2018 — 2019 |
Amlung, Michael T. |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Intracortical Myelin as a Novel Neural Marker of Alcohol Use Disorder
PROJECT SUMMARY / ABSTRACT Theoretical models of alcohol use disorder (AUD) argue that dysfunction in frontal lobe-mediated neural circuitry contributes to executive function deficits that are hallmark neurocognitive features of the disorder. Empirical support for these models is extensive, with prior studies reporting pronounced deficits in cortical thickness and white matter integrity in the frontal lobes and associated regions. However, considerably less is known about the impact of AUD on myelinated neurons localized in deeper cortical layers (i.e., intracortical myelin; ICM). These ICM fibers play a crucial role in speeding and synchronizing of neural signals throughout cortex, thereby helping to support optimal cognitive functioning. We hypothesize that ICM deficits directly contribute to executive function impairment in AUD. Importantly, standard techniques for quantifying cortical thickness via magnetic resonance imaging (MRI) lack neurobiological specificity with respect to the disruption of un-myelinated vs. myelinated cortical tissue in AUD. However, recent methodological advances in structural MRI have enabled in vivo estimation of ICM thickness. The proposed study will utilize a recently-developed T1- weighted pulse sequence that yields high intracortical contrast to examine deficits in ICM as a novel neural marker of AUD. The study has three aims: 1) to compare ICM thickness between individuals with AUD and matched controls; 2) to examine associations between ICM and clinical indicators of alcohol misuse (drinking quantity/frequency and AUD severity) and three domains of executive functioning (response inhibition, delay discounting, working memory) and processing speed; and 3) to explore sex differences in ICM. As the first investigation of ICM in AUD, this study will provide proof-of-concept of whether deficits in ICM are present in comparison with control individuals as well as contextualize variation in ICM within relevant clinical and neurocognitive indices of AUD. If successful, the study will also provide preliminary data for a future longitudinal R01 study investigating the predictive utility of ICM and its recovery over the course of AUD treatment. In sum, we believe that the ICM imaging approach is a distinct methodological innovation that has considerable potential to increase our ability to disentangle subtle differences in cortical morphology that may serve as novel neural markers of AUD in future clinical and research applications.
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0.954 |
2019 — 2021 |
Amlung, Michael T. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Using Neuroeconomics to Characterize State-Based Increases and Decreases in Alcohol Value
PROJECT SUMMARY/ABSTRACT Neuroeconomics integrates concepts and methods from psychology, economics, and cognitive neuroscience to understand the neurobiological foundations of decision making, and has been increasingly applied to understanding alcohol use disorder (AUD). A novel application of neuroeconomics is the study of alcohol demand, or the value of alcohol as measured by cost-benefit preferences. Alcohol demand paradigms have considerable ecological validity by measuring the impact of internal and external influences on alcohol decision-making, such as price, environmental cues, affective states, or external contingencies. Behaviorally, alcohol demand is elevated among individuals with higher levels of alcohol misuse and predicts treatment response. Alcohol demand also exhibits state-like properties, including increases following exposure to alcohol-related cues and decreases in the presence of significant next-day responsibilities. The overall goal of the proposed studies is to characterize the neural activity that subserves these established behavioral findings using a novel functional MRI paradigm. The first aim is to examine the patterns of neural activation underlying increases in the value of alcohol in response to alcohol cues. To do so, the first study will use a within-subjects design to identify differences in neural activity associated with demand decisions following a validated in- scanner cue exposure protocol consisting of exposure to neutral beverage cues and exposure to alcohol beverage cues in a sample of adult heavy drinkers. The second aim is to investigate the changes in neural activity associated with decreases in the value of alcohol in response to next day responsibilities. To do so, a second study will use a within-subjects design, comparing demand-related neural activity following a standard instructional set and an instructional set that imposes a significant work-related responsibility the next day. Using a novel neuroeconomics approach, these studies combine a highly ecologically-valid alcohol demand paradigm with two experimental manipulations that model clinically-relevant influences on drinking decisions. Studying these contextual influences may help clarify the neural signatures that underlie drinking moderation vs. unconstrained drinking, and how these processes are impacted by AUD. If successful, these studies will provide a foundation for examining neural predictors of successful recovery or response to treatment vs. relapse. More broadly, findings from these studies have high potential to significantly enhance the clinical relevance of alcohol neuroscience.
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0.954 |