Differences in neural activation as a function of risk-taking task parameters.

Despite evidence supporting a relationship between impulsivity and naturalistic risk-taking, the relationship of impulsivity with laboratory-based measures of risky decision-making remains unclear. One factor contributing to this gap in our understanding is the degree to which different risky decision-making tasks vary in their details. We conducted an fMRI investigation of the Angling Risk Task (ART), which is an improved behavioral measure of risky decision-making.

The dependence of lipid asymmetry upon polar headgroup structure.

The effect of lipid headgroup structure upon the stability of lipid asymmetry was investigated. Using methyl-β-cyclodextrin -induced lipid exchange, sphingomyelin (SM) was introduced into the outer leaflets of lipid vesicles composed of phosphatidylglycerol, phosphatidylserine (PS), phosphatidylinositol, or cardiolipin, in mixtures of all of these lipids with phosphatidylethanolamine (PE), and in a phosphatidylcholine/phosphatidic acid mixture. Efficient SM exchange (>85% of that expected for complete replacement of the outer leaflet) was obtained for every lipid composition studied.

Risk-taking behavior: dopamine D2/D3 receptors, feedback, and frontolimbic activity.

Decision-making involves frontolimbic and dopaminergic brain regions, but how prior choice outcomes, dopamine neurotransmission, and frontostriatal activity are integrated to affect choices is unclear. We tested 60 healthy volunteers using the Balloon Analogue Risk Task (BART) during functional magnetic resonance imaging. In the BART, participants can pump virtual balloons to increase potential monetary reward or cash out to receive accumulated reward; each pump presents greater risk and potential reward (represented by the pump number).

Up in smoke? A preliminary open-label trial of nicotine replacement therapy and cognitive behavioral motivational enhancement for smoking cessation among youth in Los Angeles.

In 2008-2009, we conducted a 6-week, open-label trial of transdermal nicotine replacement therapy and practical counseling for 34 adolescents seeking smoking cessation in Los Angeles. Dependent outcomes were study retention, use of the patch, and 7-day quit status at the end-of-study and at follow-up visits. Predictors of outcomes included cigarette dependence, withdrawal symptoms, demographic and psychiatric measures, and other substance use.

Methamphetamine-induced increases in putamen gray matter associate with inhibitory control.

Rationale: Problematic drug use is associated with difficulty in exerting self-control over behaviors, and this difficulty may be a consequence of atypical morphometric characteristics that are exhibited by drug-experienced individuals. The extent to which these structural abnormalities result from drug use or reflect neurobiological risk factors that predate drug use, however, is unknown.

Objectives: The purpose of this study is to determine how methamphetamine affects corticostriatal structure and how drug-induced changes relate to alterations in inhibitory control.

Mapping peptide thiol accessibility in membranes using a quaternary ammonium isotope-coded mass tag (ICMT).

The plasma membrane contains a diverse array of proteins, including receptors, channels, and signaling complexes, that serve as decision-making centers. Investigation of membrane protein topology is important for understanding the function of these types of protein. Here, we report a method to determine protein topology in the membrane that utilizes labeling of cysteine with isotope-coded mass tags.

Proving lipid rafts exist: membrane domains in the prokaryote Borrelia burgdorferi have the same properties as eukaryotic lipid rafts.

Lipid rafts in eukaryotic cells are sphingolipid and cholesterol-rich, ordered membrane regions that have been postulated to play roles in many membrane functions, including infection. We previously demonstrated the existence of cholesterol-lipid-rich domains in membranes of the prokaryote, B. burgdorferi, the causative agent of Lyme disease [LaRocca et al.

Greater risk sensitivity of dorsolateral prefrontal cortex in young smokers than in nonsmokers.

Rationale: Despite a national reduction in the prevalence of cigarette smoking, ~19% of the adult US population persists in this behavior, with the highest prevalence among 18-25-year-olds. Given that the choice to smoke imposes a known health risk, clarification of brain function related to decision-making, particularly involving risk-taking, in smokers may inform prevention and smoking cessation strategies.

Objectives: This study aimed to compare brain function related to decision-making in young smokers and nonsmokers.

Effects of the Youth Empowerment Seminar on impulsive behavior in adolescents.

Purpose: Because impulsivity during adolescence predicts health-risk behaviors and associated harm, interventions that attenuate impulsivity may offer protection. We evaluated effects of the Youth Empowerment Seminar (YES!), a biopsychosocial workshop for adolescents that teaches skills of stress management, emotion regulation, conflict resolution, and attentional focus, on impulsive behavior.

Methods: High school students (14-18 years of age) in the United States participated in YES! during their physical education classes.

Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain.

Central sensitization and dysregulation of peripheral substance P and neurokinin-1 receptor (NK-1R) signaling are associated with chronic abdominal pain in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Although positron emission tomography (PET) has demonstrated that patients with injury-related chronic pain have diminished NK-1R availability in the brain, it is unknown whether these deficits are present in IBD and IBS patients, who have etiologically distinct forms of non-injury-related chronic pain. This study's aim was to determine if patients with IBD or IBS exhibit deficits in brain expression of NK-1Rs relative to healthy controls (HCs), the extent to which expression patterns differ across patient populations, and if these patterns differentially relate to clinical parameters.

Sphingolipids and membrane domains: recent advances.

There is growing evidence that cell membranes can contain domains with different lipid and protein compositions and with different physical properties. Furthermore, it is increasingly appreciated that sphingolipids play a crucial role in the formation and properties of ordered lipid domains (rafts) in cell membranes. This review describes recent advances in our understanding of ordered membrane domains in both cells and model membranes.

Contribution of olivofloccular circuitry developmental defects to atypical gaze in autism.

Individuals with autism demonstrate atypical gaze, impairments in smooth pursuit, altered movement perception and deficits in facial perception. The olivofloccular neuronal circuit is a major contributor to eye movement control. This study of the cerebellum in 12 autistic and 10 control subjects revealed dysplastic changes in the flocculus of eight autistic (67%) and two control (20%) subjects.

Analyzing transmembrane protein and hydrophobic helix topography by dual fluorescence quenching.

The location of fluorescent groups relative to the lipid bilayer can be evaluated using fluorescence quenchers embedded in the membrane and/or dissolved in aqueous solution. Quenching can be used to define the membrane topography of membrane proteins and individual membrane-embedded hydrophobic helices by combining it with the placement of fluorescent groups, including Trp, at defined sequence positions. This chapter briefly discusses various quenching methods for studies of membrane protein topography and provides detailed protocols for dual quencher analysis, a rapid, highly sensitive, and experimentally flexible approach in which the information gained from both a membrane-embedded and aqueous quencher is combined.

Lipid exchange between Borrelia burgdorferi and host cells.

Borrelia burgdorferi, the agent of Lyme disease, has cholesterol and cholesterol-glycolipids that are essential for bacterial fitness, are antigenic, and could be important in mediating interactions with cells of the eukaryotic host. We show that the spirochetes can acquire cholesterol from plasma membranes of epithelial cells. In addition, through fluorescent and confocal microscopy combined with biochemical approaches, we demonstrated that B.

Acyl chain length and saturation modulate interleaflet coupling in asymmetric bilayers: effects on dynamics and structural order.

A long-standing question about membrane structure and function is the degree to which the physical properties of the inner and outer leaflets of a bilayer are coupled to one another. Using our recently developed methods to prepare asymmetric vesicles, coupling was investigated for vesicles containing phosphatidylcholine (PC) in the inner leaflet and sphingomyelin (SM) in the outer leaflet. The coupling of both lateral diffusion and membrane order was monitored as a function of PC and SM acyl chain structure.

Altering hydrophobic sequence lengths shows that hydrophobic mismatch controls affinity for ordered lipid domains (rafts) in the multitransmembrane strand protein perfringolysin O.

The hypothesis that mismatch between transmembrane (TM) length and bilayer width controls TM protein affinity for ordered lipid domains (rafts) was tested using perfringolysin O (PFO), a pore-forming cholesterol-dependent cytolysin. PFO forms a multimeric barrel with many TM segments. The properties of PFO mutants with lengthened or shortened TM segments were compared with that of PFO with wild type TM sequences.

The dependence of lipid asymmetry upon phosphatidylcholine acyl chain structure.

Lipid asymmetry, the difference in inner and outer leaflet lipid composition, is an important feature of biomembranes. By utilizing our recently developed MβCD-catalyzed exchange method, the effect of lipid acyl chain structure upon the ability to form asymmetric membranes was investigated. Using this approach, SM was efficiently introduced into the outer leaflet of vesicles containing various phosphatidylcholines (PC), but whether the resulting vesicles were asymmetric (SM outside/PC inside) depended upon PC acyl chain structure.

An evaluation of the evidence that methamphetamine abuse causes cognitive decline in humans.

Methamphetamine (MA) is one of the most commonly abused illicit substances worldwide. Among other problems, abuse of the drug has been associated with reduced cognitive function across several domains. However, much of the literature has not attempted to differentiate cognitive difficulties caused by MA abuse from preexisting cognitive difficulties that are likely caused by other factors.

Elevated gray matter volume of the emotional cerebellum in women with premenstrual dysphoric disorder.

Objective: Premenstrual dysphoric disorder (PMDD) is characterized by severe, negative mood symptoms during the luteal phase of each menstrual cycle. We recently reported that women with PMDD show a greater increase in relative glucose metabolism in the posterior cerebellum from the follicular to the luteal phase, as compared with healthy women, and that the phase-related increase is proportional to PMDD symptom severity. We extended this work with a study of brain structure in PMDD.

Anandamide externally added to lipid vesicles containing trapped fatty acid amide hydrolase (FAAH) is readily hydrolyzed in a sterol-modulated fashion.

We show that anandamide (AEA) externally added to model membrane vesicles containing trapped fatty acid amide hydrolyase (FAAH) can be readily hydrolyzed, demonstrating facile, rapid anandamide movement across the lipid bilayer. The rate of hydrolysis is significantly facilitated by cholesterol and coprostanol, but not by cholesterol sulfate. The effects of sterol upon hydrolysis by FAAH bound to the outer surface of the bilayer were much smaller, although they followed the same pattern.

Effects of methamphetamine abuse and serotonin transporter gene variants on aggression and emotion-processing neurocircuitry.

Individuals who abuse methamphetamine (MA) exhibit heightened aggression, but the neurobiological underpinnings are poorly understood. As variability in the serotonin transporter (SERT) gene can influence aggression, this study assessed possible contributions of this gene to MA-related aggression. In all, 53 MA-dependent and 47 control participants provided self-reports of aggression, and underwent functional magnetic resonance imaging while viewing pictures of faces.

Striatal dopamine D₂/D₃ receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans.

Impulsive behavior is thought to reflect a traitlike characteristic that can have broad consequences for an individual's success and well-being, but its neurobiological basis remains elusive. Although striatal dopamine D₂-like receptors have been linked with impulsive behavior and behavioral inhibition in rodents, a role for D₂-like receptor function in frontostriatal circuits mediating inhibitory control in humans has not been shown. We investigated this role in a study of healthy research participants who underwent positron emission tomography with the D₂/D₃ dopamine receptor ligand [¹⁸F]fallypride and BOLD fMRI while they performed the Stop-signal Task, a test of response inhibition.

Effects of leptin deficiency and replacement on cerebellar response to food-related cues.

Leptin affects eating behavior partly by altering the response of the brain to food-related stimuli. The effects of leptin on brain structure have been observed in the cerebellum, where leptin receptors are most densely expressed, but the function of leptin in the cerebellum remains unclear. We performed a nonrandomized, prospective interventional study of three adults with genetically mediated leptin deficiency.