Browsing by Author "Oberlin, Brandon G."
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Item Alcohol Use Disorder Interventions Targeting Brain Sites for Both Conditioned Reward and Delayed Gratification(SpringerLink, 2020-01) Oberlin, Brandon G.; Shen, Yitong I.; Kareken, David A.; Psychiatry, School of MedicineAlcohol use disorder is a destructive compulsion characterized by chronic relapse and poor recovery outcomes. Heightened reactivity to alcohol-associated stimuli and compromised executive function are hallmarks of alcohol use disorder. Interventions targeting these two interacting domains are thought to ameliorate these altered states, but the mutual brain sites of action are yet unknown. Although interventions on alcohol cue reactivity affect reward area responses, how treatments alter brain responses when subjects exert executive effort to delay gratification is not as well-characterized. Focusing on interventions that could be developed into effective clinical treatments, we review and identify brain sites of action for these two categories of potential therapies. Using activation likelihood estimation (ALE) meta-analysis, we find that interventions on alcohol cue reactivity localize to ventral prefrontal cortex, dorsal anterior cingulate, and temporal, striatal, and thalamic regions. Interventions for increasing delayed reward preference elicit changes mostly in midline default mode network regions, including posterior cingulate, precuneus, and ventromedial prefrontal cortex-in addition to temporal and parietal regions. Anatomical co-localization of effects appears in the ventromedial prefrontal cortex, whereas effects specific to delay-of-gratification appear in the posterior cingulate and precuneus. Thus, the current available literature suggests that interventions in the domains of cue reactivity and delay discounting alter brain activity along midline default mode regions, specifically in the ventromedial prefrontal cortex for both domains, and the posterior cingulate/precuneus for delay-of-gratification. We believe that these findings could facilitate targeting and development of new interventions, and ultimately treatments of this challenging disorder.Item Associations between regional brain physiology and trait impulsivity, motor inhibition, and impaired control over drinking(Elsevier, 2015-08-30) Weafer, Jessica; Dzemidzic, Mario; Eiler, William J. A. II; Oberlin, Brandon G.; Wang, Yang; Kareken, David A.; Department of Neurology, IU School of MedicineTrait impulsivity and poor inhibitory control are well-established risk factors for alcohol misuse, yet little is known about the associated neurobiological endophenotypes. Here we examined correlations among brain physiology and self-reported trait impulsive behavior, impaired control over drinking, and a behavioral measure of response inhibition. A sample of healthy drinkers (n = 117) completed a pulsed arterial spin labeling (PASL) scan to quantify resting regional cerebral blood flow (rCBF), as well as measures of self-reported impulsivity (Eysenck I7 Impulsivity scale) and impaired control over drinking. A subset of subjects (n = 40) performed a stop signal task during blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess brain regions involved in response inhibition. Eysenck I7 scores were inversely related to blood flow in the right precentral gyrus. Significant BOLD activation during response inhibition occurred in an overlapping right frontal motor/premotor region. Moreover, impaired control over drinking was associated with reduced BOLD response in the same region. These findings suggest that impulsive personality and impaired control over drinking are associated with brain physiology in areas implicated in response inhibition. This is consistent with the idea that difficulty controlling behavior is due in part to impairment in motor restraint systems.Item Behavioral Measurement of Sensation Seeking Shows Positive Association with Risky Behaviors(Office of the Vice Chancellor for Research, 2015-04-17) Bates, Sage M.; Myslinski, Jeremy S.; Winters, Drew E.; De Jesus, Jean S.; Cyders, Melissa A.; Oberlin, Brandon G.Sensation seeking (SS; the tendency to seek out experiences that are highly varied, novel, and intense, and the willingness to take risks in order to have such experiences) is strongly related to risky behavior. However, most prior research has relied on self-report assessments of SS, which are limited by subject biases and lack of insight. This study is designed to develop and optimize a behavioral assessment of SS to be used in future brain imaging studies, and to evaluate the relationship of this behavior with selfreported SS and risky behaviors. The novel behavioral SS task employed in this study presents participants with olfactory sensory stimuli and assesses the individual’s preference to seek varied, novel, and intense sensations, with the risk of an unpleasant stimulus (“Varied”; e.g. strong orange, rose, linalyl acetate, and propionic acid) vs. weaker and mildly pleasant sensations (“Standard”; weak vanillin, orange, and rose) across two twenty-trial sessions. Hypothesis: greater preference for “Varied” odors will correlate with self-reported SS and risky behaviors. Odorants are presented as a 1-sec burst via an airdilution olfactometer within a filtered airstream. Participants are being recruited from the Introduction to Psychology class at IUPUI (currently n = 11 total, mean age (SD) = 21.2, (5.4), n = 8 women, n = 7 Caucasian). The mean preference for “Varied” was 50%, range = 28-75%. Preference for “Varied” showed a moderate relationship with negative risky behaviors (r = 0.35) and SS (Zuckerman Thrill/Adventure seeking subscale; r = 0.48), suggesting that the behavioral task is associating as expected with these self-report variables. These preliminary data suggests the feasibility of behavioral SS assessment; behavioral characterization will permit examination of how SS influences brain activity, without the limitations of self-report. How SS affects choice of and reactions to new and exciting experiences has important research and clinical implications.Item Brain response in heavy drinkers during cross-commodity alcohol and money discounting with potentially real rewards: A preliminary study(Elsevier, 2023-07-06) Lungwitz, Elizabeth A.; Dzemidzic, Mario; Shen, Yitong I.; Plawecki, Martin H.; Oberlin, Brandon G.; Psychiatry, School of MedicineBackground: Alcohol use disorder (AUD) is associated with exaggerated preference for immediate rewards, a candidate endophenotype for use disorders. Addiction symptomology is often well-described by the preference for immediate intoxication over other delayed prosocial rewards. We measured brain activation in AUD-implicated regions during a cross-commodity delay discounting (CCD) task with choices for immediate alcohol and delayed money. Methods: Heavy drinkers (n=24) experienced a brief intravenous alcohol infusion prime, regained sobriety, then chose between 'One Shot' and delayed money in an adjusting delay CCD task (sober and intoxicated); also during fMRI (sober). Participants also performed a behavioral sensation seeking task and completed self-report inventories of other risk factors. We assessed brain activation to choices representing immediate intoxication versus delayed money rewards in a priori regions of interest defined within the framework of Addictions NeuroImaging Assessment. Results: Activation to CCD choice versus control trials activated paralimbic and ventral frontal cortical regions, including orbital and medial prefrontal cortex, posterior cingulate/retrosplenial cortex, angular and superior frontal gyri. We detected no differences between immediate or delayed choices. Left medial orbitofrontal cortex activation correlated with alcohol-induced wanting for alcohol; females showed greater activation than males. Behavioral sensation seeking correlated with right nucleus accumbens task engagement. Conclusions: Alcohol decision-making elicited activation in regions governing reward, introspection, and executive decision-making in heavy drinkers, demonstrating the utility of laboratory tasks designed to better model real-world choice. Our findings suggest that the brain processes subserving immediate and delayed choices are mostly overlapping, even with varied commodities.Item Brain responses during delay discounting in youth at high-risk for substance use disorders(Elsevier, 2021) Butcher, Tarah J.; Dzemidzic, Mario; Harezlak, Jaroslaw; Hulvershorn, Leslie A.; Oberlin, Brandon G.; Psychiatry, School of MedicineOffspring of parents with substance use disorders (SUD) discount future rewards at a steeper rate on the monetary delay discounting task (DD) than typically developing youth. However, brain activation during DD has yet to be studied in drug naïve youth with a family history (FH) of SUD. Here, we investigate brain activation differences in high-risk youth during DD. We recruited substance naïve youth, aged 11–12, into three groups to compare brain activation during DD: (1) High-risk youth (n = 35) with a FH of SUD and externalizing psychiatric disorders, (2) psychiatric controls (n = 25) who had no FH of SUD, but with equivalent externalizing psychiatric disorders as high-risk youth, and (3) a healthy control group (n = 24) with no FH of SUD and minimal psychopathology. A whole-brain voxel wise analysis of the [Delay > Baseline], [Immediate > Baseline], and [Control > Baseline] contrasts identified functional regions of interest, from which extracted parameter estimates were tested for significant group differences. Relative to control youth, high-risk youth showed stronger activation in the left posterior insula and thalamus when making delayed choices, and stronger activation of the parahippocampal gyrus when making both delayed and control choices (ps < 0.05). Activation in the left posterior insula negatively correlated with both subscales of the Emotion Regulation Checklist, and positively correlated with the Stroop interference effect (ps < 0.05). Our findings suggest possible heritable SUD risk neural markers that distinguish drug naïve high-risk youth from psychiatric and healthy controls.Item Changes in substance use, recovery, and quality of life during the initial phase of the COVID-19 pandemic(Public Library of Science, 2024-05-22) Lewandowski, Megayn E.; Delawalla, Colette N.; Butcher, Tarah J.; Oberlin, Brandon G.; Psychiatry, School of MedicineBackground: The COVID-19 pandemic disrupted lives on a massive scale. While the pandemic appeared to worsen mental health outcomes broadly, its effects on alcohol/substance use and recovery are unclear. Many studies convolved the sociopolitical unrest beginning in May 2020 with the pandemic. We assessed pandemic-related changes in substance use, recovery involvement, and quality of life among US adults at two specified time periods that isolated pandemic effects from potentially confounding sociopolitical factors. Objectives: We tested the following hypotheses: the pandemic and consequent policies (1) increased use of alcohol and illicit substances in active users; (2) increased use of alcohol/substances among people in early recovery; (3) reduced participation in recovery activities among those in early recovery, and that (4) use amount and use events correlated with impulsivity in both groups and that (5) substance use and abstinence correlated with resilience. Methods: We recruited 1,685 participants through Amazon's Mechanical Turk (MTurk). We assessed demographics, quality of life, alcohol/substance use, recovery activities, and measures of impulsivity and resilience at two time points, pre-pandemic and (early) during-pandemic. Only n = 45 (Active Users; males n = 32) and n = 34 (Recovery; males n = 20) passed data quality checks and were included in the primary analyses. Results: Among Active Users, weekly alcohol consumption and days spent using alcohol and illicit substances decreased during the pandemic. Resilience negatively correlated with pandemic-related substance use in early recovering participants. Significant reduction in the quality of life was coincident with a trend of lower recovery activity participation (31% decline) during the pandemic. Conclusions: The reduced alcohol/substance use and participation in recovery activities might be expected from conditions that promote social isolation. The high prevalence of low-quality data from MTurk cautions for careful use of online data sourcing.Item Corticostriatal and dopaminergic response to beer flavor with both fMRI and [11C]raclopride Positron Emission Tomography(Wiley, 2016-09) Oberlin, Brandon G.; Dzemidzic, Mario; Harezlak, Jaroslaw; Kudela, Maria A.; Tran, Stella M.; Soeurt, Christina M.; Yoder, Karmen K.; Kareken, David A.; Neurology, School of MedicineBackground Cue-evoked drug seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine transmission. Using [11C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST dopamine (DA) release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST BOLD responses to beer flavor are related to VST DA release and motivation to drink. Methods Male beer drinkers (n=28, age=24±2, drinks/week=16±10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade® (appetitive control). We tested for correlations between blood oxygenation level dependent (BOLD) activation in fMRI and VST DA responses in PET, and drinking-related variables. Results Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest. Conclusions Both imaging modalities showed a right lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males), and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting.Item The disengaging brain: Dynamic transitions from cognitive engagement and alcoholism risk(Elsevier, 2020-04) Amico, Enrico; Dzemidzic, Mario; Oberlin, Brandon G.; Carron, Claire R.; Harezlak, Jaroslaw; Goñi, Joaquín; Kareken, David A.; Neurology, School of MedicineHuman functional brain connectivity is usually measured either at “rest” or during cognitive tasks, ignoring life’s moments of mental transition. We propose a different approach to understanding brain network transitions. We applied a novel independent component analysis of functional connectivity during motor inhibition (stop signal task) and during the continuous transition to an immediately ensuing rest. A functional network reconfiguration process emerged that: (i) was most prominent in those without familial alcoholism risk, (ii) encompassed brain areas engaged by the task, yet (iii) appeared only transiently after task cessation. The pattern was not present in a pre-task rest scan or in the remaining minutes of post-task rest. Finally, this transient network reconfiguration related to a key behavioral trait of addiction risk: reward delay discounting. These novel findings illustrate how dynamic brain functional reconfiguration during normally unstudied periods of cognitive transition might reflect addiction vulnerability, and potentially other forms of brain dysfunction.Item THE EFFECT OF ETHANOL ON IMPULSIVITY IN HIGH ALCOHOL PREFERRING MICE(2010-07-21T20:19:33Z) Oberlin, Brandon G.; Grahame, Nicholas; Fetterman, J. Gregor; Kareken, David; McBride, William J.Impulsivity is associated with addiction in many human studies. Delay discounting (DD) is often used to measure impulsive choice in humans and animals. In DD testing, a small immediate reward is pitted against a larger delayed reward, and relative preference is assessed. The relative contribution of ethanol to impulsivity in alcoholism is not well-understood, therefore I will test the hypothesis that ethanol exposure will increase impulsivity in High Alcohol Preferring (HAP) mice as measured in an adjusting amount DD task. Selectively bred HAP mice were exposed to ethanol and tested in DD in 3 different experiments. Experiment 1: ad lib homecage ethanol drinking for 21 days and 17 days were used to expose mice to ethanol. Additionally, mice were tested in DD while “currently drinking” vs. “abstinent”. In experiment 2, to achieve higher blood alcohol concentrations, mice were injected with 3.5 g/kg ethanol 8 times and tested before and after in DD. In both experiments 1 and 2, mice were tested at only 2 delays (0.5 sec and 10 sec), to maximize sensitivity to detect shifts in choice behavior. In experiment 3, mice responded for 8% ethanol or 0.01% saccharin at a full range of delays: 0, 1, 2, 4, and 8 sec. Experiment 1 did not reveal any impact of ethanol drinking on impulsivity. Experiment 2 revealed a strong trend of reduced impulsivity in the 10 sec delay group after ethanol injections. Experiment 3 revealed reduced impulsivity at the 8 sec delay in the group responding for ethanol, and also revealed a significant correlation between higher ethanol drinking and reduced impulsivity. These data were unexpected, and imply that the a priori hypothesis not only should be rejected, but that the opposite hypothesis may be true: ethanol decreases impulsivity, at least with high dose exposure and in responding for it as a reinforcer. This effect was similar to the effect observed in other studies with amphetamine, which consistently decreases impulsivity. Ethanol may have been exerting an amphetamine-like effect on impulsivity at the doses tested here. There is no evidence in the data generated in these studies that ethanol increases impulsivity.Item Externalizing personality traits, empathy, and gray matter volume in healthy young drinkers(Elsevier, 2016-02-28) Charpentier, Judith; Dzemidzic, Mario; West, John; Oberlin, Brandon G.; Eiler, William J. A. II; Saykin, Andrew J.; Kareken, David A.; Department of Neurology, IU School of MedicineExternalizing psychopathology has been linked to prefrontal abnormalities. While clinically diagnosed subjects show altered frontal gray matter, it is unknown if similar deficits relate to externalizing traits in non-clinical populations. We used voxel-based morphometry (VBM) to retrospectively analyze the cerebral gray matter volume of 176 young adult social to heavy drinkers (mean age=24.0±2.9, male=83.5%) from studies of alcoholism risk. We hypothesized that prefrontal gray matter volume and externalizing traits would be correlated. Externalizing personality trait components-Boredom Susceptibility-Impulsivity (BS/IMP) and Empathy/Low Antisocial Behaviors (EMP/LASB)-were tested for correlations with gray matter partial volume estimates (gmPVE). Significantly large clusters (pFWE<0.05, family-wise whole-brain corrected) of gmPVE correlated with EMP/LASB in dorsolateral and medial prefrontal regions, and in occipital cortex. BS/IMP did not correlate with gmPVE, but one scale of impulsivity (Eysenck I7) correlated positively with bilateral inferior frontal/orbitofrontal, and anterior insula gmPVE. In this large sample of community-dwelling young adults, antisocial behavior/low empathy corresponded with reduced prefrontal and occipital gray matter, while impulsivity correlated with increased inferior frontal and anterior insula cortical volume. These findings add to a literature indicating that externalizing personality features involve altered frontal architecture.