Understanding the Effects and Adverse Reactions of Deep Brain Stimulation: Is It Time for a Paradigm Shift Toward a Focus on Heterogenous Biophysical Tissue Properties Instead of Electrode Design Only?

Deep brain stimulation (DBS) has been proven to be an effective treatment modality for various late-stage neurological and psychiatric disorders. However, knowledge on the electrical field distribution in the brain tissue is still scarce. Most recent attempts to understand electric field spread were primarily focused on the effect of different electrodes on rather simple tissue models. The influence of microanatomic, biophysical tissue properties in particular has not been investigated in depth. Ethical concerns restrict thorough research on field distribution in human in vivo brain tissue. By means of a simplified model, we investigated the electric field distribution in a broader area of the subthalamic nucleus (STN). Pivotal biophysical parameters including conductivity, permittivity and permeability of brain tissue were incorporated in the model. A brain tissue model was created with the finite element method (FEM). Stimulation was mimicked with parameters used for monopolar stimulation of patients suffering from Parkinson’s disease. Our results were visualized with omnidirectional and segmented electrodes. The stimulated electric field was visualized with superimpositions on a stereotactic atlas (Morel). Owing to the effects of regional tissue properties near the stimulating electrode, marked field distortions occur. Such effects include, for example, isolating effects of heavily myelinated neighboring structures, e.g., the internal capsule. In particular, this may be illustrated through the analysis of a larger coronal area. While omnidirectional stimulation has been associated with vast current leakage, higher targeting precision was obtained with segmented electrodes. Finally, targeting was improved when the influence of microanatomic structures on the electric spread was considered. Our results confirm that lead design is not the sole influence on current spread. An omnidirectional lead configuration does not automatically result in an omnidirectional spread of current. In turn, segmented electrodes do not automatically imply an improved steering of current. Our findings may provide an explanation for side-effects secondary to current leakage. Furthermore, a possible explanation for divergent results in the comparison of the intraoperative awake patient and the postoperative setting is given. Due to the major influence of biophysical tissue properties on electric field shape, the local microanatomy should be considered for precise surgical targeting and optimal hardware implantation

Medical Students Knowledge and Attitude Towards Direct-To-Consumer Genetic Tests

Aims: This study reports on the attitudes of 179 Italian Medical Students to direct-to-consumer genetic test and to participation in research practices. Methods: Data were collected using a self-completion online questionnaire sent to 380 medical students at the faculty of Medicine of the Università Cattolica del Sacro Cuore in Rome, Italy. Questions pertained issues related to awareness and attitudes towards genetic testing, reactions to hypothetical results, and views about contributing to scientific research. Results: The response rate was 47.1%. Less than 50% of students were aware of DTC genetic test. Seventy-four percent of the sample were interested in undergoing DTC genetic test, and the main reason was being aware on genetic predisposition to diseases. Among those who were not willing to undergo a genetic test, the main reason was the lack of confidence in the results. In the hypothetical situations of an increased disease risk after undergoing DTC genetic testing, respondents would take actions to reduce that risk, while in the opposite scenario they would feel unaffected because of the probabilistic nature of the test. Conclusions: We reported a good level of awareness about DTC genetic test and a high interest in undergoing DTC genetic test in our sample. Nevertheless, opinions and reactions are strongly dependent by the hypothetical good or bad result that the test could provide and by the context whereby a genetic test could be performed. Respondents seem to be exposed to the risk of psychological harms, and a strong regulation regarding their use is required

Modelling the vertical gradient of nitrogen dioxide in an urban area

Introduction Land use regression models environmental predictors to estimate ground-floor air pollution concentration surfaces of a study area. While many cities are expanding vertically, such models typically ignore the vertical dimension. Methods We took integrated measurements of NO 2 at up to three different floors on the facades of 25 buildings in the mid-sized European city of Basel, Switzerland. We quantified the decrease in NO 2 concentration with increasing height at each facade over two 14-day periods in different seasons. Using predictors of traffic load, population density and street configuration, we built conventional land use regression (LUR) models which predicted ground floor concentrations. We further evaluated which predictors best explained the vertical decay rate . Ultimately, we combined ground floor and decay models to explain the measured concentrations at all heights. Results We found a clear decrease in mean nitrogen dioxide concentrations between measurements at ground level and those at higher floors for both seasons. The median concentration decrease was 8.1% at 10 m above street level in winter and 10.4% in summer. The decrease with height was sharper at buildings where high concentrations were measured on the ground and in canyon-like street configurations. While the conventional ground floor model was able to explain ground floor concentrations with a model R 2 of 0.84 (RMSE 4.1 μg/m 3 ), it predicted measured concentrations at all heights with an R 2 of 0.79 (RMSE 4.5 μg/m 3 ), systematically overpredicting concentrations at higher floors. The LUR model considering vertical decay was able to predict ground floor and higher floor concentrations with a model R 2 of 0.84 (RMSE 3.8 μg/m 3 ) and without systematic bias. Discussion Height above the ground is a relevant determinant of outdoor residential exposure, even in medium-sized European cities without much high-rise. It is likely that conventional LUR models overestimate exposure for residences at higher floors near major roads. This overestimation can be minimized by considering decay with height

Der Stellenwert der tiefen Hirnstimulation bei der schwer behandelbaren sowie therapierefraktären Depression

Die tiefe Hirnstimulation («THS») ist ein minimalinvasives, neurochirurgisches und hypothesengeleitetes Therapieverfahren zur dauerhaften, lokalen Regulation pathologischer Regelkreise. Während die Depression ein heterogenes Syndrom mit multifaktorieller Ätiopathogenese darstellt, fördert die neurowissenschaftliche Forschung die Evidenz zur Identifikation von Mechanismen auf Netzwerkebene, die in der Pathophysiologie der Depression eine tragende Rolle spielen. Der folgende Beitrag gibt einen Überblick über den Stellenwert der THS bei der therapieresistenten oder schwer behandelbaren Depression. Dabei möchten wir praxisnah den Bekanntheitsgrad der THS fördern und die Herausforderungen bei Therapie und Implementierung diskutieren. The Value of Deep Brain Stimulation in Difficult-To-Treat and Treatment-Refractory Depression Abstract: Deep Brain Stimulation ("DBS") is a minimally invasive, neurosurgical and hypothesis-driven therapeutic procedure for permanent local regulation of pathological circuits. While depression represents a heterogeneous syndrome with multifactorial etiopathogenesis, neuroscience research is advancing evidence to identify network-level mechanisms that play an important role in the pathophysiology of depression. In the following article, we will review the role of DBS in treatment-resistant or difficult-to-treat depression. The aim is to increase the awareness of DBS and to discuss the challenges of its therapy and implementation

Engagement of basal amygdala‐nucleus accumbens glutamate neurons in the processing of rewarding or aversive social stimuli

Basal amygdala (BA) neurons projecting to nucleus accumbens (NAc) core/shell are primarily glutamatergic and are integral to the circuitry of emotional processing. Several recent mouse studies have addressed whether neurons in this population(s) respond to reward, aversion or both emotional valences. The focus has been on processing of physical emotional stimuli, and here, we extend this to salient social stimuli. In male mice, an iterative study was conducted into engagement of BA‐NAc neurons in response to estrous female (social reward, SR) and/or aggressive‐dominant male (social aversion, SA). In BL/6J mice, SR and SA activated c‐Fos expression in a high and similar number/density of BA‐NAc neurons in the anteroposterior intermediate BA (int‐BA), whereas activation was predominantly by SA in posterior (post‐)BA. In Fos‐TRAP2 mice, compared with SR‐SR or SA‐SA controls, exposure to successive presentation of SR‐SA or SA‐SR, followed by assessment of tdTomato reporter and/or c‐Fos expression, demonstrated that many int‐BA‐NAc neurons were activated by only one of SR and SA; these SR/SA monovalent neurons were similar in number and present in both magnocellular and parvocellular int‐BA subregions. In freely moving BL/6J mice exposed to SR, bulk GCaMP6 fibre photometry provided confirmatory in vivo evidence for engagement of int‐BA‐NAc neurons during social and sexual interactions. Therefore, populations of BA‐NAc glutamate neurons are engaged by salient rewarding and aversive social stimuli in a topographic and valence‐specific manner; this novel evidence is important to the overall understanding of the roles of this pathway in the circuitry of socio‐emotional processing

Stress deficits in reward behaviour are associated with and replicated by dysregulated amygdala-nucleus accumbens pathway function in mice

Reduced reward interest/learning and reward-to-effort valuation are distinct, common symptoms in neuropsychiatric disorders for which chronic stress is a major aetiological factor. Glutamate neurons in basal amygdala (BA) project to various regions including nucleus accumbens (NAc). The BA-NAc neural pathway is activated by reward and aversion, with many neurons being monovalent. In adult male mice, chronic social stress (CSS) leads to reduced discriminative reward learning (DRL) associated with decreased BA-NAc activity, and to reduced reward-to-effort valuation (REV) associated, in contrast, with increased BA-NAc activity. Chronic tetanus toxin BA-NAc inhibition replicates the CSS-DRL effect and causes a mild REV reduction, whilst chronic DREADDs BA-NAc activation replicates the CSS effect on REV without affecting DRL. This study provides evidence that stress disruption of reward processing involves the BA-NAc neural pathway; the bi-directional effects implicate opposite activity changes in reward (learning) neurons and aversion (effort) neurons in the BA-NAc pathway following chronic stress

MESoR - Management and exploitation of solar resource knowledge

CD-ROMKnowledge of the solar resource is essential for the planning and operation of solar energy systems. A number of data bases giving information on solar resources have been developed over the past years. The result is a fragmentation of services each having each own mechanism of access and all are giving different results due to different methods, input data and base years. The project MESoR, co-funded by the European Commission, reduces the associated uncertainty by setting up standard benchmarking rules and measures for comparing the data bases, user guidance to the application of resource data and unifying access to various data bases

Neuromodulation of the “Moral Brain” – Evaluating Bridges Between Neural Foundations of Moral Capacities and Normative Aims of the Intervention

The question of whether neuroscience has normative implications or not becomes practically relevant when neuromodulation technologies are used with the aim of pursuing normative goals. The historical burden of such an endeavor is grave and the current knowledge of the neural foundations of moral capacities is surely insufficient for tailored interventions. Nevertheless, invasive and non-invasive neuromodulation techniques are increasingly used to address complex health disturbances and are even discussed for enhancement purposes, whereas both aims entail normative objectives. Taking this observation as an initial position, our contribution will pursue three aims. First, we summarize the potential of neuromodulation techniques for intervening into the “moral brain” using deep brain stimulation as a paradigmatic case and show how neurointerventions are changing our concepts of agency and personality by providing a clearer picture on how humans function. Second, we sketch the “standard model” explanations with respect to ethically justifying such interventions, which rely on a clear separation between normative considerations (“setting the goals of the intervention” or “the desired condition”) and empirical assessments (“evaluating the outcome of the intervention” or “the actual condition”). We then analyze several arguments that challenge this “standard model” and provide bridges between the empirical and normative perspective. We close with the observation that maintaining an analytical distinction between the normative and empirical perspective is reasonable, but that the practical handling of neuromodulation techniques that involve normative intervention goals is likely to push such theoretical distinctions to their limits

Deep Brain Stimulation: In Search of Reliable Instruments for Assessing Complex Personality-Related Changes

During the last 25 years, more than 100,000 patients have been treated with Deep Brain Stimulation (DBS). While human clinical and animal preclinical research has shed light on the complex brain-signaling disturbances that underpin e.g., Parkinson’s disease (PD), less information is available when it comes to complex psychosocial changes following DBS interventions. In this contribution, we propose to more thoroughly investigate complex personality-related changes following deep brain stimulation through refined and reliable instruments in order to help patients and their relatives in the post-surgery phase. By pursuing this goal, we first outline the clinical importance DBS has attained followed by discussing problematic and undesired non-motor problems that accompany some DBS interventions. After providing a brief definition of complex changes, we move on by outlining the measurement problem complex changes relating to non-motor symptoms currently are associated with. The latter circumstance substantiates the need for refined instruments that are able to validly assess personality-related changes. After providing a brief paragraph with regard to conceptions of personality, we argue that the latter is significantly influenced by certain competencies which themselves currently play only a tangential role in the clinical DBS-discourse. Increasing awareness of the latter circumstance is crucial in the context of DBS because it could illuminate a link between competencies and the emergence of personality-related changes, such as new-onset impulse control disorders that have relevance for patients and their relatives. Finally, we elaborate on the field of application of instruments that are able to measure personality-related changes