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Parkinson's Disease (PD) is a multifaceted and progressive disorder characterized by a diverse range of motor and non-motor symptoms. The complexity of PD necessitates a multidisciplinary approach to manage both motor symptoms, such as bradykinesia, gait disturbances and falls, and non-motor symptoms, including cognitive dysfunction, sleep disturbances, and mood disorders, which significantly affect patients' quality of life. Pharmacotherapy, particularly dopaminergic replacement therapy, has advanced to alleviate many symptoms. However, these medications can also induce side effects or aggravate symptoms like hallucinations or orthostatic dysfunction, highlighting the need for comprehensive patient management. The optimal care for PD patients involves a team of specialists, including neurologists, physical and occupational therapists, speech-language pathologists, psychologists, and other medical professionals, to address the complex and individualized needs of each patient. Here, we illustrate the necessity of such a multidisciplinary approach in four illustrative PD cases with different disease stages and motor and non-motor complications. The patients were treated in different treatment settings (specialized outpatient clinic, day clinic, inpatient care including neurorehabilitation). The biggest challenge lies in organizing and implementing such comprehensive care effectively across different clinical settings., (© 2024. The Author(s).)

Background: Obstructive lung disease (OLD) is increasingly prevalent among persons living with HIV (PLWH). However, the role of proteases in HIV-associated OLD remains unclear., Methods: We combined proteomics and peptidomics to comprehensively characterize protease activities. We combined mass spectrometry (MS) analysis on bronchoalveolar lavage fluid (BALF) peptides and proteins from PLWH with OLD (n = 25) and without OLD (n = 26) with a targeted Somascan aptamer-based proteomic approach to quantify individual proteases and assess their correlation with lung function. Endogenous peptidomics mapped peptides to native proteins to identify substrates of protease activity. Using the MEROPS database, we identified candidate proteases linked to peptide generation based on binding site affinities which were assessed via z-scores. We used t-tests to compare average forced expiratory volume in 1 s per predicted value (FEV1pp) between samples with and without detection of each cleaved protein and adjusted for multiple comparisons by controlling the false discovery rate (FDR)., Findings: We identified 101 proteases, of which 95 had functional network associations and 22 correlated with FEV1pp. These included cathepsins, metalloproteinases (MMP), caspases and neutrophil elastase. We discovered 31 proteins subject to proteolytic cleavage that associate with FEV1pp, with the top pathways involved in small ubiquitin-like modifier mediated modification (SUMOylation). Proteases linked to protein cleavage included neutrophil elastase, granzyme, and cathepsin D., Interpretations: In HIV-associated OLD, a significant number of proteases are up-regulated, many of which are involved in protein degradation. These proteases degrade proteins involved in cell cycle and protein stability, thereby disrupting critical biological functions., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Estimates of the spectrum and frequency of pathogenic variants in Parkinson's disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson's disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Obstructive lung disease (OLD) is increasingly prevalent among persons living with HIV (PLWH). However, the role of proteases in HIV-associated OLD remains unclear., Methods: We combined proteomics and peptidomics to comprehensively characterize protease activities. We combined mass spectrometry (MS) analysis on bronchoalveolar lavage fluid (BALF) peptides and proteins from PLWH with OLD (n=25) and without OLD (n=26) with a targeted Somascan aptamer-based proteomic approach to quantify individual proteases and assess their correlation with lung function. Endogenous peptidomics mapped peptides to native proteins to identify substrates of protease activity. Using the MEROPS database, we identified candidate proteases linked to peptide generation based on binding site affinities which were assessed via z-scores. We used t-tests to compare average forced expiratory volume in 1 second per predicted value (FEV1pp) between samples with and without detection of each cleaved protein and adjusted for multiple comparisons by controlling the false discovery rate (FDR)., Findings: We identified 101 proteases, of which 95 had functional network associations and 22 correlated with FEV1pp. These included cathepsins, metalloproteinases (MMP), caspases and neutrophil elastase. We discovered 31 proteins subject to proteolytic cleavage that associate with FEV1pp, with the top pathways involved in small ubiquitin-like modifier mediated modification (SUMOylation). Proteases linked to protein cleavage included neutrophil elastase, granzyme, and cathepsin D., Interpretations: In HIV-associated OLD, a significant number of proteases are up-regulated, many of which are involved in protein degradation. These proteases degrade proteins involved in cell cycle and protein stability, thereby disrupting critical biological functions., Competing Interests: Additional Declarations: No competing interests reported.

The phase delay introduced by photodetectors can be affected by intensity, reverse bias, and temperature through different effects. An optical pilot tone superimposed on the detected signal allows an independent measurement of such phase errors in the complete photodetection chain and provides an opportunity to correct them. This allows to further separate readout noise from the measurement, providing a more performant and intensity-invariant phase readout. We test the functional principle on a setup demonstrating an improved phase noise performance and a reduced phase walk below 10 mHz in particular. This benefits applications that require accurate timing or signal phase determination with photodiodes.

Background: Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability., Objective: We sought to characterize the role of EIF4A2 variants in dystonic conditions., Methods: We undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts., Results: We report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees., Conclusions: Our findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Dopamine agonists are an important component of Parkinson's therapy. When weighing up the various therapy options, therapy with levodopa has recently been increasingly preferred due to its stronger efficacy and the ostensibly lower rate of side effects. The advantage of the lower incidence of motor complications during therapy with dopamine agonists was neglected. The occurrence of side effects can be explained by the different receptor affinity to the individual dopaminergic and non-dopaminergic receptors of the individual dopamine agonists. However, the different affinity to individual receptors also explains the different effect on individual Parkinson symptoms and can, therefore, contribute to a targeted use of the different dopamine agonists. Since comparative studies on the differential effect of dopamine agonists have only been conducted for individual substances, empirical knowledge of the differential effect is of great importance. Therefore, the guidelines for the treatment of Parkinson's disease do not consider the differential effect of the dopamine agonists. The historical consideration of dopamine agonists within Parkinson's therapy deserves special attention to be able to classify the current discussion about the significance of dopamine agonists., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

We present a fully bonded, misalignment-free, diode-pumped Yb:ceramic (Yb:Y 2 O 3 ) oscillator producing 190-fs pulses at a repetition frequency of 2.185 GHz. Self-starting Kerr-lens-modelocked operation was obtained from both outputs of the ring cavity with an average combined output power of 14-30 mW for pump powers from 380-670 mW. The fully bonded design provided self-starting, turnkey operation, with a relative intensity noise of 0.025% from 1 Hz-1 MHz. Tuning of the pulse repetition rate over a 120 kHz range was demonstrated for a 2°C change in temperature. Chirped-pulse amplification in a semiconductor optical amplifier was shown to increase the pulse average power to 69 mW and the pulse energy (peak power) from 2.5 pJ (12 W) to 32 pJ (71 W).

Patients with idiopathic Parkinson's disease develop symptoms of the hallucination-psychosis spectrum in more than 20%. Most common are visual hallucinations. The pathogenesis of hallucinations mainly depends on disease duration, the distribution and extent of alpha-synuclein pathology, and modulating effects of the dopaminergic therapy. When managing PD hallucinations both anti-delirogenic actions and medication management are important. However, decrease in dopaminergic medication may lead to critical worsening of akinesia. If appropriate neuroleptic medication - essentially quetiapin or clozapin - can be considered. Instead, anti-dopaminergic neuroleptics should not be used owing to their pro-akinetic side-effects. Here, we provide therapy recommendations to manage PD hallucinations based on an up-to-date targeted review of the literature and expert-based empirical evidence., Competing Interests: Daniel Weiss berichtet Vortrags- und Beratungshonorare, sowie Reise- und Forschungszuschüsse von Abbott, Abbvie, Bial, Boston Scientific, Medtronic, STADA; Günther Höglinger berichtet Vortragshonorare von Abbvie, Bayer Vital, Bial, Biogen, Bristol Myers Squibb, Kyowa Kirin, Roche, Teva, UCB, Zambon;Kirsten Zeuner erhielt Forschungsunterstützung der Firma Strathmann, sie war in Beratungsgremien (Advisory Boards) für die Firmen Bial, Merz, Ipsen und Alexion tätig. Sie erhielt Vortragshonorare von Bayer Vital GmbH, BIAL, AbbVie Allergan und Merz. Sie war für das Bundesministerium für Arzneimittel und Medizinprodukte als Gutachterin tätig. David Weise: Honorare für Vorträge oder als Berater von Abbvie, Allergan, Bial, Biogen, Daichii Sankyo, Ipsen, Kyowa Kirin, Licher MT, Merz, Roche, Stada Pharm und UCB Pharma.Heinz Reichmann was acting on Advisory Boards and gave lectures and received research grants within the last 5 years from Bial, Desitin, Eisai, Kyowa-Kirin, Merz, Novartis, UCB Pharma, Zambon., (Thieme. All rights reserved.)

Introduction: Although shared genetic factors have been previously reported between dystonia and other neurologic conditions, no sequencing study exploring such links is available. In a large dystonic cohort, we aimed at analyzing the proportions of causative variants in genes associated with disease categories other than dystonia., Methods: Gene findings related to whole-exome sequencing-derived diagnoses in 1100 dystonia index cases were compared with expert-curated molecular testing panels for ataxia, parkinsonism, spastic paraplegia, neuropathy, epilepsy, and intellectual disability., Results: Among 220 diagnosed patients, 21% had variants in ataxia-linked genes; 15% in parkinsonism-linked genes; 15% in spastic-paraplegia-linked genes; 12% in neuropathy-linked genes; 32% in epilepsy-linked genes; and 65% in intellectual-disability-linked genes. Most diagnosed presentations (80%) were related to genes listed in ≥1 studied panel; 71% of the involved loci were found in the non-dystonia panels but not in an expert-curated gene list for dystonia., Conclusions: Our study indicates a convergence in the genetics of dystonia and other neurologic phenotypes, informing diagnostic evaluation strategies and pathophysiological considerations., Competing Interests: Declaration of competing interest None of the authors report disclosures concerning the present manuscript., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

On a group level, satisfaction with botulinum neurotoxin (BoNT) treatment in neurological indications is high. However, it is well known that a relevant amount of patients may not respond as expected. The aim of this study is to evaluate the BoNT treatment outcome on an individual level using a statistical single-case analysis as an adjunct to traditional group statistics. The course of the daily perceived severity of symptoms across a BoNT cycle was analyzed in 20 cervical dystonia (CD) and 15 hemifacial spasm (HFS) patients. A parametric single-case autoregressive integrated moving average (ARIMA) time series analysis was used to detect individual responsiveness to BoNT treatment. Overall, both CD and HFS patients significantly responded to BoNT treatment with a gradual worsening of symptom intensities towards BoNT reinjection. However, only 8/20 CD patients (40%) and 5/15 HFS patients (33.3%) displayed the expected U-shaped curve of BoNT efficacy across a single treatment cycle. CD (but not HFS) patients who followed the expected outcome course had longer BoNT injection intervals, showed a better match to objective symptom assessments, and were characterized by a stronger certainty to control their somatic symptoms (i.e., internal medical locus of control). In addition to standard evaluation procedures, patients should be identified who do not follow the mean course-of-treatment effect. Thus, the ARIMA single-case time series analysis seems to be an appropriate addition to clinical treatment studies in order to detect individual courses of subjective symptom intensities.

We demonstrate a method for measuring a surface map of a spherical body with interferometric optical point sensors while rotating the test subject. The setup takes advantage of the excellent performance of heterodyne interferometry at nanometer levels and suppression of common-mode errors, as a cylindrical mirror mounted adjacent to the sphere is used as a reference. Future space based missions for gravitational wave research demand an improved inertial reference sensor with reduced acceleration noise levels. Spherical test masses can enable increased performance by suspension-free operation, contrary to cuboid solutions suffering from cross-coupling of attitude control noise into test mass position. However, interferometric readout is affected by surface irregularities and test mass attitude. An accurate surface map for compensation of the center of gravity readout should be established, by characterization either a priori or in-flight, when optical path length changes due to the surface occur in the measurement bandwidth.

Dystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking. Here, a biomarker is reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, a leading subtype among the individually rare monogenic dystonias. It was derived by applying a support vector machine to an episignature of 113 DNA CpG sites, which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at least 1× log-fold change of methylation. This classifier was accurate both when tested on the general population and on samples with various other deficiencies of the epigenetic machinery, thus allowing for definitive evaluation of variants of uncertain significance and identifying patients who may profit from deep brain stimulation, a highly successful treatment in KMT2B-deficient dystonia. Methylation was increased in KMT2B deficiency at all 113 CpG sites. The coefficients of variation of the normalized methylation levels at these sites also perfectly classified the samples with KMT2B-deficient dystonia. Moreover, the mean of the normalized methylation levels correlated well with the age at onset of dystonia (P = 0.003)-being lower in samples with late or incomplete penetrance-thus serving as a predictor of disease onset and severity. Similarly, it may also function in monitoring the recently envisioned treatment of KMT2B deficiency by inhibition of DNA methylation., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Purpose: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with predominant progressive degeneration of motor neurons and motor deficits, but non-motor symptoms (NMS) such as cognitive and behavioural deficits are frequent and underestimated in current diagnostic pathways. Autonomic dysfunction has occasionally been described, although its frequency and relevance are unclear. The aim of this study was to investigate the role of the autonomic nervous system in ALS using a multimodal approach., Methods: Thirty-seven ALS patients and 40 healthy sex- and age-matched controls were included. NMS were studied with the NMS assessment scale for Parkinson's disease and an autonomic subscale was calculated. Cardioautonomic innervation at rest and whilst standing was assessed by different parameters of heart rate variability. Morphological changes (cross-sectional area) of the vagus and median nerves for control were measured with high-resolution ultrasound., Results: Non-motor symptoms in general were more frequent in ALS patients and correlated inversely with the ALS Functional Rating Scale whereas the autonomic subscore of the NMS assessment scale for Parkinson's disease did not differ between the two groups and was not related to functional impairment. Cardioautonomic assessment solely revealed an increased heart rate at rest in ALS patients, whereas the other heart rate variability parameters did not differ from controls. Structural sonographic investigation of the vagus and median nerves was similar in both groups., Conclusions: Using a multimodal approach evidence was found for a rather mild cardio-sympathetic overactivity in ALS patients. Overall, autonomic dysfunction seems to be subtle and is not related to the functional state of ALS patients., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Energy harvesting has an essential role in the development of reliable devices for environmental wireless sensor networks (EWSN) in the Internet of Things (IoT), without considering the need to replace discharged batteries. Thermoelectric energy is a renewable energy source that can be exploited in order to efficiently charge a battery. The paper presents a simulation of an environment monitoring device powered by a thermoelectric generator (TEG) that harvests energy from the temperature difference between air and soil. The simulation represents a mathematical description of an EWSN, which consists of a sensor model powered by a DC/DC boost converter via a TEG and a load, which simulates data transmission, a control algorithm and data collection. The results section provides a detailed description of the harvested energy parameters and properties and their possibilities for use. The harvested energy allows supplying the load with an average power of 129.04 μW and maximum power of 752.27 μW. The first part of the results section examines the process of temperature differences and the daily amount of harvested energy. The second part of the results section provides a comprehensive analysis of various settings for the EWSN device's operational period and sleep consumption. The study investigates the device's number of operational cycles, quantity of energy used, discharge time, failures and overheads.

We report a 1.5-GHz Kerr-lens mode-locked (KLM) Yb: Y 2 O 3 ring laser constructed by directly bonding the cavity components onto an aluminum baseplate. Stable unidirectional operation with an output power ≥10 m W was obtained for pump-diode currents of 300-500 mA, corresponding to a total electrical power consumption of 1.5 W. After repetition rate stabilization, a comparison with a conventionally constructed identical laser showed a 50% reduction in phase noise. In free-running operation the bonded laser showed superior passive repetition rate stability. The bonding process follows an already proven integration approach in space-borne instrumentation, mapping a development pathway for KLM lasers in aerospace applications.

Objective: Vestibular evoked myogenic potentials (VEMP) were investigated to differentiate between parkinsonian syndromes. We correlated balance and VEMP parameters to investigate the VEMP brainstem circuits as possible origin for postural instability., Methods: We assessed clinical status, ocular and cervical VEMP (oVEMP, cVEMP) and conducted a balance assessment (posturography, Activities-specific Balance Confidence Scale, Berg Balance Scale, modified Barthel Index) in 76 subjects: 30 with Parkinson's disease (PD), 16 with atypical parkinsonism (AP) and 30 healthy controls. VEMP were elicited by using a mini-shaker on the forehead., Results: Patients with PD had a prolonged oVEMP n10 in comparison to controls and prolonged p15 compared to controls and AP. Patients with AP showed reduced oVEMP amplitudes compared to PD and controls. CVEMP did not differ between groups. Postural impairment was higher in AP compared to controls and PD, particularly in the rating scales. No correlations between VEMP and posturography were found. A support vector machine classifier was able to automatically classify controls and patient subgroups with moderate to good accuracy based on oVEMP latencies and balance questionnaires., Conclusions: Both oVEMP and posturography, but not cVEMP, may be differentially affected in PD and AP. We did not find evidence that impairment of the cVEMP or oVEMP pathways is directly related to postural impairment., Significance: OVEMP and balance assessment could be implemented in the differential diagnostic work-up of parkinsonian syndromes., 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 © 2021 International Federation of Clinical Neurophysiology. All rights reserved.)

Background: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications., Objectives: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity)., Methods: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses., Results: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81., Conclusions: The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.)

Background: Subjective symptom complaints often do not match the expert's ratings in focal dystonia. Nonetheless, perceived symptom intensities drive compliance and outcome of botulinum neurotoxin (BoNT) treatment., Methods: Perception of symptom development across a BoNT cycle was obtained in 21 cervical dystonia (CD) and 15 hemifacial spasm (HFS) patients at four time points during a BoNT cycle. Subjective assessments were recorded by means of a quality-of-life questionnaire and a patient diary containing items related to subjective severity of disease, mood, pain, social impairment, and quality of life. Medical investigation used the Tsui score and TWSTRS, and a HFS rating score, respectively., Results: In both patient groups, subjective intensities were strongly associated with psychological variables. Only in CD did objective assessment moderately correlate with subjective ratings solely at the beginning and the end of the BoNT cycle. Overall, the beneficial effects of BoNT treatment were only loosely associated with subjective experiences in both groups., Conclusion: The emotional situation should be assessed regularly in patients undergoing BoNT therapy., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: Degeneration of dopaminergic neurons in the substantia nigra projecting to the striatum is responsible for the motor symptoms in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established procedure to alleviate these symptoms in advanced PD. Yet the mechanism of action, especially the effects of STN-DBS on the availability of striatal dopamine transporter (DAT) as a marker of nigrostriatal nerve cell function, remains largely unknown. The aim of this study was therefore to evaluate whether 1) DAT availability changes within 1 year of STN-DBS and 2) the clinical outcome can be predicted based on preoperative DAT availability., Methods: Twenty-seven PD patients (mean age 62.7 ± 8.9 years; mean duration of illness 13.0 ± 4.9 years; PD subtypes: akinetic-rigid, n = 11; equivalence, n = 13; and tremor-dominant, n = 3) underwent [123I]FP-CIT SPECT preoperatively and after 1 year of STN-DBS. DAT availability as determined by the specific binding ratio (SBR) was assessed by volume of interest (VOI) analysis of the caudate nucleus and the putamen ipsilateral and contralateral to the clinically more affected side., Results: Unified Parkinson's Disease Rating Scale (UPDRS) III scores improved significantly (mean preoperative on medication 25.6 ± 12.3, preoperative off medication 42.3 ± 15.2, postoperative on medication/off stimulation 41.4 ± 13.2, and postoperative on medication/on stimulation 16.1 ± 9.4; preoperative on medication vs postoperative on medication/on stimulation, p = 0.006), while the levodopa-equivalent daily dose was reduced (mean preoperative 957 ± 440 mg vs postoperative 313 ± 189 mg, p < 0.001). The SBR did not differ significantly before and 1 year after DBS, regardless of PD subtype. Preoperative DAT availability was not related to the change in UPDRS III score, but the change in DAT availability was significantly correlated with the change in UPDRS III score (contralateral head of the caudate VOI, p = 0.014; contralateral putamen VOI, p = 0.018)., Conclusions: Overall, DAT availability did not change significantly after 1 year of STN-DBS. However, on an individual basis, the improvement in UPDRS III score was associated with an increase in DAT availability, whereas DAT availability before STN-DBS surgery did not predict the clinical outcome. Whether a subtype-specific pattern of preoperative DAT availability can become a reliable predictor of successful STN-DBS must be evaluated in larger study cohorts.

Background: Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia., Methods: For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow., Findings: We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism., Interpretation: In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations., Funding: Else Kröner-Fresenius-Stiftung, Technische Universität München, Helmholtz Zentrum München, Medizinische Universität Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

There has been one previous report of a cohort of patients with variants in Chromodomain Helicase DNA-binding 3 (CHD3), now recognized as Snijders Blok-Campeau syndrome. However, with only three previously-reported patients with variants outside the ATPase/helicase domain, it was unclear if variants outside of this domain caused a clinically similar phenotype. We have analyzed 24 new patients with CHD3 variants, including nine outside the ATPase/helicase domain. All patients were detected with unbiased molecular genetic methods. There is not a significant difference in the clinical or facial features of patients with variants in or outside this domain. These additional patients further expand the clinical and molecular data associated with CHD3 variants. Importantly we conclude that there is not a significant difference in the phenotypic features of patients with various molecular disruptions, including whole gene deletions and duplications, and missense variants outside the ATPase/helicase domain. This data will aid both clinical geneticists and molecular geneticists in the diagnosis of this emerging syndrome.

Broadband high-speed absorption spectroscopy using swept-wavelength external cavity quantum cascade lasers (ECQCLs) is applied to measure multiple pyrolysis and combustion gases in biomass burning experiments. Two broadly-tunable swept-ECQCL systems were used, with the first tuned over a range of 2089-2262 cm -1 (4.42-4.79 µm) to measure spectra of CO 2 , H 2 O, and CO. The second was tuned over a range of 920-1150 cm -1 (8.70-10.9 µm) to measure spectra of ammonia (NH 3 ), ethene (C 2 H 4 ), and methanol (MeOH). Absorption spectra were measured continuously at a 100 Hz rate throughout the burn process, including inhomogeneous flame regions, and analyzed to determine time-resolved gas concentrations and temperature. The results provide in-situ, dynamic information regarding gas-phase species as they are generated, close to the biomass fuel source.

Interferometric laser ranging is an enabling technology for high-precision satellite-to-satellite tracking within the context of Earth observation, gravitational wave detection, or formation flying. In orbit, the measurement system is affected by environmental influences, particularly satellite attitude jitter and temperature fluctuations, imposing an instrument design with a high level of thermal stability and insensitivity to rotations around the spacecraft center of mass. The new design concept presented here combines different approaches for dynamic heterodyne laser ranging and features the inherent beam-tracking capabilities of a retroreflector in a mono-axial configuration. It allows for a continuously adjustable distance between the optical bench and the location of its fiducial point, facilitating future inter-satellite tracking with nanometer accuracy, e.g., the next-generation gravity mission.

The heart receives parasympathetic and to a lesser degree sympathetic input via the vagus nerve. Here, we investigated whether morphological changes of the cervical vagus nerves (VN) as assessed by high-resolution ultrasound (HRUS) correlated with the autonomic cardiac innervation. Measurement of heart rate variability (HRV) and HRUS of the VNs were performed in 88 healthy subjects (50 female; mean age 56 ± 18 years). HRV parameters and the cross-sectional area (CSA) of the VNs correlated both inversely with age. We also found an inverse correlation between the left VN-CSA and HRV as well as parasympathetic parameters. The results imply an asymmetric parasympathetic (vagal) innervation of the heart., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Degeneration of nuclei of the brainstem, especially parts of the vagal nuclei complex and the reticular formation, in Parkinson's disease (PD) may in part be responsible for nonmotor signs like obstipation, cardiac dysfunction and rapid eye movement sleep behavior disorder (RBD). The aim of the study was to establish a new blink reflex (BR) variant involving the vagal nuclei complex and the reticular formation and to investigate BR comprehensively using 3 different afferent routes in PD., Methods: In this cross-sectional observational study in 30 PD patients and 30 age and sex matched healthy controls, BR was elicited by stimulation of the auricular branch of the vagus nerve (ABVN) and compared to conventional BR variants evoked by the trigeminal and median nerve., Results: BRs could be elicited reliably by stimulation of ABVN in both groups. In none of the three BR variants, latencies or amplitudes differed between PD patients and controls. In PD, BR parameters were not related to cognition or presence of RBD., Conclusion: The present study did not provide evidence for malfunctioning of neural circuits subserving BRs elicited by three different afferents in PD., Significance: Brainstem circuits mediating these BR variants may be spared from neurodegeneration in PD., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Abnormal oscillatory activity in the subthalamic nucleus (STN) may be relevant for motor symptoms in Parkinson's disease (PD). Apart from deep brain stimulation, transcranial magnetic stimulation (TMS) may be suitable for altering these oscillations. We speculated that TMS to different cortical areas (primary motor cortex, M1, and dorsal premotor cortex, PMd) may activate neuronal subpopulations within the STN via corticofugal neurons projecting directly to the nucleus. We hypothesized that PD symptoms can be ameliorated by a lasting decoupling of STN neurons by associative dual-site repetitive TMS (rTMS). Associative dual-site rTMS (1 Hz) directed to PMd and M1 ("ADS-rTMS") was employed in 20 PD patients treated in a blinded, placebo-controlled cross-over design. Results: No adverse events were noted. We found no significant improvement in clinical outcome parameters (videography of MDS-UPDRS-III, finger tapping, spectral tremor power). Variation of the premotor stimulation site did not induce beneficial effects either. A single session of ADS-rTMS was tolerated well, but did not produce a clinically meaningful benefit on Parkinsonian motor symptoms. Successful treatment using TMS targeting subcortical nuclei may require an intervention over several days or more detailed physiological information about the individual brain state and stimulation-induced subcortical effects.

For more than three decades, Botulinum neurotoxin (BoNT) has been used to treat a variety of clinical conditions such as spastic or dystonic disorders by inducing a temporary paralysis of the injected muscle as the desired clinical effect. BoNT is known to primarily act at the neuromuscular junction resulting in a biochemical denervation of the treated muscle. However, recent evidence suggests that BoNT's pharmacological properties may not only be limited to local muscular denervation at the injection site but may also include additional central effects. In this review, we report and discuss the current evidence for BoNT's central effects based on clinical observations, neurophysiological investigations and neuroimaging studies in humans. Collectively, these data strongly point to indirect mechanisms via changes to sensory afferents that may be primarily responsible for the marked plastic effects of BoNT on the central nervous system. Importantly, BoNT-related central effects and consecutive modulation and/or reorganization of the brain may not solely be considered "side-effects" but rather an additional therapeutic impact responsible for a number of clinical observations that cannot be explained by merely peripheral actions.

Background: Amyloid-β (Aβ) and [18F]FDG PET are established as amyloid pathology and neuronal injury biomarkers. Early after administration Aβ PET images have the potential to replace [18F]FDG PET images allowing dual biomarker delivery by the administration of a single tracer. For [18F]FDG PET data, a correlation with cognitive performance is known., Objective: The aim of this study was to investigate whether early after administration [11C]PiB PET data also correlate with cognitive performance., Methods: The early after administration [11C]PiB PET data of 31 patients with cognitive impairment were evaluated. CERAD subtests were summarized to five cognitive domains. The resulting z scores were correlated with the PET data on a voxel- and VOI-based approach. Additional subgroup analyses (MCI versus dementia, Aβ-positive versus Aβ-negative subjects) were performed., Results: Significant correlations between cognitive performance and early after administration [11C]PiB PET data were found between left temporo-parietal SUVR and language domain, bilateral occipital as well as left temporal SUVR and executive function, left pre- and postcentral SUVRs, and visuospatial abilities. For the episodic and immediate memory domains, the analysis at the high significance level did not show any correlated cluster, however, the exploratory analysis did., Conclusion: Our study revealed correlations between deficits in different cognitive domains and regional early after administration [11C]PiB PET data similar to those known from [18F]FDG PET studies. Thus, our data support the assumption that early [11C]PiB PET data have a potential as neuronal injury biomarker. Head-to-head double-tracer studies of larger cohorts are needed to confirm this assumption.

Background: Recent histopathological studies revealed degeneration of the dorsal motor nucleus early in the course of Parkinson's disease (PD). Degeneration of the vagus nerve (VN) axons following neurodegeneration of brainstem vagal nuclei should be detectable by high-resolution ultrasound (HRUS) as a thinning of the VNs. Methods: We measured both VNs cross-sectional area (VN-CSA) of 35 patients with PD and 35 age- and sex-matched healthy controls at the level of the thyroid gland using HRUS. Results: On both sides, the VN-CSA was significantly smaller in PD patients than in controls (right: 2.1 ± 0.4 vs. 2.3 ± 0.5 mm2, left 1.5 ± 0.4 vs. 1.8 ± 0.4 mm2; both p < 0.05). There was no correlation between the right or left VN-CSA and age, the Hoehn & Yahr stage, disease duration, the motor part of the Unified Parkinson's Disease Rating Scale score, the Montreal Cognitive Assessment score, or the Non-motor Symptoms Questionnaire, and Scale for Parkinson's disease score including its gastrointestinal domain. Conclusions: These findings provide evidencethat atrophy of the VNs in PD patients can be detected in-vivo by HRUS.

Objective: To investigate whether consolidation after motor learning can be facilitated by offline (post-training) transcranial direct current stimulation (tDCS) in patients with multiple sclerosis (MS)., Methods: In this cross-sectional double-blind interventional study, effects of tDCS on motor consolidation were examined in 14 patients with relapsing remitting MS [median Expanded Disability Status Scale score 2.0 (range 1-4)] and 14 age- and sex-matched healthy controls. tDCS with the anode placed over the left primary motor cortex and the cathode placed over the right supraorbital region was applied immediately after a training session of an explicit sequential finger-tapping task that was performed with the right (dominant) hand. Task performance was retested after an interval of 8 h to assess consolidation. Participants took part in two experimental sessions separated by at least 7 days which differed with respect to type of post-training tDCS, i.e., sham and verum stimulation., Results: Patients with MS performed worse than controls in functional motor tests and the motor sequence task. However, learning speed and magnitude of online performance increments during the training session were comparable to controls. While post-training tDCS facilitated motor consolidation in controls, patients with MS did not benefit from this type of intervention., Conclusion: Absence of post-training tDCS-induced facilitation of consolidation in patients with MS suggests that the interaction of tDCS with the motor consolidation network is inefficient. Identification of the underlying disease-related mechanisms will have important implications for the design of studies aiming to promote motor recovery in MS by non-invasive brain stimulation.

Competing Interests: Alle Autoren erklären hiermit, dass die Erstellung dieser Arbeit unabhängig von materiellen Interessen erfolgte und die Darstellung der Inhalte produktneutral gehalten sind.

Vagus nerve stimulation (VNS) has become a well-established therapy for epilepsy and depression, and is emerging to treat inflammatory disease, with the cervical vagus nerve (CVN) as major stimulation site. CVN morphometries are missing for VNS, considering its variability. Morphometric data were obtained from CVNs in 27 cadavers, including branching patterns and histology. Cross-sectional area, greater and lesser diameters averaged 7.2 ± 3.1 mm 2 , 5.1 ± 1.5 and 4.1 ± 1.3 mm, and were ≤11.0 mm 2 , ≤7.0 and ≤5.8 mm in 90% of the specimens, respectively. Midline distance (position lateral to the laryngeal eminence) and skin distance (anterior-posterior from skin) averaged 34.5 ± 6.2 and 36.2 ± 9.4 mm, ≤49.0 and ≤41.0 mm in 90%, respectively. Nerve dimensions and surface topography correlated closely, but without gender-, side- or branching-dependent differences. The nerve fascicle number averaged 5.2 ± 3.5. Vagal arteries were observed in 49% of the cases. Negative correlations were found for age and cross-sectional area, as well as subperineural vessel count. Detailed anatomical data on the CVN and its vascularity are given, forming the morphometric basis for VNS refinement, filling an evident gap in light of the CVN being a structure with variable positions and branching. A 35 × 35-mm rule may apply for the CVN position, irrespective of branching or positional variation.

Introduction: Reported sonographic reference values for the vagus nerves (VNs) vary greatly. We aimed to generate reference values in a large cohort and examine intrarater, interrater, and across-ultrasound systems agreement., Methods: The VNs of 60 healthy subjects were examined by 2 sonographers and with 2 ultrasound systems. Cross-sectional areas (CSAs) of each VN were assessed at the level of the carotid sinus [proximal measurement level (ML)] and thyroid gland (distal ML)., Results: Mean VN CSA was significantly larger on the right side (proximal ML: 2.7 ± 0.6 mm 2 vs. 2.1 ± 0.5 mm 2 ; distal ML: 2.6 ± 0.6 mm 2 vs. 1.9 ± 0.4 mm 2 ). VN CSA decreased with increasing age. There were good intrarater, interrater, and across-ultrasound systems agreements., Discussion: The right VN CSA is significantly larger than the left. These side- and age-specific reference values for the VN may be useful for future studies. Muscle Nerve 57: 766-771, 2018., (© 2017 Wiley Periodicals, Inc.)

Background: Flow diversion (FD)-a young technique using stents with highly increased surface coverage-was introduced to treat complex aneurysms without intra-aneurysmal material placement and has amended the spectrum of endovascular techniques such as stent-assisted coil occlusion considerably. However, ischemic complications, a common side effect in FD, occur more frequently compared with the conventional endovascular approaches and certainly limit the indication of this technique. Our study aimed to investigate the feasibility and efficacy of stent-assisted coiling using low profile self-expandable stents, which exhibit only moderate flow-redirecting properties and therefore represent a combination of hemodynamic endovascular and occlusive endosaccular therapy., Materials and Methods: 39 Patients were included in our retrospective study. Occlusion rates were assessed 6 months after the procedure in a total of 27 cases using the Raymond scale., Results: Complete occlusion (Raymond I) was achieved in 24/27 aneurysms. Small neck remnants (Raymond II) were evident in 3/27 aneurysms. There were no cases with sac remnant or complete persistence of aneurysmal filling (Raymond III and IV)., Conclusion: Our study demonstrates interventional treatment of intracranial aneurysms using flow-redirecting stent-assisted coiling to be technically feasible and highly effective in aneurysmal occlusion. We believe that this approach is outstanding in the prevention of long-term aneurysmal reperfusion and exhibits a more acceptable risk profile than highly efficient FD techniques.

Power and precision grasps are two interrelated, kinematically distinct types of finger movements. We examined whether these types of motor actions may be spatially differently represented in the human central nervous system. In healthy participants representations of finger movements were mapped by delivering single pulse TMS to multiple scalp regions covering the left primary motor cortex (M1). Finger joint motions were recorded from the right hand using a data glove. Principal component analysis was used to extract local subspaces representing the TMS-evoked movement data from each scalp region. Voluntary power and precision grasps were reconstructed with these subspaces. The spatial properties of these reconstructions were analyzed for each grasp type using a general linear model. We found overlapping, yet distinct spatial representations for precision and power grasps with precision grasps represented slightly posterior compared to a more uniform distribution for power grasps. Differential spatial encoding of both grasp types may point towards a representation of power grasps within a phylogenetically older M1 area at the crown of the precentral gyrus and of precision grasps in a newer area in the depth of the central sulcus. Results also support the idea of separate synergistic movement representations in the human motor system., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Activity-dependent changes of postsynaptic Ca2+-concentration are influenced by a variety of different Ca2+-channels and play an important role in synaptic plasticity. Paired associative stimulation (PAS) and theta-burst stimulation (TBS) are noninvasive magnetic stimulation protocols used in human subjects to induce lasting corticospinal excitability changes that have been likened to synaptic long-term potentiation and long-term depression. To better characterize the Ca2+-related physiological mechanisms underlying PAS- and TBS-induced plasticity, we examined the impact of different Ca2+-sources. PAS-induced facilitation of corticospinal excitability was blocked by NMDA-receptor blocker dextromethorphan (DXM) and L-type voltage gated Ca2+ channels (VGCC) blocker nimodipine (NDP), but turned into depression by T-type VGCC blocker ethosuximide (ESM). Although, surprisingly, static corticospinal excitability was increased by the combination of DXM and NDP, PAS-induced facilitation was blocked. TBS-induced facilitation of corticospinal excitability, which has previously been shown to be turned into depression by L-type VGCC blocker NDP (Wankerl K, Weise D, Gentner R, Rumpf J, Classen J. 2010. L-type voltage-gated Ca2+ channels: a single molecular switch for long-term potentiation/long-term depression-like plasticity and activity-dependent metaplasticity in humans. J Neurosci. 30(18):6197-6204.), was blocked, but not reverted, by T-type VGCC blocker ESM. The different patterns of Ca2+-channel modulation of PAS- and TBS-induced plasticity may point to an important role of backpropagating action potentials in PAS-induced plasticity, similar as in spike-timing dependent synaptic plasticity, and to a requirement of dendritic Ca2+-dependent spikes in TBS-induced plasticity., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

This paper describes the concept of the hyperspectral Earth-observing thermal infrared (TIR) satellite mission HiTeSEM (High-resolution Temperature and Spectral Emissivity Mapping). The scientific goal is to measure specific key variables from the biosphere, hydrosphere, pedosphere, and geosphere related to two global problems of significant societal relevance: food security and human health. The key variables comprise land and sea surface radiation temperature and emissivity, surface moisture, thermal inertia, evapotranspiration, soil minerals and grain size components, soil organic carbon, plant physiological variables, and heat fluxes. The retrieval of this information requires a TIR imaging system with adequate spatial and spectral resolutions and with day-night following observation capability. Another challenge is the monitoring of temporally high dynamic features like energy fluxes, which require adequate revisit time. The suggested solution is a sensor pointing concept to allow high revisit times for selected target regions (1-5 days at off-nadir). At the same time, global observations in the nadir direction are guaranteed with a lower temporal repeat cycle (>1 month). To account for the demand of a high spatial resolution for complex targets, it is suggested to combine in one optic (1) a hyperspectral TIR system with ~75 bands at 7.2-12.5 µm (instrument NEDT 0.05 K-0.1 K) and a ground sampling distance (GSD) of 60 m, and (2) a panchromatic high-resolution TIR-imager with two channels (8.0-10.25 µm and 10.25-12.5 µm) and a GSD of 20 m. The identified science case requires a good correlation of the instrument orbit with Sentinel-2 (maximum delay of 1-3 days) to combine data from the visible and near infrared (VNIR), the shortwave infrared (SWIR) and TIR spectral regions and to refine parameter retrieval., Competing Interests: The authors declare no conflict of interest.

Objectives: The cervical part of the vagus nerve (CVN) has become an important target for stimulation therapy to treat epilepsy and psychiatric conditions. For this purpose, the CVN is visualized in the carotid sheath, assuming it to be localized dorsomedially between the carotid artery (CA) and the internal jugular vein (JV). The aim of our morphological study was therefore to revisit the CVN relationships to the CA and JV, hypothesizing it to have common variations to this classical textbook anatomy., Materials and Methods: Positional relations of the CVN, CA and JV were investigated in the carotid sheath of 35 cadavers at the C3 to C6 level. Positional relations of the CVN, CA and JV were documented on the basis of a 3 × 3 chart., Results: Eighteen different arrangements of the CVN, CA and JV were observed. The typical topographic relationship of the CVN dorsomedially between the CA and JV was only found in 42% of all cases. The CVN was located dorsally or (dorso-)laterally to the CA in 80% and dorsally or (dorso-)medially of the JV in 96% of all cases., Conclusions: Classical textbook anatomy of the CVN is only present in a minority of cases. Positional variations in contrast to textbook anatomy are considerably more frequent than previously described, which might be a hypothetical morphological explanation for the lack of efficacy or side effects of CVN stimulation. Furthermore, the position of the CVN relative to the internal jugular vein is more consistent than to the CA., (© 2017 International Neuromodulation Society.)

The subthalamic nucleus (STN) plays a crucial role in the surgical treatment of Parkinson's disease (PD). Studies investigating optimal protocols for STN visualization using state of the art magnetic resonance imaging (MRI) techniques have shown that susceptibility weighted images, which display the magnetic susceptibility distribution, yield better results than T1-weighted, T2-weighted, and T2*-weighted contrasts. However, these findings are based on young healthy individuals, and require validation in elderly individuals and persons suffering from PD. Using 7T MRI, the present study set out to investigate which MRI contrasts yielded the best results for STN visualization in 12 PD patients and age-matched healthy controls (HC). We found that STNs were more difficult to delineate in PD as reflected by a lower inter-rater agreement when compared to HCs. No STN size differences were observed between the groups. Analyses of quantitative susceptibility mapping (QSM) images showed a higher inter-rater agreement reflected by increased Dice-coefficients. The location of the center of mass of the STN was not affected by contrast. Overall, contrast-to-noise ratios (CNR) were higher in QSM than in T2*-weighted images. This can at least partially, explain the higher inter-rater agreement in QSM. The current results indicate that the calculation of QSM contrasts contributes to an improved visualization of the entire STN. We conclude that QSM contrast is the preferred choice for the visualization of the STN in persons with PD as well as in aging HC.

Introduction: In this study we evaluated freehand 3D ultrasound (3DUS) of the median nerve in comparison to 2D ultrasound (2DUS) and assessed the influence of tilting the transversal plane on cross-sectional area (CSA) measurement., Methods: Two examiners investigated the median nerves of 22 healthy subjects over a distance of 20 cm using 3DUS. Image quality and CSA were assessed at random points within the virtual 3D volume and compared with 2DUS., Results: Image quality within the virtual 3D volume was good/sufficient/poor in 53.0%/40.2%/6.8% (examiner 1) and 21.6%/69.6%/8.8% (examiner 2), respectively. CSA measurements with 3DUS were smaller than with 2DUS (-12% and -17%; Wilcoxon test, P < 0.001). Interrater agreement for 3DUS and intermethod agreement between 2DUS and 3DUS were moderate. Stepwise tilting of the transversal plane increased CSA significantly., Conclusion: Freehand 3DUS of the median nerve over 20 cm is feasible and may help overcome some of the limitations and pitfalls of 2DUS. Muscle Nerve 55: 206-212, 2017., (© 2016 Wiley Periodicals, Inc.)

Consolidation, by which performance increments after a training intervention are secured and sometimes generated, is reduced in elderly humans. The present study addressed the question whether transcranial direct current stimulation (tDCS) applied after motor training improves consolidation of explicit motor sequence learning in healthy older humans. In the first experiment, anodal or cathodal tDCS to the left primary motor cortex, anodal tDCS to premotor cortex, or sham tDCS was applied immediately after completion of a finger sequence learning task. Performance was retested at 8 and 22 hours after the initial training session. Whereas all groups achieved similar performance at the end of training, off-line improvements differed between groups at later retesting, depending on the type of intervention. Relative to the other 3 interventions, anodal tDCS to primary motor cortex (M1) led to performance improvements already at retesting 8 hours after initial learning and were maintained on the next day. In the second experiment, effects of the timing of post-training anodal tDCS to M1 with respect to the end of training were studied. Participants received anodal tDCS of M1 immediately or 60 or 120 minutes after training and were retested on sequence performance 8 hours post training. Only application of tDCS immediately after the end of training, but not after 1 or 2 hours, enhanced off-line consolidation. These findings suggest that anodal tDCS applied off-line immediately post training to M1 interacts specifically with early processes promoting consolidation of motor sequence learning in healthy older individuals., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In the context of our investigations on novel inertial reference sensors for space applications, we have explored a design utilizing an optical readout of a spherical proof mass. This concept enables full drag-free operations, hence reducing proof mass residual acceleration noise to a minimum. The main limitations of this sensor are errors in position determination of the center of mass of the proof mass due to the surface topography and the involved path length changes upon rotation. One solution is to apply a surface map for correction of the measurement data, thus improving the precision of position determination. This article presents the results of our one-dimensional interferometric surface topography measurements of a sphere, achieving uncertainties of ≈10  nm, as a first step to realize a complete surface map. The measurement setup consists of two heterodyne interferometers positioned in an opposing configuration, which measure the surface topography while the sphere is continuously rotated by a rotation stage.

Space applications demand light weight materials with excellent dimensional stability for telescopes, optical benches, optical resonators, etc. Glass-ceramics and composite materials can be tuned to reach very low coefficient of thermal expansion (CTE) at different temperatures. In order to determine such CTEs, very accurate setups are needed. Here we present a dilatometer that is able to measure the CTE of a large variety of materials in the temperature range of 140 K to 250 K. The dilatometer is based on a heterodyne interferometer with nanometer noise levels to measure the expansion of a sample when applying small amplitude controlled temperature signals. In this article, the CTE of a carbon fiber reinforced polymer sample has been determined with an accuracy in the 10 -8 K -1 range.

Purpose: [(18)F]FDG is a commonly used neuronal injury biomarker for early and differential diagnosis of dementia. Typically, the blood supply to the brain is closely coupled to glucose consumption. Early uptake of the Aβ tracer [(11)C]PiB on PET images is mainly determined by cerebral blood flow and shows a high correlation with [(18)F]FDG uptake. Uptake data for (18)F-labelled Aβ PET tracers are, however, scarce. We investigated the value of early PET images using the novel Aβ tracer [(18)F]FBB in the diagnosis of Alzhimers disease (AD)., Methods: This retrospective analysis included 22 patients with MCI or dementia who underwent dual time-point PET imaging with either [(11)C]PiB (11 patients) or [(18)F]FBB (11 patients) in routine clinical practice. Images were acquired 1 - 9 min after administration of both tracers and 40 - 70 min and 90 - 110 min after administration of [(11)C]PiB and [(18)F]FBB, respectively. The patients also underwent [(18)F]FDG brain PET imaging. PET data were analysed visually and semiquantitatively. Associations between early Aβ tracer uptake and dementia as well as brain atrophy were investigated., Results: Regional visual scores of early Aβ tracer and [(18)F]FDG PET images were significantly correlated (Spearman's ρ = 0.780, P < 0.001). Global brain visual analysis revealed identical results between early Aβ tracer and [(18)F]FDG PET images. In a VOI-based analysis, the early Aβ tracer data correlated significantly with the [(18)F]FDG data (r = 0.779, P < 0.001), but there were no differences between [(18)F]FBB and [(11)C]PiB. Cortical SUVRs in regions typically affected in AD on early Aβ tracer and [(18)F]FDG PET images were correlated with MMSE scores (ρ = 0.458, P = 0.032, and ρ = 0.456, P = 0.033, respectively). A voxel-wise group-based search for areas with relatively higher tracer uptake on early Aβ tracer PET images compared with [(18)F]FDG PET images revealed a small cluster in the midbrain/pons; no significant clusters were found for the opposite comparison., Conclusion: Early [(18)F]FBB and [(11)C]PiB PET brain images are similar to [(18)F]FDG PET images in AD patients, and these tracers could potentially be used as biomarkers in place of [(18)F]FDG. Thus, Aβ tracer PET imaging has the potential to provide biomarker information on AD pathology and neuronal injury. The potential of this approach for supporting the diagnosis of AD needs to be confirmed in prospective studies in larger cohorts.

Left posterior inferior frontal gyrus (pIFG) and supramarginal gyrus (SMG) are key regions for phonological decisions, whereas angular gyrus (ANG) and anterior IFG (aIFG) are associated with semantics. However, it is less clear whether the functional contribution of one area changes in the presence of a dysfunctional area within the network. Using repetitive transcranial magnetic stimulation (rTMS), we first tested whether perturbing one area would disrupt behavior. Second, we applied a condition-and-perturb approach, combining parietal offline rTMS with frontal online rTMS to investigate how the functional contribution of a frontal region changes in the presence of a dysfunctional parietal region. We found that rTMS over SMG or pIFG delayed phonological decisions, but this was not enhanced by combining supramarginal rTMS with pIFG rTMS. In contrast, semantic decisions were only impaired when angular rTMS was combined with aIFG rTMS. We infer that offline rTMS caused a dysfunction of ANG which increased the functional relevance of aIFG for semantic decisions and sensitized this network to the disruptive effects of aIFG rTMS. The results provide causal evidence that ANG and aIFG contribute to semantics and that the functional significance of one area within this network depends on the functional integrity of the other., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Five studies tested the effects that soul beliefs have on reactions to end-of-the-world scenarios. In Studies 1 and 2, participants who firmly believe in an immortal soul showed less resistance to an article predicting the end of humanity than those without such belief. However, in Studies 3 to 5, thoughts of symbolic immortality made soul believers more resistant to scientific evidence predicting the end of humanity. These results suggest that belief in an immortal soul provides psychological protection against the threat of humanity's demise that does not hold for symbolic immortality beliefs., (© 2015 by the Society for Personality and Social Psychology, Inc.)

Objective: This study was undertaken to address the question of whether pigmentation may be mechanistically linked with Parkinson's disease., Methods: In a cross-sectional, observational study, 116 healthy subjects received transcranial sonography of the substantia nigra. Pigmentation phenotype was assessed using the Fitzpatrick skin phototype classification, and five additional phenotypic pigmentation traits as well as a photographic method (Melanin index) in a subgroup of 46 subjects., Results: Lighter skin phototype was associated with larger echogenic substantia nigra area and increased prevalence of abnormally enlarged echogenic substantia nigra area. The strongest association of substantia nigra echogenicity and phenotypic pigmentation traits was found for hair color and facial tanning., Interpretation: Findings suggest an increasing prevalence of structural abnormality of substantia nigra with decreasing darkness of skin and thus may provide additional evidence in favor of a pathogenic link of pigmentation and Parkinson's disease., (© 2015 International Parkinson and Movement Disorder Society.)