Stroke survivors not only suffer from severe motor, speech and neurocognitive deficits, but in many cases also from a "lack of pleasure" and a reduced motivational level. Especially apathy and anhedonic symptoms can be linked to a dysfunction of the reward system. Rewards are considered as important co-factor for learning, so the question arises as to why and how this affects the rehabilitation of stroke patients. We investigated reward behaviour, learning ability and brain network connectivity in acute (3-7d) mild to moderate stroke patients (n = 28) and age-matched healthy controls (n = 26). Reward system activity was assessed using the Monetary Incentive Delay task (MID) during magnetoencephalography (MEG). Coherence analyses were used to demonstrate reward effects on brain functional network connectivity. The MID-task showed that stroke survivors had lower reward sensitivity and required greater monetary incentives to improve performance and showed deficits in learning improvement. MEG-analyses showed a reduced network connectivity in frontal and temporoparietal regions. All three effects (reduced reward sensitivity, reduced learning ability and altered cerebral connectivity) were found to be closely related and differed strongly from the healthy group. Our results reinforce the notion that acute stroke induces reward network dysfunction, leading to functional impairment of behavioural systems. These findings are representative of a general pattern in mild strokes and are independent of the specific lesion localisation. For stroke rehabilitation, these results represent an important point to identify the reduced learning capacity after stroke and to implement individualised recovery exercises accordingly.

Healthy aging is accompanied by multi-faceted changes. Especially within the brain, healthy aging exerts substantial impetus on core parts of cognitive and motivational networks. Rewards comprise basic needs, such as food, sleep, and social contact. Thus, a functionally intact reward system remains indispensable for elderly people to cope with everyday life and adapt to their changing environment. Research shows that reward system function is better preserved in the elderly than most cognitive functions. To investigate the compensatory mechanisms providing reward system stability in aging, we employed a well-established reward paradigm (Monetary Incentive Delay Task) in groups of young and old participants while undergoing EEG measurement. As a new approach, we applied EEG connectivity analyses to assess cortical reward-related network connectivity. At the behavioral level, our results confirm that the function of the reward system is preserved in old age. The mechanisms identified for maintaining reward system function in old age do not fit into previously described models of cognitive aging. Overall, older adults exhibit lower reward-related connectivity modulation, higher reliance on posterior and right-lateralized brain areas than younger adults, and connectivity modulation in the opposite direction than younger adults, with usually greater connectivity during non-reward compared to reward conditions. We believe that the reward system has unique compensatory mechanisms distinct from other cognitive functions, probably due to its etymologically very early origin. In summary, this study provides important new insights into cortical reward network connectivity in healthy aging.

Acute-onset neurodegenerative diseases in older patients are rare clinical cases, especially when the degeneration only affects specific regions of the nervous system. Several neurological disorders have been described in which the degeneration of brain parenchyma originates from and/or primarily affects the brain stem. Clinical diagnosis in these patients, however, is often complicated due to a poor understanding of these diseases and their underlying mechanisms. In this manuscript we report on a 73-year-old female who had experienced a sudden onset of complex neurological symptoms that progressively worsened over a period of 2 years. Original evaluation had suggested a MRI-negative stroke as underlying pathogenesis. The combination of patient’s medical history, clinical examination and exceptional pattern of brain stem degeneration presenting as “kissing swan sign” in MR imaging was strongly suggestive of acute onset of Alexander’s disease. This leukoencephalopathy is caused by GFAP (glial fibrilary acidic protein) gene mutations and may present with brain stem atrophy and stroke-like onset of symptoms in elderly individuals. However, a pathognomonic GFAP gene mutation could not be identified by Sanger sequencing. After an extended differential diagnosis and exclusion of other diseases, a definite diagnosis of the patient’s condition presently remains elusive. However, whole-exome sequencing performed from patient’s blood revealed 12 potentially disease-causative heterozygous variants, amongst which several have been associated with neurological disorders in vitro and in vivo – in particular the axon degeneration-related NMNAT2 gene.

There is a high prevalence of neuropsychiatric sequelae in post-COVID syndrome, most commonly chronic fatigue, the mechanisms of which remain poorly understood. As altered function of the reward system has been suggested as a causal factor, we aimed to distinguish whether reward processing or task-unspecific cognitive operations are impaired in post-COVID syndrome. Our cohort study included 24 patients diagnosed with post-COVID syndrome and 24 demographically matched healthy controls. Questionnaire assessment of neuropsychiatric symptoms and socio-demographic variables, the Monetary Incentive Delay Task during an fMRI scan, and pupillary measurements were performed. In addition to clinical neuropsychiatric symptoms, participants in the post-COVID group demonstrated significantly slower task performance compared to healthy controls, although the function of behavioral reward circuits appeared unimpaired. However, the influence of rewarding cues on post-COVID patients increased significantly over time during task performance, correlating with temporally delayed activation of the left frontal gyrus and increased activity in task-unspecific brain regions in post-COVID patients. Furthermore, slower reaction times on the task were associated with a lower pupil diameter and a higher pupillary unrest index. This study proposes that post-COVID syndrome is a process that may not affect reward processing, but leads to neural hypoarousal and temporally altered brain activity in frontal and task-unspecific brain regions.

Background/Objectives: Early and accurate prediction of stroke severity is crucial for optimizing guided therapeutic decisions and improving outcomes. This study investigates the predictive value of lesion size and functional connectivity for neurological deficits, assessed by the National Institutes of Health Stroke Scale (NIHSS score), in patients with acute or subacute subcortical ischemic stroke. Methods: Forty-four patients (mean age: 68.11 years, 23 male, and admission NIHSS score 4.30 points) underwent high-resolution anatomical and resting-state functional Magnetic Resonance Imaging (rs-fMRI) within seven days of stroke onset. Lesion size was volumetrically quantified, while functional connectivity within the motor, default mode, and frontoparietal networks was analyzed using seed-based correlation methods. Multiple linear regression and cross-validation were applied to develop predictive models for stroke severity. Results: Our results showed that lesion size explained 48% of the variance in NIHSS scores (R² = 0.48, cross-validated R² = 0.49). Functional connectivity metrics alone were less predictive but enhanced model performance when combined with lesion size (achieving an R² = 0.71, cross-validated R² = 0.73). Additionally, left hemisphere connectivity features were particularly informative, as models based on left-hemispheric connectivity outperformed those using right-hemispheric or bilateral predictors. This suggests that the inclusion of contralateral hemisphere data did not enhance, and in some configurations, slightly reduced, model performance—potentially due to lateralized functional organization and lesion distribution in our cohort. Conclusions: The findings highlight lesion size as a reliable early marker of stroke severity and underscore the complementary value of functional connectivity analysis. Integrating rs-fMRI into clinical stroke imaging protocols offers a potential approach for refining prognostic models. Future research efforts should prioritize establishing this approach in larger cohorts and analyzing additional biomarkers to improve predictive models, advancing personalized therapeutic strategies for stroke management.