Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for ...development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects.
This article is part of the Special Issue Section entitled ‘Neuroimaging in Neuropharmacology’.
•Acute alcohol affects regional brain metabolism and functional connectivity.•Alcohol pre-treatment alters responses of brain regions evoked by cognitive tasks.•Alcohol effects occur in brain regions that govern motivation and behavior control.•fMRI responses to alcohol may be neural signatures of alcohol effects on behavior.
Kinetoplastids, a group of flagellated protists that are often insect intestinal parasites, encounter various sources of oxidative stress. Such stressors include reactive oxygen species, both ...internally produced within the protist, and induced externally by host immune responses. This investigation focuses on the role of a highly conserved aspartate-based protein phosphatase, PTP-Interacting protein (PIP39) in managing oxidative stress. In addition to its well accepted role in a Trypanosoma brucei life stage transition, there is evidence of PIP39 participation in the T. brucei oxidative stress response. To examine whether this latter PIP39 role may exist more broadly, we aimed to elucidate PIP39’s contribution to redox homeostasis in the monoxenous parasite Leptomonas seymouri. Utilizing CRISPR-Cas9-mediated elimination of PIP39 in conjunction with oxidative stress assays, we demonstrate that PIP39 is required for cellular tolerance to oxidative stress in L. seymouri, positing it as a putative regulatory node for adaptive stress responses. We propose that future analysis of L. seymouri PIP39 enzymatic activity, regulation, and potential localization to a specialized organelle termed a glycosome will contribute to a deeper understanding of the molecular mechanisms by which protozoan parasites adapt to oxidative environments. Our study also demonstrates success at using gene editing tools developed for Leishmania for the related L. seymouri.
•Deletion of the protein PIP39 in Leptomonas seymouri results in sensitivity to oxidative stress.•CRISPR-Cas9 gene editing strategies designed for Leishmania species work in L. seymouri.•Studies in monoxenous kinetoplastids may illuminate primary roles for conserved proteins.
Evidence of sensitization following stimulants administration in humans is just emerging, which prevents reaching more definitive conclusions in favor or against a purported protective role of ...stimulant treatments for ADHD for the development of substance use disorders. Existing evidence from both animal and human research suggest that stimulants produce neurophysiological changes in the brain reward system, some of which could be persistent. This could be relevant in choosing optimal treatments for young patients with ADHD who have additional clinical risk factors for substance abuse (e.g. conduct disorder (CD) and/or familial addictions). Here we stipulate that, while the majority of youth with ADHD greatly benefit from treatments with stimulants, there might be a subpopulation of individuals whose neurobiological profiles may confer risk for heightened vulnerability to the effects of stimulants on the responsiveness of the brain reward system. We propose that focused human research is needed to elucidate the unknown effects of prolonged stimulant exposure on the neurophysiology of the brain reward system in young patients with ADHD.
•Evidence showing sensitization effects of stimulants in animals is substantial while there is minimal evidence for sensitization in humans.•ADHD and SUD share common features of the brain reward system responsiveness to stimulant.•Some ADHD individuals may have unique neurobiological profiles possibly linked to susceptibility to sensitization and risk for substance use.•There no studies to inform the clinically relevant question if sensitization should be considered when youth are exposed to stimulants.•Proposed new lines of research that may provide more definitive answers are discussed.
We compare the evidence from human neuroimaging studies for and against two of the major hypotheses of how alterations in the brain's reward system underlie addiction. One of these, the impulsivity ...hypothesis, proposes that addiction is characterized by excessive sensitivity to reward combined with a failure of inhibition. The other, the reward‐deficiency hypothesis, proposes that addicted individuals have a reduced response to nondrug rewards that leads them to seek drugs in preference to more socially acceptable goals. Positron emission tomographic (PET) studies of dopamine receptor density and dopamine release strongly support the reward‐deficiency hypothesis, while the more recent and numerous functional magnetic resonance imaging (fMRI) studies of goal‐directed behavior provide both support and contradiction for each of the hypotheses. Differences in the time scale on which PET and fMRI make measurements probably account for differences in results, at least in part. It is likely that aspects of brain function described by both the impulsivity and reward‐deficiency hypotheses contribute to the pathophysiology of addiction.
The Adolescent Brain Cognitive Development (ABCD) study is poised to be the largest single-cohort long-term longitudinal study of neurodevelopment and child health in the United States. Baseline data ...on N= 4521 children aged 9–10 were released for public access on November 2, 2018. In this paper we performed principal component analyses of the neurocognitive assessments administered to the baseline sample. The neurocognitive battery included seven measures from the NIH Toolbox as well as five other tasks. We implemented a Bayesian Probabilistic Principal Components Analysis (BPPCA) model that incorporated nesting of subjects within families and within data collection sites. We extracted varimax-rotated component scores from a three-component model and associated these scores with parent-rated Child Behavior Checklist (CBCL) internalizing, externalizing, and stress reactivity. We found evidence for three broad components that encompass general cognitive ability, executive function, and learning/memory. These were significantly associated with CBCL scores in a differential manner but with small effect sizes. These findings set the stage for longitudinal analysis of neurocognitive and psychopathological data from the ABCD cohort as they age into the period of maximal adolescent risk-taking.
This article asks how an anti‐racist, feminist anthropology can help us understand the expansion of the radical right, with a focus on the online white nationalist movement. It demonstrates how ...homophobia and anti‐feminism are two of many pathways into the online white nationalist movement. In effect, white nationalists work through online venues to racialize homophobia and anti‐feminism. They articulate a view of white racialization where gender and sexuality are central to ideas about biological and cultural superiority. Through tracing the linkages between gender, sexuality, and race in different ideations of the white nationalist movement, this article shows a continuity of these core ideas to white nationalism across different manifestations of the movement, even as the expression of them has changed. An aim of this article is to demonstrate the ways an anti‐racist, feminist anthropology provides tools to understand how concerns about gender animate this authoritarian movement.
While abortion foes in the United States rhetorically promote “life,” discursive invocations of death are foundational to antiabortion advocacy. Pro‐life strategists have made gains mandating the ...mourning of aborted fetuses through fetal burial bills, which require abortion providers to cremate or bury fetal tissue from abortion procedures. Fetal burial bills are inextricably tied to biopolitical regimes that make and manage grievable life. Drawing on cultural anthropology, feminist social science, critical race theory, and long‐term research on white evangelicalism, this article examines government documents (e.g., Indiana statutes, court rulings, health reports, legislative activity, and state prosecutions) to provide a discursive critique of Indiana's fetal burial law. Constructions of aborted fetuses as grievable human life and the formations of personhood they promote undergird what anthropologist Leith Mullings called the necropolitics of reproduction—a framework explaining how reproduction is constitutive of political regimes that use systemic violence to determine who (or what) lives and dies. Legal conceptions of fetal personhood that hyper‐value fetal subjects entwine with systemic racism, Christian ideology, and anti‐environmentalism to diminish the Black and Brown bodies and environments on which their futures depend. This case is a bellwether for broader dynamics in anti‐abortion policy and activism in the post‐Roe era.
Insomnia symptoms are negatively related to opioid use disorder (OUD) treatment outcomes, possibly reflecting the influence of sleep on neurofunctional domains implicated in addiction. Moreover, the ...intersection between OUD recovery and sleep represents an area well-suited for the development of novel, personalized treatment strategies. This study assessed the prevalence of clinically significant insomnia symptoms and characterized its neurofunctional correlates among a clinical sample of adults with OUD receiving buprenorphine. Adults (N = 129) receiving buprenorphine for OUD from an outpatient clinic participated in a cross-sectional survey. Participants completed an abbreviated version of NIDA's Phenotyping Assessment Battery, which assessed 6 neurofunctional domains: sleep, negative emotionality, metacognition, interoception, cognition, and reward. Bivariate descriptive statistics compared those with evidence of clinically significant insomnia symptoms (Insomnia Severity Index ISI score of greater than or equal to11) to those with minimal evidence of clinically significant insomnia symptoms (ISI score of less than or equal to10) across each of the neurofunctional domains. Roughly 60% of participants reported clinically significant insomnia symptoms (ISI score of greater than or equal to11). Experiencing clinically significant insomnia symptoms was associated with reporting greater levels of depression, anxiety, post-traumatic stress, stress intolerance, unhelpful metacognition, and interoceptive awareness (ps<0.05). Participants with evidence of clinically significant insomnia were more likely to report that poor sleep was interfering with their OUD treatment and that improved sleep would assist with their treatment (ps<0.05). Insomnia was prevalent among adults receiving buprenorphine for OUD. Insomnia was associated with neurofunctional performance, which may impact OUD treatment trajectories. Our findings indicate potential targets in the development of personalized treatment plans for patients with co-morbid insomnia and OUD. To inform the development of novel treatment strategies, more research is needed to understand the potential mechanistic links between sleep disturbances and substance use.
•In men, coinhibition of the autonomic nervous system predicted proactive aggression.•In women, augmented parasympathetic fear reactivity predicted proactive aggression.•Greater sympathetic fear ...reactivity predicted reactive aggression for men and women.
Reactive aggression is posited to occur as a result of hypersensitivity to threat, whereas fearlessness may drive proactive aggression. This study aimed to test if physiological fear reactivity differentially relates to self-report reactive and proactive aggression using immersive virtual reality fear (VR) induction. We collected subjective fear ratings and sympathetic (SNS; skin conductance) and parasympathetic (PNS; respiratory sinus arrhythmia) nervous system reactivity during an interactive VR horror video. Results showed that for men and women, reactive aggression was related to heightened SNS fear reactivity. For men, proactive aggression was related to hypoarousal of the PNS and SNS (coinhibition) during fear induction, whereas augmented PNS was related to proactive aggression in women. These results support the fearlessness hypothesis for proactive aggression in men, but this does not replicate in women. By contrast, hypersensitivity to fear is related to reactive aggression for both men and women.
Purpose of Review
A wealth of epidemiological and cohort research, together with a healthy dose of anecdote, has characterized late adolescence and emerging adulthood as a time of increased substance ...use and other risky behaviors. This review will address whether differences between adolescents or between adolescents and other age groups in dopaminergic mesolimbic recruitment by (nondrug) rewards inferred from functional magnetic resonance imaging (fMRI) could partially explain morbidity and mortality from risky-behavior-related causes in adolescents.
Recent Findings
Recent findings do not suggest a definitive directionality with regard to whether increased vs decreased mesolimbic responsiveness to nondrug rewards correlates with real-world risk-taking. Inconsistent relationships between reward activation and real-world risky behavior in these reports reflect in part methodological differences as well as conceptual differences between populations in terms of whether tepid mesolimbic recruitment by rewards is a marker of psychiatric health.
Summary
There are several potential reasons why the directionality of relationships between reward-elicited brain activation and substance use risk (specifically) might differ. These factors include differences between adolescents in histories/exposure of substance use, motivation for substance use, the component of the instrumental behavior being studied, and the cognitive demands of the incentive tasks. Systematic manipulation of these discrepant study factors might offer a way forward to clarify how motivational neurocircuit function relates to addiction risk in adolescents.
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