Amelioration of Binge Eating by Nucleus Accumbens Shell Deep Brain Stimulation in Mice Involves D2 Receptor Modulation

Hedonic overconsumption contributing to obesity involves altered activation within the mesolimbic dopamine system. Dysregulation of dopamine signaling in the nucleus accumbens shell (NAS) has been implicated in reward-seeking behaviors, such as binge eating, which contributes to treatment resistance in obesity (Wise, 2012). Direct modulation of the NAS with deep brain stimulation (DBS), a surgical procedure currently under investigation in humans for the treatment of major depression, obsessive–compulsive disorder, and addiction, may also be effective in ameliorating binge eating. Therefore, we examined the ability of DBS of the NAS to block this behavior in mice. c-Fos immunoreactivity was assessed as a marker of DBS-mediated neuronal activation. NAS DBS was found to reduce binge eating and increased c-Fos levels in this region. DBS of the dorsal striatum had no influence on this behavior, demonstrating anatomical specificity for this effect. The dopamine D2 receptor antagonist, raclopride, attenuated the action of DBS, whereas the D1 receptor antagonist, SCH-23390, was ineffective, suggesting that dopamine signaling involving D2 receptors underlies the effect of NAS DBS. To determine the potential translational relevance to the obese state, chronic NAS DBS was also examined in diet-induced obese mice and was found to acutely reduce caloric intake and induce weight loss. Together, these findings support the involvement of the mesolimbic dopamine pathways in the hedonic mechanisms contributing to obesity, and the efficacy of NAS DBS to modulate this system

MR-Guided Focused Ultrasound Versus Radiofrequency Capsulotomy for Treatment-Refractory Obsessive-Compulsive Disorder: A Cost-Effectiveness Threshold Analysis

Meta-analytic techniques support neuroablation as a promising therapy for treatment-refractory obsessive-compulsive disorder (OCD). This technique appears to offer a more favorable complication rate and higher utility than deep brain stimulation. Moreover, these pooled findings suggest that bilateral radiofrequency (RF) capsulotomy has marginally greater efficacy than stereotactic radiosurgery or cingulotomy. MR-guided focused ultrasound (MRgFUS) capsulotomy is an emerging approach with a potentially more favorable profile than RF ablation and radiosurgery, with preliminary data suggesting safety and efficacy. As a clinical trial is being developed, our study examined the cost and clinical parameters necessary for MRgFUS capsulotomy to be a more cost-effective alternative to RF capsulotomy. A decision analytical model of MRgFUS with RF capsulotomy for OCD was performed using outcome parameters of percent surgical improvement in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score, complications, and side effects. The analysis compared measured societal costs, derived from Medicare reimbursement rates, and effectiveness, based on published RF data. Effectiveness was defined as the degree to which MRgFUS lowered Y-BOCS score. Given that MRgFUS is a new therapy for OCD with scant published data, theoretical risks of MRgFUS capsulotomy were derived from published essential tremor outcomes. Sensitivity analysis yielded cost, effectiveness, and complication rates as critical MRgFUS parameters defining the cost-effectiveness threshold. Literature search identified eight publications (162 subjects). The average reduction of preoperative Y-BOCS score was 56.6% after RF capsulotomy with a 22.6% improvement in utility, a measure of quality of life. Complications occurred in 16.2% of RF cases. In 1.42% of cases, complications were considered acute-perioperative and incurred additional hospitalization cost. The adverse events, including neurological and neurobehavioral changes, in the other 14.8% of cases did not incur further costs, although they impacted utility. Rollback analysis of RF capsulotomy yielded an expected effectiveness of 0.212 quality-adjusted life years/year at an average cost of $24,099. Compared to RF capsulotomy, MRgFUS was more cost-effective under a range of possible cost and complication rates. While further study will be required, MRgFUS lacks many of the inherent risks associated with more invasive modalities and has potential as a safe and cost-effective treatment for OCD

Simple Sequence Repeats in the National Longitudinal Study of Adolescent Health: An Ethnically Diverse Resource for Genetic Analysis of Health and Behavior

Simple sequence repeats (SSRs) are one of the earliest available forms of genetic variation available for analysis and have been utilized in studies of neurological, behavioral, and health phenotypes. Although findings from these studies have been suggestive, their interpretation has been complicated by a variety of factors including, among others, limited power due to small sample sizes. The current report details the availability, diversity, and allele and genotype frequencies of six commonly examined SSRs in the ethnically diverse, population-based National Longitudinal Study of Adolescent Health (Add Health). A total of 106,743 genotypes were generated across 15,140 participants that included four microsatellites and two di-nucleotide repeats in three dopamine genes (DAT1, DRD4, DRD5), the serotonin transporter (5HTT), and monoamine oxidase A (MAOA). Allele and genotype frequencies showed a complex pattern and differed significantly between populations. For both di-nucleotide repeats we observed a greater allelic diversity than previously reported. The availability of these six SSRs in a large, ethnically diverse sample with extensive environmental measures assessed longitudinally offers a unique resource for researchers interested in health and behavior

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD

Spatial access priority mapping (SAPM) with fishers : a quantitative GIS method for participatory planning

Spatial management tools, such as marine spatial planning and marine protected areas, are playing an increasingly important role in attempts to improve marine management and accommodate conflicting needs. Robust data are needed to inform decisions among different planning options, and early inclusion of stakeholder involvement is widely regarded as vital for success. One of the biggest stakeholder groups, and the most likely to be adversely impacted by spatial restrictions, is the fishing community. In order to take their priorities into account, planners need to understand spatial variation in their perceived value of the sea. Here a readily accessible, novel method for quantitatively mapping fishers’ spatial access priorities is presented. Spatial access priority mapping, or SAPM, uses only basic functions of standard spreadsheet and GIS software. Unlike the use of remote-sensing data, SAPM actively engages fishers in participatory mapping, documenting rather than inferring their priorities. By so doing, SAPM also facilitates the gathering of other useful data, such as local ecological knowledge. The method was tested and validated in Northern Ireland, where over 100 fishers participated in a semi-structured questionnaire and mapping exercise. The response rate was excellent, 97%, demonstrating fishers’ willingness to be involved. The resultant maps are easily accessible and instantly informative, providing a very clear visual indication of which areas are most important for the fishers. The maps also provide quantitative data, which can be used to analyse the relative impact of different management options on the fishing industry and can be incorporated into planning software, such as MARXAN, to ensure that conservation goals can be met at minimum negative impact to the industry. This research shows how spatial access priority mapping can facilitate the early engagement of fishers and the ready incorporation of their priorities into the decision-making process in a transparent, quantitative way

The Herschel-SPIRE Legacy Survey (HSLS): the scientific goals of a shallow and wide submillimeter imaging survey with SPIRE

A large sub-mm survey with Herschel will enable many exciting science opportunities, especially in an era of wide-field optical and radio surveys and high resolution cosmic microwave background experiments. The Herschel-SPIRE Legacy Survey (HSLS), will lead to imaging data over 4000 sq. degrees at 250, 350, and 500 micron. Major Goals of HSLS are: (a) produce a catalog of 2.5 to 3 million galaxies down to 26, 27 and 33 mJy (50% completeness; 5 sigma confusion noise) at 250, 350 and 500 micron, respectively, in the southern hemisphere (3000 sq. degrees) and in an equatorial strip (1000 sq. degrees), areas which have extensive multi-wavelength coverage and are easily accessible from ALMA. Two thirds of the of the sources are expected to be at z > 1, one third at z > 2 and about a 1000 at z > 5. (b) Remove point source confusion in secondary anisotropy studies with Planck and ground-based CMB data. (c) Find at least 1200 strongly lensed bright sub-mm sources leading to a 2% test of general relativity. (d) Identify 200 proto-cluster regions at z of 2 and perform an unbiased study of the environmental dependence of star formation. (e) Perform an unbiased survey for star formation and dust at high Galactic latitude and make a census of debris disks and dust around AGB stars and white dwarfs

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank