This project investigates how Drosophila larvae respond behaviorally and neurologically to red and blue light stimuli, with the aim of uncovering how light perception and spatial awareness evolve during development. In Phase I, larvae were exposed to red or blue light, and reaction times were quantified through head movements. Across two timepoints, larvae demonstrated distinct response patterns, with blue light eliciting faster reactions initially, while red light prompted longer but more consistent response times. A significant positive correlation was found between distance from the light source and reaction time in both groups (r = 1.00 for blue, r = 0.98 for red), suggesting that spatial variables modulate sensory processing. In Phase II, neural activity was observed using GCaMP6f and RCaMP1b, a genetically encoded calcium indicator. Preliminary data show a correlation between light proximity and calcium activity, supporting the behavioral trends observed. This work contributes to our understanding of early sensory development and supports the "Survival of the Fastest" theory, proposing that rapid behavioral and neuronal response to stimuli is evolutionarily advantageous. Future work will focus on age-specific comparisons and circuit-level mapping.

Adverse Childhood Experiences (ACEs) have been linked to a range of cognitive health issues. MRI-based brain age prediction is a valuable tool for assessing brain health that has resulted from recent advancements in machine learning. These algorithms can predict an individual’s brain age and its difference from chronological age—referred to as the Brain Age Gap (BAG). While research has explored various factors influencing brain aging, the impact of ACEs on BAG remains underexplored. Thus, this study examines if childhood adversity is associated with accelerated brain aging in non-Hispanic Black and White individuals. Participants consisted of cognitively normal older adults from the Rush Memory and Aging Project and the Minority Aging Research Study who self-identified as Black (N=233) or White (N=619). Childhood adversity was categorized into a median split of low (Black=0-8; White=0-7) or high (Black=9-58; White=8-44). Linear regression analyses determined if childhood adversity was associated with BAG, including education and sex as covariates. Higher levels of childhood adversity were significantly associated with higher BAG values (i.e., higher predicted brain age) in White individuals (B=0.697, SE=0.348, p=0.046). No significant association was found in Black individuals. This study provides preliminary evidence that childhood adversity may be linked to accelerated brain aging in White individuals. The lack of association in Black individuals may suggest that other mechanisms may influence brain aging in this group.

Mood disorders are becoming increasingly prevalent among the adolescent population, impacting approximately 15% of individuals. These disorders manifest psychopathological behaviors, including emotional hyper- or hyporeactivity and maladaptive avoidance. Dysregulation of the behavioral activation system (BAS), which regulates goal-striving behavior, has been identified as a predisposing factor in mood disorder onset. However, it remains unclear how specific neural underpinnings may promote or inhibit BAS-related behaviors. This study aimed to explore the relationship between neural markers of reward sensitivity and reward response—subcomponents of the BAS—and response to positive affect (RPA), a behavioral measure of one’s response to rewarding outcomes. Using EEG methods, we examined the role of the RewP, an event-related potential, and frontal asymmetry during computerized tasks of reward receipt and approach toward goals. The study will examine several mediational and correlational models to characterize the relationship between RPA and these neural markers. Although current research is more robust regarding the relationship between mood disorder symptomatology and its identified neurophysiological markers, little research has studied the neural correlates of RPA. This study will determine if RPA shares any neural markers that correspond to the activation or deactivation of the BAS, potentially bridging the gap between neurophysiology and behavior.

Alzheimer’s disease (AD) is a neurodegenerative disease marked by amyloid-beta plaques and neurofibrillary tangles, leading to dementia and memory loss. However, a small subset of individuals, termed Non-Demented with Alzheimer’s Neuropathology (NDAN), exhibit AD pathology without cognitive decline, suggesting the presence of innate protective mechanisms. Previous research has outlined two key contributors to resilience in NDAN: neuronal hypertrophy and an antioxidant response, both involving the upregulation of the HIF2A pathway. HIF2A, a hypoxic-induced transcription factor, has demonstrated cellular protection in previous studies and induces downstream erythropoietin (EPO) expression, which has shown neuroprotective properties as well, but has not been studied in a HIF2A-dependent manner. This study investigates whether HIF2A and EPO expression are elevated in NDAN hippocampal tissue compared to AD and control cases. Using samples obtained from the Banner Sun Health Brain Bank, we performed immunohistochemistry, followed by imaging with ZEN Microscopy Software and quantitative analysis with QuPath. Preliminary findings showed that the intensity of EPO in the NDAN cases was significantly higher than in the AD and control cases. Analysis of HIF2 is ongoing, but early results suggest a potential role in mediating resilience to tau pathology. This research highlights protective biological processes observed in human cases that may inform future therapeutic strategies aimed at enhancing the brain’s natural defenses.

Huntington’s disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin protein (HTT) and is characterized by a progressive neuronal loss in the brain. HAP40, a protein encoded by the F8a gene and known to interact with HTT, has been critical for maintaining cortical development as its genetic knockout leads to cortical loss and atrophy. This project explores the relationship between cell death and the loss of the HAP40 protein utilizing these cortically-deleted HAP40 knockout mice (Emx1-Cre;F8a-cKO). Fluoro jade staining, a marker of cell degeneration, revealed an age specific pattern of neuronal degeneration that began in a layer-specific manner by P21 followed by an increase throughout predominantly upper-layer cortical neurons by P35. Additionally, specific cell death pathways such as ferroptosis and apoptosis were checked through GPX4 and cleaved Caspase 3 immunofluorescence staining. Preliminary results suggest an overlap between high GPX4 and Cleaved Caspase 3 expression in microglia that are in the same layer-specific region that has astrocytosis starting at P21 in these cortically-deleted HAP40 knockout mice. Both of these proteins are implicated in ferroptosis and apoptosis, respectively, although recent literature has suggested that cell-specific expression of these proteins in microglia, but not in neurons, promote cell death through pyroptosis. These findings help contribute to our understanding of HAP40’s involvement in cell survival and preventing degeneration.