Neurobiological Impact of HIV Infection and Chronic Cannabis Use

Neuroimaging research has identified brain alterations linked with the human immunodeficiency virus (HIV) that contribute to cognitive declines characterizing the disease. Given cannabis’s (CB’s) anti-inflammatory properties, use prevalence among people living with HIV (PLWH), and impact on neurocognition, my dissertation utilizes a between-groups study design to interrogate separate and interactive effects of HIV and CB on fMRI measures of brain activity. We investigate (1) task-based brain activity at the regional-level, (2) insular resting-state functional connectivity (rsFC) at the circuit-level, and (3) large-scale brain network interactions at the systems-level. Participants (N=114) were stratified into four groups (HIV+/CB+; HIV+/CB-; HIV-/CB+; HIV-/CB-) and underwent fMRI scanning while completing an Error Awareness Task (EAT) and while at rest. Participants also completed a battery of instruments including subjective reports of cognitive failures, and objective measures of cognition and medication management abilities. Blood samples quantified disease severity (viral load) and inflammation (tumor necrosis factor alpha [TNF-α]). Regarding task-based brain activity, PLWH displayed a lack of error-related deactivation in two default mode network (DMN) regions (posterior cingulate cortex [PCC], medial prefrontal cortex [mPFC]). Across all participants, reduced error-related PCC deactivation correlated with reduced medication management abilities and mediated the effect of HIV on such abilities. Regarding insular circuitry, we observed interactive HIVxCB effects on rsFC between two anterior insula (aI) subregions and sensorimotor cortices such that, CB use normalized altered rsFC that was observed among non-using PLWH and correlated with decreased somatic complaints and increased inflammation. Finally, regarding large-scale network interactions, PLWH displayed increased salience network (SN)-DMN rsFC that was associated with diminished error-awareness. These results demonstrate that insufficient error-related DMN suppression and heightened SN-DMN rsFC are linked with HIV and have consequences for error-processing and medication management. Additionally, these outcomes suggest a potential normalizing effect of CB on altered insula-sensorimotor neurocircuitries among PLWH and begin to elucidate inflammatory mechanisms through which CB use may impact brain function in the context of HIV

Rapid assessment of psychological and epidemiological correlates of COVID-19 concern, financial strain, and health-related behavior change in a large online sample

16 pagesCOVID-19 emerged in November 2019 leading to a global pandemic that has not only resulted in widespread medical complications and loss of life, but has also impacted global economies and transformed daily life. The current rapid response study in a convenience online sample quickly recruited 2,065 participants across the United States, Canada, and Europe in late March and early April 2020. Cross-sectional findings indicated elevated anxiety and depressive symptoms compared to historical norms, which were positively associated with COVID-19 concern more strongly than epidemiological data signifying risk (e.g., world and country confirmed cases). Employment loss was positively associated with greater depressive symptoms and COVID-19 concern, and depressive symptoms and COVID-19 concern were significantly associated with more stringent self-quarantine behavior. The rapid collection of data during the early phase of this pandemic is limited by under-representation of non-White and middle age and older adults. Nevertheless, these findings have implications for interventions to slow the spread of COVID-19 infection.This research was supported by funding from Ann Swindells Endowment to the University of Oregon. The funding sources had no role in the study design, data collection and analysis, or submission process

Rapid assessment of psychological and epidemiological correlates of COVID-19 concern, financial strain, and health-related behavior change in a large online sample

16 pagesCOVID-19 emerged in November 2019 leading to a global pandemic that has not only resulted in widespread medical complications and loss of life, but has also impacted global economies and transformed daily life. The current rapid response study in a convenience online sample quickly recruited 2,065 participants across the United States, Canada, and Europe in late March and early April 2020. Cross-sectional findings indicated elevated anxiety and depressive symptoms compared to historical norms, which were positively associated with COVID-19 concern more strongly than epidemiological data signifying risk (e.g., world and country confirmed cases). Employment loss was positively associated with greater depressive symptoms and COVID-19 concern, and depressive symptoms and COVID-19 concern were significantly associated with more stringent self-quarantine behavior. The rapid collection of data during the early phase of this pandemic is limited by under-representation of non-White and middle age and older adults. Nevertheless, these findings have implications for interventions to slow the spread of COVID-19 infection.This research was supported by funding from Ann Swindells Endowment to the University of Oregon. The funding sources had no role in the study design, data collection and analysis, or submission process

Chronic cigarette smoking is linked with structural alterations in brain regions showing acute nicotinic drug-induced functional modulations

Background Whereas acute nicotine administration alters brain function which may, in turn, contribute to enhanced attention and performance, chronic cigarette smoking is linked with regional brain atrophy and poorer cognition. However, results from structural magnetic resonance imaging (MRI) studies comparing smokers versus nonsmokers have been inconsistent and measures of gray matter possess limited ability to inform functional relations or behavioral implications. The purpose of this study was to address these interpretational challenges through meta-analytic techniques in the service of clarifying the impact of chronic smoking on gray matter integrity and more fully contextualizing such structural alterations. Methods We first conducted a coordinate-based meta-analysis of structural MRI studies to identify consistent structural alterations associated with chronic smoking. Subsequently, we conducted two additional meta-analytic assessments to enhance insight into potential functional and behavioral relations. Specifically, we performed a multimodal meta-analytic assessment to test the structural?functional hypothesis that smoking-related structural alterations overlapped those same regions showing acute nicotinic drug-induced functional modulations. Finally, we employed database driven tools to identify pairs of structurally impacted regions that were also functionally related via meta-analytic connectivity modeling, and then delineated behavioral phenomena associated with such functional interactions via behavioral decoding. Results Across studies, smoking was associated with convergent structural decreases in the left insula, right cerebellum, parahippocampus, multiple prefrontal cortex (PFC) regions, and the thalamus. Indicating a structural?functional relation, we observed that smoking-related gray matter decreases overlapped with the acute functional effects of nicotinic agonist administration in the left insula, ventromedial PFC, and mediodorsal thalamus. Suggesting structural-behavioral implications, we observed that the left insula?s task-based, functional interactions with multiple other structurally impacted regions were linked with pain perception, the right cerebellum?s interactions with other regions were associated with overt body movements, interactions between the parahippocampus and thalamus were linked with memory processes, and interactions between medial PFC regions were associated with face processing. Conclusions Collectively, these findings emphasize brain regions (e.g., ventromedial PFC, insula, thalamus) critically linked with cigarette smoking, suggest neuroimaging paradigms warranting additional consideration among smokers (e.g., pain processing), and highlight regions in need of further elucidation in addiction (e.g., cerebellum). Electronic supplementary material The online version of this article (doi:10.1186/s12993-016-0100-5) contains supplementary material, which is available to authorized users

A CBT-based mobile intervention as an adjunct treatment for adolescents with symptoms of depression: a virtual randomized controlled feasibility trial

BackgroundHigh rates of adolescent depression demand for more effective, accessible treatment options. A virtual randomized controlled trial was used to assess the feasibility and acceptability of a 5-week, self-guided, cognitive behavioral therapy (CBT)-based mobile application, Spark, compared to a psychoeducational mobile application (Active Control) as an adjunct treatment for adolescents with depression during the COVID-19 pandemic.MethodsA community sample aged 13–21, with self-reported symptoms of depression, was recruited nationwide. Participants were randomly assigned to use either Spark or Active Control (NSpark = 35; NActive Control = 25). Questionnaires, including the PHQ-8 measuring depression symptoms, completed before, during, and immediately following completion of the intervention, evaluated depressive symptoms, usability, engagement, and participant safety. App engagement data were also analyzed.Results60 eligible adolescents (female = 47) were enrolled in 2 months. 35.6% of those expressing interest were consented and all enrolled. Study retention was high (85%). Spark users rated the app as usable (System Usability Scalemean = 80.67) and engaging (User Engagement Scale-Short Formmean = 3.62). Median daily use was 29%, and 23% completed all levels. There was a significant negative relationship between behavioral activations completed and change in PHQ-8. Efficacy analyses revealed a significant main effect of time, F = 40.60, p < .001, associated with decreased PHQ-8 scores over time. There was no significant Group × Time interaction (F = 0.13, p = .72) though the numeric decrease in PHQ-8 was greater for Spark (4.69 vs. 3.56). No serious adverse events or adverse device effects were reported for Spark users. Two serious adverse events reported in the Active Control group were addressed per our safety protocol.ConclusionRecruitment, enrollment, and retention rates demonstrated study feasibility by being comparable or better than other mental health apps. Spark was highly acceptable relative to published norms. The study's novel safety protocol efficiently detected and managed adverse events. The lack of significant difference in depression symptom reduction between Spark and Active Control may be explained by study design and study design factors. Procedures established during this feasibility study will be leveraged for subsequent powered clinical trials evaluating app efficacy and safety.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT0452459

Concert recording 2017-04-23b

[Track 1]. Slowing down. I. Rotations in an emergency [Track 2]. II. Under the city [Track 3]. III. Forfeit [Track 4]. IV. Something comfortable to fall into / Jeremiah Flannery

A sustainable ocean for all

Welcome to the opening editorial of npj Ocean Sustainability. This new interdisciplinary journal aims to provide a unique forum for sharing research, critically debating issues, and advancing practical solutions to achieve ocean sustainability. The ocean and people are deeply interconnected. Thus, decision-makers require integrative, interdisciplinary, and transdisciplinary knowledge to design solutions and approaches based on the multitude of visions for what a sustainable ocean entails. For that reason, the journal recognizes the benefits of knowledge pluralism and equally welcomes research from natural and social sciences; from marine ecology to Indigenous Studies; from the legal, policy, and management sciences to medical sciences, to arts and humanities. We acknowledge the fundamental need to understand and integrate the environmental and human dimensions into ocean research and management to effectively ensure long-term sustainable ocean use and conservation. We also acknowledge that while the ocean is “one” from a biophysical standpoint, there is a “plurality” of values and relationships between humans and the ocean, emerging from multiple geographical and historical specificities that need to be accounted for

Repeated administration of the GABAB receptor positive modulator BHF177 decreased nicotine self-administration, and acute administration decreased cue-induced reinstatement of nicotine seeking in rats

Abstract: Rationale $\gamma$-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA$_B$ receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA$_B$ receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with GABA$_B$ receptor agonists, GABA$_B$ receptor positive modulators are potentially improved therapeutic compounds for the treatment of drug dependence compared with agonists. Objectives and methods: We examined whether the acute effects of the GABA$_B$ receptor positive modulator N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177) on nicotine self- administration and food-maintained responding under a fixed-ratio 5 schedule of reinforcement were maintained after repeated administration. The effects of acute BHF177 administration on cue-induced nicotine- and food-seeking behavior, a putative animal model of relapse, were also examined. Results: Repeated administration of BHF177 for 14 days decreased nicotine self-administration, with small tolerance observed during the last 7 days of treatment, whereas BHF177 minimally affected food-maintained responding. Acute BHF177 administration dose-dependently blocked cue-induced reinstatement of nicotine-, but not food-, seeking behavior after a 10-day extinction period. Conclusions: These results showed that BHF177 selectively blocked nicotine self-administration and prevented cueinduced reinstatement of nicotine seeking, with minimal effects on responding for food and no effect on cue-induced reinstatement of food seeking. Thus, GABA$_B$ receptor positive modulators could be useful therapeutics for the treatment of different aspects of nicotine dependence by facilitating smoking cessation by decreasing nicotine intake and preventing relapse to smoking in humans

Nutritional values of tortoises relative to ungulates from the Middle Stone Age levels at Blombos Cave, South Africa: Implications for foraging and social behaviour

The site of Blombos Cave (BBC), Western Cape, South Africa has been a strong contributor to establishing the antiquity of important aspects of modern human behaviour, such as early symbolism and technological complexity. However, many linkages between Middle Stone Age (MSA) behaviour and the subsistence record remain to be investigated. Understanding the contribution of small fauna such as tortoises to the human diet is necessary for identifying shifts in overall foraging strategies as well as the collecting and processing behaviour of individuals unable to participate in large-game hunting. This study uses published data to estimate the number of calories present in tortoises as well as ungulates of different body size classes common at South African sites. A single tortoise (Chersina angulata) provides approximately 3332 kJ (796 kcal) of calories in its edible tissues, which is between 20 and 30% of the daily energetic requirements for an active adult (estimated between 9360 kJ [3327 kcal] and 14,580 kJ [3485 kcal] per day). Because they are easy to process, this would have made tortoises a highly-ranked resource, but their slow growth and reproduction makes them susceptible to over-exploitation. Zooarchaeological abundance data show that during the ca. 75 ka (thousands of years) upper Still Bay M1 phase at BBC, tortoises contributed twice as many calories to the diet relative to ungulates than they did during the ca. 100 ka lower M3 phase. However, in spite of the abundance of their fossils, their absolute caloric contribution relative to ungulates remained modest in both phases. At the end of the site's MSA occupation history, human subsistence strategies shifted to emphasise high-return large hunted mammals, which likely precipitated changes in the social roles of hunters and gatherers during the Still Bay