Neuroscience and Neurobiology Commons^™

Constructing A Parameterized Stimuli Space Suitable To Induce Controlled Changes In Human And Machine Perceptual Systems, Andrew Frankel

Dissertations, Theses, and Capstone Projects

Traditional computer vision applications focus on objective tasks, such as object detection, classification, or segmentation. Much of human experience is inherently subjective, such as our personal response to artwork. Individualized experiences are challenging to replicate in a controlled laboratory environment, as those experiences depend on the unique history and internal models of the observer. This work presents a technique to construct a 2-dimensional parameterized stimuli space suitable to induce controlled changes in the perceptual systems of both human and machine observers. Our contributions are threefold:

1. Using a balanced dataset of 8,800 fine art images spanning 11 art movements and 88 …

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The Psychophysiology Of Primary And Secondary Variants Of Psychopathic Traits In Youth, Ines Guariguata

Dissertations, Theses, and Capstone Projects

Psychopathy is a cluster of personality traits marked by a pervasive callousness, lack of shame or remorse, deceitfulness, a persona of confidence and charm, shallow emotional connection, general lack of insight into their actions, and an absence of anxiety (Glenn & Raine, 2014; Hare, 2003). Research suggests that there are distinct etiological pathways to the development of psychopathic traits and that their responses to treatment are different (Craig et al., 2021; Yildrim & Derksen, 2015; Fleming et al., 2023). Primary variants show a low-fear, low-anxiety profile during stress, and have a genetic basis (Craig et al., 2021; Yildrim & Derksen, …

Vertex-Based Analysis Of Cerebral Blood Flow And Fractional Amplitude Of Low-Frequency Fluctuations (Cbf-Falff) Coupling In Moderate-To-Severe Traumatic Brain Injury During The First Year Post-Injury, Vaidehi Hemkumar Patel

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is known to involve damage in the neurovascular unit. TBI may disrupt the brain’s neurovascular coupling–the relationship between cerebral blood flow and neural activity–that can lead to cognitive and functional impairments. This study attempted to non-invasively investigate neurovascular coupling in patients with moderate to severe TBI (msTBI) during the first year post-injury using a combined metric of cerebral blood flow (CBF) and fractional amplitude of low-frequency fluctuations (fALFF), a proxy for spontaneous neural activity. Using arterial spin labeling (ASL) and functional MRI sequences, CBF and fALFF were measured in 29 msTBI patients 3-, 6- and 12-months …

An Erp Study Of Attentional Blink And Inhibition Of Return, Caesar Ekya

Dissertations, Theses, and Capstone Projects

Attention can be allocated over time and space and it has long been speculated whether these are a part of the same or different attentional mechanisms. Attentional Blink (AB) and Inhibition of Return (IOR) are cognitive phenomena that are used in experimental settings to study temporal attention (AB) and spatial attention (IOR) respectively. Though known for being representative of different types of attention, they nevertheless display similar characteristics, making them intriguing choices to study the interplay between temporal and spatial attention. For this study we chose a dual-stream rsvp paradigm that would elicit both AB and IOR within the same …

Evidence For Interactive Effects Of Inhibitory And Prospective Intolerance Of Uncertainty And Stimulus-Level Uncertainty On Threat Safety Discrimination Learning, Kyoko Yazaki

Dissertations, Theses, and Capstone Projects

Fear is a fundamental component of human learning, critical for survival, and extensively studied through Pavlovian conditioning paradigms (LeDoux & Pine, 2016). This thesis examines the interplay between stimulus-level uncertainty and individual differences in intolerance of uncertainty (IU) on threat-safety discrimination learning. Using a within-subject design, participants were conditioned to certain (100% reinforcement), uncertain (50% reinforcement), and safety (0% reinforcement) cues through the pairing of colored visual stimuli with aversive electrical shocks. Discrimination learning was assessed using both implicit (SCR) and explicit (self-reported US expectancy estimates and unpleasantness ratings) measures.

The present study (n = 102) replicated previous findings showing …

Atorvastatin Alters Neuronal Morphology Data Set, Carolyn L. Pytte

Publications and Research

Statins are highly effective and widely prescribed cholesterol lowering drugs. However, statins cross the blood-brain barrier and decrease neural cholesterol in animal models, raising concern that long-term statin use may impact cholesterol-dependent structures and functions in the brain. Cholesterol is a fundamental component of cell membranes and experimentally decreasing membrane cholesterol has been shown to alter cell morphology in vitro. In addition, brain regions that undergo adult neurogenesis rely on local brain cholesterol for the manufacture of new neuronal membranes. Thus neurogenesis may be particularly vulnerable to long-term statin use. Here we asked whether oral statin treatment impacts neurogenesis …

Investigation Of Rna-Binding Protein Expression Changes In The Hippocampus Following Doxorubicin And Cyclophosphamide Treatment, Lijie Chen

Dissertations and Theses

This study investigated the molecular mechanisms underlying chemotherapy-induced cognitive impairment (CICI) following doxorubicin and cyclophosphamide treatment in a rat model, revealing three significant alterations in hippocampal tissue: selective downregulation of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) (21% decrease, p=0.0298), compromised astrocytic network integrity evidenced by reduced GFAP-positive area in cornu ammonis 3 (CA3) (24%, pB=0.026) and dentate gyrus (DG) (19%, pB=0.027) regions, and elevated cellular senescence marker p19Arf specifically in DG (69%, pB=0.033) and CA3 (27%, pB=0.024). The inverse relationship between hnRNPA1 reduction and p19Arf elevation suggests a potential mechanistic link between RNA dysregulation and senescence induction, with pronounced vulnerability in …

Resting-State Eeg Microstate Features For Major Depressive Disorder Classification, George M. V. Quinn

Dissertations, Theses, and Capstone Projects

Neuroimaging studies have revealed consistent abnormalities in functional connectivity within specific neural networks that may serve as biomarkers for major depressive disorder (MDD). It is important to find inexpensive, non-invasive techniques that target these biomarkers to make diagnosis easier and more objective. EEG microstates are quasi-stable potential topographies that are thought to reflect the quasi-stable network activity of the underlying neural generators. MDD has been shown to alter features of the four canonical EEG microstates (A, B, C, D) with some conflicting results. The most consistent network abnormalities in MDD are found in the anterior default mode network, and this …

Voltage Set Points For Sodium Channel Inactivation: Intrinsic And Modulatory Mechanisms, Akshay Sharma

Dissertations, Theses, and Capstone Projects

During an action potential, voltage-gated sodium channels (VGSC) control sodium ion flow into the cytoplasm of cells by using membrane voltage to alter channel conformation. These membrane proteins exhibit three main functional conformations: closed, open, and fast-inactivated, with transitions between these states dependent on membrane voltage and kinetics. The channels open within 1 millisecond and swiftly transition from open to fast-inactivated within 1-2 milliseconds following membrane depolarization. Subsequent membrane repolarization resets the channels to the closed state. Notably, even at mildly depolarized potentials that preclude channel opening, VGSCs can undergo transitions between the closed and inactivated states, known as closed-state …

Repurposing Bt-11 To Treat Alzheimer’S Disease: Exploring The Glutathione-S-Transferase Lancl2 As A Target, Emily Birnbaum

Dissertations, Theses, and Capstone Projects

Approximately 99.6% of potential Alzheimer’s drugs fail, thus developing successful drugs is a high priority. The failure at developing successful drugs relates to the complex nature of the disease itself. Many components act together to trigger a cascade that ultimately results in neurodegeneration and cognitive dysfunction associated with the disease. In building a multiplex model of Alzheimer’s it is important to understand its specific biological mechanisms. One of these key pathological mechanisms is neuroinflammation. Understanding the pathways involved in neuroinflammation in Alzheimer’s is an urgent need, as it poses a promising avenue for future effective therapeutics. Specifically, as many investigational …

Meconium: A Potential Means To Predicting Later-Life Cognition, Leah Duran

Dissertations, Theses, and Capstone Projects

Maternal perinatal stress is a commonly experienced, yet chronically undiagnosed condition (CDC, 2010). Literature has suggested that perinatal stress exposure has long lasting implications of the developing child both physically and mentally (Behrman et al., 2007; Hobel et al., 2008; Bowman et al., 2004; Polanska et al., 2017; Van de Bergh et. al, 2020). The use of meconium in the clinical setting has become one that serves a purpose of detection in medical conditions like in utero drug exposure. Using meconium as a predictor for brain behavior, however, is still an emerging concept in the literature. It is quickly gaining …

Competitive And Noncompetitive Credit Assignment To Reward Cues In The Lateral Orbitofrontal Cortex, Mihwa Kang

Dissertations, Theses, and Capstone Projects

This dissertation investigates the mechanisms underlying variations in credit assignment to reward cues, with a focus on the lateral orbitofrontal cortex (lOFC). The lOFC has long been implicated in signaling reward expectancies, with controversy as to whether it signals the economic value of future outcomes, their sensory features to guide behavior or both. However, whether the lOFC signals the relative (competition-dependent) or absolute (contiguity-dependent) credit of cues is unknown. To address this, I employed a combination of novel behavioral assays, in-vivo electrophysiological recordings and optogenetic stimulation in rats. In Chapter 2, I tested the suitability of a self-initiating variant of …

Flanker Task Performance In Young And Older Adults: A Behavioral And Erp Study, Fatima Medrano

Dissertations, Theses, and Capstone Projects

Research suggests that as we get older, executive function abilities decline (Hasher & Zacks, 1988; Salthouse, 1996). One affected ability is that of inhibitory control, which aids in monitoring our responses to non-target stimuli or information. Current research on inhibition reveals inconsistencies across studies. Monitoring brain responses during the Flanker (used to measure inhibitory control) task may add valuable insight into the processes underlying group differences behaviorally, by studying the N200 and P300 event-related potentials which have been associated with inhibitory control processes. This study investigated whether there are differences between older and younger adults in inhibitory control and whether …

Cross-Linguistic Differences In Neural Encoding And Processing Of Stop Consonants: The Impact Of Language Experience On Attention Allocation, Aline Dos Santos Oliveira

Dissertations, Theses, and Capstone Projects

This study aims to examine the intricate relationship between language experience and the neural processing of stop consonant speech sounds. Previous research has shown minimal differences in amplitudes and latencies of cortical Auditory Evoked Potentials (AEPs) to speech sounds across listeners from various language backgrounds. It is only towards the later latencies (around the P2 peak at 200 ms), that there have been suggestions of cross-linguistic differences. In addition, a recent study, observed an AEP difference between monolinguals and bilinguals when processing speech, specifically an "Nd effect”. The Nd effect, which is an increased negativity of the AEP is proposed …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses and Dissertations

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …

The Divided Self: Internal Conflict In Literature, Philosophy, Psychology, And Neuroscience, Yulia Greyman

Dissertations, Theses, and Capstone Projects

This thematic project examines the notion of self-division, particularly in terms of the conflict between cognition and metacognition, across the fields of philosophy, psychology, and, most recently, the cognitive and neurosciences. The project offers a historic overview of models of self-division, as well as analyses of the various problems presented in theoretical models to date. This work explores how self-division has been depicted in the literary works of Edgar Allan Poe, Don DeLillo, and Mary Shelley. It examines the ways in which artistic renderings alternately assimilate, resist, and/or critique dominant philosophical, psychological, and scientific discourses about the self and its …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Effects Of Transcranial Direct Current Stimulation On Metamemory Vary By Task Difficulty, Tiffanie T. Li

Dissertations, Theses, and Capstone Projects

Metamemory is broadly defined as the awareness of one’s memory and consists, in part, of a process referred to as monitoring, where one is assessing the contents of their memory. Feeling of knowing (FOK) is one metamemory monitoring judgment where one rates how strongly they believe they will remember a currently unrecalled item. Prior work has shown that HighDefinition Transcranial Direct Current Stimulation (HD-tDCS) over the dorsal lateral prefrontal cortex (DLPFC) led to greater metamemory accuracy and that HD-tDCS over the anterior temporal lobe (ATL) led to better recall for medium difficulty questions. Other work has also shown that effects …

Neurochemical Signaling Of Reward-Based Learning In Ventral Tegmental Area Dopamine Neurons, Kyla F. Wholley

Dissertations, Theses, and Capstone Projects

Ventral tegmental area (VTA) dopamine neurons signal and participate in reward-related learning. Specifically, dopamine is postulated to encode reward-related environmental stimuli to compute reward prediction errors (RPEs). It is through the computation and maintenance of RPEs that learning occurs. However, little is known about the neural mechanisms that underlie how dopamine neurons compute RPEs and facilitate reward-related learning. The present study utilized fiber photometry in conjunction with a Pavlovian reward-based task to identify how GABA inputs to VTA dopamine neurons contribute to the computation of RPEs and reward-based behavior. Activity of GABA inputs to VTA dopamine neurons increased for reward-predicting …

The Role Of Glutamate In The Medial Prefrontal Cortex In The Acquistion And Expression Of Conditioned Approach, Rudolf Nisanov

Dissertations, Theses, and Capstone Projects

A series of experiments were conducted to assess the role of glutamatergic stimulation in the dorsal and ventral regions of the medial prefrontal cortex (mPFC) in both the acquisition and expression of reward-related learning using a Pavlovian conditioning paradigm, the conditioned-approach paradigm. Rats with surgically implanted cannulas were exposed to Pavlovian conditioning sessions that occurred on three alternative days (acquisition) or seven consecutive days (expression). These 60-min conditioning sessions consisted of 30 pairings of light (CS) and food pellets (US) presented under a random time schedule. After a two-day break, rats underwent a session with no CS or US and …

A Causal Inference Approach For Spike Train Interactions, Zach Saccomano

Dissertations, Theses, and Capstone Projects

Since the 1960s, neuroscientists have worked on the problem of estimating synaptic properties, such as connectivity and strength, from simultaneously recorded spike trains. Recent years have seen renewed interest in the problem coinciding with rapid advances in experimental technologies, including an approximate exponential increase in the number of neurons that can be recorded in parallel and perturbation techniques such as optogenetics that can be used to calibrate and validate causal hypotheses about functional connectivity. This thesis presents a mathematical examination of synaptic inference from two perspectives: (1) using in vivo data and biophysical models, we ask in what cases the …

Investigating The Roles Of Dapk, P53/Cep-1, And Mitochondrial Damage In Necrotic Neurodegeneration In C. Elegans, Anil Singh

Dissertations and Theses

Stroke is one of the leading causes of death in the U.S., with minority groups, suffering higher fatality rates. Stroke is caused by ischemia, where occlusion of blood supply to the brain results in neurodegeneration. Most of the damage is attributed to excitotoxicity, where an accumulation of the neurotransmitter glutamate in the synapse overstimulates postsynaptic neurons and ultimately leads to cell death (largely by necrosis). Stroke treatments are often ineffective, due to the delay between the onset of stroke and the delivery of effective treatment. To address this, we focus our study on putative later-acting mediators of excitotoxicity such as …

Insights Into The Molecular Roles Of Foxr2 In The Pathology Of Primary Pediatric Brain Tumors, Rajendra Gharbaran

Publications and Research

Forkhead box gene R2 (FOXR2) belongs to the family of FOX genes which codes for highly conserved transcription factors (TFs) with critical roles in biological processes ranging from development to organogenesis to metabolic and immune regulation to cellular homeostasis. A number of FOX genes are associated with cancer development and progression and poor prognosis. A growing body of evidence suggests that FOXR2 is an oncogene. Studies suggested important roles for FOXR2 in cancer cell growth, metastasis, and drug resistance. Recent studies showed that FOXR2 is overexpressed by a subset of newly identified entities of embryonal tumors. This review discusses the …

Characterization Of Pathological Tau Mutants, Charles J. Mcdonald

Dissertations, Theses, and Capstone Projects

Tau is a protein expressed exclusively in glia and neurons in the central nervous system and implicated in several neurogenerative diseases called “tauopathies”. Among all the tauopathies, one third is characterized by the presence of genetic mutations leading to the synthesis of tau proteins with single amino acid substitutions at specific locations and affecting protein function. While most of the initial studies have emphasize the functional role of tau as modulator of the axonal cytoskeleton, it has recently been well accepted that tau is also an intrinsically disordered protein that tends to form membraneless organelles called coacervates, due to a …

Metabolic Control Of Proliferation And Differentiation In Oligodendrocytes, Sami Sauma

Dissertations, Theses, and Capstone Projects

Oligodendrocytes (OLs) are specialized cells whose membrane extension, called myelin, wraps the axons providing insulation, trophic and metabolic support, and is essential for proper functioning of the central nervous system. Inappropriate myelin formation, damage or dysfunction of oligodendrocytes has been identified in several neurological disorders and often precedes the loss of neuronal cells. OLs derive from proliferating oligodendrocyte progenitor cells (OPCs), which exit from the cell cycle and undergo a series of transcriptional and epigenetic events, including histone post-translational modifications, resulting in morphological and functional changes. Our lab previously identified elevated levels of histone acetylation in proliferating OPCs during the …

Examining Metacognitive Access To Low-Level Ensemble Representations, Vladimir Mudragel

Dissertations, Theses, and Capstone Projects

Ensemble perception is a process that allows our sensory systems to rapidly extract summary information about the stimuli in the environment. For example, we are able to get a sense of the average number of items in a group of similar items (Burr & Ross, 2008; Halberda, Sires, & Feigenson, 2006) or the average size of a group of similar shapes of different sizes (Ariely, 2001). It is theorized that the qualitative result of ensemble perception is that it provides a gist impression of the current environment, which then enables attentional processes in the brain to determine which parts of …

A Novel Therapeutic Strategy For Alzheimer’S Disease: Sex-Dependent Mechanisms Altered By The Hdac Inhibitor Rg2833 In A Transgenic Rat Model, Kelechi Ndukwe

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is the most common cause of dementia. In the United States, AD affects about 6.2 million Americans and is projected to reach 13.8 million by 2050. Currently, there are no effective therapies for AD and therapies targeting epigenetic mechanisms have shown to be effective in improving cognitive performance in animal models of AD. However, until now no study has reported sex-dependent mechanisms leading to differential expression of genes that contribute to changes in AD pathology. From our in silico studies, we identified an FDA-approved drug, RG2833 (N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide) that penetrates the blood brain barrier and can potentially ameliorate …

Electrophysiological Signatures Of Stress Adaptability In The Bnst-Vta Pathway, Yuka Miura

Dissertations, Theses, and Capstone Projects

Chronic stress has detrimental effects on psychological and physiological health. Incapability to adapt to chronic stress can lead to depression, anxiety disorders, and addiction. The brain regions critical for reward processing share diverse physiological and molecular changes linked to depressive-like behaviors as a result of chronic stress. Cumulative evidence shows that counteraction or prevention of these alterations in neurons, occasionally in a projection-specific manner, can enhance stress adaptation or resilience.

Chronic stress induces various changes in the brain, including in the bed nucleus of the stria terminalis (BNST) and the ventral tegmental area (VTA). The neural projections from the BNST …

Automatic Analysis Of The Frequency, Vigor, And Complexity Of Spontaneous Locomotion Bouts Of Mice With Loss And Gain Of Function Of The G Protein-Coupled Receptor Smoothened In Cholinergic Neurons, Aleksandra Feshchenko

Dissertations, Theses, and Capstone Projects

Locomotion, a fundamental behavior, is classically assessed using simple metrics of velocity and total distance moved in an open field. This behavior however offers rich data about the organization and breadth of actions an animal can take while only facing limitations due to the bio-mechanical constraints of the organism. Importantly, these actions are not biased towards a particular task-solution space imposed by many behavioral paradigms. Here, to analyze motor complexity in freely ambulating mice, we developed a method for the automatic and unbiased identification of locomotor bouts which we call Bout Finder (BF). This analysis utilizes Open Feld data to …