Electromyographic Characteristics of Postactivation Effect in Dopamine-Dependent Spectrum Models Observed in Parkinson's Disease and Schizophrenia.

This study aimed to test the hypothesis that the postactivation effect (PAE, involuntary normal muscle tone) is modified by dopaminergic mechanisms. The PAE was tested with surface electromyography (sEMG) in the "off medication" phase in participants with Parkinson's disease (PDoff) and in the "on medication" state in participants with schizophrenia (SZon), which modeled hypodopaminegic conditions, and in participants with PD "on medication" (PDon) and in participants with SZ "off medication" (SZoff) state which modeled the hyperdopaminergic conditions. Healthy age-matched participants constituted the control group (HC, n = 11). In hyperdopaminergic models, PAE was triggered in 71.3% of participants in SZoff and in 35.7% in PDon conditions. In the hypodopaminergic models, PAE was triggered in 12% in SZon and in 21.4% in PDoff conditions. In the HC group, PAE was present in 91% of participants. In the HC and PD groups, the mean frequency and correlation dimension of sEMG at PAE was higher than that during voluntary isometric contraction. In conclusion, in hypodopaminergic models, PAE triggering was inhibited. The manifestations and EMG characteristics of PAE in people with PD or SZ may indicate dopaminergic dysfunction.

Cognitive training and brain stimulation in patients with cognitive impairment: a randomized controlled trial.

BACKGROUND: Repeated sessions of training and non-invasive brain stimulation have the potential to enhance cognition in patients with cognitive impairment. We hypothesized that combining cognitive training with anodal transcranial direct current stimulation (tDCS) will lead to performance improvement in the trained task and yield transfer to non-trained tasks. METHODS: In our randomized, sham-controlled, double-blind study, 46 patients with cognitive impairment (60-80 years) were randomly assigned to one of two interventional groups. We administered a 9-session cognitive training (consisting of a letter updating and a Markov decision-making task) over 3 weeks with concurrent 1-mA anodal tDCS over the left dorsolateral prefrontal cortex (20 min in tDCS, 30 s in sham group). Primary outcome was trained task performance (letter updating task) immediately after training. Secondary outcomes included performance in tasks testing working memory (N-back task), decision-making (Wiener Matrices test) and verbal memory (verbal learning and memory test), and resting-state functional connectivity (FC). Tasks were administered at baseline, at post-assessment, and at 1- and 7-month follow-ups (FU). MRI was conducted at baseline and 7-month FU. Thirty-nine participants (85%) successfully completed the intervention. Data analyses are reported on the intention-to-treat (ITT) and the per-protocol (PP) sample. RESULTS: For the primary outcome, no difference was observed in the ITT (ß = 0.1, 95%-CI [- 1.2, 1.3, p = 0.93] or PP sample (ß = - 0.2, 95%-CI [- 1.6, 1.2], p = 0.77). However, secondary analyses in the N-back working memory task showed that, only in the PP sample, the tDCS outperformed the sham group (PP: % correct, ß = 5.0, 95%-CI [- 0.1, 10.2], p = 0.06, d-prime ß = 0.2, 95%-CI [0.0, 0.4], p = 0.02; ITT: % correct, ß = 3.0, 95%-CI [- 3.9, 9.9], p = 0.39, d-prime ß = 0.1, 95%-CI [- 0.1, 0.3], p = 0.5). Frontoparietal network FC was increased from baseline to 7-month FU in the tDCS compared to the sham group (pFDR < 0.05). Exploratory analyses showed a correlation between individual memory improvements and higher electric field magnitudes induced by tDCS (ρtDCS = 0.59, p = 0.02). Adverse events did not differ between groups, questionnaires indicated successful blinding (incidence rate ratio, 1.1, 95%-CI [0.5, 2.2]). CONCLUSIONS: In sum, cognitive training with concurrent brain stimulation, compared to cognitive training with sham stimulation, did not lead to superior performance enhancements in patients with cognitive impairment. However, we observed transferred working memory benefits in patients who underwent the full 3-week intervention. MRI data pointed toward a potential intervention-induced modulation of neural network dynamics. A link between individual performance gains and electric fields suggested dosage-dependent effects of brain stimulation. Together, our findings do not support the immediate benefit of the combined intervention on the trained function, but provide exploratory evidence for transfer effects on working memory in patients with cognitive impairment. Future research needs to explore whether individualized protocols for both training and stimulation parameters might further enhance treatment gains. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov (NCT04265378). Registered on 7 February 2020. Retrospectively registered.

Resonant Light Emission from Graphene/Hexagonal Boron Nitride/Graphene Tunnel Junctions.

Single-layer graphene has many remarkable properties but does not lend itself as a material for light-emitting devices as a result of its lack of a band gap. This limitation can be overcome by a controlled stacking of graphene layers. Exploiting the unique Dirac cone band structure of graphene, we demonstrate twist-controlled resonant light emission from graphene/hexagonal boron nitride (h-BN)/graphene tunnel junctions. We observe light emission irrespective of the crystallographic alignment between the graphene electrodes. Nearly aligned devices exhibit pronounced resonant features in both optical and electrical characteristics that vanish rapidly for twist angles θ ≳3°. These experimental findings can be well-explained by a theoretical model in which the spectral photon emission peak is attributed to photon-assisted momentum conserving electron tunneling. The resonant peak in our aligned devices can be spectrally tuned within the near-infrared range by over 0.2 eV, making graphene/h-BN/graphene tunnel junctions potential candidates for on-chip optoelectronics.

Detecting medication errors associated with the use of beta-lactams in the Russian Pharmacovigilance database.

BACKGROUND: Comprehensive analysis of all available data in spontaneous reports (SRs) can reveal previously unidentified medication errors (MEs). METHODS: To detect MEs, we performed a retrospective analysis of SRs submitted to the Russian pharmacovigilance database in the period from January 01, 2012, to August 01, 2014. This study evaluated SRs of cases where beta-lactam antibiotics were the suspected drug. RESULTS: A total of 3608 SRs were analyzed. MEswere detected in 1043 reports (28.9% of all cases). The total number of detected errors was 1214. Reporters themselves indicated MEs in 29 SRs. A term denoting an ME was selected in the "Adverse Reactions" section in 18 of these SRs, whereas in the other 11 reports information on the ME was found only in the "Case narrative" section. MEs were associated with wrong indications in 32.5% of the cases; 61.0% of these cases were viral infections. Various dosing regimen violations constituted 29.7% of MEs. A contraindicated drug was administered in 17.3% of all detected MEs, most commonly to a patient with a history of allergy to the suspected drug or severe hypersensitivity reactions to other drugs of the same group. CONCLUSION: Automatic identification of MEs in the pharmacovigilance database is sometimes precluded by the absence of a code for the respective episode in the "Adverse Reactions" section, even when the error was detected by the reporter. The most frequent types of MEs associated with the use of beta-lactams in Russia are the leading risk factors of growing bacterial resistance.

Cognitive training and brain stimulation in prodromal Alzheimer's disease (AD-Stim)-study protocol for a double-blind randomized controlled phase IIb (monocenter) trial.

BACKGROUND: Given the growing older population worldwide, and the associated increase in age-related diseases, such as Alzheimer's disease (AD), investigating non-invasive methods to ameliorate or even prevent cognitive decline in prodromal AD is highly relevant. Previous studies suggest transcranial direct current stimulation (tDCS) to be an effective method to boost cognitive performance, especially when applied in combination with cognitive training in healthy older adults. So far, no studies combining tDCS concurrent with an intense multi-session cognitive training in prodromal AD populations have been conducted. METHODS: The AD-Stim trial is a monocentric, randomized, double-blind, placebo-controlled study, including a 3-week tDCS-assisted cognitive training with anodal tDCS over left DLPFC (target intervention), compared to cognitive training plus sham (control intervention). The cognitive training encompasses a letter updating task and a three-stage Markov decision-making task. Forty-six participants with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) will be randomized block-wise to either target or control intervention group and participate in nine interventional visits with additional pre- and post-intervention assessments. Performance in the letter updating task after training and anodal tDCS compared to sham stimulation will be analyzed as primary outcome. Further, performance on the second training task and transfer tasks will be investigated. Two follow-up visits (at 1 and 7 months post-training) will be performed to assess possible maintenance effects. Structural and functional magnetic resonance imaging (MRI) will be applied before the intervention and at the 7-month follow-up to identify possible neural predictors for successful intervention. SIGNIFICANCE: With this trial, we aim to provide evidence for tDCS-induced improvements of multi-session cognitive training in participants with SCD and MCI. An improved understanding of tDCS effects on cognitive training performance and neural predictors may help to develop novel approaches to counteract cognitive decline in participants with prodromal AD. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04265378 . Registered on 07 February 2020. Retrospectively registered. Protocol version: Based on BB 004/18 version 1.2 (May 17, 2019). SPONSOR: University Medicine Greifswald.

Photobiomodulation of lymphatic drainage and clearance: perspective strategy for augmentation of meningeal lymphatic functions.

There is a hypothesis that augmentation of the drainage and clearing function of the meningeal lymphatic vessels (MLVs) might be a promising therapeutic target for preventing neurological diseases. Here we investigate mechanisms of photobiomodulation (PBM, 1267 nm) of lymphatic drainage and clearance. Our results obtained at optical coherence tomography (OCT) give strong evidence that low PBM doses (5 and 10 J/cm2) stimulate drainage function of the lymphatic vessels via vasodilation (OCT data on the mesenteric lymphatics) and stimulation of lymphatic clearance (OCT data on clearance of gold nanorods from the brain) that was supported by confocal imaging of clearance of FITC-dextran from the cortex via MLVs. We assume that PBM-mediated relaxation of the lymphatic vessels can be possible mechanisms underlying increasing the permeability of the lymphatic endothelium that allows molecules transported by the lymphatic vessels and explain PBM stimulation of lymphatic drainage and clearance. These findings open new strategies for the stimulation of MLVs functions and non-pharmacological therapy of brain diseases.

Nonlinear parameters of surface EMG in schizophrenia patients depend on kind of antipsychotic therapy.

UNLABELLED: We compared a set of surface EMG (sEMG) parameters in several groups of schizophrenia (SZ, n = 74) patients and healthy controls (n = 11) and coupled them with the clinical data. sEMG records were quantified with spectral, mutual information (MI) based and recurrence quantification analysis (RQA) parameters, and with approximate and sample entropies (ApEn and SampEn). Psychotic deterioration was estimated with Positive and Negative Syndrome Scale (PANSS) and with the positive subscale of PANSS. Neuroleptic-induced parkinsonism (NIP) motor symptoms were estimated with Simpson-Angus Scale (SAS). Dyskinesia was measured with Abnormal Involuntary Movement Scale (AIMS). We found that there was no difference in values of sEMG parameters between healthy controls and drug-naïve SZ patients. The most specific group was formed of SZ patients who were administered both typical and atypical antipsychotics (AP). Their sEMG parameters were significantly different from those of SZ patients taking either typical or atypical AP or taking no AP. This may represent a kind of synergistic effect of these two classes of AP. For the clinical data we found that PANSS, SAS, and AIMS were not correlated to any of the sEMG parameters. CONCLUSION: with nonlinear parameters of sEMG it is possible to reveal NIP in SZ patients, and it may help to discriminate between different clinical groups of SZ patients. Combined typical and atypical AP therapy has stronger effect on sEMG than a therapy with AP of only one class.

Surface EMG parameters in schizophrenia patients.

The aim of the study was to compare a variety of surface EMG (sEMG) parameters in several groups of schizophrenia (SZ, n=69) patients and healthy controls (n=44). We computed spectral, mutual information (MI) based and recurrence quantification analysis (RQA) parameters of sEMG. The major finding is that sEMG of the controls had higher values of the MI-based parameter, mean and median spectrum frequencies, and lower values of most of RQA parameters. It means higher content of recurrent fragments in sEMG of SZ patients. We suggest that the differences might be caused by either denervation/renervation process of single muscle fibers in SZ patients and/or by increased motor unit synchronization induced by antipsychotic therapy.