaktivität vor und nach einem Hirnschlag haben können.

Das Projekt gliedert sich in drei Teile: 1) Charakterisierung des Schlaf-Wach-Rhythmus im Zusammenhang mit funktionellen Defiziten bei Nagetieren und Menschen, die einen Schlaganfall erlitten haben. 2) Untersuchung der Reaktionsfähigkeit von Hirnschaltkreisen auf bestimmte Arten von Stimulation, sowohl im kranken als auch im gesunden Gehirn von Tier und Mensch. 3) Der Wissenstransfer von neuen oder alternativen Therapien zur Rehabilitation von Schlaganfallpatienten. Für die Studie werden modernste Technologien verwendet  – Hochdichte –Elektroenzephalographie (high-density EEG), Optogenetik, bildgebende Verfahren und transkraniale magnetische Stimulation (TMS).

Hirnschlag ist die häufigste Ursache für permanente Behinderungen und die dritthäufigste Todesursache bei Erwachsen. Grosse Fortschritte wurden bei der Prävention und Behandlung von akutem Hirnschlag erzielt. Die verfügbaren Behandlungen zur Rehabilitation nach einem Schlaganfall jedoch basieren meist noch immer ausschliesslich auf Training und Übungen. Die Ergebnisse dieser Studie sollen zu Entwicklung neuer Therapien, verbesserter Rehabilitation und Erhöhung der Lebensqualität von Hirnschlagpatienten beitragen.

Direct link to Lay Summary Last update: 09.10.2015

Lay Summary (English)

Lead
Brain functions are supported by multiple cell types, including neuronal and non-neuronal cells, that are connected into complex networks. When the connectivity between those cells is altered or disrupted, the functioning of the brain is impaired. In stroke, the interruption of blood supply to the neural circuits result in connectivity damage and permanent disabilities. Experimental evidence suggest that some type of brain state, including sleep, can protect brain tissue from stroke and “repair” the damaged circuits. This project will investigate the neuronal mechanism underlying the protective effect of sleep on brain connectivity and network activity before and after stroke in animals and humans. Completion of this project will help to better understand the neuronal substrate of stroke and improve stroke rehabilitation in patients.
Lay summary
The project combines complementary techniques in animals and humans, and is divided into three phases: 1) the characterization of sleep/wake rhythm in rodents and humans having undergone a stroke in relationship to functional outcomes; 2) the study of network reactivity to specific stimuli in healthy and stroke brain from animal and humans, and 3) the translation of new/alternative  therapeutic strategies in the rehabilitation of stroke patients. We will use a collection of state-of-the-art technologies including high-density electroencephalography, optogenetic manipulation of neural circuits, neuroimaging methods, and transcranial magnetic stimulation. Perspectives include a better understanding of the causes and consequences of the perturbed electrical activity of the brain during sleep in stroke patients, as well as brain connectivity changes during the rehabilitation phase.

Stroke is the first cause of permanent disability and the third cause of mortality in adults. Major advances have been made in stroke prevention and in the management of acute stroke, but the post-stroke rehabilitation is still mainly based on training and exercise. The outcomes of this project aim to better understand the brain mechanism of stroke protection and recovery and the development of new therapeutic approaches for the clinical management of stroke patients to eventually improve their rehabilitation process and the quality of life.
Direct link to Lay Summary Last update: 09.10.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine
Colombo Michele Angelo, Napolitani Martino, Boly Melanie, Gosseries Olivia, Casarotto Silvia, Rosanova Mario, Brichant Jean-Francois, Boveroux Pierre, Rex Steffen, Laureys Steven, Massimini Marcello, Chieregato Arturo, Sarasso Simone (2019), The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine, in NeuroImage, 189, 631-644.
Sleep as a model to understand neuroplasticity and recovery after stroke: Observational, perturbational and interventional approaches
Mensen Armand, Pigorini Andrea, Facchin Laura, Schöne Cornelia, D'Ambrosio Sasha, Jendoubi Jasmine, Jaramillo Valeria, Chiffi Kathrin, Eberhard-Moscicka Aleksandra K., Sarasso Simone, Adamantidis Antoine, Müri René M., Huber Reto, Massimini Marcello, Bassetti Claudio (2019), Sleep as a model to understand neuroplasticity and recovery after stroke: Observational, perturbational and interventional approaches, in Journal of Neuroscience Methods, 313, 37-43.
Abstracts - Cortical perturbations reveal local sleep-like down states in cortical perilesional area
CattaniAnna (2018), Abstracts - Cortical perturbations reveal local sleep-like down states in cortical perilesional area, in Journal of Sleep Research, 27, e12751-e12751.
Loss of consciousness is related to hyper-correlated gamma-band activity in anesthetized macaques and sleeping humans
Bola Michał, Barrett Adam B., Pigorini Andrea, Nobili Lino, Seth Anil K., Marchewka Artur (2018), Loss of consciousness is related to hyper-correlated gamma-band activity in anesthetized macaques and sleeping humans, in NeuroImage, 167, 130-142.
Sleep-like bistability, loss of causality and complexity in the brain of Unresponsive Wakefulness Syndrome patients
Rosanova Mario, Sarasso Simone, Pigorini Andrea, Massimini Marcello (2018), Sleep-like bistability, loss of causality and complexity in the brain of Unresponsive Wakefulness Syndrome patients, in bioRxiv, 1.
The spectral features of EEG responses to transcranial magnetic stimulation of the primary motor cortex depend on the amplitude of the motor evoked potentials.
Fecchio Matteo, Pigorini Andrea, Comanducci Angela, Sarasso Simone, Casarotto Silvia, Premoli Isabella, Derchi Chiara-Camilla, Mazza Alice, Russo Simone, Resta Federico, Ferrarelli Fabio, Mariotti Maurizio, Ziemann Ulf, Massimini Marcello, Rosanova Mario (2017), The spectral features of EEG responses to transcranial magnetic stimulation of the primary motor cortex depend on the amplitude of the motor evoked potentials., in PloS one, 12(9), 0184910-0184910.
Sleep, Preconditioning and Stroke
Pincherle Alessandro, Pace Marta, Sarasso Simone, Facchin Laura, Dreier Jens P., Bassetti Claudio L. (2017), Sleep, Preconditioning and Stroke, in Stroke, 48(12), 3400-3407.
Global and local complexity of intracranial EEG decreases during NREM sleep
Schartner Michael M., Pigorini Andrea, Gibbs Steve A., Arnulfo Gabriele, Sarasso Simone, Barnett Lionel, Nobili Lino, Massimini Marcello, Seth Anil K., Barrett Adam B. (2017), Global and local complexity of intracranial EEG decreases during NREM sleep, in Neuroscience of Consciousness, niw022-niw022.

Collaboration

Group / person Country
Types of collaboration
R. Müri, Dept. of Neurology, Inselspital Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
K. Schindler, Dept. of Neurology, Inselspital Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
SSSSC 2019 Swiss Society for Sleep Research, Sleep Medicine and Chronobiology Poster Slow wave promotes sleep-dependent plasticity during stroke recovery 27.06.2019 Fribourg, Switzerland Facchin Laura;
Organization for Human Brain Mapping 2019 Poster Changes in Sleep slow wave activity as a potential correlate of hemispatial neglect amelioration 13.06.2019 Rom, Italy Eberhard-Moscicka Aleksandra;
Organization for Human Brain Mapping 2019 Poster Spatial asymmetries in free visual exploration and line bisection tasks - relationship and time-course 11.06.2019 Rom, Italy Eberhard-Moscicka Aleksandra;
European Congress of Clinical Neurophysiology Poster P50-S State dependent changes in cortical reactivity: Comparison between transcranial and intracranial stimulation 08.06.2019 Warschau, Poland Parmigiani Sara;
Chalfront Centre Seminar Series - Department of Clinical & Experimental Epilepsy Talk given at a conference Local Sleep in awake stroke patients 15.04.2019 London, Great Britain and Northern Ireland D'Ambrosio Sasha;
BENESCO Sleep Science Winterschool Poster Contralesional inhibitory theta burst simulation and its effect on visual neglect and sleep slow wave activity 04.03.2019 Wengen, Switzerland Eberhard-Moscicka Aleksandra;
BENESCO Winter Research Meeting Poster Slow wave promotes sleep-dependent pasticity during stroke recovery 03.03.2019 Wengen, Switzerland Facchin Laura;
The Day of BioMedical Research 2018 Poster The influence of inhibitory theta burst stimulation over the intact hemisphere on visual neglect and sleep parameters 07.11.2018 Bern, Switzerland Eberhard-Moscicka Aleksandra; Studer Kathrin;
24th Congress of the European Sleep Research Society (ESRS) 2018 Poster Cortical perturbation reveal local sleep-like down states in perilesional areas 28.09.2018 Basel, Switzerland D'Ambrosio Sasha;
Congress of the European Sleep Research Society (ESRS) Talk given at a conference What can we learn from sleep EEG changes during development for stroke recovery processes? 28.09.2018 Basel, Switzerland Huber Reto;
24th Congress of the European Sleep Research Society (ESRS) 2018 Talk given at a conference What can we learn from sleep EEG changes during development for stroke recovery processes 28.09.2018 Basel, Switzerland Huber Reto;
24th Congress of the European Sleep Research Society (ESRS) 2018 Talk given at a conference Perilesional induction of sleep slow waves improves motor recovery after ischemic stroke 28.09.2018 Basel, Switzerland Facchin Laura;
24th Congress of the European Sleep Research Society (ESRS) 2018 Talk given at a conference Thalamic control of slow waves onset and traveling 28.09.2018 Basel, Switzerland Adamantidis Antoine;
Neural Coding 2018 Poster Inferring the degree of causal interactions within physical systems from their surface dynamics 09.09.2018 Turin, Italy Cattani Anna;
CNS*2019 Talk given at a conference A modelling approach for describing stimulation and electrophysiological recordings of unconscious and conscious brain states” during the workshop: "Computational modelling of brain networks in Electroencephalography" 13.07.2018 Barcelona, Spain Cattani Anna;
11th FENS Forum of Neuroscience Poster Optogenetic control of sleep slow waves to improve recovery after ischemic stroke 07.07.2018 Berlin, Germany Facchin Laura;
Duke-NUS Medical School Individual talk Sleep and brain plasticity during development 01.07.2018 Singapur, Singapore Huber Reto;
Understanding consciousness – a scientific quest for the 21st centery Poster Inferring the degree of causal interactions within physical systems from their surface dynamics 22.06.2018 Barcelona, Spain Cattani Anna;
University of Oxford Cortex Club Individual talk Sleep and brain development. 01.05.2018 Oxford, Great Britain and Northern Ireland Huber Reto;
Gordon Research Conference „Sleep Regulation and Function" Talk given at a conference Sleep and its role in promoting brain development. Introduction as Discussion Leader 01.03.2018 Galveston, United States of America Huber Reto;
Neuronest, Università degli studi di Milano Poster Simultaneous hd-EEG and stereo-EEG recordings during intracerebral single pulse electrical stimulation: from macro to meso-scale 01.03.2018 Milan, Italy D'Ambrosio Sasha;
1st Sleep Science Winter School Poster Optogenetic Control Of Sleep Slow Waves To Improve Recovery After Ischemic Stroke 01.03.2018 Wengen, Switzerland Facchin Laura;
Annual Meeting of the Swiss Society for Neuroscience (SSN) Poster Optogenetic Modulation Of Sleep Slow Wave After Focal Ischemic Stroke 09.02.2018 Zurich, Switzerland Facchin Laura;
Le congrès du sommeil Talk given at a conference Rôle des ondes lentes en condition de perturbation (Slow waves from a perturbational perspective) 23.11.2017 Marseille, France Pigorini Andrea;
Clincial Neuroscience in Bern Talk given at a conference Optogenetic Modulation Of Sleep Slow Wave After Focal Ischemic Stroke 08.11.2017 Bern, Switzerland Facchin Laura;
Tag der Klinischen Forschung 2017 (DBMR) Poster Spatial asymmetries in free visual exploration and line bisection tasks – relationship and time-course 31.10.2017 Bern, Switzerland Eberhard-Moscicka Aleksandra;
Berner Schlaf-Wach Tage: 3. SYMPOSIUM ZENTRUM FÜR EXPERIMENTELLE NEUROLOGIE (ZEN) «10 YEARS OF OPTOGENETICS IN SLEEP RESEARCH» Talk given at a conference Optogenetic modulation of sleep slow wave during stroke recovery 27.10.2017 Bern, Switzerland Facchin Laura;
World Association Of Sleep Medicine Foundation Talk given at a conference Advanced analysis of sleep spindles: from healthy to damaged brains 11.10.2017 Prague, Czech Republic Mensen Armand;
Clinical Neuroscience Bern - Annual Meeting 2017 Poster Spatial asymmetries in free visual exploration and line bisection tasks - relationship and time-course 08.09.2017 Bern, Switzerland Eberhard-Moscicka Aleksandra;
Clinical Neuroscience Bern - Annual Meeting 2017 Talk given at a conference Optogenetic Modulation Of Sleep Slow Wave After Focal Ischemic Stroke 08.09.2017 Bern, Switzerland Facchin Laura;
5th Science Factory: TMS-EEG Workshop and Summer School Poster Cortical perturbations reveal local sleep-like down states in cortical perilesional areas 04.09.2017 Espoo, Finland D'Ambrosio Sasha;
CUTTINGEEG - 3rd Symposium on cutting-edge methods for EEG-research Poster Simultaneous hd-EEG and stereo-EEG recordings during intracerebral single pulse stimulation: mapping the Perturbational Complexity Index 19.06.2017 Glasgow, Great Britain and Northern Ireland Pigorini Andrea;
Neuroscience ZNZ Retreat Poster Recovering from stroke: What is the role of sleep? 19.05.2017 Zürich, Switzerland Heyse Natalie;
28th Symposium on Cerebral Blood Flow, Metabolism and Function and 13th Conference on quantification of Brain Function with PET Poster Optogenetic Manipulation of Sleep Slow Wave After Focal Ischemic Stroke 01.04.2017 Berlin, Germany Facchin Laura;
BENESCO Winter Research Meeting Poster Optogenetic Modulation Of Sleep Slow Wave After Focal Ischemic Stroke 09.03.2017 Wengen, Switzerland Facchin Laura;
Dutch National Sleep Congress Talk given at a conference Sleep and development of the brain. Keynote lecture. 01.03.2017 Ermelo, Netherlands Huber Reto;
Deutsche Gesellschaft für Schlafforschung und Schlafmedizin Individual talk Schlaf und Hirnentwicklung 01.02.2017 Regensburg, Germany Huber Reto;
Congress of the European Sleep Research Society Talk given at a conference Sleep and performance during development 01.10.2016 Bologna, Italy Huber Reto;
European Sleep Research Society Poster Optogenetic Manipulation of Sleep Slow Wave After Focal Ischemic Stroke 13.09.2016 Bologna, Italy Schöne Cornelia; Facchin Laura;
European Sleep Research Society Poster Optimizing detection and analysis of slow waves, spindles and saw-tooth waves in sleep EEG 13.09.2016 Bologna, Italy Mensen Armand;
International Child Neurology Congress Talk given at a conference The synaptic homeostasis hypothesis and ESES 01.08.2016 Amsterdam, Netherlands Huber Reto;
Biennial Meeting of the International Society for Developmental Neuroscience. Talk given at a conference Sleep evolution in childhood and brain development. Plenary lecture 01.04.2016 Antibes, France Huber Reto;


Self-organised

Title Date Place
Sleep and Wakefulness - A Dyadic Life 04.03.2019 Milano, Italy
Sleep and Wakefulness: a dyadic life 04.03.2019 Milano, Italy

Awards

Title Year
Poster Prize of the DBMR for the best clinical project 2018

Associated projects

Number Title Start Funding scheme
179443 Manipulating cortical synchronization by means of closed-loop acoustic stimulation during sleep - method optimization and proof of concept study in childhood epilepsy 01.03.2019 Project funding (Div. I-III)

Abstract

Major advances were made in stroke prevention and acute management. Conversely, recovery from stroke can be promoted only by neurorehabilitation. Animal and human data have shown that this occurs thank to neuroplasticity processes involving ipsi- and contralesional areas. Since sleep promotes learning and memory, and more generally neuroplasticity, we postulate that sleep-related mechanisms may modulate stroke recovery. Specifically, we hypothesize that perilesional slow waves -which reflect neuronal bistability (an alternation between depolarized ON and hyperpolarized OFF states)- may have a favorable function in the initial phase post-stroke promoting homeostatic adjustments of cortical excitability, while beeing detrimental in the chronic phase because disrupting intracortical information processing.In order to test these hypotheses, we designed a three-steps research strategy:1) observational approach: ipsi- and contralesional sleep-wake high density EEG changes will be assessed in rodents and human with hemispheric stroke from the acute to the chronic stage and correlated with functional outcome;2) perturbational approach: the reactivity and connectivity of the perilesional cortex -as measures of cortical bistability- will be assessed by transcranial magnetic stimulation (TMS) during functional recovery after stroke in humans; 3) interventional approach: manipulations of cortical bistability will be performed in mice (with optogenetics) and humans (with TMS) after stroke and assessed in terms of their effects on functional outcome.The multimodal and translational approach chosen for this proposal has never been used previously in this context. The methodological feasibility of the animal and clinical experiments and the ability to recruite stroke patients for clinical-neurophysiological projects were repeatedly proven in the past by the four research teams. The demonstration that sleep related processes may play a role in neuroplasticity and functional outcome after stroke and the understanding of the network and cellular mechanisms involved are expected to have major neuroscientific and clinical implications.
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