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Senior Theses in Neuroscience

Neuroscience majors complete a one-semester or two-semester senior thesis.  The one-semester thesis is essentially an NIH grant proposal that consists of an integrative review and research proposal on a neuroscience topic of the student’s choice.  The two-semester thesis allows students to actually conduct their research proposal and include their findings as preliminary data in their NIH grant proposal.  See the “Roadmap of Our Neuroscience Major” https://www.depauw.edu/academics/departments-programs/psychology/a-roadmap-of-our-neuroscience-major/ for additional details about the structure of our major.

 

Spring 2019 (NEURO 481) 

Fall 2018 (N480) 

NAME

Project Summary

 Bradley Burton

Future Pharmacological Treatment For Alzheimer’s Disease 

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world today, and progresses from undetectable neurobiological markers in the preclinical stage of development, to the end result of full- blown dementia leading to death. The presence of the neurobiological markers occur during the teenage years into young adulthood, and may go undetected until the presence of mild cognitive impairment (MCI), which is the stage between the expected cognitive decline of normal aging and the more serious decline of dementia. The neurobiological markers that make up the preclinical stage, and in which many studies have concluded as the pathogenesis of Alzheimer’s Disease are: The accumulation of extracellular beta-amyloid plaques (Aβ), and the formation of intracellular neurofibrillary tangles (NFT). The accumulation of extracellular Aβ-plaques block neuronal signals from being transmitted between neurons. The formation of intracellular NFTs are due to the hyperphosphorylation of the tau protein, causing the microtubule to collapse, which is responsible for transporting important nutrients across synapses. The combination of the two pathogenesis’ eventually lead to neuronal dysfunction and cell death, beginning the progression of AD. Alzheimer’s disease is diagnosed in three stages: mild, moderate, and severe. The current treatment for AD is the use of acetylcholinesterase inhibitors (AChEIs), which act by inhibiting the enzymes that are responsible for the breakdown of acetylcholine, therefore increasing the amount of acetylcholine available at the synapse improving cognition, mood, and behavior. In reality, AChEIs do not stop or slow down the progression of AD, but instead prolong the individual’s experience of living with the symptoms. This study will demonstrate a new innovative pharmacological treatment for the progression of AD. The new innovative treatment will include a regular aerobic exercise routine and the use of an antihistamine, known as Latrepirdine (Dimebon). The benefits of physical activity on physical function and cognitive performance in patients with AD are receiving increased attention due to the lack of a disease modifying medical treatment in AD[1]. Latrepirdine, is a non-selective antihistamine that previous research has shown to have mitochondrial stabilizing properties, which will prevent the hyperphosphorylation of the tau protein, and will lead to improvement in neuronal function and inhibition of cell death. With the incorporation of Latrepirdine and physical activity, the proposed research will use neuroimaging techniques such as resting state functional Magnetic Resonance Imaging(RS-fMRI), Magnetic Resonance Imaging(MRI), and Positron Emission Tomography (PET) to measure brain activation patterns, BOLD responses, and the impact of Aβ-plaques and NFT’s towards the progression of AD. The knowledge that will be gained from the proposed research will provide insight into earlier detection of Aβ-plaques and NFT’s, said to be the pathogenesis of AD, as well as new evidence towards a new pharmacological treatment to prevent the AD.

 

Kaitlyn Daanen

 

Risk-Taking Behavior, Reward Processing, and Pharmaceutical Opioid Addiction

More than 115 people die every day in the United States due to opioid overdose. The number of fatalities totaled 49,068 in 2017 alone, more than doubling the number of deaths caused by homicides. Specifically, abuse of pharmaceutical opioids has been at a steady increase in recent years due to a lack of education about its highly addictive nature and the excess quantities prescribed by physicians. Abuse and dependency of heroin and other drugs, such as cocaine, have revealed impairments in behavioral adjustment, associative learning, and value evaluation. As a result, individuals suffering from substance use disorders often engage in high-risk behavior despite the long-term adverse consequences of maladaptive learning. Furthermore, individuals with drug addictions are motivated by immediate reward, inhibiting their ability to regulate disadvantageous behavior. Although much research exists on illicit drugs, further research is needed on pharmaceutical opioids in relation to risk behavior and reward processing. To measure pharmaceutical opioid’s effects on risk behavior and reward processing, two neuroimaging techniques followed by a self-control report will be conducted. Resting-state functional magnetic resonance imaging (rsfMRI) uses low frequency BOLD signals at a resting or task-negative state to map neural interconnectivity of specific brain regions. Task-active fMRI data will be collected during completion of the Balloon Analog Risk Task (BART) to compare different functional activity between patients and healthy subjects. While research has been conducted on various illicit drugs, further research is needed on pharmaceutical opioids and their effects on risk behavior. Analyzing results from rsfMRI, fMRI, and self-reports of self-control will highlight further relationships between pharmaceutical opioids, risk behavior, and reward processing. The knowledge gained from this proposed research will provide insight as how to better combat the rising opioid crisis alongside formulating more extensive treatment and recovery plans for those suffering from opioid use disorder (OUD). 

Caliani Gaytan

 

Socioeconomic Status, Motor Abilities, and Short Interval Intracortical Inhibition in Children with ADHD

Attention-deficit hyperactivity disorder(ADHD) is one of the most common neurodevelopmental disorders to affect children worldwide. This disorder manifests itself in children most prominently in areas of inattention, impulsivity, and hyperactivity (2). These symptoms can have a severe impact in child's health, academic, and social life with effects lasting through adulthood for about 30-50% of children with ADHD (8). Research shows that children with ADHD experience less activation in their frontal lobes, primarily in their motor cortex which provides an explanation as to why motor deficits are experienced in these children (3,8). Yet, it is unclear whether these deficits are able to differentiate the severity levels of ADHD. Research also shows that ADHD has a hereditary component (2), but it is unclear to what extent ADHD is due to environmental factors or genetics. Socioeconomic status (SES) is a factor that has been shown to be positively correlated with psychological disorders (7). Yet, there has been little research on the effects SES on children with ADHD. The proposed research will explore these factors and will give new insight on the potential impact of SES on the severity of symptoms in children with ADHD since there has been very little research on the relationship between SES and ADHD. To measure SES, the Hollingshead Parent History Questionnaire Assessment of Socioeconomic Status (12) will be used. To assess for severity of ADHD symptoms, motor abilities and SICI will be recorded. Motor deficits/abilities will be assessed using the Physical and Neurological Examination for Soft Signs (PANESS; 12). The level of reduced short interval intracortical inhibition (SICI; 12) will be assessed using transcranial magnetic stimulation (TMS; 12). In order to gain a better understanding of the relationship among SES, ADHD, motor deficits, and SICI, the proposed research has two specific aims: 1) Replicate the findings found in a research study done by Donald .L. Gilbert (12) by examining the relationship between motor deficits and the level of reduced SICI and its impact on the severity of ADHD symptoms.   2) To extend the research done by D.L Gilbert (12) by examining how the SES of the child is associated with the severity of ADHD symptoms found by the relationship between motor deficits and the level of reduced SICI. The information gained from this proposed research will provide insight into the relationship between motor deficits and SICI as a measure of ADHD symptom severity. It will also provide a better understanding of what role SES plays in children with ADHD. A clearer understanding of these relationships will allow for improvement in treatment and resources provided to children with ADHD from low SES households. 

 

Elizabeth MacNeille

 

The Microbiome and Early-Onset Autism Spectrum Disorder 

Autism Spectrum Disorder (ASD) consists of deficits in social communication, patterns of restricted and repetitive behavior across contexts, and reduction in theory of mind. ASD severity ranges from minor to severe symptoms regarding factors like social interaction. ASD diagnoses have spiked in the past ~15 years, highlighting the importance of studying the etiology of this disorder. Various causal factors involved in ASD have been identified, including genetic predisposition and socioeconomic status, and a new potential link has been discovered regarding the microbiome. The gut-brain axis suggests a role for gut bacteria that influence neural function. Among the factors that influence microbiome composition are the type of infant feeding (breastfeeding vs formula feeding), delivery type (vaginal birth vs c-section), and antibiotic use (present or absent within the first 3 years of life). Microbial patterns observed in people with ASD include increased clostridium counts, and reduced microbiome diversity in comparison to neurotypical controls. These differences in microbiome composition may suggest a relationship to ASD symptoms. One of the common ways to test for an aspect ofASD is by using the false-belief task to test for theory of mind (ToM). This proposal seeks to compare the three predictor variables, to microbiome composition (diversity and clostridium counts), and to ASD symptoms (ToM test). Children between ages 3-6 will be used since this is the age when ToM is commonly developed, and when ASD symptoms typically first appear. This proposed research will investigate whether microbiome composition has a true effect on ASD. Thus, this will expand on the current knowledge regarding the etiology of the disorder. 

 

 Kaitlyn Malley

Patterns of Plasticity of the Motor Cortex in Amputee and Amelic Rats

There are 2 million amputees in the United States with 186,000 new cases each year and 2,250 people born with congenital limb atrophy each year (1, 2). In the past, there have been limited resources to mediate the physical disability of these individuals. However, the development of brain-machine interfaces (BMIs) has provided opportunities to these groups of people that were previously unattainable. The success of BMIs are dependent upon a number of factors including signal acquisition and signal classification (3). As a result of their disability, the motor cortex of amputees and amelics has undergone plasticity, which results in the reorganization of regions of the brain critical to BMI function. In order to properly translate user intent to action, the cortical plasticity of amputees and amelics must be understood. However, the reorganization of the motor cortex in amputees is different from the reorganization that occurs in amelics (4). Therefore, it is imperative to understand the trends in plasticity and how they differ across these groups in order to develop BMIs applicable to their specific disability. No research has systematically manipulated the degree and timing of insult to a limb and analyzed the resulting plasticity. This study will determine if plasticity occurs in a systematic and predictable manner. The proposed study will have three aims: 1) to establish a viable rat model for comparing amputees to those with congenital limb atrophy, 2) to quantify the degree of structural reorganization using diffusion tensor imaging (DTI), and 3) to quantify the degree of changes in inputs and outputs of the motor cortex using Transcranial Magnetic Stimulation (TMS) and electromyography (EMG). Specifically, the research will strive to understand the differences between the motor cortex plasticity of amputees and amelics in order to develop increasingly-relevant BMIs.

 

Anna Munoz Morales

 

Understanding the Political Divide: A Closer Look at How News Consumption May Influence Political Evaluation

In recent years, research has shown that the political divide has deepened and the breadth of political news sources has congruently expanded. Furthermore, highly polarized news has now infiltrated the industry. The developing field of neuropolitics has found that political affiliation is correlated with activation in brain structures associated with conflict monitoring, threat detection, and empathizing. However, understanding how political news consumption affects these same neurocognitive mechanisms is poorly understood. The proposed study will examine how individual’s political news consumption is associated with characteristic brain activation patterns and whether these patterns might give us a more nuanced understanding of the ways in which partisan and ambiguous messages are processed. To measure the effects of news consumption on the brain, both behavioral and neuroimaging techniques will be adopted. Two-hundred subjects ranging in political ideology, age, and gender will be recruited. After assessing each subjects’ political affiliation and news consumption habits via respective surveys, functional magnetic resonance imagining (fMRI) will be used to measure each subject’s brain activity as they evaluate vetted political statements. In order to understand the cognitive effect associated with both political affiliation and news consumption, the proposed research has three specific aims: 1) to establish participants’ political affiliation and political news consumption habits via respective surveys and questionnaires 2) to replicate past findings that demonstrate political affiliation correlated to certain brain activation patterns and examine how news consumption affects these brain activation patterns using fMRI and 3) to examine how political affiliation and news consumption respectively influence neural activation in empathy- related brain structures. The knowledge gained from the proposed research will establish new ways to consider how news consumption influences politically-rooted behaviors. 

Purva Patel

 

Changes in D2R Availability After Bariatric Surgery

Obesity is a complex disease that increases the risk of developing type 2 diabetes, heart disease, stroke, arthritis, liver disease, and certain types of cancer. Its causes range from economic and policy dynamics to environmental influences, social norms, and individual and genetic factors, and its rate continues to increase each year. This increase has led to the majority of U.S. states having adult obesity rates between 25 and 35 percent in 2017.1 Hence, research in obesity is extremely critical. The current literature on obesity demonstrates that weight gain is associated with diminished striatal dopamine receptor availability. However, it remains unclear if this phenomenon is reversible. A common and highly successful treatment for obese individuals, that results in long-term weight loss is Roux-en-y gastric bypass (RYGB) surgery, though, the process through which RYGB works is still not well understood. Therefore, the proposed research study has two aims: 1.) to determine whether lower D2R availability is a cause or effect of obesity and 2.) to examine D2R availability long term and identify whether D2R levels increase to normal levels after significant weight loss through RYGB. Additionally, the study also aims to learn more about RYGB in order to further improve its clinical outcomes. To achieve this, male Sprague–Dawley (SD) rats rendered obese on a high-fat diet will receive a RYGB or sham surgery and be tested for D2R availability at different time points before and after the surgery. The unique use of a rat model in this study will provide insight on the impact of bariatric-surgery-induced-weight-loss on reward pathways, increase understanding of RYGB, and allow for better patient selection and management. 

SPRING 2019 (N481)

NAME

PROJECT SUMMARY

 Ellason Freeman

You’re hired...if you’re pretty: The neural time course and effect of beauty bias on attribute processing during professional hiring decisions

People are often expected to make assessments about others from quick observations or evaluations. According to attribution theory, people minimize the amount of information processing needed to make an assessment by passively searching for the first causal explanation available. Therefore, easily accessible information such as race, sex, gender, or appearance is often used to make evaluations about others, and these evaluations can be influenced by implicit biases based off of external characteristics. The beauty bias, a bias that attributes positive characteristics to physically attractive individuals, is used to make judgments about others in various decision-making settings. When making hiring decisions, many professionals fall victim to the influence of implicit biases, such as beauty bias. The existing literature shows that when all else is equal, physically attractive individuals are hired, promoted, and paid a higher salary over unattractive individuals. Behavioral evidence shows the influence of the beauty bias on hiring and promotional decision-making, but no neural data exist. Neuroscience data reveals that brain components such as the N170, LPP, and P300 are sensitive to the physical attractiveness of faces and processing of facial attractiveness effects other neural processing such as trustworthiness or fairness. The proposed study will expand upon previous findings by exploring the neural mechanisms underlying the effect of the beauty bias in hiring decisions through event-related potentials (ERP). We will specifically examine the neural time course of the discrimination between attractive and unattractive faces by measuring N170, LPP, and P300 in a hiring decision-making task. The proposed study has two specific aims: 1) to examine the time course of attractiveness and qualification processing (e.g. years of experience), allowing us to observe whether facial attractiveness elicits an earlier ERP, thereby priming qualification processing, and 2) to evaluate the effect of the beauty bias in ambiguous situations by observing the effect of changing facial attractiveness and qualifications of the stimulus person. Overall, our research will provide neural data showing how and when the beauty bias affects hiring decisions. 

 

Chris Pieper

 

Long Term Effects of Moral Decision Making from Amphetamine Prescriptions in Adolescents

Amphetamines are some of the most widely prescribed medications in America, and are prescribed to adolescents at a particularly high rate. These drugs are commonly prescribed to adolescents and adults with either Attention Deficit Disorder (ADD) or Attention Deficit Hyperactivity Disorder (ADHD), and according to a survey conducted by the Center of Disease Control roughly 9.4% of children in America were diagnosed with ADHD in 2016. While the effectiveness of the medication at relieving the symptoms of these conditions has been studied and shown numerous times, the effects that these amphetamines have on other behaviors has been studied very little. In 2008 Robert Larue published evidence that suggested the introduction of amphetamines in children between the age of 4 and 6 changes the chosen play patterns of the child (Larue, 2008), so it is a logical next step to further isolate how these medicines are affecting behaviors they are not targeted for. Amphetamines are agonists of the dopamine circuits within the frontal lobe and reward pathways of the brain, yet there are no studies aimed at determining whether or not amphetamine prescriptions might alter the behavior of these regions over an extended period of time. Previous research has shown that frontal areas of the brain (VMPFC, Medial Frontal Gyrus) that are affected by these dopamine circuits are also involved in making moral decisions (Greene, 2002). The proposed research will look for a link between amphetamine prescriptions in adolescents and moral decision making tendencies over the initial 6 month course of the treatment through the use of fMRI investigation as well as questionnaire reports. 

Zane Roberts

 

The Neuroscientific Connections Between the Olfactory System and Attraction 

The human sense of smell is important in day-to-day functions, such as differentiating between aversive and attractive odors, finding foods, and even finding mates. Animals such as syrian hamsters and mice often rely on a sense of smell in order to find and attract mates (1,2). Behavioral studies in animals have paved the way for both animal neuroscience research, as well as behavioral studies into the connection between human attraction and human sense of smell. For example, humans that are anosmic, or unable to smell, have reported that they enjoy sex less than those with the ability to smell (3). Dating sites have also cropped up, simultaneously gathering information on behavioral attraction to other humans and the sense of smell (4). The interest in behavioral connections between scent and mate selection on a behavioral also sparked an interest into possible chemicals that could trigger such behavioral effects. A strong possibility is the MHC, or major histamine complex. The MHC is largely responsible for the regulation of the immune system, but has also been linked to a potential chemical in scent-based attraction. In theory, the scent of the MHC is a determinant of compatible immune systems, with differing system yielding stronger babies. However, the preference for a different MHC can be influenced, with a variety of factors, such as women taking contraceptives (5). Despite all the study into the behavioral effects of scent and attraction, there are surprisingly few studies that delve into the neurological side of scent-based attraction in humans. My proposed study would seek to provide neural overlap in humans between scent and attraction, with particular regards towards the reward center of the brain, with structures such as the orbitofrontal cortex, the ventral pallidum, and the insular cortex. The brain structures mentioned will be studied using MRI scanning, given the depth of the brain structures as well as the relative ease of use in combination with a scent delivery system. The proposed study possesses two aims: the first is to establish that there is an activation of reward center of the brain, and the second is to compare activations across a control of five attractive scents and five non-attractive scents. The knowledge gained will provide insight into the connections between smell and attraction from a neurological viewpoint.