[Telemedicine Care of Dementia Patients During the COVID-19 Pandemic]. / Telemedizinische Betreuung von Demenzerkrankten in der COVID-19 Pandemie.

In our multidisciplinary memory center at Jena University Hospital, we initiated a regular video consultation for patients at risk of developing dementia or with dementia disease and their relatives at the beginning of the SARS-CoV2 pandemic in spring 2020.Over a 12-month period, we conducted a systematic survey of satisfaction among patients in regular face-to-face contact (F2F) and video consultations (VC).The aim of this study was to evaluate the potential use of telemedicine in older people with incipient cognitive deficits in the context of dementia. In particular, we aimed to evaluate patient satisfaction and feasibility.Initial presentations to our memory center for suspected dementia were evaluated in a standardized regular on-site setting (n=50) and in a standardized video consultation (n=40). In both settings, a neuropsychologist's and a physician's consultation were performed consecutively. Both groups were similarly distributed in terms of age and sex (71.4 vs. 72.3 years, 52 vs. 50% female (F2F vs. VC)). Cognitive status was slightly better in the VC group (ACE III significant, MMST not significant).In the survey of the patients using a 12-question inventory (patient satisfaction, rated 1 to 5), there was no significant difference between the two groups overall. However, the F2F tended to be rated slightly better here in terms of advice. More than 80% of the physicians and neuropsychologists rated the technical process of VC as good/very good.A general assessment of the cognitive deficits by physicians and neuropsychologists correlated extremely highly with the results of the subsequent specific testing (MMST and ACE) in F2F and VC. With a tendency to better agreement in VC, the difference between the correlations was not significant.Overall, we could not find any significant differences in patients' satisfaction between VC and classical F2F presentation. Technical aspects in the preparation of a VC and during a VC were less problematic than initially anticipated.

The importance of different learning stages for motor sequence learning after stroke.

The task of learning predefined sequences of interrelated motor actions is of everyday importance and has also strong clinical importance for regaining motor function after brain lesions. A solid understanding of sequence learning in stroke patients can help clinicians to optimize and individualize rehabilitation strategies. Moreover, to investigate the impact of a focal lesion on the ability to successfully perform motor sequence learning can enhance our comprehension of the underlying physiological principles of motor sequence learning. In this article, we will first provide an overview of current concepts related to motor sequence learning in healthy subjects with focus on the involved brain areas and their assumed functions according to the temporal stage model. Subsequently, we will consider the question of what we can learn from studies investigating motor sequence learning in stroke patients. We will first focus on the implications of lesion location. Then, we will analyze whether distinct lesion locations affect specific learning stages. Finally, we will discuss the implications for clinical rehabilitation and suggest directions for further research.

The Effect of Endovascular Thrombectomy Studies on the Decision to Transfer Patients in a Telestroke Network.

Background/Introduction: In 2015, five high-quality trials demonstrated the effectiveness of endovascular thrombectomy for certain patients. Patient selection for transfer to a hub hospital is mostly focused on the patient's eligibility for a potential thrombectomy. However, it remains challenging to correctly select those patients with the highest probability of undergoing a thrombectomy. Materials and Methods: In this study, we investigated which factors promote or impede the transfer of patients and whether the impact of these factors has changed since the publication of the five randomized thrombectomy studies in 2015. We analyzed 12,048 cases of telestroke consultation from the stroke telemedicine network in Thuringia (SATELIT) and compared the decision-making process related to patient transfer based on consultations that occurred before and after 2015. Results: In both time intervals, we found that the patient's age and the identification of a proximal vessel occlusion independently influenced the decision to transfer a patient. The age factor remained unchanged over time. A known proximal intracranial vessel occlusion had a strong positive influence on the decision to transfer patients. Discussion: The decision of whether to transfer a patient is currently focused on the identification of intracranial vessel occlusion. However, the age of the patient remains an unchanged but important factor that might be overemphasized. The time elapsed from symptom onset to consultation was not found to have an independent influence on the decision-making process, so it might be underemphasized. Conclusions: The decision-making process to transfer a patient within our telestroke network has been strongly affected by the publication of the endovascular thrombectomy studies, but those studies are not solely optimized for this aim.

Knowledge, Motivation and Sustainability: Divergent Effects of a Staff Training Program on Residents and Specialists in Acute Stroke Care.

BACKGROUND: To improve the clinical efficiency of acute stroke management, we implemented a new staff training intervention. The training consisted of a case-based discussion of recent thrombolysis cases with the entire neurologic staff for 1 year. Here, we sought to determine whether the effects of this training were sustained after the discontinuation of the intervention. METHODS: All thrombolysis cases prior to the intervention (2015, 2016), during the time of training (2017) and after the discontinuation of the training (2018) were recorded and compared. The primary outcome parameter was door-to-needle time. RESULTS: Door-to-needle time decreased from 37 minutes in the preintervention period to 28 minutes during the intervention period (P < .001). After the discontinuation of training, there was a nonsignificant trend toward an increase in door-to-needle time (31 minutes). Performance remained unchanged for residents (<6 years of neurologic training; 30.8-31.2 minutes), while the performance of specialists (>6 years of neurologic training) significantly decreased (from 25.4 minutes during the intervention to 31.7 minutes after discontinuation, P = .047). By using regression analysis to control for multiple confounding factors, we found a significant association between the intervention and an improved patient outcome (P = .008). CONCLUSIONS: The present results demonstrate improved treatment of stroke patients by a regular case-based discussion of recent thrombolysis cases. After discontinuation, the effects were sustained for the residents but not for the specialists. The results suggest that improved knowledge in residents is the main reason for better performance, while the performance of specialists was more affected by motivation.

Talk About Thrombolysis. Regular Case-Based Discussions of Stroke Thrombolysis Improve Door-to-Needle Time by 20.

BACKGROUND: The outcome of stroke patients can be improved by a rapid initiation of thrombolytic therapy. Here, we sought to determine whether an additional simple but thorough case-based discussion of recent thrombolysed cases with the entire neurologic staff can improve the door-to-needle time without changes to the implemented stroke protocol. METHODS: For every performed thrombolysis, a route card, consisting of a timeline with 3 time points and target times, had to be completed by the attending neurologist. Times and reasons for delays were noted. All thrombolysed cases were then reviewed in a 14-day-rhythm with the entire neurologic staff. The responsible stroke consultant gave details and reasons for delays. Possibilities to avoid delays were then discussed with the whole team. All thrombolyses were prospectively recorded and compared with thrombolyses of the 2 preinterventional years. The primary outcome parameter was the door-to-needle time. RESULTS: The door-to-needle time decreased from 37 minutes in the preintervention period (N = 154) to 28 minutes during the intervention (N = 97; P < .001). Performance was improved for residents (<6 years of neurologic training) as well as for the specialists (>6 years of neurologic training). Improvements in the performance of specialists were significantly greater than those of residents. CONCLUSIONS: The present study demonstrates improved treatment of stroke patients by a simple, non-time-consuming intervention that combines education with a potential increase in staff motivation. This intervention is effective in a tertiary academic stroke center with a previously implemented sophisticated stroke protocol but should also improve treatment delays in primary stroke centers.

The Influence of Eye Closure on Somatosensory Discrimination: A Trade-off Between Simple Perception and Discrimination.

We often close our eyes to improve perception. Recent results have shown a decrease of perception thresholds accompanied by an increase in somatosensory activity after eye closure. However, does somatosensory spatial discrimination also benefit from eye closure? We previously showed that spatial discrimination is accompanied by a reduction of somatosensory activity. Using magnetoencephalography, we analyzed the magnitude of primary somatosensory (somatosensory P50m) and primary auditory activity (auditory P50m) during a one-back discrimination task in 21 healthy volunteers. In complete darkness, participants were requested to pay attention to either the somatosensory or auditory stimulation and asked to open or close their eyes every 6.5 min. Somatosensory P50m was reduced during a task requiring the distinguishing of stimulus location changes at the distal phalanges of different fingers. The somatosensory P50m was further reduced and detection performance was higher during eyes open. A similar reduction was found for the auditory P50m during a task requiring the distinguishing of changing tones. The function of eye closure is more than controlling visual input. It might be advantageous for perception because it is an effective way to reduce interference from other modalities, but disadvantageous for spatial discrimination because it requires at least one top-down processing stage.

Transfer of Patients in a Telestroke Network: What Are the Relevant Factors for Making This Decision?

Background/Introduction: Current telestroke network consultations are focused on decision-making in the hyperacute stage of stroke management. The two main questions in telestroke consultations are whether thrombolysis should be initiated and whether the patient should be transferred to a hub hospital. Although guidelines exist for initiating intravenous thrombolytic therapy, the question of whether patients should be transferred is far more elusive. MATERIALS AND METHODS: In this study, we investigated the factors involved in the decision to transfer stroke patients to a hub hospital. We were particularly interested in identifying factors that promote or impede the transfer of patients. We enrolled 1,615 cases of telestroke consultation of the University Hospital Jena. RESULTS: The two main factors that independently influenced the probability of transferring a patient were the patient's age and the identification of a proximal vessel occlusion. Interestingly, factors such as the severity of symptoms and the time elapsed from symptom onset were not found to have an independent influence on the decision to transfer a patient. The transfer of most patients was justified by the possibility of performing interventional reperfusion therapy. DISCUSSION: We discuss the effectiveness of the current decision-making process and possible ways to improve decision-making for a more effective selection of patients who would benefit from transfer. CONCLUSION: The decision-making process to a transfer patient is not standardized and constitutes a trade-off between the intention to treat all possible patients while avoiding the transfer of patients without treatment options.

Measuring eye states in functional MRI.

BACKGROUND: In many functional magnetic resonance imaging (fMRI) studies, experimental design often depends on the eye state (i.e., whether the participants had their eyes open or closed). Closed eyes during an fMRI is the general convention, particularly when patients are in a resting-state, but the eye state is difficult to verify. Although knowledge of the impact of the eye state on brain activity is steadily growing, only a few research groups have implemented standardized procedures to monitor eye movements and eye state. These procedures involve advanced methods that are costly (e.g., fMRI-compatible cameras) and often time-consuming (e.g., EEG/EOG). RESULTS: We present a simple method that distinguishes open from closed eyes utilizing functional MR images alone. The utility of this method was demonstrated on fMRI data from 14 healthy subjects who had to open and close their eyes according to a predetermined protocol (3.0 T MRI scanner, EPI sequence with 3 × 3 × 3 mm voxels, TR 2.52 s). CONCLUSION: The method presented herein is capable of extracting the movement direction of the eyes. All described methods are applicable for pre- and post-normalized MR images and are freely available through a MATLAB toolbox.

Parallel processing of somatosensory information: Evidence from dynamic causal modeling of MEG data.

The advent of methods to investigate network dynamics has led to discussion of whether somatosensory inputs are processed in serial or in parallel. Both hypotheses are supported by DCM analyses of fMRI studies. In the present study, we revisited this controversy using DCM on magnetoencephalographic (MEG) data during somatosensory stimulation. Bayesian model comparison was used to allow for direct inference on the processing stream. Additionally we varied the duration of the time-window of analyzed data after the somatosensory stimulus. This approach allowed us to explore time dependent changes in the processing stream of somatosensory information and to evaluate the consistency of results. We found that models favoring a parallel processing route best describe neural activities elicited by somatosensory stimuli. This result was consistent for different time-windows. Although it is assumed that the majority of somatosensory information is delivered to the SI, the current results indicate that at least a small part of somatosensory information is delivered in parallel to the SII. These findings emphasize the importance of data analysis with high temporal resolution.

Excitatory and inhibitory mechanisms underlying somatosensory habituation.

Habituation is a basic process of learning in which repeated exposure to a sensory stimulus leads to a decrease in the strength of neuronal activations and behavioral responses. In addition to increases in neuronal activity, sensory stimuli can also lead to decreases in neuronal activity. Until now, the effects of habituation on stimulus-induced neuronal deactivations have not been investigated. We performed functional magnetic resonance imaging in 30 healthy subjects during repetitive unilateral somatosensory stimulation and combined this analysis with a psychophysiological examination of changes in the perception threshold. Consistent with the literature, we found a time-dependent decrease of the positive blood oxygenation level-dependent (BOLD) response (indicative of habituation) in the primary somatosensory cortex (SI) contralateral to the stimulus. In contrast, the negative BOLD response (NBR) in the ipsilateral SI did not show a decrease in amplitude; instead, an increase in amplitude was found, i.e., a stronger NBR (increased response). The increased NBR was associated with an increased perception threshold of the nonstimulated hand. These findings suggest that habituation is not primarily characterized by a decrease in the neuronal response to repeated stimuli but rather a widespread change in the balance between excitatory and inhibitory effects that favors inhibitory effects.

Simplifying Multimodal Clinical Research Data Management: Introducing an Integrated and User-friendly Database Concept.

BACKGROUND: Clinical research, particularly in scientific data, grapples with the efficient management of multimodal and longitudinal clinical data. Especially in neuroscience, the volume of heterogeneous longitudinal data challenges researchers. While current research data management systems offer rich functionality, they suffer from architectural complexity that makes them difficult to install and maintain and require extensive user training. OBJECTIVES: The focus is the development and presentation of a data management approach specifically tailored for clinical researchers involved in active patient care, especially in the neuroscientific environment of German university hospitals. Our design considers the implementation of FAIR (Findable, Accessible, Interoperable, and Reusable) principles and the secure handling of sensitive data in compliance with the General Data Protection Regulation. METHODS: We introduce a streamlined database concept, featuring an intuitive graphical interface built on Hypertext Markup Language revision 5 (HTML5)/Cascading Style Sheets (CSS) technology. The system can be effortlessly deployed within local networks, that is, in Microsoft Windows 10 environments. Our design incorporates FAIR principles for effective data management. Moreover, we have streamlined data interchange through established standards like HL7 Clinical Document Architecture (CDA). To ensure data integrity, we have integrated real-time validation mechanisms that cover data type, plausibility, and Clinical Quality Language logic during data import and entry. RESULTS: We have developed and evaluated our concept with clinicians using a sample dataset of subjects who visited our memory clinic over a 3-year period and collected several multimodal clinical parameters. A notable advantage is the unified data matrix, which simplifies data aggregation, anonymization, and export. THIS STREAMLINES DATA EXCHANGE AND ENHANCES DATABASE INTEGRATION WITH PLATFORMS LIKE KONSTANZ INFORMATION MINER (KNIME): . CONCLUSION: Our approach offers a significant advancement for capturing and managing clinical research data, specifically tailored for small-scale initiatives operating within limited information technology (IT) infrastructures. It is designed for immediate, hassle-free deployment by clinicians and researchers.The database template and precompiled versions of the user interface are available at: https://github.com/stebro01/research_database_sqlite_i2b2.git.

Connecting the dots: Motor and default mode network crossroads in post-stroke motor learning deficits.

BACKGROUND: Strokes frequently result in long-term motor deficits, imposing significant personal and economic burdens. However, our understanding of the underlying neural mechanisms governing motor learning in stroke survivors remains limited - a fact that poses significant challenges to the development and optimisation of therapeutic strategies. OBJECTIVE: This study investigates the diversity in motor learning aptitude and its associated neurological mechanisms. We hypothesised that stroke patients exhibit compromised overall motor learning capacity, which is associated with altered activity and connectivity patterns in the motor- and default-mode-network in the brain. METHODS: We assessed a cohort of 40 chronic-stage, mildly impaired stroke survivors and 39 age-matched healthy controls using functional Magnetic Resonance Imaging (fMRI) and connectivity analyses. We focused on neural activity and connectivity patterns during an unilateral motor sequence learning task performed with the unimpaired or non-dominant hand. Primary outcome measures included task-induced changes in neural activity and network connectivity. RESULTS: Compared to controls, stroke patients showed significantly reduced motor learning capacity, associated with diminished cerebral lateralization. Task induced activity modulation was reduced in the motor network but increased in the default mode network. The modulated activation strength was associated with an opposing trend in task-induced functional connectivity, with increased connectivity in the motor network and decreased connectivity in the DMN. CONCLUSIONS: Stroke patients demonstrate altered neural activity and connectivity patterns during motor learning with their unaffected hand, potentially contributing to globally impaired motor learning skills. The reduced ability to lateralize cerebral activation, along with the enhanced connectivity between the right and left motor cortices in these patients, may signify maladaptive neural processes that impede motor adaptation, possibly affecting long-term rehabilitation post-stroke. The contrasting pattern of activity modulation and connectivity alteration in the default mode network suggests a nuanced role of this network in post-stroke motor learning. These insights could have significant implications for the development of customised rehabilitation strategies for stroke patients.

Persistent cognitive slowing in post-COVID patients: longitudinal study over 6 months.

BACKGROUND: Fatigue is a frequent and one of the most debilitating symptoms in post-COVID syndrome (PCS). Recently, we proposed that fatigue is caused by hypoactivity of the brain's arousal network and reflected by a reduction of cognitive processing speed. However, it is unclear whether cognitive slowing is revealed by standard neuropsychological tests, represents a selective deficit, and how it develops over time. OBJECTIVES: This prospective study assesses whether PCS patients show deficits particularly in tests relying on processing speed and provides the first longitudinal assessment focusing on processing speed in PCS patients. METHODS: Eighty-eight PCS patients with cognitive complaints and 50 matched healthy controls underwent neuropsychological assessment. Seventy-seven patients were subsequently assessed at 6-month follow-up. The Test for Attentional Performance measured tonic alertness as primary study outcome and additional attentional functions. The Neuropsychological Assessment Battery evaluated all key cognitive domains. RESULTS: Patients showed cognitive slowing indicated by longer reaction times compared to control participants (r = 0.51, p < 0.001) in a simple-response tonic alertness task and in all more complex tasks requiring speeded performance. Reduced alertness correlated with higher fatigue (r = - 0.408, p < 0.001). Alertness dysfunction remained unchanged at 6-month follow-up (p = 0.240) and the same was true for most attention tasks and cognitive domains. CONCLUSION: Hypoarousal is a core deficit in PCS which becomes evident as a selective decrease of processing speed observed in standard neuropsychological tests. This core deficit persists without any signs of amelioration over a 6-month period of time.

Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study.

Background: COVID-19 survivors may experience a wide range of chronic cognitive symptoms for months or years as part of post-COVID-19 conditions (PCC). To date, there is no definitive objective cognitive marker for PCC. We hypothesised that a key common deficit in people with PCC might be generalised cognitive slowing. Methods: To examine cognitive slowing, patients with PCC completed two short web-based cognitive tasks, Simple Reaction Time (SRT) and Number Vigilance Test (NVT). 270 patients diagnosed with PCC at two different clinics in UK and Germany were compared to two control groups: individuals who contracted COVID-19 before but did not experience PCC after recovery (No-PCC group) and uninfected individuals (No-COVID group). All patients with PCC completed the study between May 18, 2021 and July 4, 2023 in Jena University Hospital, Jena, Germany and Long COVID clinic, Oxford, UK. Findings: We identified pronounced cognitive slowing in patients with PCC, which distinguished them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. Cognitive slowing was evident even on a 30-s task measuring simple reaction time (SRT), with patients with PCC responding to stimuli ∼3 standard deviations slower than healthy controls. 53.5% of patients with PCC's response speed was slower than 2 standard deviations from the control mean, indicating a high prevalence of cognitive slowing in PCC. This finding was replicated across two clinic samples in Germany and the UK. Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in patients with PCC. Furthermore, cognitive slowing on the SRT was highly correlated with the poor performance of patients with PCC on the NVT measure of sustained attention. Interpretation: Together, these results robustly demonstrate pronounced cognitive slowing in people with PCC, which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. This might be an important factor contributing to some of the cognitive impairments reported in patients with PCC. Funding: Wellcome Trust (206330/Z/17/Z), NIHR Oxford Health Biomedical Research Centre, the Thüringer Aufbaubank (2021 FGI 0060), German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890).

Perceptual plasticity is mediated by connectivity changes of the medial thalamic nucleus.

It is well known that the threshold for somatosensory perception may adapt to different inputs. Recent studies suggest the presence of a modulating effect of somatosensory inputs on the spinal dorsal horn. However, the effects of somatosensory inputs on cerebral processing and, in particular, on the functional and effective connectivity of the somatosensory brain network, are poorly understood. In this study, we investigated the longitudinal impact of somatosensory stimuli on the resting-state functional connectivity and effective connectivity of the somatosensory brain network. We performed resting-state functional magnetic resonance imaging (fMRI) in 12 healthy subjects before and after unilateral electrical median nerve stimulation. We combined this analysis with a psychophysiological examination of changes of the perception threshold. We found that the unilateral median nerve stimulation increased the perception thresholds bilaterally and increased the resting-state functional and effective connectivity between most cortical areas of the somatosensory network. The major finding, however, was a decreased resting-state functional connectivity between both secondary somatosensory cortices and the bilateral medial nuclear complex of the thalamus. This decreased connectivity was correlated with increased perception thresholds. These findings emphasize the importance of the medial thalamic nucleus for the perceptual awareness of somatosensory stimuli.

Reward network dysfunction is associated with cognitive impairment after stroke.

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.

Visual stimulation by extensive visual media consumption can be beneficial for motor learning.

In this randomized controlled intervention trial, we investigated whether intense visual stimulation through television watching can enhance visual information processing and motor learning performance. 74 healthy young adults were trained in a motor skill with visual information processing demands while being accommodated in a controlled environment for five days. The experimental manipulation (n = 37) consisted of prolonged television watching (i.e., 8 h/day, + 62.5% on average) to induce intense exposure to visual stimulation. The control group (n = 37) did not consume visual media. The groups were compared by motor learning performance throughout the study as well as pre/post visual attention parameters and resting-state network connectivity in functional MRI. We found that the intervention group performed significantly better in the motor learning task (+ 8.21% (95%-CI[12.04, 4.31], t(70) = 4.23, p < 0.001) while showing an increased capacity of visual short-term memory (+ 0.254, t(58) = - 3.19, p = 0.002) and increased connectivity between visual and motor-learning associated resting-state networks. Our findings suggest that the human brain might enter a state of accentuated visuomotor integration to support the implementation of motor learning with visual information processing demands if challenged by ample input of visual stimulation. Further investigation is needed to evaluate the persistence of this effect regarding participants exposed to accustomed amounts of visual media consumption.Clinical Trials Registration: This trial was registered in the German Clinical Trials Register/Deutsches Register klinischer Studien (DRKS): DRKS00019955.

A hypoarousal model of neurological post-COVID syndrome: the relation between mental fatigue, the level of central nervous activation and cognitive processing speed.

BACKGROUND: Knowledge on the nature of post-COVID neurological sequelae often manifesting as cognitive dysfunction and fatigue is still unsatisfactory. OBJECTIVES: We assumed that cognitive dysfunction and fatigue in post-COVID syndrome are critically linked via hypoarousal of the brain. Thus, we assessed whether tonic alertness as a neurocognitive index of arousal is reduced in these patients and how this relates to the level of central nervous activation and subjective mental fatigue as further indices of arousal. METHODS: 40 post-COVID patients with subjective cognitive dysfunction and 40 matched healthy controls underwent a whole-report paradigm of briefly presented letter arrays. Based on report performance and computational modelling according to the theory of visual attention, the parameter visual processing speed (VPS) was quantified as a proxy of tonic alertness. Pupillary unrest was assessed as a measure of central nervous activation. The Fatigue Assessment Scale was applied to assess subjective mental fatigue using the corresponding subscale. RESULTS: VPS was reduced in post-COVID patients compared to controls (p = 0.005). In these patients, pupillary unrest (p = 0.029) and mental fatigue (p = 0.001) predicted VPS, explaining 34% of the variance and yielding a large effect with f2 = 0.51. CONCLUSION: In post-COVID patients with subjective cognitive dysfunction, hypoarousal of the brain is reflected in decreased processing speed which is explained by a reduced level of central nervous activation and a higher level of mental fatigue. In turn, reduced processing speed objectifies mental fatigue as a core subjective clinical complaint in post-COVID patients.

Impact of an online guided physical activity training on cognition and gut-brain axis interactions in older adults: protocol of a randomized controlled trial.

Introduction: By 2050, the worldwide percentage of people 65 years and older is assumed to have doubled compared to current numbers. Therefore, finding ways of promoting healthy (cognitive) aging is crucial. Physical activity is considered an effective approach to counteract not only physical but also cognitive decline. However, the underlying mechanisms that drive the benefits of regular physical activity on cognitive function are not fully understood. This randomized controlled trial aims to analyze the effect of an eight-week standardized physical activity training program in older humans on cognitive, brain, and gut-barrier function as well as the relationship between the resulting changes. Methods and analysis: One-hundred healthy participants aged 60 to 75 years will be recruited. First, participants will undergo an extensive baseline assessment consisting of neurocognitive tests, functional and structural brain imaging, physical fitness tests, and gut-microbiome profiling. Next, participants will be randomized into either a multi-component physical activity group (experimental condition) or a relaxation group (active control condition), with each training lasting 8 weeks and including an equal number and duration of exercises. The whole intervention will be online-based, i.e., participants will find their intervention schedule and all materials needed on the study website. After the intervention phase, participants will have their post-intervention assessment, which consists of the same measures and tests as the baseline assessment. The primary outcome of this study is the change in the cognitive parameter of visual processing speed from baseline to post-measurement, which will on average take place 10 weeks after the randomization. Secondary outcomes related to cognitive, brain, and microbiome data will be analyzed exploratory. Clinical trial registration: https://drks.de/search/de/trial/DRKS00028022.