Eating Disorder Symptomatology Among Young Adult Cigarette and E-Cigarette Users.

Objective: Tobacco use is elevated among individuals with eating disorders (EDs). Yet, further research is needed to understand associations between cigarette and e-cigarette use patterns and ED symptomatology. To gain a more comprehensive understanding of tobacco use and EDs, this study characterized ED symptomatology and tobacco use patterns, including exclusive cigarette use, e-cigarette use, dual use, and nonuse. Method: Young adults aged 18-24 years who self-reported exclusive cigarette, e-cigarette, dual, or nonuse (N = 2500) were recruited via Lucid, an online survey management company. Participants completed questionnaires assessing body dissatisfaction, global ED psychopathology, binge eating and self-induced vomiting frequency, and demographics. ED diagnostic groups included: anorexia nervosa (AN), bulimia spectrum eating disorders (BSED), atypical AN, and night eating syndrome (NES). Results: Multinomial logistic models revealed those with AN were more likely to be dual users, those with atypical AN were more likely to be exclusive e-cigarette users, and participants with a BSED or NES were more likely to be exclusive e-cigarette or dual users, compared to those without an ED. General linear models suggested body dissatisfaction and global ED psychopathology were higher among exclusive e-cigarette and dual users, while binge eating and self-induced vomiting frequencies were greater among all tobacco use groups compared to nonusers. Discussion: Our findings suggest young adults with ED symptomatology were more likely to be users of e-cigarettes exclusively or dual users. It will be necessary to examine how these associations manifest using longitudinal and clinical populations in future research.

The neural correlates of value representation: From single items to bundles.

One of the core questions in Neuro-economics is to determine where value is represented. To date, most studies have focused on simple options and identified the ventromedial prefrontal cortex (VMPFC) as the common value region. We report the findings of an fMRI study in which we asked participants to make pairwise comparisons involving options of varying complexity: single items (Control condition), bundles made of the same two single items (Scaling condition) and bundles made of two different single items (Bundling condition). We construct a measure of choice consistency to capture how coherent the choices of a participant are with one another. We also record brain activity while participants make these choices. We find that a common core of regions involving the left VMPFC, the left dorsolateral prefrontal cortex (DLPFC), regions associated with complex visual processing and the left cerebellum track value across all conditions. Also, regions in the DLPFC, the ventrolateral prefrontal cortex (VLPFC) and the cerebellum are differentially recruited across conditions. Last, variations in activity in VMPFC and DLPFC value-tracking regions are associated with variations in choice consistency. This suggests that value based decision-making recruits a core set of regions as well as specific regions based on task demands. Further, correlations between consistency and the magnitude of signal change with lateral portions of the PFC suggest the possibility that activity in these regions may play a causal role in decision quality.

Essential Role of Social Context and Self-Efficacy in Daily Paretic Arm/Hand Use After Stroke: An Ecological Momentary Assessment Study With Accelerometry.

OBJECTIVE: To determine the momentary effect of social-cognitive factors, in addition to motor capability, on post-stroke paretic arm/hand use in the natural environment. DESIGN: A 5-day observational study in which participants were sent 6 Ecological Momentary Assessment (EMA) prompts/day. SETTING: Participants' daily environment. PARTICIPANTS: Community-dwelling, chronic stroke survivors with right-dominant, mild-moderate upper extremity paresis (N=30). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Time duration of bimanual and unimanual paretic arm/hand use indexed by accelerometry; social-cognitive factors (social context, self-efficacy, mood) captured by EMA; motor capability of the paretic limb measured by Fugl-Meyer Upper Extremity Motor Assessment (FM). RESULTS: After accounting for participants' motor capability, we found that momentary social context (alone or not) and self-efficacy significantly predicted post-stroke paretic arm/hand use behavior in the natural environment. When participants were not alone, paretic arm/hand movement increased both with and without the less-paretic limb (bimanual and unimanual movements, P=.018 and P<.001, respectively). Importantly, participants were more likely to use their paretic arm/hand (unimanually) if they had greater self-efficacy for limb use (P=.042). EMA repeated-measures provide a real-time approach that captures the natural dynamic ebb and flow of social-cognitive factors and their effect on daily arm/hand use. We also observed that people with greater motor impairments (FM<50.6) increase unimanual paretic arm/hand movements when they are not alone, regardless of motor capability. CONCLUSIONS: In addition to motor capability, stroke survivors' momentary social context and self-efficacy play a role in paretic arm/hand use behavior. Our findings suggest the development of personalized rehabilitative interventions which target these factors to promote daily paretic arm/hand use. This study highlights the benefits of EMA to provide real-time information to unravel the complexities of the biopsychosocial (ie, motor capability and social-cognitive factors) interface in post-stroke upper extremity recovery.

The Early Impact of Social Distancing Measures on Drug Use.

BACKGROUND AND OBJECTIVES: Social distancing policies have been widely adopted in response to the COVID-19 pandemic. High levels of social connection are positively associated with beneficial health outcomes, while social isolation is associated with poor long-term health outcomes including reduced life expectancy. The present study evaluates the impact of social distancing measures during the early period of COVID-19 on substance use behaviors among those in the United States. Methods: We used an internet-based survey with participants (n = 157; 86 male) reporting a history of problems related to drug use. We relied on ANOVA and logistic regression techniques to assess the associations between social connection and substance use. Results: People with more severe drug use problems reported feeling more socially isolated during social distancing. Those who primarily use alcohol reported higher global feelings of social connection than those who primarily use opioids. During social distancing, participants reported an increase in alcohol and cigarette consumption, and a decrease in cocaine use. Lastly, those who reported using drugs for social reasons were less likely to have decreased substance use during social distancing. Conclusions: The current study provides evidence that social distancing guidelines have impacted both substance use behaviors and feelings of social and physical connection. Further, there are differential impacts based on drug of choice. These results advance delineation of the connection between sociality and drug use.

Adolescent emotional disorder symptoms and transdiagnostic vulnerabilities as predictors of young adult substance use during the COVID-19 pandemic: mediation by substance-related coping behaviors.

The COVID-19 pandemic presents unique stressors (e.g. social isolation) that may increase substance use risk among young adults with a history of emotional disturbance. This study examined whether emotional disorder symptoms and transdiagnostic vulnerabilities during adolescence predicted young adult substance use during COVID-19, and whether using substances to cope with the pandemic's social conditions mediated these associations. Adolescents (N = 2,120) completed baseline surveys assessing transdiagnostic emotional vulnerabilities (anhedonia, distress intolerance, anxiety sensitivity, negative urgency) and symptoms (major depression[MD], generalized anxiety[GAD], panic disorder[PD], social phobia[SP], obsessive-compulsive disorder[OCD]) in adolescence (September-December 2016; M[SD] age = 17.45[0.38]). At follow-up (May-August 2020; M[SD] age = 21.16[0.39]), past 30-day substance use and using substances to cope with social isolation during the pandemic were reported. Adjusted models showed that baseline distress intolerance, anxiety sensitivity, negative urgency, and MD symptoms each significantly predicted higher number of past-month single-substance using days and number of substances used at follow-up (ßs = 0.04-0.06). In each case, associations were mediated by tendency to use substances to cope with the pandemic (ßindirect range: 0.028-0.061). To mitigate disproportionate escalation of substance use in young adults with a history of certain types of emotional disturbance, interventions promoting healthy coping strategies to deal with the pandemic's social conditions warrant consideration.

Present-state dependency in valuation of the future.

Ainslie's target article provides a map of distinct mechanisms relevant to self-control, potentially providing needed precision to the field. He also breaks new ground in characterizing the symbiotic relationship between suppression and resolve. In this commentary, I argue that one behaviorism-based feature of his framework, present-state independence, is unjustified and unnecessary for the broader claims of the theory.

Expectancy and affective response to challenging balance practice conditions in individuals with Parkinson's disease.

Psychological states can influence motor performance and learning. In Parkinson's disease (PD), placebo effects or expectancies for pharmacological treatment benefits are not uncommon, but little is known about whether self-efficacy, beliefs about personal performance capabilities, may play a role in this population. To address this question, we investigated whether experimental manipulations designed to enhance self-efficacy would benefit motor performance and learning in PD. A motor learning paradigm was utilized to determine the short-term (i.e., practice) and longer-term (i.e., retention) impact of self-efficacy enhancement when 44 individuals with PD (Hoehn and Yahr stage I-III) acquired a challenging balance skill. Using stratified randomization by Hoehn and Yahr stage, participants were assigned to a control group or one of two investigational groups: (a) an expectancy-relevant statement that encouraged an incremental mindset in which the balance skill, though initially challenging, was acquirable with practice (incremental theory group, IT), and (b) the expectancy-relevant statement in combination with a criterion for successful performance (incremental theory plus success criteria group, IT + SC). All groups improved their balance performance, but contrary to expectations, investigational groups did not outperform the control group at practice or retention. Unexpectedly, the IT + SC group reported greater nervousness than the control and IT groups, suggesting that the employed success criteria may have induced performance-related anxiety. Regression analyses revealed that self-efficacy increase from initial practice predicted performance at the end of practice and at retention. These findings highlight the potential contribution of psychological factors on motor function and rehabilitation in individuals with PD.

Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards.

Prior studies suggest that fructose compared with glucose may be a weaker suppressor of appetite, and neuroimaging research shows that food cues trigger greater brain reward responses in a fasted relative to a fed state. We sought to determine the effects of ingesting fructose versus glucose on brain, hormone, and appetitive responses to food cues and food-approach behavior. Twenty-four healthy volunteers underwent two functional magnetic resonance imaging (fMRI) sessions with ingestion of either fructose or glucose in a double-blinded, random-order cross-over design. fMRI was performed while participants viewed images of high-calorie foods and nonfood items using a block design. After each block, participants rated hunger and desire for food. Participants also performed a decision task in which they chose between immediate food rewards and delayed monetary bonuses. Hormones were measured at baseline and 30 and 60 min after drink ingestion. Ingestion of fructose relative to glucose resulted in smaller increases in plasma insulin levels and greater brain reactivity to food cues in the visual cortex (in whole-brain analysis) and left orbital frontal cortex (in region-of-interest analysis). Parallel to the neuroimaging findings, fructose versus glucose led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods. These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing and may promote feeding behavior.

Resting state hypothalamic response to glucose predicts glucose-induced attenuation in the ventral striatal response to food cues.

Feeding behavior is regulated by a complex interaction of central nervous system responses to metabolic signals that reflect nutrient availability and to food cues that trigger appetitive responses. Prior work has shown that the hypothalamus is a key brain area that senses and responds to changes in metabolic signals, and exposure to food cues induces the activation of brain areas involved in reward processing. However, it is not known how the hypothalamic responses to changes in metabolic state are related to reward responses to food cues. This study aimed to understand whether changes in hypothalamic activity in response to glucose-induced metabolic signals are linked to food-cue reactivity within brain areas involved in reward processing. We combined two neuroimaging modalities (Arterial Spin Labeling and Blood Oxygen Level Dependent) to measure glucose-induced changes in hypothalamic cerebral blood flow (CBF) and food-cue task induced changes in brain activity within reward-related regions. Twenty-five participants underwent a MRI session following glucose ingestion and a subset of twenty individuals underwent an additional water session on a separate day as a control condition (drink order randomized). Hunger was assessed before and after drink consumption. We observed that individuals who had a greater reduction in hypothalamic CBF exhibited a greater reduction in left ventral striatum food cue reactivity (Spearman's rho = 0.46, P = 0.048) following glucose vs. water ingestion. These results are the first to use multimodal imaging to demonstrate a link between hypothalamic metabolic signaling and ventral striatal food cue reactivity.

Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence.

BACKGROUND: Individuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D2-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D2/D3 receptor availability is negatively correlated with the preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence. METHODS: Fifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [(18)F]fallypride. RESULTS: MA users displayed steeper temporal discounting (p = 0.030) and lower striatal D2/D3 receptor availability (p < 0.0005) than controls. Discount rate was negatively correlated with striatal D2/D3 receptor availability, with the relationship reaching statistical significance in the combined sample (r = -0.291, p = 0.016) and among MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179, p = 0.185); the slopes did not differ significantly between MA users and controls (p = 0.5). CONCLUSIONS: These results provide the first direct evidence of a link between deficient D2/D3 receptor availability and steep temporal discounting. This finding fits with reports that low striatal D2/D3 receptor availability is associated with a higher risk of relapse among stimulant users, and may help to explain why some individuals choose to continue using drugs despite knowledge of their eventual negative consequences. Future research directions and therapeutic implications are discussed.

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. Striatal dopamine D2/D3 receptor availability was negatively correlated with speed of response inhibition (stop-signal reaction time) and positively correlated with inhibition-related fMRI activation in frontostriatal neural circuitry. Correlations involving D2/D3 receptor availability were strongest in the dorsal regions (caudate and putamen) of the striatum, consistent with findings of animal studies relating dopamine receptors and response inhibition. The results suggest that striatal D2-like receptor function in humans plays a major role in the neural circuitry that mediates behavioral control, an ability that is essential for adaptive responding and is compromised in a variety of common neuropsychiatric disorders.

Sweet taste preference is associated with greater hypothalamic response to glucose and longitudinal weight gain.

The hypothalamus has an abundant expression of sweet taste receptors that play a role in glucose sensing and energy homeostasis. Evidence suggests that liking "sweets" can be associated with weight gain, but the relationship between sweet taste preference and hypothalamic regulation of appetite is unknown. This study tested the hypothesis that sweet taste preference is associated with increased hypothalamic activation in response to glucose (a purported neural marker for weight gain risk) and greater longitudinal increases in body mass index (BMI). Fifty-four adults aged 18-35 years with a mean (± SD) BMI of 27.99 ± 5.32 kg/m2 completed the study. Height and weight were measured at baseline and 6-12 months later in a subset of 36 participants. Sweet taste preference was assessed via the Monell 2-series, forced-choice tracking procedure. Arterial spin labeling magnetic resonance imaging was performed before and after oral glucose ingestion to determine hypothalamic blood flow response to glucose. Linear models were used to examine relationships between sweet taste preference and the hypothalamic response to glucose and longitudinal changes in BMI, adjusting for age, sex, and baseline BMI. Sweet taste preference was positively associated with glucose-linked hypothalamic blood flow (beta = 0.017, p = 0.043), adjusted for age, sex and BMI. We also observed a positive association between sweet taste preference and longitudinal change in BMI (beta = 0.088, p = 0.015), adjusted for age, sex and baseline BMI. These findings suggest that heightened sweet taste preference is associated with glucose-linked hypothalamic activation and may be linked to increased susceptibility for weight gain.

Different forms of self-control share a neurocognitive substrate.

Psychological and neurocognitive studies have suggested that different kinds of self-control may share a common psychobiological component. If this is true, performance in affective and nonaffective inhibitory control tasks in the same individuals should be correlated and should rely upon integrity of this region. To test this hypothesis, we acquired high-resolution magnetic resonance images from 44 healthy and 43 methamphetamine-dependent subjects. Individuals with methamphetamine dependence were tested because of prior findings that they suffer inhibitory control deficits. Gray matter structure of the inferior frontal gyrus was assessed using voxel-based morphometry. Subjects participated in tests of motor and affective inhibitory control (stop-signal task and emotion reappraisal task, respectively); and methamphetamine-dependent subjects provided self-reports of their craving for methamphetamine. Performance levels on the two inhibitory control tasks were correlated with one another and with gray matter intensity in the right pars opercularis region of the inferior frontal gyrus in healthy subjects. Gray matter intensity of this region was also correlated with methamphetamine craving. Compared with healthy subjects, methamphetamine-dependent subjects exhibited lower gray matter intensity in this region, worse motor inhibitory control, and less success in affect regulation. These findings suggest that self-control in different psychological domains involves a common substrate in the right pars opercularis, and that successful self-control depends on integrity of this substrate.

Moderators of the association between brain activation and farsighted choice.

There is equivocal support for the hypothesis that preference for later larger (LL) over sooner smaller (SS) monetary alternatives (e.g., $50 in four months over $30 today) is associated with functioning of the insula and the prefrontal cortex (especially the lateral PFC). In the present study, we re-examined overall neural correlates of choice using a procedure to minimize potential confounds between choice (which is necessarily not under experimental control) and valuation. In addition, we assessed whether choice-related brain activity is moderated by 1) overall level of delay discounting and 2) the degree of stochasticity in individuals' intertemporal choices. Twenty-one participants completed an individualized intertemporal choice task while brain activity was measured using functional Magnetic Resonance Imaging (fMRI). Across participants, LL choice was associated with activity in left dorsolateral prefrontal cortex (dlPFC), left insula/inferior frontal gyrus (IFG), frontal pole and the anterior cingulate cortex (ACC). Stochasticity positively moderated the LL>SS activity within the left insula and left IFG. Degree of discounting also interacted with choice related activity, but only outside the LL vs. SS main effect map (in the posterior cingulate cortex, and precentral/postcentral gyrus and left dlPFC). Main effect results are consistent with the notion that lateral prefrontal activity during intertemporal decisions bias selection in the direction of LL. Correlation findings indicate that choice related activity in the left insula and IFG is moderated by the stochasticity of intertemporal choices, and may reflect reduced "executive function" demands among highly consistent participants.

FGF21 response to sucrose is associated with BMI and dorsal striatal signaling in humans.

OBJECTIVE: This study examined associations between BMI and dietary sugar intake with sucrose-induced fibroblast growth factor 21 (FGF21) and whether circulating FGF21 is associated with brain signaling following sucrose ingestion in humans. METHODS: A total of 68 adults (29 male; mean [SD), age 23.2 [3.8] years; BMI 27.1 [4.9] kg/m2 ) attended visits after a 12-hour fast. Plasma FGF21 was measured at baseline and at 15, 30, and 120 minutes after sucrose ingestion (75 g in 300 mL of water). Brain cerebral blood flow responses to sucrose were measured using arterial spin labeling magnetic resonance imaging. RESULTS: Higher circulating FGF21 levels were associated with reduced blood flow in the striatum in response to sucrose (ß = -7.63, p = 0.03). This association was greatest among persons with healthy weight (ß = -15.70, p = 0.007) and was attenuated in people with overweight (ß = -4.00, p = 0.63) and obesity (ß = -12.45, p = 0.13). BMI was positively associated with FGF21 levels in response to sucrose (ß = 0.53, p = 0.02). High versus low dietary sugar intake was associated with greater FGF21 responses to acute sucrose ingestion in individuals with healthy weight (ß = 8.51, p = 0.04) but not in individuals with overweight or obesity (p > 0.05). CONCLUSIONS: These correlative findings support evidence in animals showing that FGF21 acts on the brain to regulate sugar consumption through a negative feedback loop.

Effects of addiction science on conceived freewill and responsibility.

Although there is speculation that medicalization of addiction undermines conceived agency, only relatively modest effects have been reported. Research participants generally have ideas about addiction that are informed both by personal experience and by media, and their views may not be wholly updated in response to study-information. Here we examine the potential impact of addiction science theories on perceived volition and responsibility by considering the issues in the context of a hypothetical new drug, "Z." Participants (N = 662) were provided one of three functional accounts that each corresponded to a prominent theory within addiction science: incentive-sensitization, impaired self-control, and habit-system dominance. For half of participants, additional neuroscience mechanism information was included with the functional account. Across explanations, the inclusion of mechanism information was associated with significantly less perceived volition and marginal reduction in blame, For several measures, there was a significant or marginally significant interaction between which addiction explanation was used and whether mechanism information was included, with mechanism generally having the largest impact given the impaired self-control explanation of addiction and little evidence of impact given the incentive-sensitization explanation of addiction. Taken together, these results suggest robust effects of addiction science on judgments of agency when presented in the context of a novel addiction. It is unclear whether a sustained scientific consensus around an existing theory could produce a similar impact on how people understand real addictive behavior.

Changes in Social, Romantic, and General Life Satisfaction Over the Course of a Substance Use Disorder.

Background: The pandemic has highlighted the importance of social connection for health and well-being. Satisfaction across domains of life is associated with substance use outcomes, such as risk of relapse and mortality. Previous work has delineated the relationship between substance use and social connections, yet there is a lack of research exploring the relationship between substance use and satisfaction with domains of life over time. Methods: We retrospectively assessed satisfaction with social life, romantic life, and general life across five phases of substance use among 339 adults, of whom 289 identify as formerly having a problem with substance use, and a comparison group of 50 who report no history of problematic drug use. We compared those whose primary drug of choice was alcohol, marijuana, methamphetamine, non-prescription opioids, and prescription opioids. Results: Those who used prescription opioids reported a larger drop in satisfaction in social life, romantic life, and general life during the course of substance use than those who used other drugs. However, we report no significant differences in current satisfaction, social well-being, or quality of life between people in recovery and people with no history of problematic substance use. Conclusions: These findings-alongside neuropsychological work on the opioid system and sociality-paint a picture that those who formerly used prescription opioids may experience lower satisfaction across life domains during the course of their substance use than those who used other substances. However, people in prolonged recovery-regardless of their drug of choice-all show similar levels of satisfaction compared to people with no history of problematic substance use.

A Novel Combination of Accelerometry and Ecological Momentary Assessment for Post-Stroke Paretic Arm/Hand Use: Feasibility and Validity.

Use of the paretic arm and hand is a key indicator of recovery and reintegration after stroke. A sound methodology is essential to comprehensively identify the possible factors impacting daily arm/hand use behavior. We combined ecological momentary assessment (EMA), a prompt methodology capturing real-time psycho-contextual factors, with accelerometry to investigate arm/hand behavior in the natural environment. Our aims were to determine (1) feasibility and (2) measurement validity of the combined methodology. We monitored 30 right-dominant, mild-moderately motor impaired chronic stroke survivors over 5 days (6 EMA prompts/day with accelerometers on each wrist). We observed high adherence for accelerometer wearing time (80.3%), EMA prompt response (84.6%), and generally positive user feedback upon exit interview. The customized prompt schedule and the self-triggered prompt option may have improved adherence. There was no evidence of EMA response bias nor immediate measurement reactivity. An unexpected small but significant increase in paretic arm/hand use was observed over days (12-14 min), which may be the accumulated effect of prompting that provided a reminder to choose the paretic limb. Further research that uses this combined methodology is needed to develop targeted interventions that effectively change behavior and enable reintegration post-stroke.

Obesity and Sex-Related Associations With Differential Effects of Sucralose vs Sucrose on Appetite and Reward Processing: A Randomized Crossover Trial.

Importance: Nonnutritive sweeteners (NNSs) are used as an alternative to nutritive sweeteners to quench desire for sweets while reducing caloric intake. However, studies have shown mixed results concerning the effects of NNSs on appetite, and the associations between sex and obesity with reward and appetitive responses to NNS compared with nutritive sugar are unknown. Objective: To examine neural reactivity to different types of high-calorie food cues (ie, sweet and savory), metabolic responses, and eating behavior following consumption of sucralose (NNS) vs sucrose (nutritive sugar) among healthy young adults. Design, Setting, and Participants: In a randomized, within-participant, crossover trial including 3 separate visits, participants underwent a functional magnetic resonance imaging task measuring blood oxygen level-dependent signal in response to visual cues. For each study visit, participants arrived at the Dornsife Cognitive Neuroimaging Center of University of Southern California at approximately 8:00 am after a 12-hour overnight fast. Blood was sampled at baseline and 10, 35, and 120 minutes after participants received a drink containing sucrose, sucralose, or water to measure plasma glucose, insulin, glucagon-like peptide(7-36), acyl-ghrelin, total peptide YY, and leptin. Participants were then presented with an ad libitum meal. Participants were right-handed, nonsmokers, weight-stable for at least 3 months before the study visits, nondieters, not taking medication, and with no history of eating disorders, illicit drug use, or medical diagnoses. Data analysis was performed from March 2020 to March 2021. Interventions: Participants ingested 300-mL drinks containing either sucrose (75 g), sucralose (individually sweetness matched), or water (as a control). Main Outcomes and Measures: Primary outcomes of interest were the effects of body mass index (BMI) status and sex on blood oxygen level-dependent signal to high-calorie food cues, endocrine, and feeding responses following sucralose vs sucrose consumption. Secondary outcomes included neural, endocrine, and feeding responses following sucrose vs water and sucralose vs water (control) consumption, and cue-induced appetite ratings following sucralose vs sucrose (and vs water). Results: A total of 76 participants were randomized, but 2 dropped out, leaving 74 adults (43 women [58%]; mean [SD] age, 23.40 [3.96] years; BMI range, 19.18-40.27) who completed the study. In this crossover design, 73 participants each received water (drink 1) and sucrose (drink 2), and 72 participants received water (drink 1), sucrose (drink 2), and sucralose (drink 3). Sucrose vs sucralose was associated with greater production of circulating glucose, insulin, and glucagon-like peptide-1 and suppression of acyl-ghrelin, but no differences were found for peptide YY or leptin. BMI status by drink interactions were observed in the medial frontal cortex (MFC; P for interaction < .001) and orbitofrontal cortex (OFC; P for interaction = .002). Individuals with obesity (MFC, ß, 0.60; 95% CI, 0.38 to 0.83; P < .001; OFC, ß, 0.27; 95% CI, 0.11 to 0.43; P = .002), but not those with overweight (MFC, ß, 0.02; 95% CI, -0.19 to 0.23; P = .87; OFC, ß, -0.06; 95% CI, -0.21 to 0.09; P = .41) or healthy weight (MFC, ß, -0.13; 95% CI, -0.34 to 0.07; P = .21; OFC, ß, -0.08; 95% CI, -0.23 to 0.06; P = .16), exhibited greater responsivity in the MFC and OFC to savory food cues after sucralose vs sucrose. Sex by drink interactions were observed in the MFC (P for interaction = .03) and OFC (P for interaction = .03) after consumption of sucralose vs sucrose. Female participants had greater MFC and OFC responses to food cues (MFC high-calorie vs low-calorie cues, ß, 0.21; 95% CI, 0.05 to 0.37; P = .01; MFC sweet vs nonfood cues, ß, 0.22; 95% CI, 0.02 to 0.42; P = .03; OFC food vs nonfood cues, ß, 0.12; 95% CI, 0.02 to 0.22; P = .03; and OFC sweet vs nonfood cues, ß, 0.15; 95% CI, 0.03 to 0.27; P = .01), but male participants' responses did not differ (MFC high-calorie vs low-calorie cues, ß, 0.01; 95% CI, -0.19 to 0.21; P = .90; MFC sweet vs nonfood cues, ß, -0.04; 95% CI, -0.26 to 0.18; P = .69; OFC food vs nonfood cues, ß, -0.08; 95% CI, -0.24 to 0.08; P = .32; OFC sweet vs nonfood cues, ß, -0.11; 95% CI, -0.31 to 0.09; P = .31). A sex by drink interaction on total calories consumed during the buffet meal was observed (P for interaction = .03). Female participants consumed greater total calories (ß, 1.73; 95% CI, 0.38 to 3.08; P = .01), whereas caloric intake did not differ in male participants (ß, 0.68; 95% CI, -0.99 to 2.35; P = .42) after sucralose vs sucrose ingestion. Conclusions and Relevance: These findings suggest that female individuals and those with obesity may be particularly sensitive to disparate neural responsivity elicited by sucralose compared with sucrose consumption. Trial Registration: ClinicalTrials.gov Identifier: NCT02945475.

Obesity and Dietary Added Sugar Interact to Affect Postprandial GLP-1 and Its Relationship to Striatal Responses to Food Cues and Feeding Behavior.

It has been hypothesized that the incretin hormone, glucagon-like peptide-1 (GLP-1), decreases overeating by influencing mesolimbic brain regions that process food-cues, including the dorsal striatum. We previously showed that habitual added sugar intake was associated with lower glucose-induced circulating GLP-1 and a greater striatal response to high calorie food cues in lean individuals. Less is known about how dietary added sugar and obesity may interact to affect postprandial GLP-1 and its relationship to striatal responses to food cues and feeding behavior. The current study aimed to expand upon previous research by assessing how circulating GLP-1 and striatal food cue reactivity are affected by acute glucose consumption in participants with varied BMIs and amounts of habitual consumption of added sugar. This analysis included 72 participants from the Brain Response to Sugar Study who completed two study visits where they consumed either plain water or 75g glucose dissolved in water (order randomized; both drinks were flavored with non-caloric cherry flavoring) and underwent repeated blood sampling, a functional magnetic resonance imaging (fMRI) based food-cue task, and an ad-libitum buffet meal. Correlations between circulating GLP-1 levels, striatal food-cue reactivity, and food intake were assessed, and interactions between obesity and added sugar on GLP-1 and striatal responses were examined. An interaction between BMI and dietary added sugar was associated with reduced post-glucose GLP-1 secretion. Participants who were obese and consumed high levels of added sugar had the smallest increase in plasma GLP-1 levels. Glucose-induced GLP-1 secretion was correlated with lower dorsal striatal reactivity to high-calorie versus low-calorie food-cues, driven by an increase in reactivity to low calorie food-cues. The increase in dorsal striatal reactivity to low calorie food-cues was negatively correlated with sugar consumed at the buffet. These findings suggest that an interaction between obesity and dietary added sugar intake is associated with additive reductions in postprandial GLP-1 secretion. Additionally, the results suggest that changes to dorsal striatal food cue reactivity through a combination of dietary added sugar and obesity may affect food consumption.