Electrophysiological Signatures of Spatial Boundaries in the Human Subiculum.

Environmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. Although studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. To address this gap in the literature, we analyzed intracranial recordings from the hippocampal formation of surgical epilepsy patients (of both sexes) while they performed a virtual spatial navigation task and compared the power in three frequency bands (1-4, 4-10, and 30-90 Hz) for target locations near and far from the environmental boundaries. Our results suggest that encoding locations near boundaries elicited stronger theta oscillations than for target locations near the center of the environment and that this difference cannot be explained by variables such as trial length, speed, movement, or performance. These findings provide direct evidence of boundary-dependent neural activity localized in humans to the subiculum, the homolog of the hippocampal subregion in which most boundary cells are found in rodents, and indicate that this system can represent attended locations that rather than the position of one\u27s own body

Left versus right subcallosal cingulate deep brain stimulation for treatment-resistant depression

Deep brain stimulation (DBS) of the subcallosal cingulate has emerged as a promising therapy for treatment-resistant depression (TRD). To date, all studies have employed bilateral stimulation; however, the physiology of affect and pathophysiology of depression are known to be asymmetric across hemispheres. Unilateral stimulation may provide efficacy while decreasing risk. Five patients were exposed to unilateral open-label DBS to the subcallosal cingulate for 12 weeks each to the left and then right hemispheres in a double-blind, crossover fashion. After 12 weeks of stimulation to each hemisphere, bilateral stimulation was initiated, and patients were followed for 12 additional weeks. Additionally, nine months of long-term follow up data were collected. Left, but not right, unilateral stimulation was associated with significant decrease in depression scores; with bilateral stimulation, all patients improved and one patient remitted. No serious adverse events were associated with surgery or acute or chronic stimulation. This small study suggests that unilateral DBS to the subcallosal cingulate may be an effective treatment for TRD. All patients improved with bilateral stimulation, though antidepressant effects following 12 weeks were modest. These findings contrast somewhat with prior open-label trials, though duration of bilateral stimulation was shorter in this trial. The current study continues to confirm safety of implantation and use of DBS to the subcallosal cingulate for patients with TRD and highlights the importance of personalization of therapy, for example by hemisphere, in future trials

Incipient Social Groups: An Analysis via In-Vivo Behavioral Tracking

Social psychology is fundamentally the study of individuals in groups, yet there remain basic unanswered questions about group formation, structure, and change. We argue that the problem is methodological. Until recently, there was no way to track who was interacting with whom with anything approximating valid resolution and scale. In the current study we describe a new method that applies recent advances in image-based tracking to study incipient group formation and evolution with experimental precision and control. In this method, which we term "in vivo behavioral tracking," we track individuals' movements with a high definition video camera mounted atop a large field laboratory. We report results of an initial study that quantifies the composition, structure, and size of the incipient groups. We also apply in-vivo spatial tracking to study participants' tendency to cooperate as a function of their embeddedness in those crowds. We find that participants form groups of seven on average, are more likely to approach others of similar attractiveness and (to a lesser extent) gender, and that participants' gender and attractiveness are both associated with their proximity to the spatial center of groups (such that women and attractive individuals are more likely than men and unattractive individuals to end up in the center of their groups). Furthermore, participants' proximity to others early in the study predicted the effort they exerted in a subsequent cooperative task, suggesting that submergence in a crowd may predict social loafing. We conclude that in vivo behavioral tracking is a uniquely powerful new tool for answering longstanding, fundamental questions about group dynamics

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Anatomical Correlates of Uncontrollable Laughter With Unilateral Subthalamic Deep Brain Stimulation in Parkinson’s Disease

IntroductionSubthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for the management of motor complications in Parkinson’s disease. Uncontrollable laughter has been reported as a rare side effect of STN stimulation. The precise mechanism responsible for this unique phenomenon remains unclear. We examined in detail the DBS electrode position and stimulation parameters in two patients with uncontrollable laughter during programming after STN-DBS surgery and illustrated the anatomical correlates of the acute mood changes with STN stimulation.Case reportUnilateral STN-DBS induced uncontrollable laughter with activation of the most ventral contacts in both patients. However, the location of the electrodes responsible for this adverse effect differed between the patients. In the first patient, the DBS lead was placed more inferiorly and medially within the STN. In the second patient, the DBS lead was implanted more anteriorly and inferiorly than initially planned at the level of the substantia nigra reticulata (SNr).ConclusionUnilateral STN-DBS can induce acute uncontrollable laughter with activation of electrodes located more anterior, medial, and inferior in relationship with the standard stereotactic STN target. We suggest that simulation of ventral and medial STN, surrounding limbic structures or the SNr, is the most plausible anatomical substrate responsible for this acute mood and behavioral change. Our findings provide insight into the complex functional neuroanatomical relationship of the STN and adjacent structures important for mood and behavior. DBS programming with more dorsal and lateral contacts within the STN should be entertained to minimize the emotional side effects

Effects of experimental nitrogen deposition on soil organic carbon storage in Southern California drylands

Atmospheric nitrogen (N) deposition is enriching soils with N across biomes. Soil N enrichment can increase plant productivity and affect microbial activity, thereby increasing soil organic carbon (SOC), but such responses vary across biomes. Drylands cover ~45% of Earth's land area and store ~33% of global SOC contained in the top 1 m of soil. Nitrogen fertilization could, therefore, disproportionately impact carbon (C) cycling, yet whether dryland SOC storage increases with N remains unclear. To understand how N enrichment may change SOC storage, we separated SOC into plant-derived, particulate organic C (POC), and largely microbially derived, mineral-associated organic C (MAOC) at four N deposition experimental sites in Southern California. Theory suggests that N enrichment increases the efficiency by which microbes build MAOC (C stabilization efficiency) if soil pH stays constant. But if soils acidify, a common response to N enrichment, then microbial biomass and enzymatic organic matter decay may decrease, increasing POC but not MAOC. We found that N enrichment had no effect on C fractions except for a decrease in MAOC at one site. Specifically, despite reported increases in plant biomass in three sites and decreases in microbial biomass and extracellular enzyme activities in two sites that acidified, POC did not increase. Furthermore, microbial C use and stabilization efficiency increased in a non-acidified site, but without increasing MAOC. Instead, MAOC decreased by 16% at one of the sites that acidified, likely because it lost 47% of the exchangeable calcium (Ca) relative to controls. Indeed, MAOC was strongly and positively affected by Ca, which directly and, through its positive effect on microbial biomass, explained 58% of variation in MAOC. Long-term effects of N fertilization on dryland SOC storage appear abiotic in nature, such that drylands where Ca-stabilization of SOC is prevalent and soils acidify, are most at risk for significant C loss

Global gradients of coral exposure to environmental stresses and implications for local management

Background: The decline of coral reefs globally underscores the need for a spatial assessment of their exposure to multiple environmental stressors to estimate vulnerability and evaluate potential counter-measures. Methodology/Principal Findings: This study combined global spatial gradients of coral exposure to radiation stress factors (temperature, UV light and doldrums), stress-reinforcing factors (sedimentation and eutrophication), and stress-reducing factors (temperature variability and tidal amplitude) to produce a global map of coral exposure and identify areas where exposure depends on factors that can be locally managed. A systems analytical approach was used to define interactions between radiation stress variables, stress reinforcing variables and stress reducing variables. Fuzzy logic and spatial ordinations were employed to quantify coral exposure to these stressors. Globally, corals are exposed to radiation and reinforcing stress, albeit with high spatial variability within regions. Based on ordination of exposure grades, regions group into two clusters. The first cluster was composed of severely exposed regions with high radiation and low reducing stress scores (South East Asia, Micronesia, Eastern Pacific and the central Indian Ocean) or alternatively high reinforcing stress scores (the Middle East and the Western Australia). The second cluster was composed of moderately to highly exposed regions with moderate to high scores in both radiation and reducing factors (Caribbean, Great Barrier Reef (GBR), Central Pacific, Polynesia and the western Indian Ocean) where the GBR was strongly associated with reinforcing stress. Conclusions/Significance: Despite radiation stress being the most dominant stressor, the exposure of coral reefs could be reduced by locally managing chronic human impacts that act to reinforce radiation stress. Future research and management efforts should focus on incorporating the factors that mitigate the effect of coral stressors until long-term carbon reductions are achieved through global negotiations