Biology Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2749
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Item CORTICAL AND STRIATAL MECHANISMS OF VALUE-BASED DECISION-MAKING AND THEIR DISRUPTION IN ADDICTION(2022) Hadfield, Heather; Roesch, Matthew R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)For decisions both great and small, the brain utilizes an extensive network that integrates value assessment, reward prediction, and motivation to quickly and efficiently select the most beneficial option while minimizing aversive consequences for ourselves. Numerous psychiatric conditions, in particular drug addiction, can disrupt this network and impair decision-making behavior. It is therefore important to understand the neural underpinnings of decision-making and how neural activity and its associated behavior are disrupted by drugs of abuse. My dissertation will expand on current studies of this circuitry by examining epigenetic and neurophysiological mechanisms of value-based decision-making within two regions of the brain. In my final aim, I explore a new behavioral assay that may be used to study these and other regions relevant for value-based decision-making in the context of another complex behavior.In my first aim, I have recorded from single neurons in the rat dorsal lateral striatum (DLS) after overexpressing histone deacetylase 5 (HDAC5), an epigenetic enzyme implicated in incubation of craving, in the dorsal striatum (DS). In my second aim I used pharmacological lesion and single-neuron recording combined with cocaine self-administration techniques to study anterior insula, a region well-known for combining internal and external experience but largely under-studied in the context of higher cognitive processes. These studies were conducted while rats performed an odor-guided decision-making task in which the value of rewards were manipulated by either the delay to or the size of the reward across a series of trial blocks. I have found overexpression of HDAC5 in DS promoted inflexible, faster, and automatic behavior in the decision-making task while increasing DLS’s response to reward cues- similar to previous studies examining DLS activity and behavior after cocaine self-administration. In my studies of insula, I found recording from this region novel, global signals of reward value that seemed to reflect the overall structure of the behavioral task. Following cocaine-exposure, these signals were diminished while immediate rewards were over-represented on a trial-by-trial basis, leading to steeper discounting of delayed rewards. Additional studies lesioning this region promoted faster reaction times and increased goal-directed behavior. Together, these results provide insights into how drugs of abuse may impair behavioral flexibility and the tracking of long-term changes in reward from multiple mechanisms. However, it is still unknown how these changes in value assessment give rise to complex impairments of behavior. As a first step to addressing this issue, I used a new task to examine how chronic drug use- which disrupts both neural signals in the corticostriatal circuit and epigenetic enzymes- also impairs the complex ability to delay gratification. This final study replicated well-established findings of drug-induced reversal-learning impairment, but surprisingly did not alter decision-making. This collection of work demonstrates the complexity with which drug exposure alters neural circuitry and value-based decision-making, and additionally shows the importance of utilizing complex behavioral assays to explore the relationship between brain and behavior.Item EXPERIMENTAL MEASUREMENT OF BEHAVIORAL APPROACH MOTIVATION IN MAJOR DEPRESSIVE DISORDER(2015) SZCZEPANIK, JOANNA; LEJUEZ, CARL W; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Major Depressive Disorder (MDD) presents a significant public health challenge. Given the symptoms heterogeneity and widespread changes in brain structure and Function in MDD, there may be several subtypes of depression not sufficiently distinguished by current diagnostic criteria but important to recognize to improve clinical outcomes. One of the two core symptoms of MDD is `markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day' and is often referred to as anhedonia (DSM-IV, V). Anhedonia may have a variety of underlying causes such as not finding previously enjoyed activities appealing, lacking motivation to engage or reluctance to put forth necessary effort, and these processes may be quite unique and not differentiated by current assessment methods (Treadway & Zald, 2011). It has been long recognized that depression is associated with insufficient environmental reinforcement (Peter M. Lewinsohn & Graf, 1973) and treatments were developed to address this deficiency (Peter M. Lewinsohn, Sullivan, & Grosscup, 1980). Clinical studies of effectiveness of the Behavioral Activation Treatment for Depression (BATD), (Hopko, Lejuez, LePage, Hopko, & McNeil, 2003), suggest that an increase in the engagement in reinforcing activities may be helpful in treatment of depression. However, a crucial aspect of activity related behavior, the initial approach and engagement which necessarily precede potential experience of enjoyment, has not been sufficiently characterized. In the current work, we present the development of an experimental behavioral approach motivation paradigm (BAMP) to study approach motivation to engage in liked activities, and relate experimental results to the symptoms of depression and anhedonia to better characterize approach behavior in MDD. We sought to establish a valid behavioral measure of approach motivation in major depression that will be suitable for behavioral and neuroimaging studies of anhedonia. In the BAMP study, subjects rated activity words for the appetitive value, and later `approached' and `avoided' the stimuli in an implicit joystick task. The findings indicated reduced range of activities rated as liked by depressed patients versus healthy controls, but no difference on an approach measure of liked activities. The depressed group showed a stronger approach rather than avoidance of disliked activities. Thus, `lack of interest or pleasure' may be partially related to excessive approach of mood-maintaining negative experiences, and inadequate avoidance of disliked situations. Further study of altered approach and avoidance behavior could shed additional light on processes underlying anhedonia in Major Depressive Disorder.Item The Malleability of Cognitive Control and its Effects on Language Skills(2013) Hussey, Erika; Dougherty, Michael R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cognitive control, or executive function (EF), refers to the mental ability to regulate and adjust behavior across domains in the face of interference, conflict, or new rules. Evidence from psycholinguistics suggests a role for cognitive control in a range of language processing tasks including syntactic ambiguity resolution and verbal fluency. Separate work demonstrates that EF abilities are malleable with extensive practice, such that training improvements transfer across domains to novel tasks that rely on the same underlying EF mechanisms (an effect dubbed 'process-specificity'). In uniting these two growing literatures, this dissertation investigated the (causal) role of cognitive control for language processing through two longitudinal training interventions. In one study, I demonstrated that practicing a battery of cognitive tasks conferred selective benefits on untrained reading tasks requiring syntactic ambiguity resolution. Compared to controls, individuals who responded most to an EF training task exhibited (1) higher accuracy to comprehension questions indexing offline reinterpretation, and (2) faster real-time recovery efforts to resolve among conflicting interpretations. A second experiment extended these findings by addressing the degree to which training on a single EF task was necessary and sufficient to confer transfer to untrained, related language measures. Participants were assigned to practice a single training task that was minimally different from other training groups' tasks in terms of EF demands. By and large, participants who practiced a high-EF training task were exclusive in demonstrating a cross-assessment improvement profile consistent with a process-specific account: Pre/post benefits across a range of ostensibly different linguistic (verbal fluency, syntactic ambiguity resolution) and non-linguistic (Stroop, recognition memory) tasks were observed selectively for conditions with high-EF demands; no benefits were seen for cases when the need for cognitive control was minimized. Together, these findings provide support for the malleability of EF skills and suggest a critical (and perhaps causal) role for domain-general cognitive control in language processing. Further, the present studies indicate that within the right framework, and having appropriate linking hypotheses, cognitive training may be a viable way to improve language use.