Adolescents' behavioral and neural responses to e-cigarette advertising.

Although adolescents are a group heavily targeted by the e-cigarette industry, research in cue-reactivity has not previously examined adolescents' behavioral and neural responses to e-cigarette advertising. This study addressed this gap through two experiments. In Experiment One, adult traditional cigarette smokers (n = 41) and non-smokers (n = 41) answered questions about e-cigarette and neutral advertising images. The 40 e-cigarette advertising images that most increased desire to use the product were matched to 40 neutral advertising images with similar content. In Experiment Two, the 80 advertising images selected in Experiment One were presented to adolescents (n = 30) during an functional magnetic resonance imaging brain scan. There was a range of traditional cigarette smoking across the sample with some adolescents engaging in daily smoking and others who had never smoked. Adolescents self-reported that viewing the e-cigarette advertising images increased their desire to smoke. Additionally, all participants regardless of smoking statuses showed significantly greater brain activation to e-cigarette advertisements in areas associated with cognitive control (left middle frontal gyrus), reward (right medial frontal gyrus), visual processing/attention (left lingual gyrus/fusiform gyrus, right inferior parietal lobule, left posterior cingulate, left angular gyrus) and memory (right parahippocampus, left insula). Further, an exploratory analysis showed that compared with age-matched non-smokers (n = 7), adolescent smokers (n = 7) displayed significantly greater neural activation to e-cigarette advertising images in the left inferior temporal gyrus/fusiform gyrus, compared with their responses to neutral advertising images. Overall, participants' brain responses to e-cigarette advertisements suggest a need to further investigate the long-run impact of e-cigarette advertising on adolescents.

Self-regulation training generalizability using the regulation of craving task. An fMRI study.

Individual differences in reward salience may relate to the difficulty in regulating the effects of multiple substances (e.g., nicotine and food). Increased brain activation in reward and self-regulation (SR) regions has been evidenced while adults view appetitive cues (e.g., food pictures) to test substance use disorder treatment response. Enhancing SR with behavioral interventions may increase brain activation in SR regions and reduce responses in reward regions. Our primary analysis demonstrated increased brain activation in SR regions to smoking cues among individuals who practiced SR by delaying their first cigarette of the day for 2 weeks. However, little is known about the generalizability of SR between appetitive cues. This secondary analysis explored the influence of adherence to a SR behavioral intervention by examining the impact of practicing smoking SR on brain activation to food cues among adults who smoke. Participants (N = 65) were randomly assigned to practice SR by delaying their first daily cigarette or smoking as usual for 2-weeks. Functional magnetic resonance imaging data were collected while people were told to think of "negative" or "positive" associations with the cue. The results indicated that practicing smoking SR was linked with increased activation in the dorsolateral prefrontal cortex (dlPFC) when viewing food cues. There was no correlation between delaying smoking adherence and brain activation in the dlPFC. Exploratory analyses suggested higher dlPFC activation when people thought about "positive" associations with the food cues instead of "negative" ones. We concluded that practicing smoking SR is related to increased brain activation to food cues, suggesting potential generalizability of SR practice from smoking cues to food cues.

Potential biomarker of brain response to opioid antagonism in adolescents with eating disorders: a pilot study.

Background: Eating Disorders (ED) affect up to 5% of youth and are associated with reward system alterations and compulsive behaviors. Naltrexone, an opioid antagonist, is used to treat ED behaviors such as binge eating and/or purging. The presumed mechanism of action is blockade of reward activation; however, not all patients respond, and the optimal dose is unknown. Developing a tool to detect objective drug response in the brain will facilitate drug development and therapeutic optimization. This pilot study evaluated neuroimaging as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED. Methods: Youth aged 13-21 with binge/purge ED completed functional magnetic resonance imaging (fMRI) pre- and post-oral naltrexone. fMRI detected blood oxygenation-level dependent (BOLD) signal at rest and during two reward probes (monetary incentive delay, MID, and passive food view, PFV) in predefined regions of interest associated with reward and inhibitory control. Effect sizes for Δ%BOLD (post-naltrexone vs. baseline) were estimated using linear mixed effects modeling. Results: In 12 youth (16-21 years, 92% female), BOLD signal changes were detected following naltrexone in the nucleus accumbens during PFV (Δ%BOLD -0.08 ± 0.03; Cohen's d -1.06, p = 0.048) and anterior cingulate cortex during MID (Δ%BOLD 0.06 ± 0.03; Cohen's d 1.25, p = 0.086). Conclusion: fMRI detected acute reward pathway modulation in this small sample of adolescents with binge/purge ED. If validated in future, larger trials, task-based Δ%BOLD detected by fMRI may serve as a pharmacodynamic biomarker of opioid antagonism to facilitate the development of novel therapeutics targeting the reward pathway, enable quantitative pharmacology trials, and inform drug dosing. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04935931, NCT#04935931.

Quality control in resting-state fMRI: the benefits of visual inspection.

Background: A variety of quality control (QC) approaches are employed in resting-state functional magnetic resonance imaging (rs-fMRI) to determine data quality and ultimately inclusion or exclusion of a fMRI data set in group analysis. Reliability of rs-fMRI data can be improved by censoring or "scrubbing" volumes affected by motion. While censoring preserves the integrity of participant-level data, including excessively censored data sets in group analyses may add noise. Quantitative motion-related metrics are frequently reported in the literature; however, qualitative visual inspection can sometimes catch errors or other issues that may be missed by quantitative metrics alone. In this paper, we describe our methods for performing QC of rs-fMRI data using software-generated quantitative and qualitative output and trained visual inspection. Results: The data provided for this QC paper had relatively low motion-censoring, thus quantitative QC resulted in no exclusions. Qualitative checks of the data resulted in limited exclusions due to potential incidental findings and failed pre-processing scripts. Conclusion: Visual inspection in addition to the review of quantitative QC metrics is an important component to ensure high quality and accuracy in rs-fMRI data analysis.

Differential Probability Discounting Rates of Gamblers in an American Indian Population.

Probability discounting, a subset of behavioral economic research, has a rich history of investigating choice behavior, especially as it pertains to risky decision making. Gambling involves both choice behavior and risky decision making which makes it an ideal behavior to investigate with discounting tasks. With proximity to a casino being one of the biggest risk factors, studies into the American Indian population have been a neglected population of study. Using outcome measures from a pre-scan probability discounting task, the current study equated the scan task to evaluate behavioral and neurobiological differences in gamblers vs. non-gamblers. Gamblers showed differences in behavioral tasks (lower discounting rates) but not in patterns of neural activation.

Novel Biomarkers of Physical Activity Maintenance in Midlife Women: Preliminary Investigation.

The precision health initiative is leading the discovery of novel biomarkers as important indicators of biological processes or responses to behavior, such as physical activity. Neural biomarkers identified by magnetic resonance imaging (MRI) hold promise to inform future research, and ultimately, for transfer to the clinical setting to optimize health outcomes. This study investigated resting-state and functional brain biomarkers between midlife women who were maintaining physical activity in accordance with the current national guidelines and previously acquired age-matched sedentary controls. Approval was obtained from the Human Subjects Committee. Participants included nondiabetic, healthy weight to overweight (body mass index 19-29.9 kg/m2) women (n = 12) aged 40-64 years. Control group data were used from participants enrolled in our previous functional MRI study and baseline resting-state MRI data from a subset of sedentary (<500 kcal of physical activity per week) midlife women who were enrolled in a 9-month exercise intervention conducted in our imaging center. Differential activation of the inferior frontal gyrus (IFG) and greater connectivity with the dorsolateral prefrontal cortex (dlPFC) was identified between physically active women and sedentary controls. After correcting for multiple comparisons, these differences in biomarkers of physical activity maintenance did not reach statistical significance. Preliminary evidence in this small sample suggests that neural biomarkers of physical activity maintenance involve activations in the brain region associated with areas involved in implementing goal-directed behavior. Specifically, activation of the IFG and connectivity with the dlPFC is identified as a neural biomarker to explain and predict long-term physical activity maintenance for healthy aging. Future studies should evaluate these biomarker links with relevant clinical correlations.

Functional brain activation changes associated with practice in delaying smoking among moderate to heavy smokers: study protocol and rationale of a randomized trial (COPE).

BACKGROUND: Most smokers struggle to overcome tobacco addiction. Neuroscientific models of addiction emphasize the importance of brain regions associated with cognitive control and reward to understand the cycle of addiction and relapse. During an attempt at abstinence, the cognitive control system appears to be underpowered to override the heightened reward system of the addicted brain. Thus, one neural target for treatment is to strengthen the cognitive control system. It may be possible to improve the functioning of the cognitive control system via deliberate practice. METHODS/DESIGN: This study will determine the effects of practicing delaying smoking on brain and behavioral measures of cognitive control. Smoking patterns will be monitored for 1 week and then smokers (N = 80) will be randomized to either practice cognitive control by delaying their first cigarette of the day for 2 weeks (practice group) or they will continue monitoring only (no practice group). Functional magnetic resonance imaging will be performed while smokers regulate their responses to smoking images (i) at baseline and (ii) after 2 weeks of practice (or no practice). DISCUSSION: The primary aim of this study will be to identify the impact of practicing cognitive control on functional brain activation changes in response to smoking cues. If successful, this project will establish a neurobiological biomarker for increasing cognitive control and demonstrate the feasibility of neuroimaging methods to predict the efficacy of an intervention without a large clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03080844 . Registered March 15, 2017.