Physiological mechanisms of neurological disorders and diseases

Physiological mechanisms of neurological disorders and diseases

ARRS P3-0338, in progress (1.1.2020 - 31.12.2025), PI Simon Podnar

Status: In progress
Primary investigator: dr. Simon Podnar, IKN, UKC-LJ
Duration: 1.1.2020 - 31.12.2025
Basic information on Sicris.

The seat of the research project is at Institute for clinical neurophysiology at University clinical centre Ljubljana. MBLab heads the activities related to section "Foundations of cognition in health and disease".


The research programme »Physiological mechanisms of neurological disorders and diseases« consists of four parts.

In the first part »Pathophysiology and diagnosis of peripheral nerve and skeletal muscle disorders« we will apply a combination of clinical, electrophysiological (EMG) and ultrasonographic (US) methods to study peripheral neuropathies, motor neuron diseases and sacral nerve disorders. Using combination of these methods, we expect to improve determination of the site and etiology of peripheral nerve lesions, which is essential in decisions about the type of treatment. We intend to use a combination of EMG and US also in studies of polyneuropathies and myopathies, where we expect that systematic assessment of patients will enable us to define specific EMG and US patterns useful in diagnostics and therapy.

In the second part »Pathophysiology and diagnostics of sleep and breathing disorders« we will assess the effect of upper and lower motor neuron lesion on breathing disorders in patients with neuromuscular diseases. We will try to identify the mechanism by which sleep apneas lead to damage of the white brain matter. We will also study the pathophysiology of breathing disorders in patients with ischemic stroke in medulla. Our objective is to evaluate breathing disorders occurrence in these patients and to assess effectiveness of using polysomnography during sleep to identify patients at risk. Breathing disorders in these patients are often subclinical and are shown as changed breathing patterns during sleep, whereas unidentified can lead to respiratory failure.

Within »Foundations of cognition in health and disease« the research will be focused on further study of core questions in the areas of working memory, cognitive control and integrated brain function. Particular attention will be paid to individual differences, first, in the effort to integrate the seemingly conflicting findings on mechanisms of information maintenance in working memory, second, to understand the core mechanisms of cognitive control, and third to understand the variability in mechanisms underlying psychopathology and cognitive dysfunction as a basis for the development of efficient personalized therapies. Research will be supported with the development of novel research methods and advanced integration of multimodal neuroimaging data.

Within »Biomarkers of motor neuron diseases« we will investigate amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). These are neurological conditions where motor neuron degeneration causes movement and breathing dysfunctions. Pathophysiological mechanisms are not fully understood. With the help of better knowledge of different biomarkers of these diseases, we can expect progress in the field of diagnostics and treatment. In ALS and SMA patients, we will study various biological markers (biochemical, genetic, neuroimaging, and electrophysiological) and seek a link to the clinical aspects of the disease (functional disability, survival, impact of treatment).