Cognitive fatigue is one of the most frequent symptoms in multiple sclerosis (MS), associated with significant impairment in daily functioning and quality of life. Despite its clinical significance, progress in understanding and treating fatigue is still limited. This limitation is already caused by an inconsistent and heterogeneous terminology and assessment of fatigue. In this review, we integrate previous literature on fatigue and propose a unified schema aiming to clarify the fatigue taxonomy. With special focus on cognitive fatigue, we survey the significance of objective behavioral and electrophysiological fatigue parameters and discuss the controversial literature on the relationship between subjective and objective fatigue assessment. As MS-related cognitive fatigue drastically affects quality of life, the development of efficient therapeutic approaches for overcoming cognitive fatigue is of high clinical relevance. In this regard, the reliable and valid assessment of the individual fatigue level by objective parameters is essential for systematic treatment evaluation and optimization. Transcranial electrical stimulation (tES) may offer a unique opportunity to manipulate maladaptive neural activity underlying MS fatigue. Therefore, we discuss evidence for the therapeutic potential of tES on cognitive fatigue in people with MS.

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Following an acute COVID-19 infection, a large number of patients experience persisting symptoms for more than four weeks, a condition now classified as Long-COVID syndrome. Interestingly, the likelihood and severity of Long-COVID symptoms do not appear to be related to the severity of the acute COVID-19 infection. Fatigue is amongst the most common and debilitating symptoms of Long-COVID. Other symptomes include dyspnoea, chest pain, olfactory disturbances, and brain fog. Fatigue is also frequently reported in many other neurological diseases, affecting a broad range of everyday activities. However, despite its clinical significance, limited progress has been made in understanding its causes and developing effective treatment options. Non-invasive brain stimulation (NIBS) methods offer the unique opportunity to modulate fatigue-related maladaptive neuronal activity. Recent data show promising results of NIBS applications over frontoparietal regions to reduce fatigue symptoms. In this current paper, we review recent data on Long-COVID and Long-COVID-related fatigue (LCOF), with a special focus on cognitive fatigue. We further present widely used NIBS methods, such as transcranial direct current stimulation, transcranial alternating current stimulation, and transcutaneous vagus nerve stimulation and propose their use as possible therapeutic strategies to alleviate individual pathomechanisms of LCOF. Since NIBS methods are safe and well-tolerated, they have the potential to enhance the quality of life in a broad group of patients.

Foveal vision loss has been shown to reduce efficient visual search guidance due to contextual cueing by incidentally learned contexts. However, previous studies used artificial (T- among L-shape) search paradigms that prevent the memorization of a target in a semantically meaningful scene. Here, we investigated contextual cueing in real-life scenes that allow explicit memory of target locations in semantically rich scenes. In contrast to the contextual cueing deficits in artificial scenes, contextual cueing in patients with age-related macular degeneration (AMD) did not differ from age-matched normal-sighted controls. We discuss this in the context of visuospatial working-memory demands for which both eye movement control in the presence of central vision loss and memory-guided search may compete. Memory-guided search in semantically rich scenes may depend less on visuospatial working memory than search in abstract displays, potentially explaining intact contextual cueing in the former but not the latter. In a practical sense, our findings may indicate that patients with AMD are less deficient than expected after previous lab experiments. This shows the usefulness of realistic stimuli in experimental clinical research.

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