Upper Alpha Based Neurofeedback Training in Chronic Stroke: Brain Plasticity Processes and Cognitive Effects.

In the present study, we investigated the effects of upper alpha based neurofeedback (NF) training on electrical brain activity and cognitive functions in stroke survivors. Therefore, two single chronic stroke patients with memory deficits (subject A with a bilateral subarachnoid hemorrhage; subject B with an ischemic stroke in the left arteria cerebri media) and a healthy elderly control group (N = 24) received up to ten NF training sessions. To evaluate NF training effects, all participants performed multichannel electroencephalogram (EEG) resting measurements and a neuropsychological test battery assessing different cognitive functions before and after NF training. Stroke patients showed improvements in memory functions after successful NF training compared to the pre-assessment. Subject B had a pathological delta (0.5-4 Hz) and upper alpha (10-12 Hz) power maximum over the unaffected hemisphere before NF training. After NF training, he showed a more bilateral and "normalized" topographical distribution of these EEG frequencies. Healthy participants as well as subject A did not show any abnormalities in EEG topography before the start of NF training. Consequently, no changes in the topographical distribution of EEG activity were observed in these participants when comparing the pre- and post-assessment. Hence, our results show that upper alpha based NF training had on the one hand positive effects on memory functions, and on the other hand led to cortical "normalization" in a stroke patient with pathological brain activation patterns, which underlines the potential usefulness of NF as neurological rehabilitation tool.

Shutting Down Sensorimotor Interferences after Stroke: A Proof-of-Principle SMR Neurofeedback Study.

INTRODUCTION: Neurofeedback training aims at learning self-regulation of brain activity underlying cognitive, emotional or physiological functions. Despite of promising investigations on neurofeedback as a tool for cognitive rehabilitation in neurological diseases, such as after stroke, there is still a lack of research on feasibility and efficiency of neurofeedback in this field. METHODS: The present study aimed at investigating behavioral and electrophysiological effects of 10 sessions of sensorimotor rhythm (SMR) neurofeedback in a 74-years-old stroke patient (UG20). Based on previous results in healthy young participants, we hypothesized that SMR neurofeedback leads to a decrease in sensorimotor interferences and improved stimulus processing, reflected by changes in event-related potentials (ERPs) and electrophysiological coherence. To assess whether UG20 benefited from the training as much as healthy persons of a similar age, a healthy control group of N = 10 elderly persons was trained as well. Before and after neurofeedback training, participants took part in a multichannel electroencephalography measurement conducted during a non-verbal and a verbal learning task. RESULTS: Both UG20 and the healthy controls were able to regulate their SMR activity during neurofeedback training. Moreover, in a non-verbal learning task, changes in ERPs and coherence were observed after training: UG20 showed a better performance in the non-verbal learning task and a higher P3 amplitude after training than before, and coherence between central and parietal electrodes decreased after training. The control group also showed a behavioral improvement in the non-verbal learning task and tendencies for higher P3 amplitudes and decreased central-parietal coherence after training. Single-case analyses indicated that the changes observed in UG20 were not smaller than the changes in healthy controls. CONCLUSION: Neurofeedback can be successfully applied in a stroke patient and in healthy elderly persons. We suggest that SMR neurofeedback leads to a shutting-down of sensorimotor interferences which benefits semantic encoding and retrieval.

Specific effects of EEG based neurofeedback training on memory functions in post-stroke victims.

BACKGROUND: Using EEG based neurofeedback (NF), the activity of the brain is modulated directly and, therefore, the cortical substrates of cognitive functions themselves. In the present study, we investigated the ability of stroke patients to control their own brain activity via NF and evaluated specific effects of different NF protocols on cognition, in particular recovery of memory. METHODS: N = 17 stroke patients received up to ten sessions of either SMR (N = 11, 12-15 Hz) or Upper Alpha (N = 6, e.g. 10-12 Hz) NF training. N = 7 stroke patients received treatment as usual as control condition. Furthermore, N = 40 healthy controls performed NF training as well. To evaluate the NF training outcome, a test battery assessing different cognitive functions was performed before and after NF training. RESULTS: About 70 % of both patients and controls achieved distinct gains in NF performance leading to improvements in verbal short- and long-term memory, independent of the used NF protocol. The SMR patient group showed specific improvements in visuo-spatial short-term memory performance, whereas the Upper Alpha patient group specifically improved their working memory performance. NF training effects were even stronger than effects of traditional cognitive training methods in stroke patients. NF training showed no effects on other cognitive functions than memory. CONCLUSIONS: Post-stroke victims with memory deficits could benefit from NF training as much as healthy controls. The used NF training protocols (SMR, Upper Alpha) had specific as well as unspecific effects on memory. Hence, NF might offer an effective cognitive rehabilitation tool improving memory deficits of stroke survivors.

Bacterial expression and functional reconstitution of human heparanase.

Human heparanase is a heparan sulfate degrading enzyme located in the extracellular matrix playing a decisive role in angiogenesis and tumor metastasis. Translated as a 65 kDa inactive prae-form, the protein is processed into an 8 kDa and a 50 kDa subunit which form a non-covalently associated active heterodimer. We have expressed the two subunits separately in Escherichia coli which yielded active human heparanase upon reconstitution. The two purified subunits folded independently and secondary structure analysis by far-UV CD spectroscopy gave 33.1/11.1% α/ß content for the 50 kDa subunit and 6.9/49% α/ß content for the 8 kDa subunit. This heparanase expression system is easy and can be used for efficient screening for enzyme inhibitors.

New targets for glycosaminoglycans and glycosaminoglycans as novel targets.

Biological functions of a variety of proteins are mediated via their interaction with glycosaminoglycans (GAGs). The structural diversity within the wide GAG landscape provides individual interaction sites for a multitude of proteins involved in several pathophysiological processes. This 'GAG angle' of such proteins as well as their specific GAG ligands give rise to novel therapeutic concepts for drug development. Current glycomic technologies to elucidate the glycan structure-function relationships, methods to investigate the selectivity and specificity of glycan-protein interactions and existing therapeutic approaches to interfere with GAG-protein interactions are discussed.

Chemokine degradation by the Group A streptococcal serine proteinase ScpC can be reconstituted in vitro and requires two separate domains.

Streptococcus pyogenes is one of the most common human pathogens and possesses diverse mechanisms to evade the human immune defence. One example of its immune evasion is the degradation of the chemokine IL (interleukin)-8 by ScpC, a serine proteinase that prevents the recruitment of neutrophils to an infection site. By applying the ANTIGENome technology and using human serum antibodies, we identified Spy0416, annotated as ScpC, as a prominent antigen that induces protective immune responses in animals. We demonstrate here for the first time that the recombinant form of Spy0416 is capable of IL-8 degradation in vitro in a concentration- and time-dependent manner. Mutations in the conserved amino acid residues of the catalytic triad of Spy0416 completely abolished in vitro activity. However, the isolated predicted proteinase domain does not exhibit IL-8-degrading activity, but is dependent on the presence of the C-terminal region of Spy0416. Binding to IL-8 is mainly mediated by the catalytic domain. However, the C-terminal region modulates substrate binding, indicating that the proteolytic activity is amenable to regulation via the non-catalytic regions. The specificity for human substrates is not restricted to IL-8, since we also detected in vitro protease activity for another CXC chemokine GRO-alpha (growth-related oncogene alpha), but not for NAP-2 (neutrophil-activating protein 2), SDF (stromal-cell-derived factor)-1alpha, PF-4 (platelet factor 4), I-TAC (interferon-gamma-inducible T-cell alpha-chemoattractant), IP-10 (interferon-gamma-inducible protein 10) and MCP-1 (monocyte chemoattractant protein 1). The degradation of two human CXC chemokines in vitro, the high sequence conservation, the immunogenicity of the protein in humans and the shown protection in animal studies suggest that Spy0416 is a promising vaccine candidate for the prevention of infections by S. pyogenes.