[Late-life depression and frailty-Epidemiological, clinical and neurobiological associations]. / Depression im Alter und Frailty ­ epidemiologische, klinische und neurobiologische Zusammenhänge.

BACKGROUND: Depression is the most common mental disorder in older adults and is influenced by age-related processes. Frailty is a well-established clinical expression of ageing that implies a state of increased vulnerability to stressor events as well as increased risks of disability, hospitalization and death. Neurobiological findings will disentangle the comorbidity of frailty and depression and may inform future management of depression in old age. OBJECTIVE: This narrative review provides an overview of the comorbidity of late-life depression and frailty, with a focus on neuroscientific findings that are organized within the research domain criteria (RDoC) framework. RESULTS: More than one third of old people with depression are affected by frailty, which results in more chronic depression and in poorer efficacy and tolerability of antidepressant medication. Depression and frailty share motivational and psychomotor characteristics, particularly apathy, decreased physical activity and fatigue. In patients with frailty, altered activity of the supplementary motor cortex is associated with motor performance deficits. Patients with late-life depression and apathy are characterized by abnormal structure and altered functional connectivity of the reward network and the salience network, along with altered functional connectivity of these networks with premotor brain areas. CONCLUSION: Identifying frailty in older adults with depression is relevant for prognostic assessment and treatment. A better understanding of the neuronal mechanisms of comorbidity will provide potential targets for future personalized therapeutic interventions.

Sources for constellation errors in modulated dispersion interferometers.

Dispersion interferometry (DI) is being employed on an increasing number of fusion experiments to measure the plasma density with a minimal sensitivity to vibrations. DIs employed in high-density experiments use phase modulation techniques up to several hundred kilohertz to enable quadrature detection and to be unaffected by variations of the signal amplitude. However, the evaluation of the temporal interferogram can be a significant source for phase errors and does not have an established processing method. There are two non-approximation-based methods currently in use: one using the ratio of amplitudes in the signal's Fourier spectrum and the other using its sectioned integration. Previously, the methods could not be used simultaneously since they differ in their respective calibration point. In this paper, we present a technique to use both phase evaluation methods simultaneously using quadrature correction methods. A comparison of their strengths and weaknesses is presented based on identical measurements indicating one to be more reliable in a more static measurement scenario, while the other excels in highly dynamic ones. Several comparative experiments are presented, which identify a significant error source in the phase measurement induced by polarization rotation. Since the same effect may be induced by Faraday rotation, the results may have direct consequence on the design of the ITER dispersion interferometer/polarimeter as well as the European DEMO's interferometer concept.

Impact of Magnetic Field Configuration on Heat Transport in Stellarators and Heliotrons.

We assess the magnetic field configuration in modern fusion devices by comparing experiments with the same heating power, between a stellarator and a heliotron. The key role of turbulence is evident in the optimized stellarator, while neoclassical processes largely determine the transport in the heliotron device. Gyrokinetic simulations elucidate the underlying mechanisms promoting stronger ion scale turbulence in the stellarator. Similar plasma performances in these experiments suggests that neoclassical and turbulent transport should both be optimized in next step reactor designs.

Demonstration of reduced neoclassical energy transport in Wendelstein 7-X.

Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2, a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4. The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5. Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization.

Neural network surrogates of Bayesian diagnostic models for fast inference of plasma parameters.

We present a framework for training artificial neural networks (ANNs) as surrogate Bayesian models for the inference of plasma parameters from diagnostic data collected at nuclear fusion experiments, with the purpose of providing a fast approximation of conventional Bayesian inference. Because of the complexity of the models involved, conventional Bayesian inference can require tens of minutes for analyzing one single measurement, while hundreds of thousands can be collected during a single plasma discharge. The ANN surrogates can reduce the analysis time down to tens/hundreds of microseconds per single measurement. The core idea is to generate the training data by sampling them from the joint probability distribution of the parameters and observations of the original Bayesian model. The network can be trained to learn the reconstruction of plasma parameters from observations and the model joint probability distribution from plasma parameters and observations. Previous work has validated the application of such a framework to the former case at the Wendelstein 7-X and Joint European Torus experiments. Here, we first give a description of the general methodological principles allowing us to generate the training data, and then we show an example application of the reconstruction of the joint probability distribution of an effective ion charge Zeff-bremsstrahlung model from data collected at the latest W7-X experimental campaign. One key feature of such an approach is that the network is trained exclusively on data generated with the Bayesian model, requiring no experimental data. This allows us to replicate the training scheme and generate fast, surrogate ANNs for any validated Bayesian diagnostic model.

Vasogenic Brain Edema During Maintenance Hemodialysis : Preliminary Results from Tract-based Spatial Statistics and Voxel-based Morphometry.

BACKGROUND: Hemodialysis (HD), especially when first initiated, can cause neurological deterioration. Presumably this is due to transient cerebral edema, which has been observed using diffusion weighted magnetic resonance imaging (MRI) in experimental and human studies; however, this has not been investigated under maintenance hemodialysis (mHD). Moreover, there are no studies to date investigating regional effects of mHD on grey and white matter volumes. METHODS: In this study eight patients with end stage renal disease (ESRD) were examined immediately before and after mHD sessions with multimodal MRI, including diffusion tensor imaging (DTI) and high-resolution structural imaging. Additionally, eight healthy, age-matched and sex-matched controls were examined for comparison. Data were analyzed using tract-based spatial statistics and voxel-based morphometry. RESULTS: At baseline, ESRD patients had significantly reduced values of fractional anisotropy (FA) and axial diffusivity as well as bilaterally reduced grey matter volume in the insula, compared with controls. After the mHD session, FA further decreased while axial, radial, and mean diffusivity significantly increased ubiquitously throughout the white matter. Voxel-based morphometry revealed a corresponding significant increase in white matter volume in the central right hemisphere and splenium, as well as in cortical grey matter in the anterior medial frontal and cingulate cortex. None of the patients showed neurological deterioration. CONCLUSION: In this study ESRD patients showed white matter changes indicative of chronic microstructural damage when compared with healthy controls, as previously reported. In addition, patients showed signs of a transient extracellular cerebral edema, which has not yet been observed in the absence of neurological symptoms.

Charge exchange recombination spectroscopy at Wendelstein 7-X.

The Charge Exchange Recombination Spectroscopy (CXRS) diagnostic has become a routine diagnostic on almost all major high temperature fusion experimental devices. For the optimized stellarator Wendelstein 7-X (W7-X), a highly flexible and extensive CXRS diagnostic has been built to provide high-resolution local measurements of several important plasma parameters using the recently commissioned neutral beam heating. This paper outlines the design specifics of the W7-X CXRS system and gives examples of the initial results obtained, including typical ion temperature profiles for several common heating scenarios, toroidal flow and radial electric field derived from velocity measurements, beam attenuation via beam emission spectra, and normalized impurity density profiles under some typical plasma conditions.

Inference of temperature and density profiles via forward modeling of an x-ray imaging crystal spectrometer within the Minerva Bayesian analysis framework.

At the Wendelstein 7-X stellarator, the X-ray imaging crystal spectrometer provides line integrated measurements of ion and electron temperatures, plasma flows, as well as impurity densities from a spectroscopic analysis of tracer impurity radiation. In order to infer the actual profiles from line integrated data, a forward modeling approach has been developed within the Minerva Bayesian analysis framework. In this framework, the inversion is realized on the basis of a complete forward model of the diagnostic, including error propagation and utilizing Gaussian processes for generation and inference of arbitrary shaped plasma parameter profiles. For modeling of line integrated data as measured by the detector, the installation geometry of the spectrometer, imaging properties of the crystal, and Gaussian detection noise are considered. The inversion of line integrated data is achieved using the maximum posterior method for plasma parameter profile inference and a Markov chain Monte Carlo sampling of the posterior distribution for calculating uncertainties of the inference process. The inversion method shows a correct and reliable inference of temperature and impurity density profiles from synthesized data within the estimated uncertainties along the whole plasma radius. The application to measured data yields a good match of derived electron temperature profiles to data of the Thomson scattering diagnostic for central electron temperatures between 2 and 5 keV using argon impurities.

On using Rayleigh scattering for in situ spectral calibration of Thomson scattering diagnostics.

A new method for in situ spectral calibration of Thomson scattering diagnostics is proposed. The idea of the method is to apply a wavelength tunable optical parametric oscillator for measurements of Rayleigh scattering at different wavelengths, from which relative sensitivities can be calculated. This extends the usual approach where Rayleigh scattering is used only at a single wavelength for the absolute calibration and spectral sensitivities are obtained separately. With the new approach, the full diagnostic setup is spectrally calibrated at once. Such a calibration can be repeated at regular intervals during an experimental campaign since it does not require a break of the vacuum. In this paper, the Rayleigh scattering calibration is tested in a laboratory setup with a sample Wendelstein 7-X (W7-X) polychromator. It is shown that relative sensitivities of spectral channels can be recovered with a sufficient resolution even under conditions of significant stray light. The stray light is overcome by measuring the linear dependence of the scattered signal on the gas pressure. Good results of laboratory tests motivate the installation of the new calibration system for the Thomson scattering diagnostic at W7-X.

Collective Thomson scattering diagnostic at Wendelstein 7-X.

A Collective Thomson Scattering (CTS) diagnostic is installed at Wendelstein 7-X for ion temperature measurements in the plasma core. The diagnostic utilizes 140 GHz gyrotrons usually used for electron cyclotron resonance heating (ECRH) as a source of probing radiation. The CTS diagnostic uses a quasi-optical transmission line covering a distance of over 40 m. The transmission line is shared between the ECRH system and the CTS diagnostic. Here we elaborate on the design, installation, and alignment of the CTS diagnostic and present the first measurements at Wendelstein 7-X.

[Antipsychotic-induced motor symptoms in schizophrenic psychoses-Part 2 : Catatonic symptoms and neuroleptic malignant syndrome]. / Antipsychotikaassoziierte motorische Symptome bei schizophrenen Psychosen ­ Teil 2 : Katatone Symptome und malignes neuroleptisches Syndrom.

In rare cases, pharmacotherapy in schizophrenic psychoses can be associated with life-threatening antipsychotic-induced movement disorders. The two most severe complications are antipsychotic-associated catatonic symptoms (ACS) and neuroleptic malignant syndrome (NMS). Although both constellations necessitate rapid medical care, the diagnosis is still a clinical challenge. Although there is no established treatment of ACS (here designated as a specific subtype of catatonic symptoms), an attempt should be made with benzodiazepines and memantine can also be helpful. In severe drug-refractory cases electroconvulsive therapy (ECT) can be indicated. The NMS represents a life-threatening constellation that frequently requires intensive care unit treatment. The medicinal treatment with benzodiazepines, bromocriptine, amantadine, dantrolene and/or ECT is also advocated. Finally, this review article also summarizes the currently available literature for treatment of genuine catatonic symptoms. In conclusion, the abovementioned clinical syndromes must be rapidly recognized and treated. Early recognition and treatment of these movement disorders can under certain circumstances be lifesaving and favorably influence the later clinical outcome.

[Antipsychotic-induced motor symptoms in schizophrenic psychoses-Part 1 : Dystonia, akathisia und parkinsonism]. / Antipsychotikaassoziierte motorische Symptome bei schizophrenen Psychosen ­ Teil 1 : Dystonien, Akathisie und Parkinsonismus.

Acute antipsychotic-induced movement disorders (AIMD) are clinically relevant since they are frequently associated with high subjective distress, and since over the long-term they can negatively impact treatment adherence of patients with schizophrenic psychoses. This review article summarizes the relevant studies on the prevalence, risk factors, prevention and treatment options and instruments for early prediction of acute AIMD in schizophrenic psychoses. The current evidence and treatment recommendations are divided into three main areas: acute dystonia, akathisia, and parkinsonism. For the treatment of acute dystonia trihexyphenidyl and biperiden have shown their efficacy. Considering pharmacological treatment of akathisia, there is some preliminary evidence for medication with lipophilic beta-receptor blockers (propranolol and pindolol), clonidine, benzodiazepines, mianserin, mirtazapine und trazodone. The treatment options for drug-induced parkinsonism include reduction or switching from one antipsychotic to another with a lower affinity for dopamine D2 receptors, amantadine or in the regular administration of anticholinergic drugs. In conclusion, acute AIMD is easily to recognize but is not always effectively and durably treated. Early recognition and treatment of acute AIMD could be associated with improved treatment outcomes.

[Antipsychotic-induced motor symptoms in schizophrenic psychoses-Part 3 : Tardive dyskinesia]. / Antipsychotikaassoziierte motorische Symptome bei schizophrenen Psychosen ­ Teil 3 : Spätdyskinesien.

The treatment of schizophrenic psychoses with antipsychotic drugs (AP) is often associated with an increased risk of delayed occurrence of antipsychotic-associated movement disorders. Persistence and chronicity of such symptoms are very frequent. The risk of developing tardive dyskinesia (TD) is associated with the pharmacological effect profile of a particular AP, with treatment duration and age. This systematic review article summarizes the current study situation on prevalence, risk factors, prevention and treatment options and instruments for early prediction of TD in schizophrenic psychoses. The current data situation on treatment strategies for TD is very heterogeneous. For the treatment of TD there is preliminary evidence for reduction or discontinuation of the AP, switching to clozapine, administration of benzodiazepines (clonazepam) and treatment with vesicular monoamine transporter (VMAT2) inhibitors, ginkgo biloba, amantadine or vitamin E. Although TD can be precisely diagnosed it cannot always be effectively treated. Early detection and early treatment of TD can have a favorable influence on the prognosis and the clinical outcome.

Dual-laser wavelength Thomson scattering at Wendelstein 7-X.

This paper presents the approach of the dual-laser wavelength Thomson scattering (TS) system for the Wendelstein 7-X stellarator. The dual-laser wavelength TS method is based on two lasers with different wavelengths being fired quasi-simultaneously. This method has two advantages compared to a single laser wavelength TS system. First, the dual laser availability allows an in situ spectral calibration, and second, higher electron temperatures can be measured without any change in the spectral filter setup of the polychromators. The W7-X dual-laser wavelength TS concept is based on high power lasers: a set of standard Nd:YAG lasers with λ = 1064 nm wavelength and a Nd:YAG laser with λ = 1319 nm wavelength newly developed for this application. This laser uses a different transition line with 34% efficiency compared to the main 1064 nm Nd:YAG line. Simulations of the expected performance of the new dual-laser wavelength system show that electron temperatures up to Te = 15 keV can be measured compared to the original design parameter up to Te = 10 keV. The in situ spectral calibration can be performed using a range of temperatures from 1 keV to 10 keV using TS measurements of the 1064 nm versus 1319 nm TS simultaneously.

Bayesian uncertainty calculation in neural network inference of ion and electron temperature profiles at W7-X.

We make use of a Bayesian description of the neural network (NN) training for the calculation of the uncertainties in the NN prediction. Having uncertainties on the NN prediction allows having a quantitative measure for trusting the NN outcome and comparing it with other methods. Within the Bayesian framework, the uncertainties can be calculated under different approximations. The NN has been trained with the purpose of inferring ion and electron temperature profile from measurements of a X-ray imaging diagnostic at W7-X. The NN has been trained in such a way that it constitutes an approximation of a full Bayesian model of the diagnostic, implemented within the Minerva framework. The network has been evaluated using measured data and the uncertainties calculated under different approximations have been compared with each other, finding that neglecting the noise on the NN input can lead to an underestimation of the error bar magnitude in the range of 10%-30%.

Prospects of X-ray imaging spectrometers for impurity transport: Recent results from the stellarator Wendelstein 7-X (invited).

This paper reports on the design and the performance of the recently upgraded X-ray imaging spectrometer systems, X-ray imaging crystal spectrometer and high resolution X-ray imaging spectrometer, installed at the optimized stellarator Wendelstein 7-X. High resolution spectra of highly ionized, He-like Si, Ar, Ti, and Fe as well as H-like Ar have been observed. A cross comparison of ion and electron temperature profiles derived from a spectral fit and tomographic inversion of Ar and Fe spectra shows a reasonable match with both the spectrometers. The also measured impurity density profiles of Ar and Fe have peaked densities at radial positions that are in qualitative agreement with the expectations from the He-like impurity fractional abundances, given the measured temperature profiles. Repeated measurements of impurity decay times have been demonstrated with an accuracy of 1 ms via injection of non-recycling Ti, Fe, and Mo impurities using a laser blow-off system.

[Genuine motor phenomena in schizophrenia : Neuronal correlates and pathomechanisms]. / Genuine motorische Phänomene bei schizophrenen Psychosen : Neuronale Korrelate und Pathomechanismen.

Despite a growing body of evidence on motor dysfunction in schizophrenia spectrum disorders, the neuronal correlates of genuine motor abnormalities (GMA) are not fully elucidated at present. Moreover, the clinical relevance of a potential "motor intermediate phenotype" remains controversial. This systematic review aims at characterizing a "motor intermediate phenotype" in schizophrenia spectrum disorders. The second goal of this systematic review is to discuss GMA-associated brain alterations as potential biomarkers of psychosis risk syndrome and manifest motor symptoms against the background of current neuroimaging evidence. The detailed clinical assessment of GMA in the context of multimodal imaging could, in the future promote the early recognition of psychotic disorders and the initiation of disorder-oriented and individualized treatment. Taken as a whole the data provide initial evidence that motor dysfunction in schizophrenic spectrum disorders must be considered dimensionally. The predictive value of neurobiological results with respect to the transition to a life-threatening catatonia or the development of chronic dyskinesia, cannot currently be conclusively assessed.

[Genuine motor phenomena in schizophrenic psychoses : Theoretical background and definition of context]. / Genuine motorische Phänomene bei schizophrenen Psychosen : Theoretischer Hintergrund und Kontextdefinition.

Besides positive and negative symptoms, motor abnormalities have been increasingly recognized as central symptoms of schizophrenia. Recent investigations of antipsychotic-naive first-episode patients with schizophrenia found significantly higher rates of genuine motor abnormalities (GMA) when compared to healthy individuals. The first part of this article introduces the historical and clinical background of GMA in schizophrenia. In the second part the relevance of scientific research and clinical implication of GMA in schizophrenia are discussed. Finally, this article aims at presenting a conceptual framework and a reference system involving both genuine and drug-induced motor abnormalities. The future clinical implications of GMA research are presented and multimodal and transdiagnostic studies are advocated. Future research on GMA will not only essentially enrich the formation of psychiatric theories but also promote progress in clinical neuroscience.