Andreas A. Ioannides
Lab. For Human Brain Dynamics AAI Scientific Cultural Services Ltd Nicosia, Cyprus
Speech title: Contemplating a new (sleep staging) system describing brain activity without losing contact with the knowledge derived from the classical ways
Prof. Andreas A. Ioannides was born in Morphou, Cyprus. He studied Physics (1970-73) and completed his PhD, both at Surrey University UK (1973-76), continuing with research in nuclear Physics until 1988. Since 1986 he started research in cybernetics and biology that by 1989 narrowed its focus onto magnetoencephalography. The initial emphasis on basic theory and mathematical analysis techniques lead also to development of experimental protocols and dedicated hardware (freely donated to the community with some nowadays installed in MEG systems world-wide). Prof. Ioannides established and headed theoretical teams and set up functional neuroimaging laboratories in international centers of excellence in the UK (Open University; 1989 -98), Germany (Institute of Medicine, Research Center Juelich; 1994-8) and Japan (Brain Science Institute, RIKEN; 1998 – 2009). Fifteen PhD students and researchers who started their post-doc careers with Prof Ioannides are now leading scientist, some heading international centers of excellence in Europe, North America and Asia.
Prof. Ioannides returned to Cyprus in 2009 as the CEO of AAI Scientific Cultural Services Ltd (AAISCS) and Chief Scientist of AAISCS’s Laboratory for Human Brain Dynamics (LHBD-C). AAISCS is a private company that continues the basic neuroscience research of previous years with the additional goal of using the resulting knowledge to develop new services and products with cheaper and widely accessible technology. The company also provides support for experiments and data analysis in Electroencephalography and Magnetoencephalography. For much of the last decade Prof. Ioannides research emphasized three main areas of basic and applied research: the understanding of sleep processes and how these influence health, using the results of basic research to advance new non-invasive, non-pharmacological methods of intervention with strong emphasis on neurofeedback and the development of mass screening methods for identifying strengths and weaknesses of pupils in pre-school or in the first year of elementary school. The most recent work on sleep from LHBD-C focused on the first cycle of sleep and periods before Rapid Eye Movements (REM) sleep. These periods were found in animal experiments to be the periods with the highest density of ponto-geniculo-occipital (PGO) waves which have not yet conclusively identified in human and are periods difficult to fit into the classical sleep staging criteria. It was found that many of the related difficulties in classical sleep staging are easier to tackle with the introduction of a putative new sleep stage, REM0, characterized by high arousal and well-defined properties in the EEG and other auxiliary channels, particularly the heart rate variability (Ioannides, Orphanides and Liu, Current Research in Physiology, 2022).
ABSTRACT: “Contemplating a new (sleep staging) system describing brain activity, without losing contact with the knowledge derived from the classical ways".
Andreas A. Ioannides, Gregoris A. Orphanides and Lichan Liu
Laboratory for Human Brain Dynamics, AAI Scientific Cultural Services Ltd., Nicosia, Cyprus
Background: The introduction of formal criteria for sleep staging in the 1960s (Rechtschaffen and Kales, 1968) revolutionised the study of sleep. A massive volume of hypnograms (formal sleep records) has been amassed and is used routinely in sleep medicine and basic research.
The classical sleep staging criteria relied on visual inspection of the electroencephalography (EEG) record. Sleep experts identified high amplitude and/or highly rhythmic events that were defined as the hallmarks of each distinct sleep stages. Critically quiet periods between such events inherited the sleep stage label of the previous period. This collection of rules provided the first principled and reproducible characterisation of sleep. Nevertheless, viewed from today’s vantage view, the original sleep staging criteria were limited by the low quality of the EEG signal available over half a century ago. Today, these limitations are too obvious to ignore. Yet, recent changes in the criteria (Silber et al., 2007) do not address fundamental deficiencies, because their main goal is to improve the agreement amongst experts with practically no effort to exploit recent advances in sleep EEG and neuroimaging recordings and analysis. Next, we report our recent finding with the latest ones representing the collateral output of our search for human ponto-geniculate-occipital (PGO) waves guided by recent reports linking PGOs to heart rate (HR) surges (HRS) (Rowe et al., 1999)
Objective: Looking at the progression of our work retrospectively, we recognise both an element of serendipity from our ongoing hunt for human PGO waves. This has accelerated the almost inevitable eventual fall into the attractor of the lasting objective: to advance sleep staging in a principled way, based on sleep physiology, while preserving continuity with the rich earlier records obtained with traditional sleep staging criteria.
Methods and Results: The details of the work are already out (Ioannides et al., 2022b), which allows us to focus this short description on the distinct conceptual advances and the underlying logic of the findings. The distinct conceptual advances were:
The realization that at least some of, probably all, hallmarks of sleep stages do not have constant features or generators (at the time of the prominent EEG signal) and they do not represent brain wide reproducible excitation patterns. They are chaotic occurrences. They probably represent the rise to a chaotic and unstable period which on completion returns back to equilibrium (Dehghani et al., 2010; Frauscher et al., 2015; Ioannides et al., 2017, 2019). The only available candidates for such an equilibrium state are the quiet periods of the corresponding sleep stage.
The key conjecture is that the quiet periods are far from boring and uninteresting; they represent the foundational or “core” periods of each sleep stage. Therefore, studying the core periods could help us understand sleep, in a similar way, the study of the ground state of atoms helped us understand chemistry. In a move towards validating this conjecture, tomographic analysis was performed and already demonstrated that core periods have their own signatures that can:
o Distinguish as well, if not better the sleep stages defined by the hallmarks.
o Using core periods, it is possible to extend the characterisation into periods when sleep is disturbed and to describe transitions between sleep stages (Ioannides et al., 2022a).
o Reveal an orderly and monotonic increase in the gamma band activity in one frontal and one posterior midline dorsal areas: from awake to light and then deep sleep, culminating in a crescendo of activity during REM sleep (Ioannides et al., 2009). The identified dorsal midline areas were interpreted as the closest we are likely to come to a neural representation of self (Ioannides, 2018).
o For the hallmarks studied so far, the key precursors were identified by comparing the period before each hallmark with the core period of the sleep stage it defines. The analysis showed in each case that the chaotic periods are preceded by activity in specific brain areas, which are their putative generators.
The analysis of core periods of sleep stages has advanced our understanding of sleep, but did not remove the limitations of classical sleep stages. A detail analysis of the sleep stages and other auxiliary channels, particularly the electrocardiogram (ECG), revealed an anomaly in the classical sleep staging which showed most prominently during HRS. This anomaly could be removed by defining a new period of sleep, REM0, on the basis of simple criteria based on the variance of HR and the variance of one more electrophysiological measure (EEG, MEG or EMG) (Ioannides et al., 2022b).
Conclusions: For now, REM0 can be added, as an additional label, to the classical sleep stages to ensure continuity with the huge reservoir of hypnograms based on the classical sleep staging criteria. The association of REM0 with classical sleep staging, together with other suggestions (Simor et al., 2020) can also lead to a staged and orderly transition to a new sleep staging system if the claim of REM0 as a putative new sleep stage is validated.
Acknowledgements: Different parts of the research benefitted from work for European Space Agency (ESA, contract CY2_02 (4000127142) NEA2RS) and support from the European Regional Development Fund and the Republic of Cyprus (GRATOS EXCELLENCE/1216/0207 and CAVER COMPLEMENTARY/0916/0174). Mr. Matthew Fenech also contributed to this research under the EU Horizon project HOPE (grant number: 823958). Opinions expressed belong solely to the authors.
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Postdoctoral Researcher, Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace
Applications of neuropeptides and their receptors in neuroplasticity and neuroinflammation occurring in neurodegenerative diseases; current data. Cellular and molecular approach
Dr. Grigorios Kyriatzis is a Molecular Biologist-Geneticist and Neuroscientist. He has conducted research at Karolinska Institutet in Sweden and University of Bergen in Norway. His former research at the Institute of Neurophysiopathology in Marseille, France included the study of neuropeptide receptors in neuroinflammation and neuronal death following experimentally induced status epilepticus.
He is currently a postdoctoral researcher at the Laboratory of Pharmacology of the Department of Medicine, Democritus University of Thrace. His research focuses on neuroinflammatory processes and their impact on neurodegeneration, as well as drug target and biomarker discovery in CNS diseases via a machine learning-aided pipeline.
ABSTRACT: “Neuroplasticity, the flexibility & adaptability of the brain after inflammation".
Grigorios Kyriatzis, Invited Speech, Abstract
Neuroplasticity, the flexibility & adaptability of the brain after inflammation or injury at the central nervous system (CNS) or peripheral tissues, among others, occurs through changes in gene expression that involve neuroplastic changes (positive): synaptic long-term potentiation, reduced neuronal excitability, increased inhibition and neurogenesis (in neurodegenerative diseases). Valence, the positive or negative associative learning, that is paramount for survival, is an example of neuroplasticity mediated by synaptic plasticity onto divergent paths. In the CNS, these changes derive primarily from neuropeptides (or neuroactive peptides). Neurotensin (NT) is an endogenous neuropeptide, neurotransmitter and neuromodulator. It mediates both central and peripheral effects, among others analgesia, ethanol and addictive drug abuse, valence, and has been involved in a number of pathologies including stress/valence-related disorders. NT mediates its effects upon binding on 3 distinct receptor subtypes (NTSRs), NTSR1, NTSR2 and NTSR3. The NT system induces positive neuroplastic changes in various brain areas.
A negative form of neuroplasticity is neuroinflammation, that arises from dysregulation of activated glial cells and neuromodulators that they induce, that contribute to a variety of negative neuroplastic changes: synaptic dysregulations, enhanced neuronal excitability and reduced inhibition. We have recently shown that NTSR2 is highly expressed during neuroinflammation occurring post epilepsy and NTSR2 blockade reduces inflammation in glial cells in vitro. The strong inflammatory response is one of the main causes behind neurodegeneration that takes place in CNS diseases. The discovery of new drugs aiming at the constraint of neuroinflammation may prove to be a valuable treatment strategy.
Assistant professor in Multidisciplinary Design at the University of Twente
Speech title: The hand in Duchenne muscular dystrophy: enabling rehabilitation
My name is Kostas Nizamis (1988 Kavala, Greece) and I am an Assistant Professor in Multidisciplinary Design at the Design, Production, & Management (DPM) department at the University of Twente. I graduated as electrical and computer engineer (M.Eng) from the Democritus University of Thrace in Xanthi, Greece. After that, I acquired my degree in Biomedical Engineering (MSc.) at the University of Twente. Between November 2014 and February 2019, I performed my Ph.D. research in the department of Biomechanical Engineering, at the University of Twente, in Symbionics 1.3: Intention Amplifying in Hand Orthoses. In this project, we developed and tested a myocontrolled hand exoskeleton for people with Duchenne muscular dystrophy (https://www.youtube.com/watch?v=jpHjlFM0t3Y).
My current research interests involve the application of multidisciplinary design approaches and Systems Engineering tools and methods in developing and validating rehabilitation technologies to address high-impact societal problems.
I am currently serving as the vice-chairman of the Optimus Association (https://www.utwente.nl/en/et/dpm/optimus/) of the DPM department of the University of Twente. Additionally, I am the Director of Transfer for the Non-Profit Organization Authentia.
ABSTRACT: “The hand in Duchenne muscular dystrophy: enabling rehabilitation".
Kostas Nizamis, Invited Speech, Abstract
The hand is a very complex and versatile tool, which allows humans to interact with their immediate environment, engage in daily life activities and socialize. Individuals with Duchenne muscular dystrophy (DMD), experience years of deteriorated hand function, leading to severe dependence on caregivers. Robotic exoskeletons can provide a feasible solution for the active hand support of individuals with DMD. My work describes the development of a hand exoskeleton that meets the specific needs of individuals with DMD, in order to raise their quality of life and social participation and acceptance.
To this end, in the Symbionics project we developed the SymbiHand orthosis; an active wearable hand exoskeleton for people with DMD. My role in this project was the characterization of the hand neuro-motor function in DMD and the development and application of robust hand motor intention decoding, for the control of the SymbiHand.
Director of the Brain Simulation Section at Charité Universitätsmedizin Berlin
Speech title: Virtual Brain Cloud: Enabling Complex Simulations with Multilevel Health Data
Petra Ritter heads the Brain Simulation Section at the Charité University Medicine Berlin and Berlin Institute of Health. Her research focus is on integrating neuroimaging and computational neuroscience to discover mechanisms of brain function and dysfunction.
She serves in the leadership of large EU projects such as Virtual Brain Cloud & eBRAIN-Health and is directing EBRAINS Health Data Cloud. Petra Ritter studied medicine at the Charite where she later had been appointed a Johanna Quandt lifetime Professorship for Brain Simulation.
Since 2017, she is Director of the Brain Simulation Section at Charité Universitätsmedizin Berlin
ABSTRACT: “Virtual Brain Cloud: Enabling Complex Simulations with Multilevel Health Data".
Petra Ritter, Invited Speech, Abstract
Virtual Brain Cloud generates multilevel virtual brains of patients and healthy human controls for research and innovation. Brain data from multiple sources are being pre-processed and annotated with a common data model – such that they all relate to common spatial reference frameworks. The platform thus offers a next generation clinical research infrastructure – compliant with EU Data Protection Regulations and creates an open yet protected space for groundbreaking digital health innovation.