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• A phase-field approach to investigate crack nucleation and propagation in martensitic microstructures. • A coupled system of the time-dependent Ginzburg-Landau equation and the equilibrium equation. • Multi-variant martensitic phase transformations within the framework of a finite element method. • Martensitic specimen, with and without pre-existing crack, according to three types of martensitic embryo(s). In this work, a phase-field approach (PFA) is presented to study crack nucleation and propagation in martensitic micro-structures resulted from multi-variant martensitic phase transformations (MPT) within the framework of a finite element method (FEM). To this end, first, a coupled system of the time-dependent Ginzburg-Landau (TDGL) equation and the equilibrium equation is established based on the micro-elasticity theory, which reveals the nucleation and growth of diffusionless martensitic multi-variants forming a twinned martensitic micro-structure. The Helmholtz free energy used in this work consists of a second-degree polynomial of the phase variable, which leads to a nonlinear dependence on the order parameter in the TGDL equation. Thereafter, the nucleation and propagation of a crack is scrutinized in the obtained martensitic specimen, with and without pre-existing crack, according to three types of martensitic embryos. To do so, a damage variable is introduced to the multi-variant MPT model to study the interactions between the martensitic transformation and fracture. The key contributions of this study are not only to shed light on the evolution of the martensitic variants in the micro-structure with three types of pre-existing martensitic embryos, but also to investigate onset and growth of a crack in the martensitic specimen. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) is as an effective and safe treatment option for patients with resistant epilepsy. A SANTE Study reported that there was a gradual improvement in selected neuropsychological test results in patient with DBS in ANT. Among those improvements there were reported a number of psychiatric adverse affects. However little is studied about immediate neuropsychological effects of DBS in ANT. Recently demonstrated Voges B. et. al (2015) a stimulus- and voltage-dependent effect interrupting sleep and leading to the occurrence of neuropsychiatric symptoms (npS) (e.g. depression, mood instability, disturbed sleep) during ATN-DBS. We here present one patient with a voltage-independent developing of npS during ANT-DBS. The 45-year-old right-handed female patient with mental retardation with autistic spectrum disorder presented with focal not lesional refractory epilepsy. The average seizure frequency was 6.1 per day with a range of 1 to 16 seizures daily. After failure of 13 AED"s, a DBS-ANT was initiated at the age of 44. Follow up simultaneous EEG- video recording from 26 surface electrode contacts after beginning to stimulate with standard parameters (unipolar cyclic (1min ON/5min OFF) stimulation with 5 V stimulation amplitude, 120 Hz stimulation frequency and a pulse width of 90 μs) there were seen a directly dependence of neuropsychiatric symptoms (stereotypical movements with sitting down, torso wiggling (Body rocking) with or without singing) and impulse onset. In video-EEG monitoring we determined, that the duration of npS was also the same as impulse lasts. A clinical response to stimulation was 84 %. We improve adverse effects changing the programming settings: the amplitude was gradually reduced to two volts, the stimulation frequency 120 Hz and a pulse width of 90 μs where the same. Actual case report devoted to immediate complex behavioural disorder, which does not fulfil criteria for a complex focal seizure, and is strongly associated with unipolar bilateral stimulation of ANT. The actual clinical presentation of the DBS induced behavioural disorder semiologically coincide with the term "stereotypic movement disorder". We hypothesize that impaired function of ARAS lead to reduced behavioural suppression of impulse mediated behaviour in the patient with mental retardation. We analysed her video-EEG before she was being stimulated and noticed, that she already had a typical body movement (body rocking) but much less frequently. Obviously a DBS of ANT had had a strong influence on behavioural disorder of our patient and was reversible after adjusting the stimulation parameters. [ABSTRACT FROM AUTHOR]

The taste is a fundamental property of food-stuff indicating palatability and safety as well as hedonic value of a food. Animal research as well as human neuroimaging work has suggested multiple brain areas involved in the processing of taste. Here, we take advantage of the fact that deep brain stimulation in neuropsychiatric diseases has targeted brain areas that have been implicated in homeostatic (hypothalamus) and hedonic (Nucleus accumbens) control of ingestive behavior. We recorded local field potentials in patients receiving DBS of the hypothalamus (patient 1: Cluster headache, patient 2: pain) or the Nucleus accumbens (patient 3: anorexia, patient 4: obsessive compulsive disease, patient 5: depression) while the electrodes were externalized for initial testing of the stimulation parameters. Patients first indicated favorite and disliked foods. These foods were applied in the following way. The patient was asked to put the food in his/her mouth, to keep it in the mouth to taste it (during this phase LFPs were obtained), to spit it out and to rinse the mouth with water. Subsequently, the next trial was applied. LFPs were obtained in a bipolar fashion and subjected to Fast Fourier Transform (FFT).Distinct peaks in the spectrum were obtained that differentiated liked and disliked food in the hypothalamus and Ncl. accumbens, indicating that both brain structures are sensitive to the hedonic quality of the food. Further studies are needed to investigate the state (hungry, satiated) and trait (high vs. low external drive for eating) dependency of these taste-related responses. [ABSTRACT FROM AUTHOR]

Deep brain stimulation of the nucleus accumbens influences behaviour, e.g., in obsessive-compulsive disorder. However, the precise role of this region in human decision-making is not well understood. The nucleus accumbens is thought to influence future action selection indirectly, via an evaluation of current action outcomes. Here, we provide electrophysiological evidence for a more direct, “on-line”, behavioural role during action preparation. We recorded local field potentials from the nucleus accumbens in patients with epilepsy undergoing surgery for deep brain stimulation. We found a consistent decrease in the power of beta-oscillations (10–30 Hz) before and around the time of movements. This peri-movement beta-desynchronization was observed in seven of eight patients and was present both before instructed movements in a serial reaction time task as well as before self-paced, deliberate, choices in a decision-making task. A similar beta-decrease over sensorimotor cortex and in the subthalamic nucleus has been directly related to movement preparation and execution. Our results support the idea of a direct role of the human nucleus accumbens in action preparation and execution. [ABSTRACT FROM AUTHOR]

We report electrophysiological findings from Deep brain stimulation (DBS) of the internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (VIM) in a patient with genetically proven Myoclonus–Dystonia–Syndrom (DYT11). The syndromes of the patient were refractory to medical treatment. Methods We performed a quadruple stimulation in VIM and GPi bilaterally and recorded electrophysiological data 3 days postoperatively. We assessed local field potentials and calculated coherence between electrodes ( n = 4 per electrode trajectory, denoted as 0–3, being 0 most ventral and 3 most dorsal contact) and transfer entropy for assessment of the “information” flow in different DBS and resting conditions. Stimulation was performed with 120 Hz. Results Clinically, the patient did not show any MDS symptoms at the time of the recordings (lesion effect). At rest the predominant electrophysiological pattern comprised VIM: 7–11 Hz, GPi: 3–10 Hz bands and showed significantly higher amplitudes for the Theta and alpha bands in right VIM (contacts 0–1, 1–2). No coherence between the LFPs measured and muscle activity measured with surface electrodes on neck and arm muscles was observed, likely due to postoperative lesion effect. We then measured the effects of stimulation of one structure (VIM or GPi) on the other structure (GPi or VIM). Stimulation of the right and the left VIM showed no changes in coherence and transfer entropy in the GPi. However stimulation of the left VIM contacts 0–1/1–2 resulted in a significant increase of the amplitude of the theta-band in the right GPI 0–1/2–3. Stimulation of the left GPi at 0–1/2–3 significantly increased the amplitude in the alpha band of both VIMs. Similarly, coherence levels were also raised by low frequency stimulation at approximately 9–11 Hz. Concomittantly, a diffuse change in the transfer entropy was observed: Stimulating the left GPi 0–1/2–3 increased significantly the amplitude of the alpha frequencies in the right VIM 1–2. Finally we compared the effects of DBS of VIM and GPi of one side to the other. Simultaneous stimulation of the right VIM 0–1, 2–3 and right GPi 0–1, 2–3 significantly lowered the alpha band of the left GPi 0–1. Again, there were no changes in the coherence and the transfer entropy. In contrast stimulation of the left VIM and GPi showed no effect in amplitude, coherence nor transfer entropy in the right GPi and VIM. Conclusion We could show via stimulation of the left VIM a possible connection between the left VIM and the right GPi and vice versa, although there was no change in the transfer entropy. These results point to relais stations or other structural connections between thalamus and pallidum. In summary, thalamic or pallidal stimulation in MDS seem to be encompassing differential, though partially interconnected neurophysiological pathways. The present data provide electrophysiologcal evidence for the notion of potential beneficial quadruple DBS in MDS ( Gruber et al., 2010 ). [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of energy and protein in the diet on the recovery of milk ethanol stability (MES) induced by feed restriction. Twelve Holstein and Holstein × Jersey crossbred cows with an average of 146 ± 50 DIM, 575.4 ± 70 kg of BW, and 18.93 ± 5.46 kg/d of milk yield were distributed in a 3 × 3 Latin square design with 3 treatments and 3 experimental periods. Each experimental period lasted 24 d, comprising 3 phases: a 13-d adaptation phase (100E+100P), a 4-d induction phase for milk ethanol instability (50E+50P), and a 7-d recovery phase for MES (3 treatments). The 3 treatments during the recovery phase consisted of 3 diets aiming to meet the requirements of energy and protein (100E+100P), only energy (100E+50P), or only protein (50E+100P). The diet during the adaptation and induction phases was common for all cows. The energy and protein levels to meet each cow's requirements were based on the group average. Restriction of energy and protein reduced DM, CP, and total digestive nutrient intake for cows fed 100E+50P and 50E+100P. The lowest BW was observed for cows fed 50E+100P, with no difference for BCS. During the induction phase, MES was reduced by 9 percentage units. Cows fed 100E+100P recovered MES in the first days of the recovery phase, whereas 100E+50P slightly improved MES, and 50E+100P had a constant decrease in MES. Cows fed 100E+50P and 50E+100P produced, respectively, 3.6 and 5.9 kg less milk than those fed 100E+100P. The 50E+100P treatment exhibited the highest milk fat content and SCS, along with the lowest milk lactose content. Protein content was higher in the 100E+100P treatment. Cows fed 50E+100P showed higher serum albumin levels compared with those on the 100E+100P treatment, not differing from the 100E+50P treatment. We concluded that the complete recovery of MES in cows with feed restrictions is possible only by supplying both the energy and protein requirements in the cows' diet. However, restricting energy intake poses a greater limitation on MES recovery compared with restricting protein., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Chromosome organization plays an important role in biological processes such as replication, regulation, and transcription. One way to study the relationship between chromosome structure and its biological functions is through Hi-C studies, a genome-wide method for capturing chromosome conformation. Such studies generate vast amounts of data. The problem is exacerbated by the fact that chromosome organization is dynamic, requiring snapshots at different points in time, further increasing the amount of data to be stored. We present a novel approach called the High-Efficiency Contact Matrix Compressor (HiCMC) for efficient compression of Hi-C data., Results: By modeling the underlying structures found in the contact matrix, such as compartments and domains, HiCMC outperforms the state-of-the-art method CMC by approximately 8% and the other state-of-the-art methods cooler, LZMA, and bzip2 by over 50% across multiple cell lines and contact matrix resolutions. In addition, HiCMC integrates domain-specific information into the compressed bitstreams that it generates, and this information can be used to speed up downstream analyses., Conclusion: HiCMC is a novel compression approach that utilizes intrinsic properties of contact matrix, such as compartments and domains. It allows for a better compression in comparison to the state-of-the-art methods. HiCMC is available at https://github.com/sXperfect/hicmc ., (© 2024. The Author(s).)

Ventrointermediate thalamic stimulation (VIM-DBS) modulates oscillatory activity in a cortical network including primary motor cortex, premotor cortex, and parietal cortex. Here we show that, beyond the beneficial effects of VIM-DBS on motor execution, this form of invasive stimulation facilitates production of sequential finger movements that follow a repeated sequence. These results highlight the role of thalamo-cortical activity in motor learning., (© 2024. The Author(s).)

Objective: The concomitant stimulation of the subthalamic nucleus and the substantia nigra pars reticulata is a promising approach to improve treatment of refractory axial symptoms in Parkinson's disease. While dual stimulation of the subthalamic nucleus and the substantia nigra pars reticulata has previously shown beneficial effects on gait, the role of the substantia nigra, a crucial component of the basal ganglia circuitry, in cognitive functions such as attention and executive control remains underexplored. This study aimed to investigate the impact of selective substantia nigra pars reticulata stimulation on attentional performance in patients receiving standard deep brain stimulation of the subthalamic nucleus., Methods: Twelve patients with bilateral subthalamic nucleus stimulation underwent computerized assessment of attention using a simple reaction time task. Reaction times were assessed under standard stimulation of the subthalamic nucleus versus simultaneous stimulation of the subthalamic nucleus and the substantia nigra pars reticulata., Results: The results revealed a significant improvement in reaction times during the simple reaction time task when patients received dual stimulation compared to standard stimulation., Conclusions: Our findings provide further evidence for the pivotal role of the substantia nigra pars reticulata in cognitive functions such as attention. Despite the limitations of the study, including a small sample size, our results suggest potential benefits of simultaneous deep brain stimulation of the subthalamic nucleus and the substantia nigra pars reticulata on attentional performance in patients with Parkinson's disease. Further research with larger cohorts is warranted to confirm these findings and better understand the underlying mechanisms., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is evidence that the processing of acute stress is altered in alcohol use disorder (AUD), but little is known about how this is manifested simultaneously across different stress parameters and which neural processes are involved. The current study examined physiological and affective responses to stress and functional connectivity in AUD., Methods: Salivary cortisol samples, pulse rate, and affect ratings were collected on 2 days from 34 individuals with moderate or severe AUD during early abstinence and 34 control participants. On one of the days, stress was induced, and on the other day, a nonstressful control task was performed. Following the intervention, participants underwent functional magnetic resonance imaging to assess functional connectivity, with a focus on cortical and subcortical seed regions previously reported to be involved in AUD and/or stress., Results: For pulse rate and cortisol, stress responses were blunted in AUD, whereas the affective response was stronger. Neuroimaging analyses revealed stress-related group differences in functional connectivity, involving the connectivity of striatal seeds with the posterior default mode network, cerebellum, and midcingulate cortex and of the posterior default mode network seed with the striatum and thalamus., Conclusions: The results suggest a dissociation between subjectively experienced distress and the physiological stress response in AUD as well as stress-related alterations in functional connectivity. These findings highlight the complex interplay between chronic alcohol use and acute stress regulation, offering valuable considerations for the development of therapeutic strategies., (© 2024 The Authors.)

For the last two decades, the amount of genomic data produced by scientific and medical applications has been growing at a rapid pace. To enable software solutions that analyze, process, and transmit these data in an efficient and interoperable way, ISO and IEC released the first version of the compression standard MPEG-G in 2019. However, non-proprietary implementations of the standard are not openly available so far, limiting fair scientific assessment of the standard and, therefore, hindering its broad adoption. In this paper, we present Genie, to the best of our knowledge the first open-source encoder that compresses genomic data according to the MPEG-G standard. We demonstrate that Genie reaches state-of-the-art compression ratios while offering interoperability with any other standard-compliant decoder independent from its manufacturer. Finally, the ISO/IEC ecosystem ensures the long-term sustainability and decodability of the compressed data through the ISO/IEC-supported reference decoder., (© 2024. The Author(s).)

Background: Brain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE)., Methods: The BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study's main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression Rating Scale (HDRS-24), and the occurrence of AE., Ethics and Dissemination: The trial protocol has received approval from the Institutional Review Boards at the five participating universities. This trial holds significance in generating valuable data on a predictive biomarker for antidepressant treatment in patients with MDD. The findings will be shared with study participants, disseminated through professional society meetings, and published in peer-reviewed journals., Trial Registration: German Clinical Trial Register DRKS00032503. Registered on 17 August 2023., (© 2024. The Author(s).)

Objectives: Enhanced beta oscillations in cortical-basal ganglia (BG) thalamic circuitries have been linked to clinical symptoms of Parkinson's disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces beta band activity in BG regions, whereas little is known about activity in cortical regions. In this study, we investigated the effect of STN DBS on the spectral power of oscillatory activity in the motor cortex (MCtx) and sensorimotor cortex (SMCtx) by recording via an electrocorticogram (ECoG) array in free-moving 6-hydroxydopamine (6-OHDA) lesioned rats and sham-lesioned controls., Materials and Methods: Male Sprague-Dawley rats (250-350 g) were injected either with 6-OHDA or with saline in the right medial forebrain bundle, under general anesthesia. A stimulation electrode was then implanted in the ipsilateral STN, and an ECoG array was placed subdurally above the MCtx and SMCtx areas. Six days after the second surgery, the free-moving rats were individually recorded in three conditions: 1) basal activity, 2) during STN DBS, and 3) directly after STN DBS., Results: In 6-OHDA-lesioned rats (N = 8), the relative power of theta band activity was reduced, whereas activity of broad-range beta band (12-30 Hz) along with two different subbeta bands, that is, low (12-30 Hz) and high (20-30 Hz) beta band and gamma band, was higher in MCtx and SMCtx than in sham-lesioned controls (N = 7). This was, to some extent, reverted toward control level by STN DBS during and after stimulation. No major differences were found between contacts of the electrode grid or between MCtx and SMCtx., Conclusion: Loss of nigrostriatal dopamine leads to abnormal oscillatory activity in both MCtx and SMCtx, which is compensated by STN stimulation, suggesting that parkinsonism-related oscillations in the cortex and BG are linked through their anatomic connections., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: In recent years, advances in high-throughput sequencing technologies have enabled the use of genomic information in many fields, such as precision medicine, oncology, and food quality control. The amount of genomic data being generated is growing rapidly and is expected to soon surpass the amount of video data. The majority of sequencing experiments, such as genome-wide association studies, have the goal of identifying variations in the gene sequence to better understand phenotypic variations. We present a novel approach for compressing gene sequence variations with random access capability: the Genomic Variant Codec (GVC). We use techniques such as binarization, joint row- and column-wise sorting of blocks of variations, as well as the image compression standard JBIG for efficient entropy coding., Results: Our results show that GVC provides the best trade-off between compression and random access compared to the state of the art: it reduces the genotype information size from 758 GiB down to 890 MiB on the publicly available 1000 Genomes Project (phase 3) data, which is 21% less than the state of the art in random-access capable methods., Conclusions: By providing the best results in terms of combined random access and compression, GVC facilitates the efficient storage of large collections of gene sequence variations. In particular, the random access capability of GVC enables seamless remote data access and application integration. The software is open source and available at https://github.com/sXperfect/gvc/ ., (© 2023. The Author(s).)

Treatment resistance in alcohol use disorders (AUD) is a major problem for affected individuals and for society. In the search of new treatment options, few case studies using deep brain stimulation (DBS) of the nucleus accumbens have indicated positive effects in AUD. Here we report a double-blind randomized controlled trial comparing active DBS ("DBS-EARLY ON") against sham stimulation ("DBS-LATE ON") over 6 months in n = 12 AUD inpatients. This 6-month blind phase was followed by a 12-month unblinded period in which all patients received active DBS. Continuous abstinence (primary outcome), alcohol use, alcohol craving, depressiveness, anxiety, anhedonia and quality of life served as outcome parameters. The primary intention-to-treat analysis, comparing continuous abstinence between treatment groups, did not yield statistically significant results, most likely due to the restricted number of participants. In light of the resulting limited statistical power, there is the question of whether DBS effects on secondary outcomes can nonetheless be interpreted as indicative of an therapeutic effect. Analyses of secondary outcomes provide evidence for this, demonstrating a significantly higher proportion of abstinent days, lower alcohol craving and anhedonia in the DBS-EARLY ON group 6 months after randomization. Exploratory responder analyses indicated that patients with high baseline alcohol craving, depressiveness and anhedonia responded to DBS. The results of this first randomized controlled trial are suggestive of beneficial effects of DBS in treatment-resistant AUD and encourage a replication in larger samples., (© 2023. The Author(s).)

The network of brain structures engaged in motor sequence learning comprises the same structures as those involved in tremor, including basal ganglia, cerebellum, thalamus, and motor cortex. Deep brain stimulation (DBS) of the ventrointermediate nucleus of the thalamus (VIM) reduces tremor, but the effects on motor sequence learning are unknown. We investigated whether VIM stimulation has an impact on motor sequence learning and hypothesized that stimulation effects depend on the laterality of electrode location. Twenty patients (age: 38-81 years; 12 female) with VIM electrodes implanted to treat essential tremor (ET) successfully performed a serial reaction time task, varying whether the stimuli followed a repeating pattern or were selected at random, during which VIM-DBS was either on or off. Analyses of variance were applied to evaluate motor sequence learning performance according to reaction times (RTs) and accuracy. An interaction was observed between whether the sequence was repeated or random and whether VIM-DBS was on or off (F[1,18] = 7.89, p = .012). Motor sequence learning, reflected by reduced RTs for repeated sequences, was greater with DBS on than off (T[19] = 2.34, p = .031). Stimulation location correlated with the degree of motor learning, with greater motor learning when stimulation targeted the lateral VIM (n = 23, ρ = 0.46; p = .027). These results demonstrate the beneficial effects of VIM-DBS on motor sequence learning in ET patients, particularly with lateral VIM electrode location, and provide evidence for a role for the VIM in motor sequence learning., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Directional deep brain stimulation (dDBS) provides multiple programming options. Knowledge of the spatial lead orientation is useful for time-efficient programming. Recent studies demonstrated deviations of up to 90° from the intended orientation angle. We examined the deviation of dDBS-lead orientation for leads from two different manufacturers using intraoperative stereotactic (STX) X-ray images. Intraoperative 2D-X-ray images were acquired after implantation of the first lead (TP1) and the second lead (TP2) enabling the estimation of the spatial position of the first lead at TP1 and TP2 and of changes of the orientation for a defined time period. Two investigators retrospectively estimated the orientation of the directional marker for 64 patients. The mean deviation from intended spatial orientation was 40.8° ± 46.1° for all examined leads. The spatial orientation of the first lead did not significantly change within a period of approximately 1 h. The degree of deviation did not differ significantly between two lead manufacturers but depended on the lead fixation technique. Our results showed deviations from the intended orientation angle immediately after the insertion of dDBS leads. The initial spatial orientation remained stable for approximately 1 h and was not caused by technical properties of the implanted lead. Hence, it was most probably the result of unintended mechanical torsion during insertion and/or fixation. Because precise determination of the lead orientation is mandatory for target-oriented dDBS programming, the use of additional imaging suitable for precise 3D visualization of lead contacts and/or the positioning marker is recommended., (© 2022. The Author(s).)

The thalamus is much more than a simple sensory relay. High-order thalamic nuclei, such as the mediodorsal thalamus, exert a profound influence over animal cognition. However, given the difficulty of directly recording from the thalamus in humans, next-to-nothing is known about thalamic and thalamocortical contributions to human cognition. To address this, we analysed simultaneously-recorded thalamic iEEG and whole-head MEG in six patients (plus MEG recordings from twelve healthy controls) as they completed a visual detection task. We observed that the phase of both ongoing mediodorsal thalamic and prefrontal low-frequency activity was predictive of perceptual performance. Critically however, mediodorsal thalamic activity mediated prefrontal contributions to perceptual performance. These results suggest that it is thalamocortical interactions, rather than cortical activity alone, that is predictive of upcoming perceptual performance and, more generally, highlights the importance of accounting for the thalamus when theorising about cortical contributions to human cognition., (© 2022. The Author(s).)

Background: An increase in body weight is observed in the majority of patients with Parkinson's disease (PD) who undergo deep brain stimulation (DBS) of the subthalamic nucleus (STN) although the mechanisms are unclear., Objectives: To identify the stimulation-dependent effects on reward-associated and attention-associated neural networks and to determine whether these alterations in functional connectivity are associated with the local impact of DBS on different STN parcellations., Methods: We acquired functional task-related MRI data from 21 patients with PD during active and inactive STN DBS and 19 controls while performing a food viewing paradigm. Electrode placement in the STN was localised using a state-of-the-art approach. Based on the 3D model, the local impact of STN DBS was estimated., Results: STN DBS resulted in a mean improvement of motor function of 22.6%±15.5% (on medication) and an increase of body weight of ~4 kg within 2 years of stimulation. DBS of the limbic proportion of the STN was associated with body weight gain and an increased functional connectivity within the salience network and at the same time with a decreased activity within the reward-related network in the context of sweet food images., Conclusions: Our findings indicate increased selective attention for high-caloric foods and a sweet food seeking-like behaviour after DBS particularly when the limbic proportion of the STN was stimulated., Competing Interests: Competing interests: JKK is a consultant to Medtronic and Boston Scientific., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Anticipating social and non-social incentives recruits shared brain structures and promotes behavior. However, little is known about possible age-related behavioral changes, and how the human substantia nigra (SN) signals positive and negative social information. Therefore, we recorded intracranial electroencephalography (iEEG) from the SN of Parkinson's Disease (PD) patients (n = 12, intraoperative, OFF medication) in combination with a social incentive delay task including photos of neutral, positive or negative human gestures and mimics as feedback. We also tested a group of non-operated PD patients (n = 24, ON and OFF medication), and a sample of healthy young (n = 51) and older (n = 52) adults with behavioral readouts only. Behaviorally, the anticipation of both positive and negative social feedback equally accelerated response times in contrast to neutral social feedback in healthy young and older adults. Although this effect was not significant in the group of operated PD patients - most likely due to the small sample size - iEEG recordings in their SN showed a significant increase in alpha-beta power (9-20 Hz) from 300 to 600 ms after cue onset again for both positive and negative cues. Finally, in non-operated PD patients, the behavioral effect was not modulated by medication status (ON vs OFF medication) suggesting that other processes than dopaminergic neuromodulation play a role in driving invigoration by social incentives. Together, our findings provide novel and direct evidence for a role of the SN in processing positive and negative social information via specific oscillatory mechanisms in the alpha-beta range, and they suggest that anticipating social value in simple cue-outcome associations is intact in healthy aging and PD., (Copyright © 2021. Published by Elsevier Inc.)

Clinical effects of deep brain stimulation are largely mediated by the activation of myelinated axons. Hence, increasing attention has been paid in the past on targeting white matter tracts in addition to gray matter. Aims of the present study were: (i) visualization of discrete afferences and efferences of the nucleus accumbens (NAc), supposed to be a major hub of neural networks relating to mental disorders, using probabilistic fiber tractography and a data driven approach, and (ii) validation of the applied methodology for standardized routine clinical applications. MR-data from 11 healthy subjects and 7 measurement sessions each were acquired on a 3T MRI-scanner. For probabilistic fiber tracking the NAc as a seed region and the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), amygdala (AMY), hippocampus (HPC), dorsomedial thalamus (dmT) and ventral tegmental area (VTA) as target regions were segmented for each subject and both hemispheres. To quantitatively assess the reliability and stability of the reconstructions, we filtered and clustered the individual fiber-tracts (NAc to target) for each session and subject and performed a point-by-point calculation of the maximum cluster distances for intra-subject comparison. The connectivity patterns formed by the obtained fibers were in good concordance with published data from tracer and/or fiber-dissection studies. Furthermore, the reliability assessment of the (NAc to target)-fiber-tracts yielded to high correlations between the obtained clustered-tracts. Using DBS with directional lead technology, the workflow elaborated in this study may guide selective electrical stimulation of NAc projections., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Extensive neuroanatomical connectivity between the anterior thalamic nuclei (ATN) and hippocampus and neocortex renders them well-placed for a role in memory processing, and animal, lesion, and neuroimaging studies support such a notion. The deep location and small size of the ATN have precluded their real-time electrophysiological investigation during human memory processing. However, ATN electrophysiological recordings from patients receiving electrodes implanted for deep brain stimulation for pharmacoresistant focal epilepsy have enabled high temporal resolution study of ATN activity. Theta frequency synchronization of ATN and neocortical oscillations during successful memory encoding, enhanced phase alignment, and coupling between ATN local gamma frequency activity and frontal neocortical and ATN theta oscillations provide evidence of an active role for the ATN in memory encoding, potentially integrating information from widespread neocortical sources. Greater coupling of a broader gamma frequency range with theta oscillations at rest than during memory encoding provides additional support for the hypothesis that the ATN play a role in selecting local, task-relevant high frequency activity associated with particular features of a memory trace., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Tracking animal movements over time may fundamentally determine the success of disease control interventions. In commercial pig production growth stages determine animal transportation schedule, thus it generates time-varying contact networks showed to influence the dynamics of disease spread. In this study, we reconstructed pig networks of one Brazilian state from 2017 to 2018, comprising 351,519 movements and 48 million transported pigs. The static networks view did not capture time-respecting movement pathways. For this reason, we propose a time-dependent network approach. A susceptible-infected model was used to spread an epidemic over the pig network globally through the temporal between-farm networks, and locally by a stochastic model to account for within-farm dynamics. We propagated disease to calculate the cumulative contacts as a proxy of epidemic sizes and evaluate the impact of network-based disease control strategies in the absence of other intervention alternatives. The results show that targeting 1,000 farms ranked by degree would be sufficient and feasible to diminish disease spread considerably. Our modelling results indicated that independently from where initial infections were seeded (i.e. independent, commercial farms), the epidemic sizes and the number of farms needed to be targeted to effectively control disease spread were quite similar; indeed, this finding can be explained by the presence of contact among all pig operation types The proposed strategy limited the transmission the total number of secondarily infected farms to 29, over two simulated years. The identified 1,000 farms would benefit from enhanced biosecurity plans and improved targeted surveillance. Overall, the modelling framework provides a parsimonious solution for targeted disease surveillance when temporal movement data are available., (© 2020 Wiley-VCH GmbH.)

Introduction: Following electrode implantation, a subgroup of patients treated with deep brain stimulation (DBS) for focal epilepsy exhibits a reduction of seizure frequency before stimulation is initiated. Microlesioning of the target structure has been postulated to be the cause of this "insertional" effect (IE). We examined the occurrence and duration of this IE in a group of patients with focal epilepsy following electrode implantation in the anterior nuclei of the thalamus (ANT) and/or nucleus accumbens (NAC) for DBS treatment., Materials and Methods: Changes in monthly seizure frequency compared to preoperative baseline were assessed one month (14 patients) and five months (four patients) after electrode implantation. A group analysis between patients with implantation of bilateral ANT-electrodes (four patients), NAC-electrodes (one patient) as well as ANT and NAC-electrodes (nine patients) was performed., Results: In this cohort, seizure frequency decreased one month after electrode implantation by 57.1 ± 30.1%, p ≤ 0.001 (compared to baseline). No significant difference within stimulation target subcohorts was found (p > 0.05). Out of the four patients without stimulation for five months following electrode insertion, three patients showed seizure frequency reduction lasting two to three months, while blinded to their stimulation status., Conclusion: An IE might explain seizure frequency reduction in our cohort. This effect seems to be independent of the number of implanted electrodes and of the target itself. The time course of the blinded subgroup of epilepsy patients suggests a peak of the lesional effect at two to three months after electrode insertion., (© 2021 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals LLC on behalf of International Neuromodulation Society.)

Background: Drugs, psychotherapy, and other treatment modalities are effective for many patients with mental illness. Nonetheless, many patients do not achieve a total remission with the currently available interventions, and the recurrence rates are high. As part of the ongoing search for further treatment options for refractory disorders, there is renewed interest in focal neuromodulatory techniques, including invasive ones, and deep brain stimulation (DBS) in particular., Methods: In this review article, a group consisting of neurosurgeons, psychiatrists, and one practicing ethicist/neurologist summarizes the main aspects of the use of DBS to treat mental illness and offers recommendations on its indications and practical implementation., Results: The efficacy of DBS against mental illness has not been confirmed in the randomized, controlled trials (RCTs) that have been published to date. This may be because the follow-up times were too short. In contrast to the negative RCTs, case series have indeed shown a positive effect of DBS on severe depression, but this effect can only be seen several months after the operation., Conclusion: DBS may be a therapeutic option for selected patients with otherwise intractable mental illness. Patients should only be treated in the setting of clinical trials. RCTs with longer follow-up times must be conducted in order to substantiate, if possible, the promising evidence that has been found in case series.

Background: Therapeutic effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) may in parts be attributed to the stimulation of white matter near the targeted structure. The dentato-rubro-thalamic (DRT) tract supposed to improve tremor control in patients with essential tremor could be one candidate structure. The aim of this study was to investigate the effect of stimulation proximity to the DRT on tremor control in PD patients treated with STN-DBS., Methods: For this retrospective analysis, we included 36 consecutive patients (median age 65.5 years) treated with STN-DBS for disabling motor symptoms including tremor. Stereotactic implantation of DBS electrodes into the motor area of the STN was performed using direct MRI-based targeting and intraoperative microelectrode recording. Tremor severity was assessed preoperatively and at regular intervals postoperatively (Unified Parkinson's Disease Rating Scale III). The DRT was visualized in 60 hemispheres after probabilistic fiber tracking (3-T MRI). The position of active electrode contacts was verified on intraoperative stereotactic X-rays and postoperative CT images after co-registration with 3D treatment planning MRI/CT images. We determined the shortest distance of active contacts to the ipsilateral DRT tracts on perpendicular view slices and correlated this value with tremor change percentage., Results: Twelve patients had unilateral tremor only, and accordingly, 12 hemispheres were excluded from further imaging analysis. The remaining 60 hemispheres were associated with contralateral resting tremor. Active brain electrode contacts leading to resting tremor improvement (46 hemispheres) had a significantly shorter distance to the DRT (1.6 mm (0.9-2.1) [median (25th-75th percentiles)]) compared with contacts of non-responders (14 hemispheres, distance: 2.8 mm (2-4.6), p < 0.001)., Conclusion: This retrospective analysis suggests that in STN-DBS, better tremor control in PD patients correlates with the distance of active electrode contacts to the DRT. Tractography may optimize both individually DBS targeting and postoperative adjustment of stimulation parameters.

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

The peripartum is associated with increased incidence of severe mental illness (SMI), a greater occurrence of psychotic symptoms and psychiatric admissions. This study aimed to describe the psychiatric, medical and psycho-social risk factors affecting South African mothers who experienced peripartum psychosis. Using a prospective, descriptive design, we conducted a detailed interview and supplementary information was collected by review of clinical records. The study examined the accounts of forty mothers who experienced peripartum psychosis between 6 and 18 months postpartum. Descriptive statistics for demographic and clinical variables were completed with SPSS for Windows, version 25. Pregnancies were predominantly unplanned and more than half of participants reported prenatal substance use. Medical or psychiatric problems during pregnancy were common and the majority of dyads experienced periods of early separation. Socio-demographic factors exacerbated the challenges this group of women at high risk face, in providing nurturing care to their infants. Results highlight the need for close follow-up for women with SMI, with particular attention to substance screening and psychosocial stressors. Integrated maternal and infant mental health services are recommended.

Motivation: In an effort to provide a response to the ever-expanding generation of genomic data, the International Organization for Standardization (ISO) is designing a new solution for the representation, compression and management of genomic sequencing data: the Moving Picture Experts Group (MPEG)-G standard. This paper discusses the first implementation of an MPEG-G compliant entropy codec: GABAC. GABAC combines proven coding technologies, such as context-adaptive binary arithmetic coding, binarization schemes and transformations, into a straightforward solution for the compression of sequencing data., Results: We demonstrate that GABAC outperforms well-established (entropy) codecs in a significant set of cases and thus can serve as an extension for existing genomic compression solutions, such as CRAM., Availability and Implementation: The GABAC library is written in C++. We also provide a command line application which exercises all features provided by the library. GABAC can be downloaded from https://github.com/mitogen/gabac., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press.)

During South Africa's first two decades as a democracy, the Western Cape Province has undergone radical changes to its healthcare system in an effort to address the extensive socioeconomic inequities that remain in the aftermath of the apartheid era. Although progress has been made, there is a clear need for interventions that support parents and children receiving health services in the public sector who are vulnerable to multiple psychosocial risks associated with extreme poverty. In this mixed-method study, we examined the feasibility and acceptability of adapting an evidence-based parenting intervention called Mothering from the Inside Out that was developed for mothers who are vulnerable to similar risks in the United States. Using qualitative methods, we documented the collaborative process that was guided by principles of community-based participatory research and examined themes in the Western Cape collaborators' perspectives about the feasibility and acceptability of the intervention. Using quantitative methods, we tested the preliminary efficacy of the adapted version of Mothering from the Inside Out for improving maternal reflective functioning and mother-child interactions. Although findings from both study components indicated preliminary promise, a number of obstacles and challenges at multiple levels underscore the need for (a) flexibility and contextual support for intervention research conducted in under-resourced communities, (b) clinical sensitivity to the unique experiences of parents rearing children in highly stressful, under-resourced environments, and (c) equal partnerships that allow the expertise of local providers to inform the design proposals of consulting investigators.

Objective: The pedunculopontine nucleus (PPN) has been proposed as a new deep brain stimulation (DBS) target for the treatment in idiopathic Parkinson's syndrome (IPS) and progressive supranuclear palsy (PSP). In IPS, levodopa has been shown to induce alpha activity in the PPN, indicating a possible physiological role for these oscillations in movement control. Despite shared clinical features, the PPN is more severely affected in PSP than IPS. Here we investigated neuronal oscillations in the PPN in PSP and the influence of levodopa and movement., Methods: Local field potentials were recorded bilaterally from the PPN of 4 PSP patients at rest, with levodopa and during self-paced leg movements., Results: During rest, levodopa administration was associated with significantly increased alpha and reduced gamma activity in the PPN. Without levodopa, continuous movements were associated with reduced alpha and beta power. These differences between oscillatory power during movement and resting state were not observed with levodopa administration., Conclusion: In PSP the changes in neuronal oscillations in the PPN region on levodopa administration are similar to those reported in IPS. The enhancement of lower frequency oscillations in the PPN is possibly influenced by a dopaminergic activation of the striatal pathway and a reduced pallidal inhibition., Significance: Levodopa influences neuronal oscillations at low and high frequencies in the PPN region in Parkinsonian disorders., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Culture plays a significant role in the variations observed in the manifestation, expression, and meaning of attachment behaviors. Africa is home to multiple cultures, with distinct organizations of caregiving relationships underlying the development of attachment. This review aims to consolidate knowledge about African attachment by describing studies of infant attachment conducted in Africa since Mary Ainsworth's Ugandan findings in 1967. Electronic databases were searched with the terms "Africa" ("attachment" or "bond") and "infant." Nine studies that assessed infant attachment style with self-report or observation methods were included, but spanned only five countries. The Strange Situation Procedure was most frequently used. Most studies described dyads living in peri-urban or township areas. Multiple socioeconomic factors affecting living conditions were identified, including, unemployment, financial difficulties, limited education, poor housing, single parenthood, lack of partner support, substance abuse, and depression. Overall distributions of attachment classification proportions appear consistent with global attachment-classification patterns. Despite adverse conditions, secure attachment was relatively widespread, and some populations had low rates of avoidant attachment. Relatively high rates of disorganized attachment were found when the category was included. Africa remains an understudied continent regarding infant attachment. The continent's cultural diversity may hold important truths necessary for understanding the complex relationship between infant and attachment figure., (© 2019 Michigan Association for Infant Mental Health.)

Background: In Parkinson's disease (PD), dopamine replacement therapy (DRT) enhances the effective connectivity of the prefrontal cortex (PFC) and supplementary motor area (SMA). The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) go beyond DRT effects including highly beneficial tremor suppression., Objectives: Here, we aimed to determine DBS-related changes of a motor network using resting state fMRI in PD patients with chronic STN DBS., Methods: In a repeated-measurement design, 26 medicated PD patients (60.9 years (SD 8.9)) were investigated using resting state fMRI while bipolar STN stimulation was (i) active or (ii) switched off, and dynamic causal modelling was subsequently performed., Results: DBS improved the MDS-UPDRS-III score by 26.4% (DBS ON/Med ON vs. DBS OFF/Med ON). Active stimulation resulted in an increased effective connectivity from cerebellum to putamen (p = 0.00118). In addition, there was a stronger coupling from PFC to cerebellum (p = 0.021), as well as from cerebellum to SMA (p = 0.043) on an uncorrected level. Coupling strength from PFC to cerebellum correlated with the DBS-related change of the resting tremor subscore (r = 0.54, p = 0.031). Self-connections increased as a function of DBS in the right PFC, PMC, SMA, M1, thalamus and left cerebellum., Conclusions: DBS-related improvement of Parkinsonian signs appears to be driven by an interaction between the cerebellum and the putamen. Resting tremor suppression may be related to an enhanced prefronto-cerebellar network. Activation of the mesial premotor loop (PFC-SMA) as seen in DRT may thus be secondary due to the primary modulation of cerebellar networks., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials., Objectives: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence., Methods: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months)., Results: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ± 4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ± 4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation., Discussion: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up., Conclusion: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

: Background: Diminished emotion recognition is a known symptom in Parkinson (PD) patients and subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to further deteriorate the processing of especially negative emotions. While emotion recognition generally refers to both, implicit and explicit processing, demonstrations of DBS-influences on implicit processing are sparse. In the present study, we assessed the impact of STN-DBS on explicit and implicit processing for emotional stimuli., Methods: Under STN-DBS ON and OFF, fourteen PD patients performed an implicit as well as an explicit emotional processing task. To assess implicit emotional processing, patients were tested with a lexical decision task (LTD) combined with an affective priming paradigm, which provides emotional content through the facial eye region. To assess explicit emotional processing, patients additionally explicitly rated the emotional status of eyes and words used in the implicit task., Results: DBS affected explicit emotional processing more than implicit processing with a more pronounced effect on error rates than on reaction speed. STN-DBS generally worsened implicit and explicit processing for disgust stimulus material but improved explicit processing of fear stimuli., Conclusions: This is the first study demonstrating influences of STN-DBS on explicit and implicit emotion processing in PD patients. While STN stimulation impeded the processing of disgust stimuli, it improved explicit discrimination of fear stimuli., Competing Interests: The authors declare no conflicts of interest.

Background: Central drop foot is a common problem in patients with stroke or multiple sclerosis (MS). For decades, it has been treated with orthotic devices, keeping the ankle in a fixed position. It has been shown recently that semi-implantable functional electrical stimulation (siFES) of the peroneal nerve can lead to a greater gait velocity increase than orthotic devices immediately after being switched on. Little is known, however, about long-term outcomes over 12 months, and the relationship between quality of life (QoL) and gait speed using siFES has never been reported applying a validated tool. We provide here a report of short (3 months) and long-term (12 months) outcomes for gait speed and QoL., Methods: Forty-five consecutive patients (91% chronic stroke, 9% MS) with central drop foot received siFES (Actigait®). A 10 m walking test was carried out on day 1 of stimulation (T1), in stimulation ON and OFF conditions, and repeated after 3 (T2) and 12 (T3) months. A 36-item Short Form questionnaire was applied at all three time points., Results: We found a main effect of stimulation on both maximum (p < 0.001) and comfortable gait velocity (p < 0.001) and a main effect of time (p = 0.015) only on maximum gait velocity. There were no significant interactions. Mean maximum gait velocity across the three assessment time points was 0.13 m/s greater with stimulation ON than OFF, and mean comfortable gait velocity was 0.083 m/s faster with stimulation ON than OFF. The increase in maximum gait velocity over time was 0.096 m/s, with post hoc testing revealing a significant increase from T1 to T2 (p = 0.012), which was maintained but not significantly further increased at T3. QoL scores showed a main effect of time (p < 0.001), with post hoc testing revealing an increase from T1 to T2 (p < 0.001), which was maintained at T3 (p < 0.001). Finally, overall absolute QoL scores correlated with the absolute maximum and comfortable gait speeds at T2 and T3, and the increase in overall QoL scores correlated with the increase in comfortable gait velocity from T1 to T3. Pain was reduced at T2 (p < 0.001) and was independent of gait speed but correlated with overall QoL (p < 0.001)., Conclusions: Peroneal siFES increased maximal and comfortable gait velocity and QoL, with the greatest increase in both over the first three months, which was maintained at one year, suggesting that 3 months is an adequate follow-up time. Pain after 3 months correlated with QoL and was independent of gait velocity, suggesting pain as an independent outcome measure in siFES for drop foot.

Background: Prepulse inhibition (PPI) of the acoustic startle response, a measurement of sensorimotor gaiting, is modulated by monoaminergic, presumably dopaminergic neurotransmission. Disturbances of the dopaminergic system can cause deficient PPI as found in neuropsychiatric diseases. A target specific influence of deep brain stimulation (DBS) on PPI has been shown in animal models of neuropsychiatric disorders. In the present study, three patients with early dementia of Alzheimer type underwent DBS of the median forebrain bundle (MFB) in a compassionate use program to maintain cognitive abilities. This provided us the unique possibility to investigate the effects of different stimulation conditions of DBS of the MFB on PPI in humans., Results: Separate analysis of each patient consistently showed a frequency dependent pattern with a DBS-induced increase of PPI at 60 Hz and unchanged PPI at 20 or 130 Hz, as compared to sham stimulation., Conclusions: Our data demonstrate that electrical stimulation of the MFB modulates PPI in a frequency-dependent manner. PPI measurement could serve as a potential marker for optimization of DBS settings independent of the patient or the examiner.

Introduction: Deep Brain Stimulation (DBS) is a complex, invasive and cost-intensive therapy that requires a high level of expertise. To date, data on quality of DBS in clinical routine in the German health care system are lacking., Methods: The development of evidence-based QIs for DBS in PD patients was performed following a standardized process by a multidisciplinary board between 2014 and 2016. The process was initiated by the German Parkinson Society and followed international recommendations for developing QIs including: a systematic literature search; an appraisal of the published evidence; a consensus-based selection of the QI set; and a pilot study to assess the feasibility in implementing the QIs in clinical routine., Results: A set of 28 QIs for determining the quality of DBS in PD was established by the board covering different dimensions of health care quality (structure, process, and outcome) in different treatment phases of DBS care (pre-operative, peri-operative, and post-operative). Implementation in clinical practice was tested in a pilot study comprising three hospitals delivering DBS care. The feasibility of the QI set was evaluated positively by the participating physicians and hospitals. Mean time to document one patient was 25 min. The German-wide implementation of the defined indicator set within a dedicated quality registry (QualiPa) started in June 2016., Conclusion: QIs are a necessary requirement to monitor hospital performance in DBS care. The evidence-based approach to develop the proposed indicator set is expected to assure transparency, acceptance and long-term applicability of the QI set in Germany., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Previous imaging studies independently highlighted the role of the anterior thalamus (ANT) and nucleus accumbens (NAcc) in successful memory retrieval. While these findings accord with theoretical models, the precise temporal, oscillatory and network dynamics as well as the interplay between the NAcc and ANT in successfully retrieving information from long-term memory are largely unknown. We addressed this issue by recording intracranial electroencephalography in human epilepsy patients from the NAcc (n = 5) and ANT (n = 4) during an old/new recognition test. Our findings demonstrate that differences in event-related potentials between correctly classified old (i.e., studied) and new (i.e., unstudied) images emerged in the NAcc and ANT already between 200 and 600 ms after stimulus onset. Moreover, time-frequency analyses revealed theta (4-8 Hz) power decreases for old compared to new items in the NAcc and the opposite effect in the ANT. Importantly, Granger causality analyses revealed a directional communication from ANT to NAcc suggesting that entrainment from ANT drives successful memory retrieval. Together, our findings show evidence for the notion that the NAcc and ANT receive memory signals, and that theta oscillations may serve as a mechanism to bind these distributed neural assemblies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Previous studies on quality score compression can be classified into two main lines: lossy schemes and lossless schemes. Lossy schemes enable a better management of computational resources. Thus, in practice, and for preliminary analyses, bioinformaticians may prefer to work with a lossy quality score representation. However, the original quality scores might be required for a deeper analysis of the data. Hence, it might be necessary to keep them; in addition to lossy compression this requires lossless compression as well. We developed a space-efficient hierarchical representation of quality scores, QScomp, which allows the users to work with lossy quality scores in routine analysis, without sacrificing the capability of reaching the original quality scores when further investigations are required. Each quality score is represented by a tuple through a novel decomposition. The first and second dimensions of these tuples are separately compressed such that the first-level compression is a lossy scheme. The compressed information of the second dimension allows the users to extract the original quality scores. Experiments on real data reveal that the downstream analysis with the lossy part-spending only 0.49 bits per quality score on average-shows a competitive performance, and that the total space usage with the inclusion of the compressed second dimension is comparable to the performance of competing lossless schemes.

Objective: To evaluate deep brain stimulation (DBS) of the posterior subthalamic area (PSA) in essential tremor (ET) and compare it to the ventral intermediate nucleus of the thalamus (VIM) in terms of stimulation efficacy, efficiency, and side effects., Methods: DBS leads were implanted such that contacts were placed in the VIM, on the intercommissural line, and in the PSA. Thirteen patients with ET entered a randomized, double-blind crossover phase and completed a 1-year follow-up., Results: PSA-DBS significantly reduced tremor severity and improved quality of life. There were no relevant differences in quality and frequency of stimulation side effects between VIM and PSA, with a tendency toward greater tremor improvement with PSA stimulation. Clinical benefit was achieved at significantly lower stimulation amplitudes in the PSA. The majority of patients remained with PSA-DBS after 1 year., Conclusion: In accordance with previous retrospective investigations, our prospective data suggest that PSA-DBS is at least equally effective as but possibly more efficient than VIM-DBS., Classification of Evidence: This study provides Class I evidence that for patients with essential tremor, PSA-DBS is not significantly different from VIM-DBS in suppressing tremor, but clinical benefit from PSA-DBS is attained at lower stimulation amplitudes., (© 2018 American Academy of Neurology.)

Background: In advanced Parkinson&rsquo;s disease, the pedunculopontine nucleus region is thought to be abnormally inhibited by gamma-aminobutyric acid (GABA) ergic inputs from the over-active globus pallidus internus. Recent attempts to boost pedunculopontine nucleus function through deep brain stimulation are promising, but suffer from the incomplete understanding of the physiology of the pedunculopontine nucleus region., Methods: Local field potentials of the pedunculopontine nucleus region and the globus pallidus internus were recorded and quantitatively analyzed in a patient with Parkinson&rsquo;s disease. In particular, we compared the local field potentials from the pedunculopontine nucleus region at rest and during deep brain stimulation of the globus pallidus internus., Results: At rest, the spectrum of local field potentials in the globus pallidus internus was mainly characterized by delta-theta and beta frequency activity whereas the spectrum of the pedunculopontine nucleus region was dominated by activity only in the delta and theta band. High-frequency deep brain stimulation of the globus pallidus internus led to increased theta activity in the pedunculopontine nucleus region and enabled information exchange between the left and right pedunculopontine nuclei. Therefore, Conclusions: When applying deep brain stimulation in the globus pallidus internus, its modulatory effect on pedunculopontine nucleus physiology should be taken into account.

Motivation: Recent advancements in high-throughput sequencing technology have led to a rapid growth of genomic data. Several lossless compression schemes have been proposed for the coding of such data present in the form of raw FASTQ files and aligned SAM/BAM files. However, due to their high entropy, losslessly compressed quality values account for about 80% of the size of compressed files. For the quality values, we present a novel lossy compression scheme named CALQ. By controlling the coarseness of quality value quantization with a statistical genotyping model, we minimize the impact of the introduced distortion on downstream analyses., Results: We analyze the performance of several lossy compressors for quality values in terms of trade-off between the achieved compressed size (in bits per quality value) and the Precision and Recall achieved after running a variant calling pipeline over sequencing data of the well-known NA12878 individual. By compressing and reconstructing quality values with CALQ, we observe a better average variant calling performance than with the original data while achieving a size reduction of about one order of magnitude with respect to the state-of-the-art lossless compressors. Furthermore, we show that CALQ performs as good as or better than the state-of-the-art lossy compressors in terms of variant calling Recall and Precision for most of the analyzed datasets., Availability and Implementation: CALQ is written in C ++ and can be downloaded from https://github.com/voges/calq., Contact: voges@tnt.uni-hannover.de or mhernaez@illinois.edu., Supplementary Information: Supplementary data are available at Bioinformatics online.

Background: The pedunculopontine nucleus has been suggested as a potential deep brain stimulation target for axial symptoms such as gait and balance impairment in idiopathic Parkinson's disease as well as atypical Parkinsonian disorders., Methods: Seven consecutive patients with progressive supranuclear palsy received bilateral pedunculopontine nucleus deep brain stimulation. Inclusion criteria comprised of the clinical diagnosis of progressive supranuclear palsy, a levodopa-resistant gait and balance disorder, age <75 years, and absence of dementia or major psychiatric co-morbidities. Effects of stimulation frequencies at 8, 20, 60 and 130 Hz on motor scores and gait were assessed. Motor scores were followed up for two years postoperatively. Activities of daily living, frequency of falls, health-related quality of life, cognition and mood at 12 months were compared to baseline parameters. Surgical and stimulation related adverse events were assessed., Results: Bilateral pedunculopontine nucleus deep brain stimulation at 8 Hz significantly improved axial motor symptoms and cyclic gait parameters, while high frequency stimulation did not ameliorate gait and balance but improved hypokinesia. This improvement however did not translate into clinically relevant benefits. Frequency of falls was not reduced. Activities of daily living, quality of life and frontal cognitive functions declined, while mood remained unchanged., Conclusion: Bilateral pedunculopontine nucleus deep brain stimulation in progressive supranuclear palsy generates frequency-dependent effects with improvement of cyclic gait parameters at low frequency and amelioration of hypokinesia at high frequency stimulation. However, these effects do not translate into a clinically important improvement., (Copyright © 2018. Published by Elsevier Ltd.)

Stereotactically guided radiofrequency thermoablation (RFTA) for epilepsy has been frequently applied over the last 40 years. Radiofrequency electrodes with temperature control function generate a coagulation lesion with clearly defined borders. In combination with high-resolution MRI imaging, this technique allows minimally-invasive ablation of periventricular nodular heterotopias, small focal type II dysplasias, and hypothalamic hamartomas. This review summarises the literature addressing this topic mainly regarding technical aspects. In essence, RFTA is a safe treatment option for patients suffering from epileptogenic pathologies visible on MRI-images., (Copyright © 2018. Published by Elsevier B.V.)