Browsing by Author "Adcock, Rachel Alison"
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Item Open Access Cognitive Neurostimulation: Learning to Volitionally Invigorate Mesolimbic Reward Network Activation(2015) MacInnes, JeffThe brain’s dopaminergic system is critical to adaptive behaviors, and is centrally implicated in various pathologies. For decades, research has aimed at better characterizing what drives the mesolimbic dopamine system and the resulting influence on brain physiology and behavior in both humans and animals. To date, the dominant modes of research have relied on extrinsic approaches: pharmacological manipulations, direct brain stimulation, or delivering behavioral incentives in laboratory tasks. A critical open question concerns whether individuals can modulate activation within this system volitionally. That is, can individuals use self-generated thoughts and imagery to invigorate this system on their own? This process can be referred to as “cognitive neurostimulation” -- a precise and non-invasive stimulation of neural systems via cognitive and behavioral strategies. And if not, can they be taught to do so? Recent technological advances make it feasible to present human participants with information about ongoing neural activations in a fast and spatially precise manner. Such feedback signals might enable individuals to eventually learn to control neural systems via fine-tuning of behavioral strategies. The studies described herein investigate whether individuals can learn to volitionally invigorate activation within the mesolimbic reward network. We demonstrate that under the right training context, individuals can successfully learn to generate cognitive states that elicit and sustain activation in the ventral tegmental area (VTA), the source of dopamine production within the mesolimbic network. Although participants were explicitly trained to increase VTA activation, multiple mesolimbic regions exhibited increased connectivity during and after training. Together, these findings suggest new frameworks for aligning psychological and biological perspectives, and for understanding and harnessing the power of neuromodulatory systems.
Item Open Access Dissociable Influence of Reward and Punishment Motivation on Declarative Memory Encoding and its Underlying Neurophysiology(2012) Murty, Vishnu PradeepMemories are not veridical representations of the environment. Rather, an individual's goals can influence how the surrounding environment is represented in long-term memory. The present dissertation aims to delineate the influence of reward and punishment motivation on human declarative memory encoding and its underlying neural circuitry. Chapter 1 provides a theoretical framework for investigating motivation's influence on declarative memory. This chapter will review the animal and human literatures on declarative memory encoding, reward and punishment motivation, and motivation's influence on learning and memory. Chapter 2 presents a study examining the behavioral effects of reward and punishment motivation on declarative memory encoding. Chapter 3 presents a study examining the neural circuitry underlying punishment-motivated declarative encoding using functional magnetic resonance imaging (fMRI), and compares these findings to previous studies of reward-motivated declarative encoding. Chapter 4 presents a study examining the influence of reward and punishment motivation on neural sensitivity to and declarative memory for unexpected events encountered during goal pursuit using fMRI. Finally, Chapter 5 synthesizes these results and proposes a model of how and why motivational valence has distinct influences on declarative memory encoding. Results indicated that behaviorally, reward motivation resulted in more enriched representations of the environment compared to punishment motivation. Neurally, these motivational states engaged distinct neuromodulatory systems and medial temporal lobe (MTL) targets during encoding. Specifically, results indicated that reward motivation supports interactions between the ventral tegmental area and the hippocampus, whereas, punishment motivation supports interactions between the amygdala and parahippocampal cortex. Together, these findings suggest that reward and punishment engage distinct systems of encoding and result in the storage of qualitatively different representations of the environment into long-term memory.
Item Open Access Expectation Modulates Episodic Memory Formation via Dopaminergic Circuitry(2016) Stanek, Jessica KateEpisodic memory formation is shaped by expectation. Events that generate expectations have the capacity to influence memory. Additionally, whether subsequent events meet or violate expectations has consequences for memory. However, clarification is still required to illuminate the circumstances and direction of memory modulation. In the brain, the mechanisms by which expectation modulates memory formation also require consideration. The dopamine system has been implicated in signaling events associated with different states of expectancy; it has also been shown to modulate episodic memory formation in the hippocampus. Thus, the studies included in this dissertation utilized both functional magnetic resonance imaging (fMRI) and behavioral testing to examine when and how the dopaminergic system supports the modulation of memory by expectation. The work aimed to characterize the activation of dopaminergic circuitry in response to cues that generate expectancy, during periods of anticipation, and in response to outcomes that resolve expectancy. The studies also examined how each of these event types influenced episodic memory formation. The present findings demonstrated that novelty and expectancy violation both drive dopaminergic circuitry capable of contributing to memory formation. Consistent with elevated dopaminergic midbrain and hippocampus activation for each, expected versus expectancy violating novelty did not differentially affect memory success. We also showed that high curiosity expectancy states drive memory formation. This was supported by activation in dopaminergic circuitry that was greater for subsequently remembered information only in the high curiosity state. Finally, we showed that cues that generate high expected reward value versus high reward uncertainty differentially modulate memory formation during reward anticipation. This behavioral result was consistent with distinct temporal profiles of dopaminergic action having differential downstream effects on episodic memory formation. Integrating the present studies with previous research suggests that dopaminergic circuitry signals events that are unpredicted, whether cuing or resolving expectations. It also suggests that contextual differences change the contribution of the dopaminergic system during anticipation, depending on the nature of the expectation. And finally, this work is consistent with a model in which dopamine elevation in response to expectancy events positively modulates episodic memory formation.
Item Open Access Functional Brain Networks Underlying Anticipation in Motivated Behavior(2018) Vu, Mai-Anh ThiAnticipation is a state of expectancy for something that will happen, and it allows us to use past learning to prepare for and make predictions about the future. Studies have shown that anticipation influences behavioral performance, learning, and memory, and studies implicate reward-related brain circuitry. However, few studies have investigated the neural underpinnings of anticipation on a brain-wide network scale . In this set of experiments, I take an interdisciplinary cross-species approach, using in-vivo electrophysiology in mice and functional magnetic resonance imaging (fMRI) in humans, to investigate brain networks underlying anticipation in motivated behavior. Using a data-driven machine learning approach, I characterize the anticipatory network in mice running through a T-maze, and show how it is affected by behavioral perturbation in the form of a task reversal, and circuit perturbation in the form of a genetic mutant mouse line. I also validate this network in a separate cohort of mice in a variation of the T-maze task that varies in difficulty, and show how activity in this network is modulated by task difficulty and intermediate instrumental goals. Finally, I investigate this network using fMRI in human subjects performing a trivia-based task to show how this network links curiosity, a more intrinsic form of motivation, to memory. The findings from these studies provide evidence at multiple levels and across multiple species for an anticipatory network that links motivational state to cognitive performance.
Item Open Access Interoceptive Contributions to Motivational and Affective Modulators of Memory Formation(2015) Rainey, CourtneaBiological drives such as hunger, thirst, and sexual reproduction are potent motivators of behavior. Extrinsic rewards in the environment (i.e. food, drink, money) are also important behavioral and cognitive motivators. In addition to the relevance of an extrinsic reward in meeting the needs of biological drives, an individual’s sensitivity to the physiological state of their body (interoceptive awareness) would also be expected to mediate motivation for these extrinsic primary rewards (i.e. food, drink). Importantly, a better characterization of the predicted behavioral and neural interactions between interoception, motivation, and memory systems can highlight novel targets for interventions to facilitate motivation and memory for adaptive behaviors and/or impede motivation and memory for maladaptive behaviors (i.e. addiction, relapse, overeating).
The present dissertation examines how individual differences in interoceptive awareness may modulate motivated memory formation via motivational and affective mechanisms. Specifically, interoceptive accuracy is associated with increased motivation for relevant primary rewards and enhanced encoding for these rewards. However, anxiety, negatively predicted by interoceptive accuracy, negatively predicts memory the next day. Furthermore, memory for relevant primary rewards was negatively predicted by insula-parahippocampal and ventral tegmental area-hippocampal background connectivity.
Item Open Access Modulation of Active Exploratory Behaviors in Humans(2016) Clement, NathanielHuman learning and memory relies on a broad network of neural substrates, and is sensitive to a range of environmental factors and behaviors. The present studies are designed to investigate the modulation of active exploration behaviors in humans. In the current work, we operationalize exploration in two ways: participants’ spatial navigation (using a computer mouse) in environments containing rewarding and informative stimuli, and participants’ eyegaze activity while viewing images on a computer screen. The study described in Study 1 investigates the relationship between spatial exploration and reward, using participants’ reported anxiety levels to predict between-subject variability in vigor and information-seeking. The study described in Study 2 investigates the relationship between cue-outcome predictive validity and eyegaze behavior during learning; additionally, we test the extent to which differing states of expectation drive differences in eyegaze behavior to novel images. The study described in Study 3 expands on the questions raised in Study 2: using functional imaging and eyetracking, we investigate the relationship between predictive validity, gaze, and the neural systems supporting active exploration. Taken together, the findings in the present study suggest that emerging certainty in reward outcomes, rather than uncertainty, drives exploration and associative learning for events and their outcomes as well as encoding into long-term memory.
Item Open Access Motivational States Shape the Process of Information Seeking(2023) Hsiung, AbigailSeeking information is fundamental not only for making adaptive choices but also for extending our knowledge both individually and as a collective society. Understanding how people organize and carry out seeking information, remains an open and critical challenge for the field of psychology and neuroscience. In this dissertation, I approach this challenge by examining the organization of information seeking through the lens of the motivational states of an individual. I leverage behavioral, computational modeling, and neuroimaging methods to provide a multi-faceted understanding of the relationship amongst motivation, information seeking, and memory formation. In the first study, I used computational models to examine latent sampling strategies as people gathered information to guide subsequent action. These results demonstrated that unlike the optimal strategy, people perform simple accumulations instead of computing expected values, and that unlike a simple heuristic strategy, people dynamically integrate multiple sources of information in lieu of using only one source, highlighting a computationally efficient strategy that balances competing motivations for accuracy and cost minimization. In the second study, I explore how curiosity evaluates information as it unfolds over time, reporting that curiosity can promote the patience to prolong uncertainty and such patience culminates in experiencing discovery. In the third study, I extend these findings to capture the rewarding process of discovery and its impact on memory using functional magnetic resonance imaging. In the fourth study, I investigate how distinct motivational forces can drive information seeking and learning through distinct mechanisms. Collectively, the work presented in this dissertation reveals that our motivational states play a significant role in shaping our information seeking behaviors, working to balance competing goal states, and pushing us to confront and even enjoy the experience of uncertainty.
Item Open Access Neurofunctional Characterization of the At-Risk Mental State for Psychosis(2014) Sumner, Elizabeth JohnsonSchizophrenia is a complex and debilitating psychiatric illness characterized by positive symptoms like hallucinations and delusions and negative symptoms like blunting of affect, avolition, and poverty of thought. This constellation of symptoms is hypothesized to result from dopaminergic dysfunction, glutamatergic dysfunction, and dysfunctional stress-reactivity. Prior to the onset of schizophrenia there is a prodromal period when individuals begin to experience sub-clinical symptoms and decreased functioning. This period is important to study not only to help elucidate biologic mechanisms of the illness but also to potentially alter the course of the illness through early treatment. The difficulty of studying this period lies in its recognizing it prospectively. To address this researchers have begun to study the at-risk mental state, a state that is associated with a high but not inevitable risk of conversion to psychosis. The studies described in this dissertation are aimed at a neurofunctional characterization of the at-risk mental state in three primary domains: reward-anticipation, hippocampus-dependent learning, and stress-reactivity. Individuals at-risk for psychosis and age-matched healthy volunteers underwent functional magnetic resonance imaging while performing tasks targeting these domains. In the reward-anticipation task, at-risk individuals showed decreased ventral tegmental area (VTA) and dorsolateral prefrontal cortex (DLPFC) responses to reward anticipation. In the hippocampus-dependent learning task, at-risk individuals showed deficits in hippocampus-dependent memory, decreased VTA engagement, and increased DLPFC activation during learning of associations between items. In the stress-reactivity task, at-risk individuals showed increased activation in the bed nucleus of the stria terminalis/basal forebrain (BNST), anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC) in response to neutral faces. Collectively, these experiments show that neurofunctional deficits in reward-anticipation, hippocampus-dependent learning, and stress-reactivity are present in the putative prodrome, prior to the onset of psychosis. Regions implicated are those that would be expected based on current models of schizophrenia and neurofunctional studies in those with frank psychosis.
Item Open Access Pre-Learning Interventions Modulate Learning from Error(2023) Sinclair, Alyssa HannahLearning from error is an adaptive process that allows us to correct mistakes, update knowledge, and make better choices. Yet, humans do not always learn from error— motivation, emotion, prior beliefs, and individual differences can all influence learning and memory. In this dissertation, I synthesize diverse evidence from across domains to argue that lingering cognitive and neural states create a context of learning that governs how and what we learn. Here, I report three novel pre-learning interventions that effectively modulate learning from error in humans. First, I show that an imagination exercise enhances subsequent learning from feedback about health risks. Second, I demonstrate that changing beliefs about the value of errors enhances subsequent knowledge updating, especially for individuals with high anxiety. Third, I report that induced motivational states impact both reinforcement learning and subsequent memory. Taken together, these studies demonstrate that pre-learning interventions can have lingering benefits, enhancing subsequent learning from error. These findings offer inspiration for real-world interventions that could improve education, enhance belief updating, drive behavior change, motivate action, or foster curiosity.