Assessing the causal role of MRS- and EEG-based Excitation/Inhibition (im-)balance in MS-related fatigue and fatigability as well as in healthy individuals

• Applicant: Dr. Stefanie Linnhoff
• Subject Area: Human Cognitive and Systems Neuroscience ; Biological Psychology and Cognitive Neuroscience ; Cognitive, Systems and Behavioural Neurobiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 539530253

Fatigue is a common and debilitating symptom among individuals with neurological disorders, particularly multiple sclerosis (MS). It significantly reduces their quality of life and often leads to early retirement, with significant socioeconomic implications. Despite extensive research, the exact underlying mechanisms of MS-related fatigue remain unclear, primarily due to its subjective nature. To better understand and treat fatigue in MS, researchers have proposed an objective assessment of its impact on daily performance alongside subjective perception. This approach involves differentiating between subjective and objective fatigue-related changes during prolonged activity, termed "fatigability". Researchers have identified various markers, including reaction time variability and electrophysiological markers, to objectively measure fatigue. While these markers have shown promise in investigating fatigability-related changes, more research is needed to develop precise and easily measurable parameters to diagnose, understand, and differentiate MS-associated fatigue fully. Such parameters could lead to targeted, individualized treatment strategies and improve the overall management of MS-related fatigue.The planned project aims to establish the excitation/inhibition (im-)balance as an objective parameter for fatigue in MS and explore the interplay between neurochemical concentrations as well as electrophysiological alterations and fatigue manifestation. In WP-1, I aim to investigate GABA to glutamate concentrations by means of MRS as well as the excitation/inhibition ratio by means of EEG in the prefrontal cortex and their relationship to fatigue and fatigability. The paramters will be assessed before and after an exhaustive cognitive task to gain insight into the neurophysiological and neurochemical changes that occur as a result of fatigue/fatigability in different groups. Comparisons will be made between individuals with MS with and without fatigue and a healthy control group. In WP-2, I aim to investigate causal relationships for the crucial role of the E/I balance in fatigue. For this purpose, I plan to investigate the effects of repetitive transcranial direct current stimulations (tDCS) on fatigue-related dysfunctional brain activation patterns and thus on subjective and objective fatigue symptomatology in individuals with MS and fatigue. The proposed research project represents a systematic investigation of the excitation/inhibition (im-)balance in MS-related fatigue. It will provide a more comprehensive understanding of the neurophysiological and neurochemical pathomechanisms in fatigue. Based on this knowledge, causal clinical interventions can be derived and individualized in the future.

• DFG Programme: Research Grants