In motor skill learning, two different types of prediction errors have been identified: Sensory prediction errors (SPEs) and reward prediction errors (RPEs). SPEs occur when the predicted sensory consequence of a movement does not align with the observed consequence, while RPEs occur when the result of said movement deviates from the desired goal. These errors were previously believed to be processed independently, with SPEs driving implicit sensorimotor adaptation in the cerebellum and RPEs driving explicit decision-making in the striatum. Recent research, however, has suggested otherwise, finding that SPEs influence decision-making by elevating risk tolerance, while RPEs influence implicit adaptation by increasing recalibration. What remains unclear is whether RPEs influencing SPE-driven adaptation extends to the neuroanatomical level. To explore this, we utilized the visuomotor reach adaptation task, which enables isolation of SPEs and RPEs and their subsequent effects on implicit adaptation behavior. Using fMRI, we asked if cerebellar activity associated with SPEs is modulated by RPEs when both error signals are experienced in tandem compared to just SPEs alone. From this, we replicated previous behavioral findings that RPEs are insufficient to drive implicit adaptation while SPEs can regardless of RPE presence. We also observed a numerical trend consistent with literature that the combination of SPEs and RPEs drive greater adaptation than SPEs alone. While strictly exploratory and below threshold due to a limited sample size, we observed preliminary evidence of cerebellar activity associated with RPEs when both error signals were experienced. This pattern may suggest that RPEs modulate SPE processing, which could explain the enhanced adaptation when both error signals are experienced together. These results overall support the viability of our MRI-adapted task for future prediction error imaging studies, and that the current trends may manifest under more conventional thresholds with a complete sample size.

Schizophrenia is a chronic psychiatric disorder characterized by positive and negative symptoms. While recent research has extensively explored working memory deficits in schizophrenia, few studies have investigated how continuous memories evolve within working memory. This study aims to address this gap by investigating how task performance errors and attractor dynamics (stable memory states within mnemonic space) in visual working memory relate to symptom severity in schizophrenia. We used a continuous color report task with varying memory loads (1-3 items) and delay durations (500ms, 4000ms) in 47 individuals with schizophrenia and 33 healthy controls. Results demonstrated that both memory load and delay duration significantly increased angular error, with each additional memory item increasing error by approximately 7 degrees. Mean angular error significantly predicted symptom severity as measured by the Positive and Negative Syndrome Scale (PANSS) (p = 0.0207). Analysis of bias patterns across color space revealed greater variability in individuals with schizophrenia, suggesting possible disrupted attractor dynamics that warrant further research.

Addiction remains a complex and persistent public health crisis, often framed through the Brain Disease Model of Addiction (BDMA), which conceptualizes addiction as a chronic, relapsing brain disorder rooted in pathological changes. While the BDMA has contributed valuable insights into neurobiological mechanisms like dopamine dysregulation, prefrontal cortex impairments, and stress system activation, it has been critiqued for reducing addiction to individual pathology and sidelining social and environmental factors. This thesis critically evaluates the BDMA’s core assumptions– not to reject the model, but to extend it– arguing that addiction is best understood as a multi-systemic condition shaped by dynamic interactions between neurobiological, social, environmental, and stress-related systems. Drawing on neuroscience, epigenetics, and stress physiology, this thesis explores how these systems co-regulate each other through recursive feedback loops that drive both the biological and behavioral dimensions of addiction Rather than viewing social and environmental factors as peripheral risk contributors, this work positions them as core mechanisms that actively shape addiction’s neurobiology and behavioral patterns. By integrating these perspectives, the thesis moves beyond linear disease frameworks, proposing a dynamic systems model that aims to reflect the complex realities of addiction and offer a new pathway for research and intervention.

Bisphenol A (BPA), an endocrine-disrupting chemical found in numerous consumer products, has raised concerns about its potential neurotoxicity. We employed an integrative multi-omics approach, using the Neuro-2a mouse neuroblastoma cell line, to investigate the neurotoxic effects of BPA at human-relevant concentrations. This pilot study specifically aimed to determine biologically relevant doses of BPA for the Neuro2a model and characterize an in-vitro neurotoxicity profile. Initial findings indicated that high-dose BPA (100-500 µM) induced significant cytotoxicity, while lower doses (0.1-1 nM), representative of human exposure levels, did not significantly impact cell growth. Metabolomic analysis of chronic BPA exposure at such low doses revealed significant disruptions in energy homeostasis and lipid metabolism. Transcriptomic analysis of chronic low-dose BPA exposures similarly implicated genes involved in metabolic pathways, as well as in methylation and Wnt signaling. In conjunction, these findings highlight potential risk factors for neurological dysfunction and potentially neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease given similarly implicated dysregulation in these pathways. Overall, our findings support the idea that BPA may be a significant risk factor for neurological dysfunction and potentially neurodegenerative disorders by affecting key metabolic pathways, even at low, human relevant doses. The final aim of this work was to analyze EDC exposure as a mechanism of environmental racism and slow violence, drawing upon a specific case study involving Indigenous communities living near the Athabasca tar sands region of Alberta, Canada.

Working memory is vital to human cognition, providing us with the ability to temporarily hold and work with information. Deficits in working memory can manifest as attentional issues such as those present in cognitive disorders like ADHD. Higher working memory capacity (WMC) has previously been shown to be protective against the negative effects that auditory distractions can have on our cognition, meaning that the development of working memory has a direct effect on one’s susceptibility to auditory distractions in adulthood. This study specifically investigated how chronic noise exposure during the development of working memory affected one’s susceptibility to different kinds of auditory distractions in adulthood. College-aged participants who grew up in noisy city environments with consistent chronic noise exposure and quieter rural/suburban environments with less chronic noise exposure were recruited and completed an online auditory working memory complex span task with and without auditory distraction. Data analysis focused on participant distractibility in the form of worsened task performance when an auditory distractor was present. The findings showed no consistent significant differences in distractibility between those who grew up in the presence of more chronic noise exposure in cities and those who grew up in quieter environments. All participants, regardless of developmental environment, showed greater distractibility when less familiar, more artificial auditory distractors were present, hinting at a possible desensitization mechanism to familiar auditory distractors. In addition, higher baseline working memory capacity (WMC) was shown to be modestly correlated with increased susceptibility to auditory distractions, contrary to previous literature.

Sensorimotor learning involves the dynamic interplay between implicit recalibration and explicit strategic control. While prior work has distinguished between cognitive strategies such as mental rotation (MR) and response caching (RC), it remains unclear how task structure shapes their engagement during adaptation. This study examined how target set size and perturbation schedule influence strategy use in a visuomotor rotation task. Eighty-five participants performed center-out reaching movements under conditions varying in the number of target locations (2 vs. 12) and the rotation schedule (abrupt vs. gradual). Response times and movement angles were analyzed across distinct learning phases.

As predicted, low set size conditions exhibited substantial reductions in response time across training, consistent with a shift from MR to RC strategies. High set size conditions maintained elevated response times, suggesting sustained reliance on parametric computation. All groups improved in movement accuracy over time; however, larger aftereffects were observed in the low set size groups, aligning with use-dependent learning. Rotation schedule had comparatively smaller effects on both response times and accuracy.

These findings underscore the role of environmental structure in guiding cognitive strategy selection during motor adaptation and suggest implications for optimizing performance in applied settings such as neurorehabilitation and brain-machine interface design.

Aedes aegypti is a highly effective vector of mosquito-borne diseases such as Dengue, Zika, Chikungunya, and Yellow Fever. Its strong preference for human hosts is largely driven by olfactory cues, making the mosquito’s olfactory system a critical area of study for understanding and mitigating disease transmission. This thesis investigates the organization of olfactory sensory neurons (OSNs) and their projections to specific glomeruli in the antennal lobe, with a focus on five odorant receptors (Or6, Or16, Or23, Or52, and Or94) that may play roles in human odor detection. Using transgenic mosquito lines generated through CRISPR and the Q-binary expression system, fluorescently labeled olfactory sensory neurons (OSNs) were visualized via confocal microscopy. Glomerular positions were mapped and compared to existing anatomical and molecular atlases to propose new receptor–glomerulus pairings. Additionally, glomerular volumes were calculated using 3D reconstructions in ImageJ, and receptor expression was quantified across antennal segments to examine spatial distribution patterns. Results show preliminary evidence for assigning Or6 and Or94 to glomeruli PD1 and V3, respectively, and suggest revised candidate glomeruli for Or16, Or23, and Or52 based on anatomical alignment and RNA expression data. These findings contribute to a more comprehensive understanding of the Ae. aegypti olfactory system and offer valuable targets for future studies exploring host-seeking behavior and vector control. By identifying key olfactory circuits involved in human odor detection, this work supports the broader goal of disrupting mosquito-human interactions to reduce disease burden.

Psilocybin, a psychedelic compound, has recently been shown to have the potential to reopen critical periods—windows during development when neuroplasticity is heightened and the brain is especially receptive to acquiring specific skills. This property positions psilocybin as a promising therapeutic tool for promoting plasticity and facilitating rapid learning even in adulthood. In this study, we further explore this potential by administering psilocybin to mice subjected to whisker trimming at various postnatal ages. Early postnatal whisker trimming leads to tactile deficits, such as a poor ability to discriminate between different textures, since vibrissae play a critical role in allowing mice to interact with their environments. After whisker regrowth, we assessed texture discrimination abilities under psilocybin or saline conditions. Therefore, this study also provides the first detailed characterization of whisker growth and regrowth trajectories following trimming in mice. By trimming at five different postnatal ages, we aimed to identify a critical period for texture discrimination, and to determine whether a single dose of psilocybin could promote recovery of later tactile function following disruption during this sensitive window. Our results show trends that suggest psilocybin may enhance recovery of texture discrimination in an age-dependent, non-linear manner. Mice trimmed at different postnatal ages and treated with psilocybin in adulthood showed variable recovery: minimal following postnatal day 0 (P0) trimming, maximal following P15 trimming, and reduced again following P20 trimming. The peak observed for P15 trimming coincides with a known period of dendritic remodeling and synaptic refinement in the barrel cortex, the primary somatosensory area for whisker input in rodents, suggesting that psilocybin reactivates plasticity mechanisms aligned with this developmental window.

Autism spectrum disorders (ASDs) are heterogeneous disorders that are associated with social, affective, cognitive and motor abnormalities. Phelan-McDermid Syndrome, a neurodevelopmental disorder that is accompanied by autistic behavioral phenotypes, has been shown to develop with Shank3 heterozygous deletion in humans. Comparing mouse and marmoset models of a highly penetrant risk gene such as Shank3 using RNA-FISH will lead to a better understanding of the differences between primate and non-primate animal models for studying autism and its behavioral phenotypes. In this project, census data from mice and marmosets across different regions and cell types will be analyzed to understand differences in the expression of Shank2 and Shank3 between cell types and regions. Then, RNA-FISH experiments will be run based on the cell types and regions identified from the census data. Identifying these differences in expression could inform on developing better ASD models and potentially inform gene-targeted approaches in the future. I will analyze key brain structures implicated in autism, such as neocortex, striatum and thalamus, comparing regions and cell types specific expressions between mice and marmosets.

Cognitive reappraisal, or changing how one thinks about an emotional situation to change how one feels, is an effective strategy for managing emotions. Cognitive effort (i.e., the mental effort expended on a task) is thought to increase the efficacy of some emotion regulation strategies, rendering it possible that changing the modality through which people reappraise (i.e., thinking vs saying vs writing) could increase both the effort they apply and their regulation efficacy. For example, merely thinking one’s reappraisals quietly could require less effort than articulating one’s reappraisals aloud or in writing. This hypothesis is further supported by research on the neural bases of cognitive reappraisal and cognitive effort, which show that both recruit brain regions related to executive control like the dorsolateral prefrontal cortex and ventromedial prefrontal cortex. In Study 1, we found that saying reappraisals aloud led to more effective regulation of emotions generated by negative images than thinking reappraisals quietly (p < .001) with qualitative analyses of participants’ reflections on the task suggesting that saying reappraisals was more effortful than thinking them. In Study 2, we found that either saying or writing reappraisals led to more effective regulation and was more effortful than thinking reappraisals (p < .001). Surprisingly, when testing for mediation, we found that effort did not mediate the relationship between reappraisal modality and negative affect. However, we propose additional studies, both neuroscientific and behavioral, to further explain why we found a difference in reappraisal efficacy between different modalities. This work has the potential to reveal the mechanism underlying a subtle technique for increasing reappraisal efficacy, holding broad translational and theoretical impacts.

Consider a child who hears “dog” for the first time in reference to a dalmatian. How do they come to understand that “dog” refers to any dog but not any animal or just dalmatians? This example highlights a challenge all language learners face: what is the range of objects that a novel word can refer to (i.e., its extension)? Despite this challenge, children can quickly learn to properly extend novel words. We suggest that active learning plays an important role in this process, allowing children the opportunity to test their hypotheses about word extensions and clarify ambiguous cases. In this present study, we tasked children (5 to 8 years of age) and adults with learning novel words and provided them a chance to actively learn through sampling, where participants could select an object and learn if the novel word could be extended to it. We assessed participants’ sampling behaviors and found that children, similar to adults, favored conservative sampling choices that confirmed a novel word’s known extension, as opposed to exploring broader possible extensions. We also found that, with age, children more frequently explored word extension ambiguity by sampling objects that could potentially provide them with new information about the breadth or specificity of a novel word’s extension. However, overall, children were still less exploratory than prior studies might suggest. Taken together, these findings advance our understanding of how children learn word extensions by introducing active learning as a facilitator of this learning process.

Adeno-associated viruses have revolutionized neuroscience research by enabling precise delivery of genetic cargo and facilitating targeted application of techniques such as optogenetics and chemogenetics. Clinically, AAV-mediated gene therapy has recently been approved by the FDA to treat nervous system disorders. However, recent evidence unexpectedly shows that AAVs can trigger innate immune responses through activation of Toll-like receptor 9 by unmethylated CpG motifs within the viral genome, leading to dendritic loss and synaptic weakening. As AAV-based therapies continue to gain clinical approval, further characterization of AAV-induced side effects — particularly behavioral outcomes — is crucial. To protect against these effects, strategies such as systemic TLR9 inhibitors have shown promise; however, challenges remain regarding immunosuppression, specificity, efficacy, and clinical applicability. This study aims to address these two major gaps in the field. To explore the link between AAV-induced functional and structural disruptions and behavioral outcomes, I investigated the behavioral consequences of AAV administration in the central nervous system, using a modified novel object recognition and whisker nuisance assay. To protect against AAV-induced circuit damage, I developed novel candidate oligodeoxynucleotide TLR9 inhibitors, and encoded one candidate TLR9 inhibitor directly in the AAV genome. This approach targets TLR9 inhibition to only those cells that are transduced with AAV, potentially improving efficacy and reducing immunosuppression compared to systemic TLR9 inhibitors. Together, these studies aim to improve the safety and efficacy of AAV-mediated gene delivery and to expand its therapeutic potential for treating neurological diseases.

Children learn to talk through feedback loops of social interaction that drive them towards further language development. When engaged in this social interaction, the brains of children and their caregivers become coupled. One hypothesis for the origin of this coupling is the development of a shared understanding between communication partners. If true, it stands to reason that coupling would increase within dyads where children have greater command of their language and can easily convey complex ideas. To test this hypothesis, we simultaneously recorded the brains of caregivers and their 2- to 4-year-old children (N = 55) using functional Near-Infrared Spectroscopy (fNIRS). We identified each child utterance within the session, and classified its maturity. We then analyzed relationships between children’s participation in conversation (frequency and duration of utterances) and their vocal maturity (frequency, duration, and proportion of each utterance type). We found that coupling in the prefrontal cortex (PFC) was significantly increased in response to increased child laughter. Additionally, we found that the PFC of both children and their caregivers experienced an increase in activity in the moments surrounding instances of child laughter. Furthermore, we observed that language maturity does not have an effect on coupling in the PFC. We therefore suggest that coupling in the PFC may not not arise from the development of a shared understanding between interaction partners, but from moments of positive emotion within an interaction. Our study represents the first characterization of the neural dynamics of both children and their caregivers in response to child utterances of different maturities, and points towards new directions for the determination of the behavioral correlates of brain coupling.

Animals are required to rapidly generate complex behaviors from limited motor outputs in order to successfully survive and reproduce in a variety of contexts. Sensory cues from an organism’s environment drive highly specific patterning of these motor outputs, allowing them to evade threats, capture prey, and find mates. Acoustic communication is a contextually patterned behavior displayed by numerous species during mating interactions. Many organisms utilize a specific subset of motor outputs to produce sounds that they must manipulate and rearrange to propagate auditory information. However, the neural mechanisms driving the patterning of sound syllables are not well understood in any system, particularly in response to contextual information from the social environment. Drosophila melanogaster is a useful model system to study the latter interaction because males exhibit behavioral patterning through production of courtship song. During courtship, males often generate complex songs composed of three distinct song modes. Females provide social and sensory cues that males integrate to adjust their song in response to these stimuli. Here, we investigated potential neural circuit mechanisms driving the production of slow and fast pulse song in D. melanogaster—two of the syllables or modes of courtship song. Slow pulse and sine song are produced near the female, while fast pulse is produced far from the female. We leveraged single-neuron and combined optogenetic experiments, as well as new connectomic information to build on existing courtship song circuit models by confirming the involvement of neurons within the circuit, identifying other potential candidates, and examining song bout composition to gain insight into which pathways and cell types drive the production of specific song modes. In alignment with previous research, we confirmed that descending neuron cell types pMP2 and pIP10 (neurons that collect information in the brain and send their outputs to the ventral nerve cord (VNC)) largely drive the production of fast pulse song, TN1A (a VNC cell type) drives sing song production, and dPR1 (another VNC cell type) drives nonspecific pulse song generation. Additionally, combined activation of dPR1 and pMP2 with TN1A indicated a cell-intrinsic mechanism for the production of both pulse subtypes. Furthermore, using connectomic tools, we identified four additional candidates for slow pulse song production and two for fast pulse song. Finally, we discovered that proportions of sine song are higher in traces of slow pulse song than fast pulse song, indicating the potential for a similar neural mechanism driving their production. This research provides insight into the complex neural circuit mechanisms that allow species to integrate information from their environment to pattern and produce diverse behaviors.

Adolescence is a sensitive period of life shaped by environmental factors, including socioeconomic status (SES) and early adversity. While previous studies have linked early adversity to cognitive and physical outcomes, it remains unclear how these effects vary by income level or whether physical maturation mediates the influence of early adversity on cognition. This thesis investigates how early adversity—specifically prenatal stress and early life stress (ELS)—impacts adolescent cognitive development across income groups and explores whether physical development mediates these relationships. Using longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study, I compare cognitive and physical development between high- and low-income adolescents and apply linear mixed-effects models and mediation analyses to examine potential pathways. First, I show that high-income adolescents undergo earlier cognitive development, while low-income adolescents experience earlier physical development. Then, I demonstrate that both prenatal stress and ELS are significantly associated with cognitive and physical development in the high-income group, whereas only prenatal stress is significantly associated in the low-income group. This indicates that among low-income adolescents, the influence of ELS may be overshadowed by broader adversities prevalent in low-income environments. Expanding on this finding, I reveal that prenatal stress exerts a stronger influence than ELS on slowing cognitive development and accelerating physical development in the high-income group. Finally, I show that the timing of physical maturation does not mediate the relationship between early adversity and cognitive outcomes, suggesting that the stress acceleration hypothesis cannot be extended to cognitive development. I conclude by proposing that alternative mechanisms—such as emotional development—may better explain how prenatal stress and ELS shape cognitive trajectories, implying the need for interventions aimed at mitigating the long-term effects of early adversity on adolescent cognitive development.

Alzheimer’s Disease (AD) is a neurodegenerative disease affecting tens of millions of lives worldwide, and is characterized by protein aggregations called amyloid-β (Aβ) plaques and neuroimmune dysregulation. Recent research has found that 40 Hz gamma entrainment reduces Aβ load in mice, and other work has proposed that IFN-γ, an important cytokine involved in neuroimmune signalling, could increase the breakdown of Aβ plaques. Previous work out of Dr. Felipe Schiffino’s lab has corroborated and connected these findings by revealing that optogenetically induced 40 Hz gamma entrainment increases both Aβ uptake and IFN-γ levels in an AD mouse model—however, the pathway through which these increases are generated is still unclear. ICAM is a protein found in the blood-brain-barrier (BBB) responsible for mediating immune cell infiltration, and has previously been shown to be dysfunctional during AD progression. ICAM regulation is potentially implicated in our optogenetic model through neurovascular coupling, making its expression an important site for beginning to elucidate how gamma entrainment might upregulate microglial Aβ uptake and IFN-γ signalling. This research aims to consider the BBB and neuroimmune response as potential sites of repair or modulation during 40 Hz gamma optogenetic treatment of an AD mouse model. Using immunohistochemistry (IHC) for qualitative (visual inspection) and quantitative analysis, factors involved in immune cell transmigration across the BBB during AD pathogenesis were considered, including Aβ plaques, vasculature, ICAM, and immune cells. The results revealed that the optogenetic treatment did not significantly alter expression of any of these factors of interest, aligning most closely with the proposed peripheral hypothesis, which posits that increased microglial Aβ uptake is driven by IFN-γ released into the brain parenchyma from T cells in the periphery, thus not involving increased ICAM expression or immune infiltration. However, large data spread throughout the experiments reduces the reliability of these findings and constrains our interpretations of some of the trends in the data (none of which were statistically significant). Future work must utilize larger comparison groups to obtain sufficient statistical power so as to achieve a greater understanding of how this optogenetic treatment model might impact the BBB and neuroimmune axis.

In recent years, Generative-AI (GenAI) has entered the public lexicon, growing in popularity via its widespread accessibility and use. In the art domain, the use of GenAI technologies has sparked debates, ranging from copyright concerns to philosophical debates concerning whether GenAI’s creative capabilities can match that of humans. Recent psychological surveys reveal a consistent bias against artwork labeled AI-generated, though these studies fail to capture how such negative preconceptions shape how people visually process these works. Under the neuroaesthetic triad model—which links aesthetic perception to knowledge-meaning, emotion-valuation, and sensory-motor circuits—this study investigates the possibility that labeling artwork as AI-generated not only triggers a cognitive bias, leading to more critical subjective judgments, but further alters viewing behavior. To investigate this research question, a between-subjects eye-tracking experiment was conducted in which participants saw artwork under one of three viewing conditions: 1) all of the artwork was labeled AI-generated, 2) all of the artwork was labeled human-created, and 3) no origin information was provided. After viewing each artwork, subjects answered a series of Likert survey questions to gauge their perceptions, aesthetic, and emotional valuations of the work. The findings suggest that although AI-generated labels lead to more critical, subjective evaluations of the work, such evaluations do not correlate with a generalized change in viewing strategies—measured as various saccade and fixation metrics—compared to human-created and unlabeled artwork. However, there were observable viewing behavioral differences across groups for a small subset of images, suggesting that contextual label effects might be subtle, image-dependent, or reliant on obvious or salient visual anomalies. Preliminary results from a within-subjects pilot study largely replicate these findings, offering additional nuance to the interpretations of the main study and informing future research with considerations of inherent individual variability in eye-movement behavior.

This thesis examines the intersection of neuroscience and musical theatre by analyzing how A Life Worth Living—an original musical centered on adolescent mental health—both represents and modulates the Default Mode Network (DMN), a brain system associated with self-referential thought, memory, and identity (Raichle et al., 2001). Drawing on current research in cognitive neuroscience, the thesis outlines the DMN’s role in depression, suicidality, and cognitive rigidity, then explores how these processes are externalized and represented on stage through character arcs, design elements, and musical structure. Chapter 1 traces the creative development of A Life Worth Living, from its initial inspiration to its full production and reception. Chapter 2 presents a neuroscience-based literature review on the DMN, synthesizing findings from clinical research to explain its role in psychiatric disorders and therapeutic intervention. Chapter 3 uses the musical as a case study to analyze how the DMN is portrayed onstage through character psychology, sound, design, and narrative structure, while Chapter 4 expands the discussion to consider how theater itself can modulate DMN activity. Through processes like narrative therapy, emotional rehearsal, and audience empathy, theatrical storytelling is shown to activate and potentially reshape DMN-related cognitive processes. Ultimately, this thesis proposes that theater can do more than represent the mind—it can participate in changing it. By combining scientific insight with personal narrative and artistic practice, this project suggests that interdisciplinary storytelling holds unique promise for mental health education, intervention, and healing.