Neural Correlates of Polysubstance Use: Differential and Interactive Effects of Alcohol and Cannabis on the Adolescent Brain

Two of the most commonly used and abused substances by adolescents in the United States are alcohol and cannabis, which are associated with adverse medical and psychiatric outcomes. Alcohol use and cannabis use during adolescence is also associated with an increased risk of alcohol use disorder (AUD) and/or cannabis use disorder (CUD) in adulthood as well as increased likelihood of relapse after successful treatment. Despite this, much of the previous work on the neurobiology of substance use disorders has focused on adult substance use. This work has shown that individuals with AUD and/or CUD show dysfunction within reward processing, emotion processing, and executive functioning neuro-circuitries. In this dissertation, we have utilized the Monetary Incentive Delay (MID), Affective Stroop (aST), and Optimistic Bias (OB) tasks in order to examine dysfunction in these neuro-circuitries related to AUD and CUD symptomatology in a group of adolescents from a residential treatment facility and the surrounding community. The current data indicate that dysfunction in reward processing, emotion processing, and executive functioning neuro-circuitries is associated with AUD symptomatology, primarily within the MID and aST. However, dysfunction in emotion processing and executive functioning neuro-circuitries is associated with CUD neuro-circuitries across all three tasks. Moreover, there are interactive effects of AUD and CUD symptom severity on emotional processing and executive functioning neuro-circuitries within the aST and OB tasks. These data indicate differential and interactive effects of AUD and CUD on various neuro-circuitries within the adolescent brain

The Social Benefits of Wilderness

Modern culture has not yet learned to live in harmony with the rest of the natural world. This is largely because we are afflicted with inadequate institutions and personal habits. These habits and institutions are also responsible for many social ills – sexism, homophobia, etc. In particular, “the imperium” is a way of thinking and acting which encourages us to practice a heavy-handed form of standardization; it encourages us to ignore particularity. These habits and institutions – the imperium – are a result of, and reinforced by, our interpersonal interactions. The standardization of these interactions drains the wildness out of them. But to relate to an other in an ethical manner, I must assume that the other is wild, with its own integrity, will, and path. Because our experiences in wilderness are radically different than our experiences outside wilderness, the wilderness can instill in us different, better habits and understanding of relationships. In particular, the wildness of wilderness shows us the falseness of the standardized ideas and beliefs. This wildness also causes us to forge new habits of relating to others, and new beliefs about relationships and others. These new habits are social benefits, especially once we allow them to reform our identity

Coal Feeds My Family: Subsistence, Energy, and Industry in Central Appalachia

Across Central Appalachia, you can see the message scrawled across bumper stickers, protest signs, and billboards: “Coal Feeds My Family”. The metaphor of coal feeding families is one that stresses the economic importance of this extractive industry to the economy of the industrialized rural mountain South. This essay examines the change in land-human relationships through the lens of food. A contrast is drawn between homesteading’s cultivation of life and coal’s energy economy of the dead. The energy economy of the preindustrial Appalachian farm is shown to be a slight alteration from the energy cycles of the Appalachian forest. The industrial energy economy of coal, on the other hand, severed Appalachian people from their traditional agricultural energy economy, from the results of their production, from the sources of their consumption, and from the very thing, the sun, which made the preindustrial economy possible. The coal energy economy was not only made possible through various technological innovations in production and consumption, but also by certain social relations and political structures. These relations and structures remain relatively intact, in spite of the rapid disintegration of the coal economy, and their inertia explains the popularity of the slogan “Coal Feeds My Family”

Appalachian Identity as Narrative Identity

Much work in the field of Appalachian Studies seems to require the assumption that there is something that it is to be an Appalachian person. This paper draws on Paul Ricoeur’s account of personal identity as narrative identity to attempt to understand what Appalachian identity is. Ricoeur argues that, although there is a pre-narrative quality to human life itself, a narrative is required to synthesize the many different heterogeneous elements that make up our lives into a coherent whole. In creating the narratives that are our life stories, we draw not only on the pre-narrative character of life, but also on larger social and historical narratives. From this account of Ricoeur’s, I move on to discuss the way that narratives about Appalachia form and inform a concept of identity. I then compare and contrast this account of Appalachian narrative identity with other accounts of identity formation. I argue that we can only understand Appalachian identity as a type of narrative identity; it is through the historical, fictional, sociological, and artistic stories we tell about Appalachia that we understand what it means to be an Appalachian person or institution. I then turn to the work of Edward Casey on place to sketch out the way in which the lived experience of place intertwines with and informs narratives. I conclude with an account of Appalachian identity that accounts both for the narrative formation of identity and the place-based nature both of these narratives and of the experiences which inform them

Adults with autism spectrum disorders exhibit decreased sensitivity to reward parameters when making effort-based decisions

Background: Efficient effort expenditure to obtain rewards is critical for optimal goal-directed behavior and learning. Clinical observation suggests that individuals with autism spectrum disorders (ASD) may show dysregulated reward-based effort expenditure, but no behavioral study to date has assessed effort-based decision-making in ASD. Methods: The current study compared a group of adults with ASD to a group of typically developing adults on the Effort Expenditure for Rewards Task (EEfRT), a behavioral measure of effort-based decision-making. In this task, participants were provided with the probability of receiving a monetary reward on a particular trial and asked to choose between either an “easy task” (less motoric effort) for a small, stable reward or a “hard task” (greater motoric effort) for a variable but consistently larger reward. Results: Participants with ASD chose the hard task more frequently than did the control group, yet were less influenced by differences in reward value and probability than the control group. Additionally, effort-based decision-making was related to repetitive behavior symptoms across both groups. Conclusions: These results suggest that individuals with ASD may be more willing to expend effort to obtain a monetary reward regardless of the reward contingencies. More broadly, results suggest that behavioral choices may be less influenced by information about reward contingencies in individuals with ASD. This atypical pattern of effort-based decision-making may be relevant for understanding the heightened reward motivation for circumscribed interests in ASD

Designing a CRISPR-Cas9 pipeline to investigate the effects of putative genetic modifiers on Duchenne Muscular Dystrophy (DMD)

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder that affects about 1 in 3,500 live male births (Bushby et al. 2010). DMD is caused by a mutation of the Dystrophin (or DMD) gene that causes loss of dystrophin, a structural protein. Loss of dystrophin increases muscle's susceptibility to damage leading to muscle atrophy and loss of muscle function (Bass et al. 2016). Disease progression is variable in patients with DMD. Genome-wide association studies (GWAS) have identified putative genetic modifiers of DMD that may influence disease severity and variability (Bello et al. 2016; Flangian et al. 2013; Flanigan et al. 2021; Wess et al. 2018). I am using zebrafish, an established model organism to study DMD, to validate and further investigate these putative modifiers. CRISPR-Cas9 mutagenesis is highly efficient in zebrafish and can be used for rapid genetic screens by injecting Cas9 protein and a gene-specific sgRNA, targeting vital protein domains, to knock-out gene function and generate crispant fish. I designed sgRNAs to target zebrafish orthologs of DMD, LTBP4, THBS1, ETAA1, and PARD6G. Microinjection of zebrafish embryos with Cas9 and sgRNA targeting dmd causes loss of dystrophin protein, disorganization of muscle when assayed by birefringence, impaired motility, and decreased life-span of injected fish. To assay the effect of these genetic modifiers on dmd, multiplexed injections of dmd sgRNA + sgRNA targeting putative modifiers were carried out. To validate mutagenesis of putative modifiers hRMA was conducted after injection. Fish that show a dmd phenotype and mutagenesis of the putative modifier can then be used for subsequent analysis of muscle birefringence, motility, and lifespan. My data lays the foundational work to rapidly screen and identify modifiers of DMD for the development of new DMD therapeutics.Undergraduate Research Apprenticeship ProgramNationwide Children's HospitalOSU President's Research Excellence Accelerator AwardAcademic Major: Biolog

Intact hedonic responses to sweet tastes in autism spectrum disorder

The Sweet Taste Test (STT) is a standardized measure designed to index the ability to detect differences in sweet tastes (sweet taste sensitivity) and hedonic responses to sweet tastes (sweet taste liking). Profiles of response on the STT suggest enhanced hedonic responses to sweet tastes in psychiatric disorders characterized by dysfunctional reward processing systems, including binge-eating disorders and substance use disorders, and a putative mechanism governing STT responses is the brain opioid system. The present study examined STT responses in 20 adults with autism spectrum disorder (ASD) and 38 healthy control adults. There were no differences in sweet taste sensitivity or hedonic response to sweet tastes between the ASD and control groups. Within the ASD sample, ASD symptom severity was associated with sweet taste sensitivity, but not hedonic response to sweet taste. Results may ultimately shed light on brain opioid system functioning in ASD

Individual associations of adolescent alcohol use disorder versus cannabis use disorder symptoms in neural prediction error signaling and the response to novelty

Two of the most commonly used illegal substances by adolescents are alcohol and cannabis. Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with poorer decision-making in adolescents. In adolescents, level of AUD symptomatology has been negatively associated with striatal reward responsivity. However, little work has explored the relationship with striatal reward prediction error (RPE) representation and the extent to which any augmentation of RPE by novel stimuli is impacted. One-hundred fifty-one adolescents participated in the Novelty Task while undergoing functional magnetic resonance imaging (fMRI). In this task, participants learn to choose novel or non-novel stimuli to gain monetary reward. Level of AUD symptomatology was negatively associated with both optimal decision-making and BOLD response modulation by RPE within striatum and regions of prefrontal cortex. The neural alterations in RPE representation were particularly pronounced when participants were exploring novel stimuli. Level of CUD symptomatology moderated the relationship between novelty propensity and RPE representation within inferior parietal lobule and dorsomedial prefrontal cortex. These data expand on an emerging literature investigating individual associations of AUD symptomatology levels versus CUD symptomatology levels and RPE representation during reinforcement processing and provide insight on the role of neuro-computational processes underlying reinforcement learning/decision-making in adolescents

Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards

Abstract Background There has been significant progress in identifying genes that confer risk for autism spectrum disorders (ASDs). However, the heterogeneity of symptom presentation in ASDs impedes the detection of ASD risk genes. One approach to understanding genetic influences on ASD symptom expression is to evaluate relations between variants of ASD candidate genes and neural endophenotypes in unaffected samples. Allelic variations in the oxytocin receptor (OXTR) gene confer small but significant risk for ASDs for which the underlying mechanisms may involve associations between variability in oxytocin signaling pathways and neural response to rewards. The purpose of this preliminary study was to investigate the influence of allelic variability in the OXTR gene on neural responses to monetary rewards in healthy adults using functional magnetic resonance imaging (fMRI). Methods The moderating effects of three single nucleotide polymorphisms (SNPs) (rs1042778, rs2268493 and rs237887) of the OXTR gene on mesolimbic responses to rewards were evaluated using a monetary incentive delay fMRI task. Results T homozygotes of the rs2268493 SNP demonstrated relatively decreased activation in mesolimbic reward circuitry (including the nucleus accumbens, amygdala, insula, thalamus and prefrontal cortical regions) during the anticipation of rewards but not during the outcome phase of the task. Allelic variation of the rs1042778 and rs237887 SNPs did not moderate mesolimbic activation during either reward anticipation or outcomes. Conclusions This preliminary study suggests that the OXTR SNP rs2268493, which has been previously identified as an ASD risk gene, moderates mesolimbic responses during reward anticipation. Given previous findings of decreased mesolimbic activation during reward anticipation in ASD, the present results suggest that OXTR may confer ASD risk via influences on the neural systems that support reward anticipation