Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item The effects of sequence structure, age-related impairments, and Parkinson's disease on motor sequence learning(2015) Prashad, Shikha; Clark, Jane E.; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Parkinson’s disease (PD) is a neurodegenerative movement disorder that affects over one million individuals in the US with approximately 60,000 new diagnoses every year. While characterized as a movement disorder, the effect of PD and aging on learning new motor skills has yielded equivocal results. Thus, the broad objective of this dissertation is to investigate the influence of PD on motor sequence learning. We begin by examining different sequence structures and how they are affected by age before investigating the effects of PD. To address the inadequacies of previous studies using fixed order sequences, we used probabilistic sequences, in which stimuli are linked by statistical associations. The first study directly compared the learning of probabilistic sequences to fixed sequences and randomly ordered stimuli in typical young adults (18-23 years) using a modified serial reaction time (SRT) paradigm. The results suggest that both fixed and probabilistic sequence groups exhibited learning, but the underlying learning processes were different in employing online and offline learning strategies. In the second and third studies, electroencephalography (EEG) was recorded from typical young adults (18-23 years), typically aging adults (55-75 years), and patients with PD (55-75 years) while they performed the same modified SRT task. We characterized the developmental landscape of 55-75 year old adults and found that cluster analysis separated typically aging adults into groups that provided a clearer understanding of their impairments. By unraveling movement and cognitive deficits and matching participants based on functional characteristics, we found that some typically aging adults and those with PD learned the fixed sequence, but not the probabilistic sequence, indicating age-related impairments in probabilistic motor sequence learning. We found cortical activations indicative of learning, even in the absence of behavioral indications suggesting that some adults may require more practice to learn the sequence, and possible compensatory mechanisms in patients with PD. Novel applications of these techniques prove effective for a deeper understanding of the dynamic motor learning process and provide evidence that impairments observed in patients with PD may be related more to the aging process than to Parkinson’s disease.Item The Yin and Yang of Amyloids: Insights from alpha-Synuclein and the Pmel17 Repeat Domain(2011) Pfefferkorn, Candace Marie; Lee, Jennifer C; Thirumalai, Devarajan; Chemical Physics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)While amyloidogenic proteins are commonly associated with human diseases such as Alzheimer's and Parkinson's disease, it is intriguing that amyloid fibrils also are utilized for essential biological processes. A key question then is why many amyloids are harmful whereas some serve essential functional roles. To begin to address this question, the environmental factors regulating the conformational changes in the Parkinson's disease-related protein, alpha-synuclein (alpha-syn), and a critical polypeptide fragment, the repeat domain (RPT) of Pmel17, the protein required for melanin formation are examined. The role of membranes in modulating alpha-syn conformation is investigated because membranes are ubiquitous in vivo and affect alpha-syn aggregation in vitro. Using single tryptophan-containing alpha-syn variants (F4W, Y39W, F94W, Y125W) as site-specific fluorescent probes, distinct phospholipid vesicle and SDS micelle interactions have been identified and membrane binding equilibria measured. The role of specific N-terminal residues in membrane binding also has been assessed. Specifically, environments of the highly sensitive Trp4 probe in alpha-syn polypeptide fragments (residues: 1 - 4, 1 - 6, 1 - 10, and 1 - 15) upon membrane binding were characterized using steady-state fluorescence and time-resolved anisotropy. The penetration depths of alpha-syn and N-terminal peptides into the lipid bilayer also were determined using brominated lipids as heavy-atom quenchers. To simultaneously monitor alpha-syn and bilayer structure, neutron reflectometry (NR) and a sparsely-tethered bilayer lipid membrane (stBLM) were employed. Using NR and an stBLM, alpha-syn concentration dependent effects on both protein structure and membrane properties were measured. To begin to address biophysical and biochemical differences between pathological and functional amyloid, a systematic investigation of the effects of solution pH (4→7) on RPT aggregation was performed since melanosomes, acidic organelles where Pmel17 fibrils are formed, change pH during maturation. Using intrinsic tryptophan fluorescence, circular dichroism spectroscopy, and transmission electron microscopy, local, secondary, and fibril morphological structure were monitored, respectively. Notably, RPT fibril morphology can be transformed directly by changing solution pH, suggesting that pH is a natural regulatory mechanism for Pmel17 amyloid formation and its subsequent dissolution in vivo.Item Retention of a novel visuomotor gain in patients with Parkinson's disease is context-specific(2009) Venkatakrishnan, Anusha; Contreras-Vidal, José L; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Hypometria or reduced movement amplitude is a major concern in Parkinson's disease (PD) since it impairs multiple functional activities of daily living, including fine motor control tasks, such as handwriting. Recent research using virtual or computer-based environments, wherein visual information about hand movement is altered and dissociated from perception (e.g., position sense or kinesthesia) of hand movement itself, has shown increases in handwriting size in patients with PD. In fact, preliminary findings in our laboratory have shown that gradual alterations in visual feedback of movement facilitate adaptation of handwriting size in patients with PD, plausibly by recruiting neural networks other than the basal ganglia, such as those in cerebellum. The purpose of this study was to determine whether these adaptive effects persist after a week following visuomotor training in patients with PD and can favorably transfer to other functional writing and drawing tasks. Thirteen patients with Parkinson's disease and twelve healthy, age-matched subjects practiced handwriting either under gradually manipulated (intervention) or intact (placebo) visual display of handwriting size. The results from this study show for the first time, that these adaptive effects may persist for at least up to a week in PD; however, a single training session seemed inadequate to transfer these acquired changes to paper-pen writing and drawing. Additionally, experimental manipulation of task demands during training also helped maintain movement quality in patients with PD as against the placebo group. These findings have important implications in designing rehabilitative interventions to enhance functional sensorimotor performance in patients with PD.Item Vocal Dysfunction in Young-onset Parkinson's Disease(2004-08-10) Bassich-Zeren, Celia J.; McCall, G N.; Hearing and Speech Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Vocal dysfunction is well established in persons with older-onset Parkinson's disease (PD), but has not been investigated in the young-onset PD (YOPD) population. Voice deficits associated with older-onset PD mirror the characteristics of vocal aging, suggesting that our current knowledge base of laryngeal dysfunction in the PD population is confounded by aging effects. The purpose of this study was threefold: (a) to examine perceptual voice characteristics and the potential impact of voice symptoms on quality of life; (b) to compare YOPD and healthy control (HC) speakers' performance on two routinely used clinical tasks (sustained vowel phonation and laryngeal diadochokinesis); and (c) to experimentally manipulate and compare speakers' performance in producing phonatory offset-onset gestures as reflected in four phonetic contexts (each eliciting a different mechanism) across three speaking modes. Twelve YOPD speakers and twelve healthy control (HC) speakers participated. YOPD speakers reported voice symptoms of hypophonia, tremor, hoarseness, monotone, and impaired speech intelligibility. They demonstrated a mild to moderate voice handicap. Findings revealed no speaker group differences for speech intensity on sustained vowel phonation and reading tasks. YOPD speakers demonstrated a significantly decreased rate of syllable repetition and used a significantly greater number of pauses during production of one of two laryngeal diadochokinetic tasks. Acoustic measures associated with mechanisms of phonatory offset-onset demonstrated trends of speaker group differences, suggesting that YOPD speakers have impaired voicing control for mechanisms of phonatory offset-onset not associated with oral constriction. Intra-speaker group variability was observed for YOPD speakers. Inspection of speaker groups' performance across speaking modes suggested a disruption in the habitual setting of laryngeal posture in YOPD speakers; namely, they use a laryngeal postural setting that is similar to that observed in HC speakers when speaking in an aspirant or breathy voice mode. Speech masking facilitated a speaking mode change in YOPD speakers and could provide an effective and efficient treatment method for training persons with YOPD to speak in a projected mode. Vocal dysfunction is associated with YOPD and voice symptoms can appear early in the disease process, sometimes preceding onset of limb symptoms. Persons with YOPD should be routinely assessed for vocal dysfunction.