Applied Neuroscience – Irena Rektorová

• Multimodal brain MRI: search for early diagnostic and prognostic markers of neurodegeneration (human and animal studies)
• Central and peripheral pain research
• Non-invasive brain stimulation and other noninvasive interventional methods and their use in multimodal approach (MRI, EEG) to study cognitive, behavioral and affective functions in behavioral neurology and psychiatry

• Identify early diagnostic and prognostic biomarkers of neurodegenerative diseases
• Understand and control central and peripheral pain
• Use multimodal approach: MRI / EEG combination and non-invasive brain stimulation (rTMS, tDCS) to modulate cognition and behavior in patients with neurodegenerative and psychiatric diseases

The main objective of the research is the study of early imaging, biochemical and genetic markers of brain neurodegenerative diseases (from the animal model to human studies), pathophysiological mechanisms for neuropathic pain and cognitive and behavioral symptoms of Parkinson's disease, Alzheimer's disease and schizophrenia. In particular, we use multimodal imaging of the brain and spinal cord alone or in combination with non-invasive brain stimulation, such as repetitive transcranial magnetic stimulation (rTMS). The research focus is reflected in the following ongoing and recently completed projects.

Projects
Novel, Individualized Brain Stimulation, Network-based Approaches to Improve Cognition (NiBS-iCog) (GF21-13462L), Czech Science Foundation, 2021-2023

Impaired working memory (WM) plays a crucial role in normal aging, in mild cognitive impairment (MCI) and cognitive decline associated with dementia, such as Alzheimer's disease (AD). The aging-related differences in WM are hypothesized to be derived from various neurobiological roots, from which the alterations in the dynamic interplay between the large-scale brain networks have proven an important role. Recent studies have shown that cerebellar stimulation could further modulate the parts of large-scale brain networks. Non-invasive brain stimulation (NIBS) methods are capable of modulation of brain plasticity and activity. We hypothesize that we will be able to identify a multifocal NIBS protocol that can improve working memory. By successive and concurrent stimulation of multiple brain regions by transcranial alternating current stimulation (tACS) and/or repetitive transcranial magnetic stimulation (rTMS) we will study dynamic interaction between distinct cortico-cortical and subcortico-cortical brain areas. By leveraging the mechanistic aspects derived from multifocal stimulation, we aim to develop a novel closed-loop procedure utilizing EEG and tACS that would inject current based on the 'online' status of the fronto-parietal domain general nodes in healthy seniors and MCI-AD patients. The project is in coordination with swiss research team led by prof. Friedhelm Christoph Hummel at the Ecole Polytechnique Fédérale de Lausanne.

Novel Network-Based Approaches for Study of Cognitive Dysfunction in Behavioral Neurology (CoBeN) (734718), EU Horizon 2020, 2017-2021

Within this project, neural networks and brain architecture related to the motor component of speech, reading, writing and visual processing of information are examined. The study includes patients with Alzheimer's disease, Parkinson's disease and healthy controls who undergo several cognitive examination, speech and brain examinations using MR and fMRI. We will also record the production of their speech and production of written expression. In cooperation with the University of Szeged in Hungary and the University of Arizona in the United States, using methods of behavioral neurology and magnetic resonance, brain activity is investigated in connection with speech and cognitive functions in different cultures and manifestations of diseases in people speaking different languages.

Parkinson Disease with Mild cognition Impairment treated with Nicotinic agonist Drug (PD-MIND) (820880), EU Horizon 2020, 2018-2022

The needs of patients with Parkinson’s disease (PD) vary following symptom diversity. There is an unmet clinical need to treat PD with mild cognitive impairment (PD-MCI). Epidemiological and clinical studies have shown that nicotinic receptors are involved in PD and cognition. A recent clinical trial suggested that selective α7 nicotinic receptor agonist improved cognition in patients with PD. The goal of the EU-funded PD-MIND consortium is to test the Astrazeneca nicotinic α7 agonist AZD0328 in a randomised, placebo-controlled, international study on cognition in people diagnosed with PD-MCI. The consortium consists of world-leading PD-MCI experts, and engagement of the public and patient representatives will guarantee integration of end-user perspectives in the project's design and execution.

Implication of cognitive reserve in non-pharmacological intervention outcomes (StimCORE) (NU21-04-00652), Ministry of Health, 2021-2024

Diagnostics of Lewy body diseases in prodromal stage based on multimodal data analysis (NU20-04-00294), Ministry of Health, 2020-2023

Lewy body diseases (LBDs) is a term describing a group of neurodegenerative disorders (i.e. dementia with Lewy bodies and Parkinson’s disease) characterized by pathophysiological process of alfa-synuclein accumulation in specific brain regions leading to the formation of Lewy bodies inside neurons and resulting in cell death. LBDs are progressing slowly and are usually diagnosed when the neurodegenerative process has reached severe degree in which most of the targeted neurons have already been damaged. Identification of LBDs at an early stage is crucial for development of disease-modifying treatment since the neurodegeneration may be possibly stopped or treated at the onset. In the frame of this project we are going to employ a complex multimodal analysis in order to identify prodromal biomarkers of LBDs and describe underlying pathophysiological processes. Consequently, this knowledge will be used to introduce a new machine-learning based decision support system that will help to assess, diagnose and monitor LBDs. 

The effect of transcranial direct current stimulation on visual attention in mild cognitive impairment – a combined MRI and non-invasive brain stimulation study (NV18-04-00256), Ministry of Health - Health research agency, 2018-2021

Alzheimer’s disease (AD) is the most common neurodegenerative disease. It progressively causes the breakdown of cognitive functions and impairs quality of life for patients and their caregivers. In addition to memory impairment, visual attention is also compromised, even at the stage of mild cognitive impairment due to AD (MCI-AD). No treatment has been found for MCI-AD; therefore, attention has been drawn to non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), in order to enhance cognitive functions by modifying brain plasticity. In the current research, we aim to: 1. identify an optimal tDCS protocol for enhancing visual attention in MCI-AD ; 2. examine the long-term effects of the optimal multiple-session tDCS protocol in MCI-AD on visual attention including the transfer to an ecologically valid virtual environment and identify the neural underpinnings of tDCS-induced behavioral aftereffects using a combined tDCS/ MRI network-based approach.

The use of advanced magnetic resonance imaging techniques to detect pathophysiology and to improve diagnostics and practical management of degenerative compression of the cervical spinal cord (NV18-04-00159), Ministry of Health - Health research agency, 2018-2021

Degenerative cervical myelopathy (DCM) is caused by compression due to cervical canal stenosis. The relative resilience of the spinal cord tissue to the mechanical compression leads to non-myelopathic degenerative cervical cord compression (NMDCCC). Routine MRI techniques could detect spinal cord compression, but not to distinguish DCM and NMDCCC. Advanced MR techniques, such as diffusion MRI and magnetic resonance spectroscopy, provide unique tools for assessing subtle changes in spinal cord microstructure and biochemical composition, respectively, but are prone to technical challenges due to small size and position of the spinal cord. The utilization of advanced 3T scanner along with novel MRI/MRS techniques in a cohort of 50 NMDCC, 50 DCM and 50 healthy individuals will increase the sensitivity for detection of spinal cord changes and will establish sensitive markers of spinal cord tissue alteration with potential to distinguish NMDCC and DCM subjects. MRI outcomes will be related to severity of compression and clinical measures to establish their relevance in surgical planning.

Non-coding RNAs in neurogenic and neuropathic pain mechanisms and their application for risk assessment, patient stratification and personalized pain medicine (602133), FP7 - Cooperation - Health, 2013-2017

Neuroimmune changes in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs (ncRNAs) regulate both immune and neuronal processes. Therefore, the ncRNAPain project comes with the idea that ncRNAs are key master switches for chronic pain. ncRNAPain is a multidisciplinary consortium of clinical partners, molecular and system neuroscientists, bioinformatics and ncRNA experts. The ncRNAPain project focuses on the role of ncRNA specifically in neurogenic and neuropathic pain, including headaches, to elucidate the mechanism of chronic pain.

Effect of Intensive Dance-Movement Intervention on Cognitive Functions and Changes in Brain Plasticity of Seniors and Patients with Moderate Cognitive Disorder (15-33854A), Ministry of Health - Health Research Agency, 2015-2018

Alzheimer's disease (AD) is the leading cause of dementia in seniors. Pharmacological treatment modifying the course of the disease is not available and therefore more attention is paid to non-pharmacological approaches. The main objective of the project is to create a structured dance-motion program for healthy seniors (HS) and patients with mild cognitive impairment in AD (MCI) and evaluate its effect on changes in brain structure and function in these individuals. This 44-month randomized controlled trial will be performed on 120 subjects: 60 HS and 60 patients with MCI. Half of each group undergoes a six-month dance-motion intervention (50 exercise units in 60 minutes using dance choreography); the other half will form a control group. All participants will be evaluated at the beginning of the study and after 6 months using the advanced multimodal MRI protocol and resonance spectroscopy (MRS) and detailed standardized cognitive examination. The results of the project will deepen our knowledge and understanding of dance-movement intervention and its impact on HS and patients with MCI.

Effect of Non-Invasive Brain Stimulation on Hypokine Dysarthria, Micrograph and Brain Plasticity in Parkinson's Disease Patients (16-30805A), Ministry of Health - Health Research Agency, 2016-2019

The project deals with the effect of repetitive transcranial magnetic stimulation (rTMS) on hypokinetic dysarthria (HD) and micrography in patients with Parkinson's disease. In the first phase of the project we investigate the short-term effect of low-frequency and high-frequency rTMS applied to pre-defined regions of the brain. The goal is to identify the rTMS protocol and the stimulated area that will have the optimal positive effect on HD and micrography. Another objective of this study is to identify neuronal correlates of this positive effect. The effect is then detected based on writing, audio, and fMRI data analysis obtained before and after rTMS. Based on these pilot results, a re-run of rTMS will be proposed in the second phase, and will be investigated for its long-term effect on HD and for a change in brain structure and function. The results of the project will help identify the therapeutic potential of rTMS and also allow a better understanding of the long-term effect of rTMS on the internal mechanisms of the brain.

Influence of cognitive functions and brain connectivity by non-invasive brain stimulation in patients with mild cognitive impairment in Alzheimer's disease (16-31868A), Ministry of Health - Health research agency, 2016-2019

The research project aims to affect brain plasticity and improve cognitive function by using non-invasive brain stimulation (NIBS) in healthy young people, healthy seniors and those with mild cognitive disorder in Alzheimer's disease. The project is testing various new locations of stimulation, cognitive tasks and stimulus parameters, and stimulate protocols for specific groups entities. A study protocol that combines functional MRI (fMRI) - a repetitive transcranial magnetic stimulation (rTMS) - fMRI, will allow us to study the influence of age, disease and genetic risk factor (ApoE4) to change cognition and cerebral connectivity / activity induced by rTMS. The results of the study will make it easier to understand the healthy and pathological aging of the brain and bring new knowledge of the benefits of NIBS for specific groups of subjects. The results will have a significant practical impact on future non-pharmacological treatment strategies.

Identification of MRI based imaging biomarker in early detection of neuronal changes in animal models of Parkinson's disease (4SGA8588), South Moravian Region - SoMoPro, 2015-2016

The current diagnostic modalities of Parkinson's disease (PN) are limited by identifying the presence of PN based on motor symptoms; at that time, however, over 60 percent of all dopamine neurons in specific areas of the basal ganglia may be lost. The aim of this project is to create a biomarker based on magnetic resonance imaging (MRI) for early detection of alpha-synuclein accumulation indicating neuronal changes. Using the innovative neuro-imaging approach of a transgenic mouse model superfluously generating human alpha-synuclein under Thy1-promoter ((Thy1-aSyn) and rotenontoxic model PN, which according to present knowledge are suitable for detection of early prodromal PN phases, we evaluate microstructural changes using the imaging method diffusion tensors (DTI), and differences in functional connectivity by functional MRI (fMRI), this project is unique in that the DTI / fMRI results will be compared to each other (multimodal imaging and data analysis) and correlated with behavioral and neurochemical studies. On rotenone model the neuroprotective drug of minocycline is tested. We expect the results of this project to provide non-invasive, non-radioactive and cost-effective diagnosis of pre-motor phase PN and will have several concrete benefits: 1) the possibility of identifying "risk" subjects 2) disease progression monitoring to help evaluate the effect of therapy that may modify the course of the disease 3) understand the pathophysiology behind the development of PN.

Pre-clinical genotype-phenotype predictors of Alzheimer's disease and other dementia (237250), EU Joint Program - Neurodegenerative Disease Research (JPND), 2014-2016

The aim of the project is to identify the activity of neurodegenerative diseases much earlier and to distinguish the initial disease mechanisms causing the disease. The project uses new techniques to analyze genes that identify genetic (pre-morbid) risk factors. This information will be associated with early clinical markers of disease obtained from new advanced imaging techniques (PET and MRI) and neurochemistry. The significance of this risk prediction will be evaluated in longitudinal clinical trials in the participating countries.

Alignment and Standardization of Neuroimaging Methods in Atypical Parkinsonism, including Tauopathies, EU Joint Program - Neurodegenerative Disease Research (JPND), 2016-2017

The term Atypical Parkinsonism (AP) is used for neurodegenerative disorders that share several clinical features with Parkinson's disease, but have a different underlying pathology. In general, these disorders also progress much more quickly and response to symptomatic treatment is lower. Today, the development of therapies targeting the underlying pathological substrate of AP (e.g. tau protein aggregation) sparks hope for a significant improvement in treatment options. However,  further  clinical  testing  is  difficult  because  symptom-based  clinical  testing  provides  neither  accurate  early  diagnosis nor sensitive and objective markers of disease progression. Here, neuroimaging methods have shown great potential, but a broad consensus on technical standards for multi-centre studies is lacking. Moreover, exciting new imaging methods are at hand, such as tau ligands  for  PET  and  ultra-high-field MRI, which  have  unprecedented potential  to  provide early  diagnostic  markers  as well  as  very sensitive progression markers. These outcomes will help pave the way for the integration of neuroimaging in large and longitudinal multi-centre studies in AP, including therapeutic trials.