This dissertation examines the representation of Alzheimer's Disease (AD) neuronarratives (NN), works that centralize the brain or consciousness in the plot, in multiple modalities to support that argument that neuronarratives should be expanded into a transmedia genre. These modalities include neurogames, neurocomics, and neuromemoirs. These three modalities were analyzed to determine how selfhood and social networks are represented by characters or authors with Alzheimer's Disease. As AD is often viewed as the loss of selfhood and is associated with isolation, these works combat these stigmas and complicate representations of the disease. The use of images was also examined in neurogames and neurocomics as a means of expressing complex emotions without relying on text. As the selected neurocomics were written by carers or based on experiences with AD patients and the neuromemoirs were written by AD patients, these works were also analyzed as a means to provide agency for AD patients and carers. This dissertation approaches these neuronarratives through the lens and medium of hypertext. Applying this approach complicates the concept of fragmentation and memory in AD NN and reveals that selfhood in these works are constructed through the creation of many selves rather than one cohesive self or a dual self that represents the healthy and ill AD patient. Regardless of the medium, these selves remain in conversation with each other, emphasizing the active process of creating selfhood by the author's themselves and by the player or reader. Comparing the affordances and limitations of the medium reveal conversations between the digital and print mediums that may not be initially apparent. Viewing these works through hypertext de-centers AD at the core of the narrative and instead emphasizes the personhood of the patient. Expanding analytical approaches to transmedia NN provides new means of exploring selfhood and consciousness by writers, artists, and developers.

Charcot Marie Tooth disease (CMT) represents the most common inheritable peripheral group of motor and sensory disorders; affecting 1 in 2500 people worldwide. Individuals with CMT experience slow progressing weakness of the muscle, atrophy, mild loss of motor coordination and in some cases loss of sensory function in the hands and feet which could ultimately affect mobility. Dynein is an essential molecular motor that functions to transport cargos in all cells. A point mutation in the dynein heavy chain was discovered to cause CMT disease in humans, specifically CMT type 2O. We generated a knock-in mouse model bearing the same mutation(H304R) in the dynein heavy chain to study the disease. We utilized behavioral assays to determine whether our mutant mice had a phenotype linked to CMT disease. The mutant mice had motor coordination defects and reduced muscle strength compared to normal mice. To better understand the disease pathway, we obtained homozygous mutants from a heterozygous cross, and the homozygotes show even more severe deficits compared to heterozygotes. They also developed an abnormal gait which separates them from heterozygous mice. In view of the locomotor deficits observed in mutants, we examined the neuromuscular junction (NMJ) for possible impairments. We identified defects in innervation at the later stages of the study and abnormal NMJ architecture in the muscle as well. The dysmorphology of the NMJ was again worse in the homozygous mutants with reduced complexity and denervation at all the timepoints assessed. Our homozygous dynein mutants can live up to two years and therefore make the design of longitudinal studies possible. Altogether, this mouse model provides dynein researchers an opportunity to work towards establishing the link between dynein mutations, dynein dysfunction and the onset and progression of disease.

Physiological measurements have become more popular in Psychological research over the past ten years. These advancements allowed different objective sensors to become another measurement tool in a scientific arsenal of collecting data. Traditionally, performance and after task subjective measures have been used for most studies in Psychological research. With the opportunity to use these subjective measures along with objective measures, more data can be collected during research and therefore potentially produce better quality conclusions. Eye Tracking (ET), functional near infrared (fNIR), transcranial Doppler ultrasound (TCD), electrocardiogram (EKG) and the electroencephalogram (EEG) have shown great promise in their ability to produce reliable and powerful objective data for research. Consequently, these devices are being used at the same time. The simultaneous use has the potential for interference between devices. Further, these devices are used on human subjects who can find these devices uncomfortable. These issues have the ability to skew data simply due to the measurement devices used. The effort of this study was to determine if the above devices could be used simultaneously without affecting their data quality, determine if difference combinations are more or less beneficial and determine if the combination of sensors have an effect on participant experience. A negative effect from discomfort has the potential to effect data. A study was conducted utilizing the ET, EEG, EKG, fNIR and TCD together in various combinations and also alone to determine if data is compromised and to determine if the combinations have an effect on participant experience.

Huntington Disease (HD) is an autosomal dominant neurodegenerative disorder caused by a trinucleotide repeat expansion mutation in the huntingtin (HTT) gene. HD is characterized by neurological symptoms, including motor, cognitive, and psychiatric decline. A non-neurological symptom, metabolic dysfunction, is also common in HD and can cause weight change, a feature recapitulated in HD mice. There is a need for a better understanding of the weight changes associated with HD, because patients with a higher body mass index show slower disease progression. Our lab has shown that metabolic dysfunction in HD mice is the result of a disrupted circadian feeding rhythm but when HTT expression is suppressed in the brain, this is normalized. Additionally, when a normal circadian feeding rhythm is enforced, HTT protein in the brain is reduced. Together, this suggests that HTT is involved in gut-brain feedback. The gut brain axis (GBA) is the bidirectional communication pathway between the gut and central nervous system. One major component of the GBA is the gut microbiome, which has been implicated in neurological disorders. The microbiome interacts with the brain by producing short chain fatty acids, neurotransmitters, and metabolites. A plasma metabolomics study of HD mutation carriers revealed a reduction of Indole-3-propionic acid (IPA) in HD. IPA is a metabolite exclusively produced by bacteria and is a known antioxidant and anti-inflammatory. Inflammation and oxidative stress are features of HD and a reduction in circulating IPA may contribute to these aspects of the disease. This research was conducted to investigate the relationship between the relative abundance of IPA producing bacteria in the gut and the amount of plasma IPA in HD model mice. This will provide a basis for further investigation into the connection between the microbiome, bacterial metabolites, and the potential to target gut dysbiosis as a therapeutic outlet for HD.

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