This paper provides a multidisciplinary analysis of the relationship between beauty and addiction, with a focus on the emerging field of neuroaesthetics. Neuroaesthetics investigates the neural mechanisms that underlie aesthetic experiences and how the brain cognitively processes beauty. Since there is a biological foundation of this report, I will predominantly discuss neuroanatomy, neurological studies, and the overlap in neural circuitry between beauty and addiction. In addition, I will discuss the philosophical roots of beauty, as well as the environmental elements involved. Chapter 1 begins by explaining the history of beauty and its importance. I discuss the main constituents of beauty and differentiate between key terms involved in the beauty experience. In order to understand the link between beauty and addiction, it is essential to have a knowledgeable background on what beauty is. Next, I discuss the neurobiology of addiction. The main component of this chapter involves the mesolimbic and mesocortical reward pathways. I also describe neuroanatomical terms involved in addiction. The last chapter considers the implications of neuroaesthetics in various studies, which primarily involve the use of fMRIs. I discuss the sensory evaluations of beauty and the brain regions involved in the beauty experience. From this, I found that the experience of beauty activates these main brain regions: PFC, amygdala, striatum, NAcc, cingulate, VTA, and most remarkably, field A1 of the mOFC. By combining the neurological studies with studies of aesthetics, I reached the conclusion that there is an overlap in the neural pathways during the experience of beauty and during addiction. Although it is necessary for further research to be conducted to properly declare this, I discovered that the pursuit of beauty can lead to addictive behaviors, as the reward centers of the brain are activated by aesthetic experiences.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the deterioration of upper and lower motor neurons in the brain, brain stem, and spinal cord. Multiple missense mutations have been connected to familial ALS, including those in the Matrin-3 protein. Matrin-3 is an RNA and DNA-binding protein encoded by the MATR3 gene. Normally found in the nuclear matrix, Matrin-3 plays several roles vital to RNA metabolism, including splicing, RNA degradation, mRNA transport, mRNA stability, and transcription. Mutations in MATR3 leading to familial ALS include P154S and S85C, but the mechanisms through which these mutations contribute to ALS pathology remain unknown. This makes mouse models particularly useful in elucidating pathology mechanisms, ultimately having the potential to serve as preclinical models for therapeutic drugs. Because of the importance of animal models, we worked to create ALS mouse models for the MATR3 P154S and S85C mutations. We specifically generated two CRISPR/Cas9 mediated knock-in mouse models containing the MATR3 P154S or S85C mutation expressed under the control of the endogenous promoter. Both the homozygous and heterozygous P154S mice developed no physical or motor defects or shortening of lifespan compared to the wildtype mice. They also exhibited no ALS-like pathology in either the muscle or spinal cord up to 24 months. In contrast, the homozygous S85C mice exhibited significant physical and motor differences, including smaller weight, impaired gait, and shortening of lifespan. Some ALS-like pathology was observed in the muscle, but pathology remained limited in the spinal cord of the homozygous mice up to 12 months. In conclusion, our data suggests that the MATR3 P154S mutation alone does not cause ALS in vivo, while the MATR3 S85C mutation induces significant motor deficits, with pathology in the spinal cord potentially beginning at older ages not examined in our study.

An introduction to neuroscientific thought aimed at an audience that is not educated in biology. Meant to be readable and easily understood by anyone with a high school education. The first section is completed in its entirety, with outlines for the proposed final sections to be completed over the next few years.

ABSTRACT
Environmental and genetic factors influence schizophrenia risk. Individuals who have direct family members with schizophrenia have a much higher incidence. Also, acute stress or life crisis may precede the onset of the disease. This study aims to understand the effects of environment on genes related to schizophrenia risk. It investigates the impact of sleep deprivation as an acute environmental stressor on the expression of Htr2a in mice, a gene that codes for the serotonin 2A receptor (5-HT2AR). HTR2A is associated with schizophrenia risk through genetic association studies and expression is decreased in post-mortem studies of patients with the disease. Furthermore, sleep deprivation as a stressor in human trials has been shown to increase the binding capacity of 5-HT2AR. We hypothesize that sleep deprivation will increase the number of cells expressing Htr2a in the mouse anterior prefrontal cortex when compared to controls. Sleep deprived that mice express EGFP under control of the Htr2a promoter displayed anteroposterior gradients of expression across sagittal sections, with concentrations seen most densely within the prefrontal cortex as well as the anterior pretectal nucleus, thalamic nucleus, as well as the cingulate gyrus. Htr2a-EGFP expression was most densely visualized in cortical layer V and VI pyramidal neurons within the lateral prefrontal cortex of coronal sections. Furthermore, the medial prefrontal cortex contained significantly cells expressing Htr2a¬-EGFP than the lateral prefrontal cortex. Ultimately, the hypothesis was not supported and sleep deprivation did not result in more ¬Htr2a-EGFP expressing cells compared to basal levels. However, expressing cells appeared visibly brighter in sleep-deprived animals when compared to controls, indicating that the amount of intracellular Htr2a-GFP expression may be higher. This study provides strong visual representations of expression gradients following sleep deprivation as an acute stressor and paves the way for future studies regarding 5H-T2AR’s role in schizophrenia.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a devastating illness that causes the degeneration of both upper and lower motor neurons, leading to eventual muscle atrophy. ALS rapidly progresses into paralysis, with patients typically dying due to respiratory complications within three to five years from the onset of their symptoms. Even after many years of research and drug trials, there is still no cure, and current therapies only succeed in increasing life-span by approximately three months. With such limited options available for patients, there is a pressing need to not only find a cure, but also make new treatments available in order to ameliorate disease symptoms. In a genome-wide association study previously conducted by the Translational Genomics Research Institute (TGen), several single-nucleotide polymorphisms (SNPs) upstream of a novel gene, FLJ10968, were found to significantly alter risk for ALS. This novel gene acquired the name FGGY after publication of the paper. FGGY exhibits altered levels of protein expression throughout ALS disease progression in human subjects, and detectable protein and mRNA expression changes in a mouse model of ALS. We performed co-immunoprecipitation experiments coupled with mass spectrometry in order to determine which proteins are associated with FGGY. Some of these potential binding partners have been linked to RNA regulation, including regulators of the splicesomal complex such as SMN, Gemin, and hnRNP C. To further validate these findings, we have verified co-localization of these proteins with one another. We hypothesize that FGGY plays an important role in ALS pathogenesis, and we will continue to examine its biological function.

As the incidence of dementia continues to rise, the need for an effective and non-invasive method of intervention has become increasingly imperative. Music therapy has exhibited these qualities in addition to relatively low implementation costs, therefore establishing itself as a promising means of therapeutic intervention. In this review, current research was investigated in order to determine its effectiveness and uncover the neurochemical mechanisms that lead to positive manifestations such as improved memory recall, increased social affiliation, increased motivation, and decreased anxiety. Music therapy has been found to improve several aspects of memory recall. One proposed mechanism involves temporal entrainment, during which the melodic structures present in music provide a framework for chunking information. Although entrainment's role in the treatment of motor defects has been thoroughly studied, its role in treating cognitive disorders is still relatively new. Musicians have also been shown to demonstrate extensive plastic changes; therefore, it is hypothesized that non-musicians may also glean some benefits from engaging in music. Social affiliation has been found to increase due to increases in endogenous oxytocin. Oxytocin has also been shown to strengthen hippocampal spike transmission, a promising outcome for Alzheimer's patients. An increase in motivation has also been found to occur due to music's ability to tap into the reward center of the brain. Dopaminergic transmission between the VTA, NAc and higher functioning regions such as the OFC and hypothalamus has been revealed. Additionally, relaxing music decreases stress levels and modifies associated autonomic processes, i.e. heart rate, blood pressure, and respiratory rate. On the contrary, stimulating music has been found to initiate sympathetic nervous system activity. This is thought to occur by either a reflexive brainstem response or stimulus interpretation by the amygdala.

Previous research has showed that auditory modulation may be affected by pure tone
stimuli played prior to the onset of speech production. In this experiment, we are examining the
specificity of the auditory stimulus by implementing congruent and incongruent speech sounds in
addition to non-speech sound. Electroencephalography (EEG) data was recorded for eleven adult
subjects in both speaking (speech planning) and silent reading (no speech planning) conditions.
Data analysis was accomplished manually as well as via generation of a MATLAB code to
combine data sets and calculate auditory modulation (suppression). Results of the P200
modulation showed that modulation was larger for incongruent stimuli than congruent stimuli.
However, this was not the case for the N100 modulation. The data for pure tone could not be
analyzed because the intensity of this stimulus was substantially lower than that of the speech
stimuli. Overall, the results indicated that the P200 component plays a significant role in
processing stimuli and determining the relevance of stimuli; this result is consistent with role of
P200 component in high-level analysis of speech and perceptual processing. This experiment is
ongoing, and we hope to obtain data from more subjects to support the current findings.

The goal of my study is to test the overarching hypothesis that art therapy is effective because it targets emotional dysregulation that often accompanies significant health stressors. By reducing the salience of illness-related stressors, art therapy may improve overall mood and recovery, particularly in patients with cancer. After consulting the primary literature and review papers to develop psychological and neural mechanisms at work in art therapy, I created a hypothetical experimental procedure to test these hypotheses to explain why art therapy is helpful to patients with chronic illness. Studies found that art therapy stimulates activity of multiple brain regions involved in memory retrieval and the arousal of emotions. I hypothesize that patients with chronic illness have a reduced capacity for emotion regulation, or difficulty recognizing, expressing or altering illness-related emotions (Gross & Barrett, 2011). Further I hypothesize that art therapy improves mood and therapeutic outcomes by acting on the emotion-processing regions of the limbic system, and thereby facilitating the healthy expression of emotion, emotional processing, and reappraisal. More mechanistically, I propose art therapy reduces the perception or salience of stressors by reducing amygdala activity leading to decreased activation of the hypothalamic-pituitary-adrenal (HPA) axis. The art therapy literature and my hypothesis about its mechanisms of action became the basis of my proposed study. To assess the effectiveness of art therapy in alleviating symptoms of chronic disease, I am specifically targeting patients with cancer who exhibit a lack of emotional regulation. Saliva is collected 3 times a week on the day of intervention: morning after waking, afternoon, and evening. Stress levels are tested using one-hour art therapy sessions over the course of 3 months. The Perceived Stress Scale (PSS) assesses an individual's perceived stress and feelings in past and present situations, for the control and intervention group. To measure improvement in overall mood, 10 one-hour art sessions are performed on patients over 10 weeks. A one-hour discussion analyzing the participants' artwork follows each art session. The Spielberger State-Trait Anxiety Inventory (STAI) assesses overall mood for the intervention and control groups. I created rationale and predictions based on the intended results of each experiment.

Immediate early genes (IEGs) are rapidly activated in response to an environmental stimulus, and most code for transcription factors that mediate processes of synaptic plasticity, learning, and memory. EGR3, an immediate early gene transcription factor, is a mediator of biological processes that are disrupted in patients with schizophrenia (SCZ). A microarray experiment conducted by our lab revealed that Egr3 also regulates genes involved in DNA damage response. A recent study revealed that physiological neuronal activity results in the formation of DNA double-stranded breaks (DSBs) in the promoters of IEGs. Additionally, they showed that these DSBs are essential for inducing the expression of IEGs, and failure to repair these DSBs results in the persistent expression of IEGs. We hypothesize that Egr3 plays a role in repairing activity- induced DNA DSBs, and mice lacking Egr3 should have an abnormal accumulation of these DSBs. Before proceeding with that experiment, we conducted a preliminary investigation to determine if electroconvulsive stimulation (ECS) is a reliable method of inducing activity- dependent DNA damage, and to measure this DNA damage in three subregions of the hippocampus: CA1, CA3, and dentate gyrus (DG). We asked the question, are levels of DNA DSBs different between these hippocampal subregions in animals at baseline and following electroconvulsive stimulation (ECS)? To answer this question, we quantified γ-H2AX, a biomarker of DNA DSBs, in the hippocampal subregions of wildtype mice. Due to technical errors and small sample size, we were unable to substantiate our preliminary findings. Despite these shortcomings, our experimental design can be modified in future studies that investigate the role of Egr3 in activity-induced DNA damage repair.