MSCA Doctoral Researcher, Neuro-Innovation: Neuroscience

Marie Skłodowska-Curie COFUND Doctoral Researcher, Neuro-Innovation: Neuroscience 

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 101034307.

PROPOSED TOPIC FOR PHD

Combination of electrophysiological recordings with functional MRI in rodent disease models in memory research

DOCTORAL PROGRAMME

Doctoral Programme in Molecular Medicine (DPMM)

THE PRIMARY SUPERVISOR AND CO-SUPERVISORS

Professor Heikki Tanila, A. I. Virtanen Institute (primary supervisor)
Professor Olli Gröhn, A. I. Virtanen Institute
Professor Ville Kolehmainen, Department of Applied Physics
Dr. Eeva Aromaa, School of Medicine, Biomedicine

HOST RESEARCH UNIT AND HOST RESEARCH TEAM AT THE UNIVERSITY OF EASTERN FINLAND (UEF)

A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences

The Neurobiology of Memory research group aims to unveil mechanisms of long-term memory encoding at the systems level and pathophysiological mechanisms that disrupt this ability in the most important memory disorder, Alzheimer’s disease. To this end we employ multiple modern neuroscience techniques. As a disease model we use transgenic mice carrying human APP and PSEN1 mutations combined with local gene transfer with viral vector microinjection. We assess the function of neural networks by multichannel electrophysiological recordings in freely moving mice and rats and by advanced functional MRI. At the behavioral level the memory function is assessed with standard memory tests. All functional data are correlated with careful histopathological examination of the brain.

The research profile of the Tanila lab

EXPECTED PROFILE OF THE PHD CANDIDATE

This research project needs the participation of people with passion for excellence in research, innovation, and impact. We look for candidates with a background in electrophysiology, in vivo imaging and/or signal analysis and who are open to multi/interdisciplinary approaches in research. The PhD candinate needs manual skills, basic understanding of the physics of electricity, and readiness to use and modify custom-made computer algorithms in Matlab or Python for the analysis of large data sets. In addition, good communication skills in English are necessary to enable team work in an international research environment and to search necessary information in user manuals and scientific literature. As far as soft skills are concerned, we welcome candidates with a proactive, collaborative attitude who are enthusiastic about working and sharing expertise in teams. Excellent candidates actively participate in various intersectoral activities offered by the PhD programme, and are willing to spend some time abroad with our international academic partners and outside the university at our non-academic partner institutions.

SCIENTIFIC RESEARCH AREAS RELATED TO THE TOPIC

Neurosciences, Applied Physics, Biomedical Engineering

DESCRIPTION OF THE NEURO-INNOVATION RESEARCH TOPIC

A long-term puzzle in human memory research is why damage to medial temporal lobe, especially the hippocampus, prevents a subject to remember recent events without disturbing old memories. The prevailing theory is that memories are transferred from the hippocampus to large-capacity storages of the neocortex during sleep. This requires a delicate synchrony of three separate brain oscillations. Recent evidence suggests that individuals with early Alzheimer’s disease or transgenic mice modeling the disease display silent epileptic spiking during sleep that can perturb this synchrony and thus prevent the memory transfer.

This project aims at visualizing the hippocampal – cortical network that normally activates during sleep at hippocampal ripple and theta oscillations and how it is affected by epileptic hippocampal spikes. This is done in the mouse by combining hippocampal electrophysiological recording and stimulation with functional magnetic resonance imaging (fMRI), and by using the electric signal as the trigger. Detection of fast event with fMRI applies novel zero-echo time pulse sequences with advanced fMRI image reconstruction, making project truly multidisciplinary. The project can result in a scientific breakthrough in basic memory research and provide new therapeutic targets and biomedical MRI applications that have commercial potential as diagnostic tools for Alzheimer’s disease and other memory disorders.

EXCELLENCE OF THE HOST RESEARCH TEAM

Publications related to the PhD topic:

Minkeviciene R, Rheims S, Dobszay MB, Zilberter M, Hartikainen J, Fülöp L, Penke B, Zilberter Y, Harkany T, Pitkänen A, Tanila H. Amyloid β-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci 29: 3453-62, 2009.

Gureviciene I, Ishchenko I, Ziyatdinova S, Jin N, Lipponen A, Gurevicius K, Tanila H. Characterization of epileptic spiking associated with brain amyloidosis in APP/PS1 mice. Frontiers in Neurology 2019; 10:1151.

Zhurakovskaya E, Ishchenko I, Gureviciene I, Aliev R, Gröhn O, Tanila H. Impaired hippocampal-cortical coupling but preserved local synchrony during sleep in APP/PS1 mice modeling Alzheimer’s disease. Sci Rep 2019; 9:5380.

Paasonen J, Laakso H, Pirttimäki T, Stenroos P, Salo RA, Zhurakovskaya E, Lehto LJ, Tanila H, Garwood M, Michaeli S, Idiyatullin D, Mangia S, Gröhn O. Multi-band SWIFT enables quiet and artefact-free EEG-fMRI and awake fMRI studies in rat. NeuroImage 2020; 206:116338.

Hanhela M, Gröhn O, Kettunen M, Niinimäki K, Vauhkonen M, Kolehmainen V. Data-driven regularization parameter selection in dynamic MRI. J Imaging 7:38, 2021.

Research projects related to the PhD topic:

Sleep-related epileptic spiking in early Alzheimer’s disease: Characterization, spatial distribution, inference with memory encoding and pharmacological treatment of epileptic spiking detecting in APP/PS1 mice modeling Alzheimer’s disease

Next-Generation fMRI with MB-SWIFT: Validation of a new functional MRI sequence allowing simultaneous artifact-free electrophysiological recordings in rodent disease models

MULTI/INTERDISCIPLINARY COLLABORATION

This PhD research topic covers complementary areas of knowledge in basic neuroscience, behavioral neuroscience, electrophysiology, bioelectrics and biomagnetism, biomedical imaging, data analysis (time series, pictorial matrices), communication and commecialization of science. The PhD project will be co-supervised by a team of three scientists with expertise in neurophysiology, biomecial imaging and computational physics.

To advance multi/interdisciplinary collaboration, three Summer Schools will be organised jointly by the Neuro-Innovation supervisors and non-academic partners. In these, multi/interdisciplinarity and intersectoral exchange will be implemented via hands-on interaction between PhD students, supervisors, partners and other stakeholders. The students will participate among other in the following interdisciplinary courses:

• Neuro-data Hackathon, 3 ECST credits. Open and big data
• Neuro-Innovation Living Lab, 3 ECST credits. Entrepreneurial processes and commercialisation paths

Virtual Platform for multi/interdisciplinary interaction will connect all PhD students in this programme.

INTERNATIONAL COLLABORATION

The academic partner organizations will collaborate closely with us in PhD training and students are strongly encouraged to include a secondment and visits with these partners in their studies. During shorter visits (1-4 weeks), the candidate will learn more about research and methods and build international networks. During secondments, he/she will work on a research project under the supervision of the co-supervisor from the hosting organisation and utilise their infrastructure.  The candidate can also attend courses, seminars, and other events in the host organisations.

The PhD student has the opportunity to visit the Center for Magnetic Resonance Research at the University of Minnesota, MN, USA for a period that is jointly agreed. This will enable the candidate to familiarize with state-of-the-art  methodologies in functional MRI and working in the world leading research environment for the development of MRI technology.

INTERSECTORAL COLLABORATION

The Societal Impact Board of this PhD programme with 14 intersectoral partners will collaborate closely with us in PhD training, for instance on the following activities:

• Neuro-Innovation Talent Hub: monthly gathering with special guests (e.g., researchers, professionals, business experts, stakeholders) and discussions about research topics and career prospects.
• Neuro-Innovation Boot Camp: yearly competition concerning the utilisation of research results.

There is a particularly close collaborative relationship planned with the Department of Clinical Diagnostics at the Kuopio University Hospital.

IMPACT

High quality research and publications of excellence are a way to solve societal problems and challenges. This vision is shared by the collaborating partners in this doctoral program, and involvement with various stakeholders will allow the pursuit of a goal with potential for brain health innovation. The objective of the proposed research is to advance our understanding on the key neural mechanisms at the system levels that lead to the most prominent disability of Alzheimer’s disease, the loss of memory for the recent events, and develop noninvasive brain imaging techniques for the early detection of these processes. When successful the project will result in new diagnostic tools for the early diagnosis of Alzheimer’s disease, which is the key to start medical or other therapeutic interventions before irreversible brain damage has taken place. These tools have also commercial potential especially in the form of software development for EEG or MRI applications.

INCLUSIVENESS AND EQUAL OPPORTUNITIES 

The UEF policy on gender equality and equal opportunities is based on Finnish legislation and the values of the university. The goal of gender equality and equal opportunities at the university is to identify and prevent expressions, structures and functions that maintain or increase inequality and to promote gender equality and equal opportunities at all levels. The university has a Gender Equality and Equal Opportunities Programme, which describes the measures intended to implement and promote gender equality and equal opportunities among staff and students. The university takes an active approach to promoting equal opportunities and acting against discrimination.

UNIVERSITY OF EASTERN FINLAND IN BRIEF

The University of Eastern Finland is one of the most multidisciplinary universities in Finland. We are home to 16,000 students and 2,750 staff members. Our research is ranked among the best in the world in several fields. We generate research-based knowledge and make it openly accessible for the benefit of all. UEF stands for action with impact that is relevant today and tomorrow. To learn more about our university please visit our website at  www.uef.fi/en.