Search

Abstract Introduction Unilateral hyperhidrosis can be a neurological manifestation of irritations of the central or peripheral nervous system. Case presentation We present the case of a 67-year-old German man who had hyperhidrosis of his right upper body quadrant (including face, arm, and chest) following intrathoracic surgery of a left-sided pleural lipoma. Conclusion An isolated unilateral hyperhidrosis might occur after intrathoracic surgery. Besides anticholinergic drugs the use of botulinum toxin should be considered.

The interrelation between acute ischemic stroke, persistent disability, and uncertain prognosis underscores the need for improved methods to predict clinical outcomes. Traditional approaches have largely focused on analysis of clinical metrics, lesion characteristics, and network connectivity, using techniques such as resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). However, these methods are not routinely used in acute stroke diagnostics. This study introduces an innovative approach that not only considers the lesion size in relation to the National Institutes of Health Stroke Scale (NIHSS score), but also evaluates the impact of disrupted fibers and their connections to cortical regions by introducing a disconnection value. By identifying fibers traversing the lesion and estimating their number within predefined regions of interest (ROIs) using a normative connectome atlas, our method bypasses the need for individual DTI scans. In our analysis of MRI data (T1 and T2) from 51 patients with acute or subacute subcortical stroke presenting with motor or sensory deficits, we used simple linear regression to assess the explanatory power of lesion size and disconnection value on NIHSS score. Subsequent hierarchical multiple linear regression analysis determined the incremental value of disconnection metrics over lesion size alone in relation to NIHSS score. Our results showed that models incorporating the disconnection value accounted for more variance than those based solely on lesion size (lesion size explained 44% variance, disconnection value 60%). Furthermore, hierarchical regression revealed a significant improvement ( p < 0.001) in model fit when adding the disconnection value, confirming its critical role in stroke assessment. Our approach, which integrates a normative connectome to quantify disconnections to cortical regions, provides a significant improvement in assessing the current state of stroke impact compared to traditional measures that focus on lesion size. This is achieved by taking into account the lesion's location and the connectivity of the affected white matter tracts, providing a more comprehensive assessment of stroke severity as reflected in the NIHSS score. Future research should extend the validation of this approach to larger and more diverse populations, with a focus on refining its applicability to clinical assessment and long-term outcome prediction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Weigel, Klingner, Brodoehl, Wagner, Schwab, Güllmar, Mayer, Güttler, Teichgräber and Gaser.)

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&#95;database&#95;sqlite&#95;i2b2.git., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

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)., Competing Interests: All authors declare no financial or non-financial competing interests., (© 2024 The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

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 f 2  = 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., (© 2023. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Schrenk, Brodoehl, Flor, Frahm, Gaser, Hamdan, Herbsleb, Kaleta, Kattlun, Müller, Puta, Radscheidt, Ruiz-Rizzo, Saraei, Scherag, Steidten, Witte and Finke.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Neuropsychiatric symptoms are the most common sequelae of long-COVID. As accumulating evidence suggests an impact of survived SARS-CoV-2-infection on brain physiology, it is necessary to further investigate brain structural changes in relation to course and neuropsychiatric symptom burden in long-COVID. To this end, the present study investigated 3T-MRI scans from long-COVID patients suffering from neuropsychiatric symptoms (n = 30), and healthy controls (n = 20). Whole-brain comparison of gray matter volume (GMV) was conducted by voxel-based morphometry. To determine whether changes in GMV are predicted by neuropsychiatric symptom burden and/or initial severity of symptoms of COVID-19 and time since onset of COVID-19 stepwise linear regression analysis was performed. Significantly enlarged GMV in long-COVID patients was present in several clusters (spanning fronto-temporal areas, insula, hippocampus, amygdala, basal ganglia, and thalamus in both hemispheres) when compared to controls. Time since onset of COVID-19 was a significant regressor in four of these clusters with an inverse relationship. No associations with clinical symptom burden were found. GMV alterations in limbic and secondary olfactory areas are present in long-COVID patients and might be dynamic over time. Larger samples and longitudinal data in long-COVID patients are required to further clarify the mediating mechanisms between COVID-19, GMV and neuropsychiatric symptoms., Competing Interests: Declaration of Competing Interest Outside of the study, PAR received consulting and lecture fees from CSL Behring, Dr. Wilmar Schwabe, Boston Scientific, Pfizer, Bristol Myers Squibb and travel grants from Merz Pharma. All other authors state, that they have no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The integration of stimuli from different sensory modalities forms the basis for human perception. While the relevant impact of visual stimuli on the perception of other sensory modalities is recognized, much less is known about the impact of auditory stimuli on general sensory processing. This study aims to investigate the effect of acoustic stimuli on the processing of somatosensory stimuli using real noise (i.e., unpleasant everyday noise, RN) and neutral white noise ( WN ). To this purpose, we studied 20 healthy human subjects between 20 and 29 years of age (mean: 24, SD: ±1.9 years sex ratio 1:1). Somatosensory perception was evaluated using mechanical detection threshold (MDT) of the skin on the back of the dominant hand. To investigate the underlying mechanisms in the brain, fMRI was performed while applying acoustic stimulation (RN and WN) and tactile stimulation of the dominant hand. Here we show that acoustic stimulation with noise alters the perception of touch on the skin. We found that the effect of RN and WN differed. RN leads to an improved tactile perception, whereas WN impaired tactile perception. These changes go along with significant differences in brain activity and connectivity. WN is associated with a significant increase in brain activity in multiple brain areas such as the auditory and somatosensory cortex, parietal association cortex, and the thalamus compared to RN . With tactile stimulation of the skin, the flow of information in these brain areas is altered. While with RN the information flow from the thalamus to the somatosensory cortex is prominent, the network activity pattern changes under WN revealing an increase in interaction between multiple networks. Unpleasant noise inhibits the multisensory integration and enables a more efficient unimodal perception in the somatosensory system, improving perception. Whether this is to be interpreted as a temporary increase in phasic alertness or by a stronger filter function of the thalamus with a preference for unimodal stimuli is still open for debate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nuernberger, Schaller, Klingner, Witte and Brodoehl.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Opitz, Wagner, Rogenz, Maas, Schmidt, Brodoehl and Klingner.)

Learning from errors as the main mechanism for motor adaptation has two fundamental prerequisites: a mismatch between the intended and performed movement and the ability to adapt motor actions. Many neurological patients are limited in their ability to transfer an altered motor representation into motor action due to a compromised motor pathway. Studies that have investigated the effects of a sustained and unresolvable mismatch over multiple days found changes in brain processing that seem to optimize the potential for motor learning (increased drive for motor adaptation and a weakening of the current implementation of motor programs). However, it remains unclear whether the observed effects can be induced experimentally and more important after shorter periods. Here, we used task-based and resting-state fMRI to investigate whether the known pattern of cortical adaptations due to a sustained mismatch can be induced experimentally by a short (20 min), but unresolvable, sensory-motor mismatch by impaired facial movements in healthy participants by transient facial tapping. Similar to long-term mismatch, we found plastic changes in a network that includes the striatal, cerebellar and somatosensory brain areas. However, in contrast to long-term mismatch, we did not find the involvement of the cerebral motor cortex. The lack of the involvement of the motor cortex can be interpreted both as an effect of time and also as an effect of the lack of a reduction in the motor error. The similar effects of long-term and short-term mismatch on other parts of the sensory-motor network suggest that the brain-state caused by long-term mismatch can be (at least partly) induced by short-term mismatch. Further studies should investigate whether short-term mismatch interventions can be used as therapeutic strategy to induce an altered brain-state that increase the potential for motor learning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Klingner, Kattlun, Krolopp, Jochmann, Volk, Brodoehl, Guntinas-Lichius, Witte and Dobel.)

Visually induced motion sickness (VIMS) is a relevant limiting factor in the use of virtual reality (VR) devices. Understanding the origin of this problem might help to develop strategies to circumvent this limitation. Previous studies have attributed VIMS to a mismatch between visual, and vestibular information, causing ambiguity of the position of the body in relation to its surrounding. Studies using EEG have shown a shift of the power spectrum to lower frequencies while VIMS is experienced. However, little is known about the relationship between the intensity of the VIMS and the changes in these power spectra. Moreover, the effect of different varieties of VIMS on the causal relationship between brain areas is largely unknown. Here, we used EEG to study 14 healthy subjects in a VR environment who were exposed to increasing levels of mismatch between vestibular and visual information. The frequency power and the bivariate transfer entropy as a measure for the information transfer were calculated. We found a direct association between increasing mismatch levels and subjective VIMS. With increasing VIMS, the proportion of slow EEG waves (especially 1-10 Hz) increases, especially in temporo-occipital regions. Furthermore, we found a general decrease in the information flow in most brain areas but especially in brain areas involved in the processing of vestibular signals and the detection of self-motion. We hypothesize that the general shift of frequency power and the decrease in information flow while experiencing high intensity VIMS represent a brain state of a reduced ability to receive, transmit and process information. We further hypothesize that the mechanism of reduced information flow is a general reaction of the brain to an unresolvable mismatch of information. This reaction aims on transforming a currently unstable model with a high prediction error into a stable model in an environment of minimal contradictory information., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nürnberger, Klingner, Witte and Brodoehl.)

Purpose: Here we aimed to automatically classify human emotion earlier than is typically attempted. There is increasing evidence that the human brain differentiates emotional categories within 100-300 ms after stimulus onset. Therefore, here we evaluate the possibility of automatically classifying human emotions within the first 300 ms after the stimulus and identify the time-interval of the highest classification performance., Methods: To address this issue, MEG signals of 17 healthy volunteers were recorded in response to three different picture stimuli (pleasant, unpleasant, and neutral pictures). Six Linear Discriminant Analysis (LDA) classifiers were used based on two binary comparisons (pleasant versus neutral and unpleasant versus neutral) and three different time-intervals (100-150 ms, 150-200 ms, and 200-300 ms post-stimulus). The selection of the feature subsets was performed by Genetic Algorithm and LDA., Results: We demonstrated significant classification performances in both comparisons. The best classification performance was achieved with a median AUC of 0.83 (95 %- CI [0.71; 0.87]) classifying brain responses evoked by unpleasant and neutral stimuli within 100-150 ms, which is at least 850 ms earlier than attempted by other studies., Conclusion: Our results indicate that using the proposed algorithm, brain emotional responses can be significantly classified at very early stages of cortical processing (within 300 ms). Moreover, our results suggest that emotional processing in the human brain occurs within the first 100-150 ms., (Published by Elsevier B.V.)

The processing of emotions in the human brain is an extremely complex process that extends across a large number of brain areas and various temporal processing steps. In the case of magnetoencephalography (MEG) data, various frequency bands also contribute differently. Therefore, in most studies, the analysis of emotional processing has to be limited to specific sub-aspects. Here, we demonstrated that these problems can be overcome by using a nonparametric statistical test called the cluster-based permutation test (CBPT). To the best of our knowledge, our study is the first to apply the CBPT to MEG data of brain responses to emotional stimuli. For this purpose, different emotionally impacting (pleasant and unpleasant) and neutral pictures were presented to 17 healthy subjects. The CBPT was applied to the power spectra of five brain frequencies, comparing responses to emotional versus neutral stimuli over entire MEG channels and time intervals within 1500 ms post-stimulus. Our results showed significant clusters in different frequency bands, and agreed well with many previous emotion studies. However, the use of the CBPT allowed us to easily include large numbers of MEG channels, wide frequency, and long time-ranges in one study, which is a more reliable alternative to other studies that consider only specific sub-aspects.

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Spatial smoothing of functional magnetic resonance imaging (fMRI) data can be performed on volumetric images and on the extracted surface of the brain. Smoothing on the unfolded cortex should theoretically improve the ability to separate signals between brain areas that are near together in the folded cortex but are more distant in the unfolded cortex. However, surface-based method approaches (SBA) are currently not utilized as standard procedure in the preprocessing of neuroimaging data. Recent improvements in the quality of cortical surface modeling and improvements in its usability nevertheless advocate this method. In the current study, we evaluated the benefits of an up-to-date surface-based smoothing in comparison to volume-based smoothing. We focused on the effect of signal contamination between different functional systems using the primary motor and primary somatosensory cortex as an example. We were particularly interested in how this signal contamination influences the results of activity and connectivity analyses for these brain regions. We addressed this question by performing fMRI on 19 subjects during a tactile stimulation paradigm and by using simulated BOLD responses. We demonstrated that volume-based smoothing causes contamination of the primary motor cortex by somatosensory cortical responses, leading to false positive motor activation. These false positive motor activations were not found by using surface-based smoothing for reasonable kernel sizes. Accordingly, volume-based smoothing caused an exaggeration of connectivity estimates between these regions. In conclusion, this study showed that surface-based smoothing decreases signal contamination considerably between neighboring functional brain regions and improves the validity of activity and connectivity results.

Abnormal emotional reactions of the brain in patients with facial nerve paralysis have not yet been reported. This study aims to investigate this issue by applying a machine-learning algorithm that discriminates brain emotional activities that belong either to patients with facial nerve paralysis or to healthy controls. Beyond this, we assess an emotion rating task to determine whether there are differences in their experience of emotions. MEG signals of 17 healthy controls and 16 patients with facial nerve paralysis were recorded in response to picture stimuli in three different emotional categories (pleasant, unpleasant, and neutral). The selected machine learning technique in this study was the logistic regression with LASSO regularization. We demonstrated significant classification performances in all three emotional categories. The best classification performance was achieved considering features based on event-related fields in response to the pleasant category, with an accuracy of 0.79 (95% CI (0.70, 0.82)). We also found that patients with facial nerve paralysis rated pleasant stimuli significantly more positively than healthy controls. Our results indicate that the inability to express facial expressions due to peripheral motor paralysis of the face might cause abnormal brain emotional processing and experience of particular emotions.

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 Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

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., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Sensorimotor adaptation is driven by mismatch errors between desired movements and actual movement outcomes. A mismatch error can be minimized by adjusting movements or by altering the interpretation of sensory information. While the effect of mismatch errors on the motor system has received much attention, the contribution of somatosensory feedback, particularly the sensory-motor interplay in the process of adaptation, remains poorly understood. Our study analyzes the impact of peripheral deefferentation on the plasticity of the brain networks responsible for sensory-motor adaptation, focusing particularly on changes in the processing of somatosensory information. For this aim, task-based and resting-state functional MRI was performed on 24 patients in the acute state of a left-sided idiopathic peripheral facial nerve palsy. The functional connectivity of cortical and subcortical networks was analyzed and compared to a healthy control group. We found a strong involvement of the somatosensory system and the thalamus in the adaptation process following an acute peripheral deefferentation. The investigated network shows the principal pattern of a reduced connectivity between cortical areas, while the connectivity to subcortical areas (the basal ganglia and the thalamus) is increased. We suggest that the increased connectivity between the subcortical and cortical structures indicates an active sensory-motor adaptation process. We further hypothesize that the decreased functional connectivity at the cortical level reflects an unsuccessful sensorimotor adaptation process due to the inability to solve the somatosensory-motor mismatch. These results extend our understanding of the somatosensory-motor interaction in response to a mismatch signal and highlight the importance of the thalamus in this process., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Idiopathic cervical dystonia (CD) is a chronic movement disorder characterized by impressive clinical symptoms and the lack of clear pathological findings in clinical diagnostics and imaging. At present, the injection of botulinum toxin (BNT) in dystonic muscles is an effective therapy to control motor symptoms and pain in CD., Objectives: We hypothesized that, although it is locally injected to dystonic muscles, BNT application leads to changes in brain and network activity towards normal brain function., Methods: Using 3 T functional MR imaging along with advanced analysis techniques (functional connectivity, Granger causality, and regional homogeneity), we aimed to characterize brain activity in CD (17 CD patients vs. 17 controls) and to uncover the effects of BNT treatment (at 6 months)., Results: In CD, we observed an increased information flow within the basal ganglia, the thalamus, and the sensorimotor cortex. In parallel, some of these structures became less responsive to regulating inputs. Furthermore, our results suggested an altered somatosensory integration. Following BNT administration, we noted a shift towards normal brain function in the CD patients, especially within the motor cortex, the somatosensory cortex, and the basal ganglia., Conclusion: The changes in brain function and network activity in CD can be interpreted as related to the underlying cause, the effort to compensate or a mixture of both. Although BNT is applied in the last stage of the cortico-neuromuscular pathway, brain patterns are shifted towards those of healthy controls., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The question regarding whether somatosensory inputs are processed in parallel or in series has not been clearly answered. Several studies that have applied dynamic causal modeling (DCM) to fMRI data have arrived at seemingly divergent conclusions. However, these divergent results could be explained by the hypothesis that the processing route of somatosensory information changes with time. Specifically, we suggest that somatosensory stimuli are processed in parallel only during the early stage, whereas the processing is later dominated by serial processing. This hypothesis was revisited in the present study based on fMRI analyses of tactile stimuli and the application of DCM to magnetoencephalographic (MEG) data collected during sustained (260 ms) tactile stimulation. Bayesian model comparisons were used to infer the processing stream. We demonstrated that the favored processing stream changes over time. We found that the neural activity elicited in the first 100 ms following somatosensory stimuli is best explained by models that support a parallel processing route, whereas a serial processing route is subsequently favored. These results suggest that the secondary somatosensory area (SII) receives information regarding a new stimulus in parallel with the primary somatosensory area (SI), whereas later processing in the SII is dominated by the preprocessed input from the SI.

This article investigates the processing of vestibular information by interpreting current experimental knowledge in the framework of predictive coding. We demonstrate that this theoretical framework give us insights into several important questions regarding specific properties of the vestibular system. Particularly, we discuss why the vestibular network is more spatially distributed than other sensory networks, why a mismatch in the vestibular system is more clinically disturbing than in other sensory systems, why the vestibular system is only marginally affected by most cerebral lesions, and whether there is a primary vestibular cortex. The use of predictive coding as a theoretical framework further points to some problems with the current interpretation of results that are gained from vestibular stimulation studies. In particular, we argue that cortical responses of vestibular stimuli cannot be interpreted in the same way as responses of other sensory modalities. Finally, we discuss the implications of the new insights, hypotheses and problems that were identified in this review on further directions of research of vestibular information processing., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.

Eye closure even in complete darkness can improve somatosensory perception by switching the brain to a uni-sensory processing mode. This causes an increased information flow between the thalamus and the somatosensory cortex while decreasing modulation by the visual cortex. Previous work suggests that these modulations are age-dependent and that the benefit in somatosensory performance due to eye closing diminishes with age. The cause of this age-dependency and to what extent somatosensory processing is involved remains unclear. Therefore, we intended to characterize the underlying age-dependent modifications in the interaction and connectivity of different sensory networks caused by eye closure. We performed functional MR-imaging with tactile stimulation of the right hand under the conditions of opened and closed eyes in healthy young and elderly participants. Conditional Granger causality analysis was performed to assess the somatosensory and visual networks, including the thalamus. Independent of age, eye closure improved the information transfer from the thalamus to and within the somatosensory cortex. However, beyond that, we found an age-dependent recruitment strategy. Whereas young participants were characterized by an optimized information flow within the relays of the somatosensory network, elderly participants revealed a stronger modulatory influence of the visual network upon the somatosensory cortex. Our results demonstrate that the modulation of the somatosensory and visual networks by eye closure diminishes with age and that the dominance of the visual system is more pronounced in the aging brain., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Visual dominance over other senses is a well-known phenomenon. Closing the eyes, even in complete darkness, can improve somatosensory perception by switching off various aspects of visual dominance. How and if this mechanism is affected by aging remains unknown. We performed detailed neurophysiological and functional MR-imaging on healthy young and elderly participants under the conditions of opened and closed eyes. We found an improved perception threshold in both groups when the eyes were closed, but the improvement was significantly less pronounced in the elderly. fMRI data revealed increased resting activity in the somatosensory cortex with closed eyes, and the stimulus-induced activity of the secondary somatosensory cortex decreased in the young but not in the elderly. This study demonstrates that a switch towards unisensory processing via eye closure is preserved but significantly reduced in the aging brain. We suggest that the decreased ability for unisensory processing is a general phenomenon in the aging brain resulting in a shift toward multisensory integration., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We often close our eyes when we explore objects with our fingers to reduce the dominance of the visual system over our other senses. Here we show that eye closure, even in complete darkness, results in improved somatosensory perception due to a switch from visual predominance towards a somatosensory processing mode. Using a tactile discrimination task and functional neuroimaging (fMRI) data were acquired from healthy subjects with their eyes opened and closed in two environments: under ambient light and in complete darkness. Under both conditions the perception threshold decreased when subjects closed their eyes, and their fingers became more sensitive. In complete darkness, eye closure significantly increased occipital blood-oxygen-level-dependent (BOLD) activity in the somatosensory and secondary visual processing areas. This change in brain activity was associated with enhanced coupling between the sensory thalamus and somatosensory cortex; connectivity between the visual and somatosensory areas decreased. The present study demonstrates that eye closure improves somatosensory perception not merely due to the lack of visual signals; instead, the act of closing the eyes itself alters the processing mode in the brain: with eye closure the brain switches from thalamo-cortical networks with visual dominance to a non-visually dominated processing mode.

Objectives: Tissue plasminogen activator (t-PA) is the only approved thrombolytic therapy for the treatment of stroke patients. Its effectiveness is highly time dependent because of the sensitivity of brain tissue to ischemia. Because of the short half-life of t-PA, it should be administered as a bolus followed by an immediate infusion. However, in clinical practice, there are sometimes delays between the application of the bolus and the start of the infusion; in addition, interruptions of the infusion may occur. There are no recommendations regarding how to handle such situations., Methods: We simulate the effects on serum t-PA concentrations of different delays in administering t-PA using its known pharmacokinetic parameters in a 2-compartment model., Results: Our results demonstrate that even short delays of only 1 minute between bolus and infusion severely affect serum t-PA concentrations. In addition, interruptions to the infusion that are over 1 minute in duration affect serum t-PA concentrations., Conclusions: These results strongly suggest avoiding bolus-infusion delays by giving the bolus only when the infusion is ready. In case of a delayed start of the infusion, the possibilities are restricted to do nothing or to give a second bolus. We have estimated the dosing of the second bolus depending on the duration of the delay/interruption to allow for the achievement of appropriate serum t-PA concentrations. However, clinical safety data are needed to recommend the application of a second bolus.

In recent years, multiple studies have shown task-induced negative blood-oxygenation-level-dependent responses (NBRs) in multiple brain regions in humans and animals. Converging evidence suggests that task-induced NBRs can be interpreted in terms of decreased neuronal activity. However, the vascular and metabolic dynamics and functional importance of the NBR are highly debated. Here, we review studies investigating the origin and functional importance of the NBR, with special attention to the somatosensory cortex.

Vestibular neuritis is defined as a sudden unilateral partial failure of the vestibular nerve that impairs the forwarding of vestibular information from the labyrinth. The patient suffers from vertigo, horizontal nystagmus and postural instability with a tendency toward ipsilesional falls. Although vestibular neuritis is a common disease, the central mechanisms to compensate for the loss of precise vestibular information remain poorly understood. It was hypothesized that symptoms following acute vestibular neuritis originate from difficulties in the processing of diverging sensory information between the responsible brain networks. Accordingly an altered resting activity was shown in multiple brain areas of the task-positive network. Because of the known balance between the task-positive and task-negative networks (default mode network; DMN) we hypothesize that also the DMN is involved. Here, we employ functional magnetic resonance imaging (fMRI) in the resting state to investigate changes in the functional connectivity between the DMN and task-positive networks, in a longitudinal design combined with measurements of caloric function. We demonstrate an initially disturbed connectedness of the DMN after vestibular neuritis. We hypothesize that the disturbed connectivity between the default mode network and particular parts of the task-positive network might be related to a sustained utilization of processing capacity by diverging sensory information. The current results provide some insights into mechanisms of central compensation following an acute vestibular deficit and the importance of the DMN in this disease.

Cerebral plasticity includes the adaptation of anatomical and functional connections between parts of the involved brain network. However, little is known about the network dynamics of these connectivity changes. This study investigates the impact of a pure deefferentation, without deafferentation or brain damage, on the functional connectivity of the brain. To investigate this issue, functional MRI was performed on 31 patients in the acute state of Bell's palsy (idiopathic peripheral facial nerve palsy). All of the patients performed a motor paradigm to identify seed regions involved in motor control. The functional connectivity of the resting state within this network of brain regions was compared to a healthy control group. We found decreased connectivity in patients, mainly in areas responsible for sensorimotor integration and supervision (SII, insula, thalamus and cerebellum). However, we did not find decreased connectivity in areas of the primary or secondary motor cortex. The decreased connectivity for the SII and the insula significantly correlated to the severity of the facial palsy. Our results indicate that a pure deefferentation leads the brain to adapt to the current compromised state during rest. The motor system did not make a major attempt to solve the sensorimotor discrepancy by modulating the motor program.

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., (Copyright © 2012 Wiley Periodicals, Inc.)