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.
Fall 2021 and Spring 2022 (NEUR 480)
Neural Plasticity Potential in Thiamine Deficient Mice
Korsakoff’s syndrome affects 1-2% of the United States population. This disorder results in advanced deterioration of memory and overall diminishes the quality of life in those diagnosed with it. Korsakoff’s syndrome is typically follows Wernicke encephalopathy and presents as an array of symptoms including, memory loss, deterioration of coordination, droopy eyes, the urge to create stories to fill in the missing memory gaps, hallucinations, trouble with syntax, and heart and blood vessel complications (19). In a typical patient, symptoms of Wernicke encephalopathy later progress into symptoms of Korsakoff’s syndrome when left untreated. Once this transition between the two disorders begins, the consequences become irreversible (13,14). There are limited resources available to alleviate the symptoms of Korsakoff’s syndrome. In special cases where symptoms are caught and treated early enough, Vitamin B (thiamine) administration through an IV can attempt to reverse the neurological effects of the syndrome (9,13,14). However, this is not a common outcome and researchers are exploring treatment for the more common later stage patients exhibiting symptoms. Understanding the etiology, structural, and biochemical aspects of how Korsakoff’s syndrome causes the previously mentioned deficits will take treatment to the next step and advance the neuroscience field. Research has explored the structural and functional level of thiamine deficiency but doesn’t explore the full biochemical consequences and potential (6,13,14,). Therefore, the proposed research study has three aims: 1. to examine the behavioral outcomes of thiamine deficiency through the means of the 8-arm radial maze, 2. to examine the structural deficits of a mouse thiamine deficient brain using structural MRI and DTI, and 3. to examine the potential for neurogenesis using BrdU incorporation assay postmortem after inducing thiamine deficiency in mice. Specifically, this research will strive to gain insight into the behavioral, structural, and potential for neurogenesis in thiamine deficient mice to further the understanding of the mechanisms through which thiamine deficiency uses to cause irreversible brain damage.
The Intergenerational Transmission of Stress- Impact of Maternal ACE on Infant Stress Response
Intergenerational transmission of stress is the effect of parental exposure to stress on the offspring. More specifically, this effect on the offspring is typically negative. The severity and frequency of exposure to stress varies from person to person. One type of stress that is experienced while one is a child is called Adverse Childhood Experiences (ACE). ACES are out of a child’s control. While an adverse experience as a child may seem to pass quickly, they can lead to conditions that can cause death. The toll that an Adverse Childhood Experience takes on the body can be very severe and with 2 out of 3 adults reporting at least one ACE it is a very understudied area . Research has shown that these adverse experiences can lead to chronic health problems, mental illness, and substance misuse in adulthood [1,2]. Other research has demonstrated that stress while pregnant can have a significant impact on the fetus . However, little research has examined the effects of ACEs on their offspring immediately after birth, this could also be defined as the intergenerational transmission of stress. This grant attempts to close those gaps by measuring the effect of maternal ACEs on an infant's stress response. In order to understand the effect of maternal ACE on infant stress response the proposed research has two specific aims: 1) establish a correlation between maternal ACE score and newborn cortisol levels, 2) examine how an infant is able to adapt to stress through measuring the infant’s respiratory sinus arrhythmia level (RSA) through the still-face paradigm . The knowledge gained from the proposed research will provide insight to children who may not be able to deal with stress, families who would benefit from psychosocial intervention and mothers who should receive extra prenatal care to combat the effects of ACEs.
A Comparison of Functional and Structural Outcomes Between Conventional and Virtual Reality Rehabilitation Methods
Above the age of 45, 400 out of every 100,000 people have their first stroke. 1 Only 25% of stroke patients retain motor function to the level of their peers who have not had a stroke. 1 In addition, increased motor recovery is linked to a better quality of life among stroke patients. 1 Therefore, it is necessary to continue to develop methods of rehabilitation that lead to greater improvements in motor function in more patients. The proposed research project will determine whether there are differences in upper extremity functional gains between three different methods of upper extremity stroke rehabilitation. The first group of stroke patients will do conventional rehabilitation and single-player virtual reality gaming rehabilitation. The second group will do conventional rehabilitation and multiplayer virtual reality gaming rehabilitation and the third group will do conventional and recreational rehabilitation. To measure the extent of functional gains, neuroimaging and behavioural tests will be used. The participant will undergo DTI, fMRI and behavioural assessments before the training period, in the middle of training at 12 weeks and at the end of the training period at 24 weeks. The key focus of the research is to determine which method of rehabilitation may lead to the most upper limb motor recovery in stroke patients, and a secondary focus is to determine whether there is a critical period for those motor recovery gains.
Neural Activity Observed in During Ethical and Moral Decision-Making in Patients with Bipolar I Disorder Across Three Mood States
Understanding the cognitive processes of diseased and disordered brains is an extremely important topic as it can provide insight on how to diagnose and treat many of the prevalent medical issues the world is faced with today. In the United States, approximately one in five people suffer from mental illness (27). One of the more prevalent mental illnesses is bipolar disorder, which affects around 2.3 million Americans (8, 12). Research has indicated that understanding the cognitive processes that are associated with the mood states that arise from bipolar disorder could lead to better therapeutic and medicative options in the future (1, 2). Thus, this proposed study aims to investigate some of the cognitive processes that occur across the depressed, manic, and euthymic mood states of bipolar disorder. One cognitive process of interest that is directly influenced by emotional mood states is ethical and moral decision-making (19). Exploring how one’s emotional state such as expressing manic or depressive symptoms affects how moral judgments are made can lead to new insight on what cognitive functions are involved in decision-making. Additionally, investigating neural activity associated with moral judgments under certain emotional conditions could lead to a better understanding of how mood states in patients with bipolar disorder affect cognitive function. The proposed research will use MRI and fMRI scanning to visualize brain activity during ethical decision-making tasks that elucidate specific emotional responses based upon the scenario given. With analysis and comparison of differences observed in neural activity across the three mood states of bipolar disorder compared to healthy controls, novel ways to treat and diagnose patients with bipolar disorder can be developed.
Differences in the Regulation of the HPA Axis in Black and White Mothers with Postpartum Depression
Postpartum depression (PPD) is a highly relevant disorder, affecting 10-20% of mothers (1), deeming it a public health issue across the country. While PPD affects a large portion of the population in North America, many cases go undiagnosed and untreated due to the social stigma surrounding being labeled as a “depressed mother” (2). Although cases of postpartum depression remain prevalent throughout Western countries, affecting mothers, partners, and children, there are a lot of unknowns surrounding the risk factors of PPD. However, previous research suggests that stress plays a role in the onset of multiple psychological disorders, more specifically, major depressive disorder and postpartum depression (3, 4, 6, 8, 17). Specifically, it is known that too little or too much cortisol, which is secreted under stress, can affect the dysregulation of the HPA axis, a biological system that is a part of the body’s stress response (4). Research suggests that Black women are disproportionately affected by PPD (5), which in most cases, is likely due to continuous high levels of stress that is shown through their blunted awakening response. In healthy adults, the cortisol awakening response was exhibited through a 50% increase in cortisol levels upon awakening, and then gradually declined throughout the day depending on everyday stressors (5, 6). In Black women, this is not necessarily the case, which could explain why Black women are being diagnosed, and ultimately are more affected by postpartum depression than any other race.
Research also shows that oxytocin plays a role in the body’s stress response during lactation (7). Women with depressive symptoms who breastfed showed lower oxytocin secretion and higher cortisol than women who bottle-fed their infant, suggesting that the oxytocin that is secreted from lactation affects the inflammatory response, and ultimately affects the stress response. To measure cortisol and oxytocin levels, salivary and venous blood plasma samples will be taken. The Edinburgh Postnatal Depression Scale will be used to measure depressive symptoms and the Perceived Stress Scale will be used to measure self-reported perceived levels of stress. While the relationship between the HPA axis and PPD has been highly researched, the overlap is poorly understood in Black women. In order to understand the psychoneuroimmunological and biological factors that play a role in the onset of PPD in Black women, the proposed study has the following aims: 1) to measure the cortisol levels in Black and White mothers throughout the day, 2) to measure the oxytocin levels of Black and White mothers during a feeding session, and 3) to examine the relationship between the immunological measures and its effects on PPD symptoms in Black and White mothers.
An Examination of Isolation and Substance Use During the Covid-19 Pandemic
Substance Use Disorder (SUD) is a disease that affects a person’s brain and behavior and leads to an inability to control the use of a drug or medication (1). Unfortunately, this disorder is very common in the US and affects nearly 20 million American adults (2). This is about six percent of the population. Although this does not seem to be a large portion, it has been consistently growing over the last several decades. Many of the behavioral aspects of SUD as well as the physiological perpetuate the addiction itself. SUD often gets reinforced in the brain through the dopamine reward system and the ‘high’ that is produced for the user. Drug addiction can also produce behaviors such as irritability, intense cravings for the drug, self-isolation or trouble completing daily tasks (1). It is evident that Substance Use Disorder is a disease that requires more attention and research to ensure that this vulnerable population is understood and receives the care it needs. To assist in the understanding of the compounding effects of the isolation produced by COVID-19 on those with SUD, research on the subject is needed. This research proposal features a logical design that could provide insight into the mechanisms of addiction during required isolation. This study will consider three aims: 1) How if at all does substance use change in the presence of forced isolation? 2) Can isolation have an effect on the type of drug (or Drug of Choice/DOC) of an individual with SUD? and 3) Are there physiological differences in the prefrontal cortex or dopamine levels in SUD individuals in and out of isolation? Upon completion of this research, there will be a better understanding of the connection between substance use and isolation as well as more focus on a population that requires immediate attention.
Social Belonging as a Mediator of Adverse Effects of Early Childhood Trauma on the Morphology of Neural Structures in Adulthood
Adverse childhood experiences are highly prevalent in nearly all cultures and generations. According to the CDC, 61% of people report having at least one adverse childhood experience (ACE) . However, this high percentage still likely reflects an under-estimate when considering the potential reasons for children, parents, or others to decide not to report abuse or neglect. Adverse childhood experiences predict a vast array of health problems, maladaptive behaviors, mental disorders, and premature death . According to Fritz and colleagues, 30% of all mental health problems can be attributed to childhood adversity . Childhood maltreatment is the main preventable cause of psychopathology, attributable to 45% of psychotic disorders . However, not every child who experiences an ACE develops later health problems, suggesting potential mediators between stress and health.
A variety of mediators of childhood trauma have been studied including familial relationships, genetic resilience, and social inclusion/social group belonging. By investigating the effect of perceived social belonging on the brain, this study broadens its potential participants by including pathological disorders and not limiting possible support to family systems only, as well as breaking from more traditional familial and social constructs. Every human has the potential to make connections and become part of social groups, but not everyone’s group includes their blood relatives. This study aims to determine whether or not the experience of feeling supported and loved at least once in a person’s childhood can protect them against the health risks associated with adverse experiences. This study will expand past familial support, looking at any kind of group membership where people’s humanity was valued.
COVID-19 Masking Effects on ASD and Emotion Recognition
COVID-19 has had a large effect on children in the United States; in 2020, nearly 100,000 students tested positive for the virus. COVID-19 has not only had direct effects on students, but it has also had secondhand ones including a change involving how interpersonal relationships are formed in schools. Due to masking mandates, only eye regions are available for emotion recognition and face perception; this can cause an increased difficulty recognizing emotions for individuals in general, and this difficulty is magnified for those with ASD due to the eye-avoidance hypothesis. Research has found that an early sign of autism in children is a reduced attention to the eye region resulting in an absence of eye contact. Further research, including the
The proposed research will explore an emotion not traditionally focused on in past ASD research: fear. Previous research has found a gaze avoidance for anger due to the association of a threat with the emotion. Oftentimes, there is a threat involved when someone is expressing fear. Thus, fear may cause a similar gaze avoidance in individuals with ASD. In order to gain a better understanding of the effects of COVID-19 masking, the proposed study has three specific aims: 1) to examine the eye movement involved in emotion recognition in children with ASD, 2) to seek to evaluate how accurate children with ASD recognize emotions of peers in masked and unmasked stimuli, 3) to compare the amount of emotional arousal as measured with skin conductance when viewing both the masked and unmasked peer stimuli. The knowledge gained from the proposed research will provide insight into the consequences of COVID-19 masking in children with ASD in terms of emotion recognition. A more in depth understanding of emotion recognition in individuals with ASD will provide more information to the scientific community on this facet of ASD.
Analyzing the Efficacy of Tetrahydrocannabivarin in Patients with Major Depressive Disorder
The World Health Organization found that major depression was the leading cause of disability worldwide (13). Evenmore, many individuals with MDD experience their first episodes of MDD during early childhood and adolescence (9). Many people with MDD experience abnormalities of mood, appetite, and sleep schedules. Although treatment options for MDD include cognitive behavioral therapy, antidepressant medication, transcranial magnetic stimulation, and electroconvulsive therapy (ECT), these options often have unpleasant side effects, low efficacy, or are highly intrusive. Research on the use of cannabinoids in the treatment of MDD shows promise in being analgesic, anti-epileptic, anti-inflammatory, and a stimulant (1, 17).The proposed research will explore the efficacy of a newly identified cannabinoid, tetrahydrocannabivarin (THCv), on symptoms of MDD. An already well-established antidepressant, imipramine, as well as Δ9-THC will be used as an active treatment comparison for THCv. To measure the effect of THCv on symptoms of MDD, the Beck Depression Inventory (BDI) will be used to obtain subjective reports of attitude and depression. The effect of THCv, Δ9-THC, and imipramine on levels of neurotransmitters will be measured using high performance liquid chromatography with electrochemical detection (HPLC-ECD). In order to gain a better understanding of the effects of THCv on MDD, the proposed research has three specific aims: 1) to determine the correct dosing for aiding depression. Participants will be in one of four groups, either an active control group of benadryl, an imipramine treatment group, a Δ9-THC group, or a THCv treatment group, 2) to measure the metabolites of dopamine, serotonin, norepinephrine, and glutamate using HPLC-ECD of the cerebrospinal fluid to determine if THCv can be used as an antidepressant, 3) to assess the degree to which THCv reliably increases activity level and decreases symptoms of MDD via evaluation of participants with the BDI. The knowledge gained from the proposed research will provide insight into the potential beneficial effects of THCv, and the impact of a commonly prescribed treatment. A clearer understanding of these relationships will provide avenues for improved treatment development for MDD.
Neural Correlates of Insightful Analogical Reasoning
Analogical reasoning has been paid great attention by cognitive scientists over the past decades. One of its subcomponent processes, analogical mapping, which finds a shared relationship between different domains, is considered to induce a representational shift of the knowledge structure . Similarly, the experience of insight, such as aha experiences, also seems to involve reorganizing mental representations. [1,2]. One recent behavioral study showed a direct link between representational change and aha experience, using a novel task which induced conceptual shifts by using analogical reasoning between close or distant domains . Neural studies investigating the intersection between creativity and analogical reasoning have suggested that the rostrolateral prefrontal cortex serves as a core region that integrates abstract representations, and its activation is further correlated with the semantic distance between analogs [4,5]. Additionally, computational models that attempts to model human relational thinking further suggests that the memory formation and integration necessary for relational thinking is enabled by the long distance communication between prefrontal cortex and posterior regions of the brain and can be reflected by coherent oscillations in electroencephalogram (EEG) frequency bands . This is supported more broadly by various neuroscience studies which have demonstrated alpha-band activity for creative idea generation, theta- and alpha- band activity for binding relational roles for concepts, and gamma-band activity for insight problem solving [7–9]. The preceding research also shows that the insight-related gamma activity is further modulated by individual reward sensitivity . Building from these recent advances,, this proposed study investigates the differential EEG correlates of the representational shift in the insightful analogical task, which was developed in the previous study mentioned above, and provides some initial evidence of neural measures. Specifically, we have three aims: examine the neural signature of 1) the representational shift induced by close- or far- distanced analogical reasoning, 2) the insight-accompanying analogical reasoning, 3) the influence of individual reward sensitivity on the insight effect. The study will further delineate differential mechanisms of different aspects of creativity – representational change, insights, reward signals on the basis of analogical reasoning.
Brain Abnormalities in Psychopathic Individuals
Psychopathy is a personality disorder whose key characteristics are lack of empathy and blunted affect. It is not culture specific and affects about 1% of the world’s population (4). While the exact neurobiological mechanisms responsible for psychopathy have yet to be identified, abnormalities in multiple brain regions have been implicated as potential causes. In the proposed research study, four of those – the amygdala, the prefrontal cortex, the striatum, and the anterior cingulate cortex – will be investigated using magnetic resonance imaging. Eligible participants will be identified from both penitentiaries and the general community using the Triarchic Psychopathy Measure (TriPM) questionnaire as a means of determining psychopathic traits. The study will investigate the changes in volumes of the above-mentioned brain regions observed on the MRI and their correlation with individual’s scores on specific subscales of the TriPM. In addition, correlations between questionnaire scores, brain abnormalities, and whether an individual would be considered a successful (no criminal record) or unsuccessful (criminal record) psychopath will also be examined. Participants will be asked to return for a follow up 1.5 years and 2.5 years after the start of the study, to investigate whether there are additional changes in particular brain regions, and how that reflects in changes in their TriPM scores.