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- Creators: Arizona State University
- Status: Published
Description
The efficacy of deep brain stimulation (DBS) in Parkinson's disease (PD) has been convincingly demonstrated in studies that compare motor performance with and without stimulation, but characterization of performance at intermediate stimulation amplitudes has been limited. This study investigated the effects of changing DBS amplitude in order to assess dose-response characteristics, inter-subject variability, consistency of effect across outcome measures, and day-to-day variability. Eight subjects with PD and bilateral DBS systems were evaluated at their clinically determined stimulation (CDS) and at three reduced amplitude conditions: approximately 70%, 30%, and 0% of the CDS (MOD, LOW, and OFF, respectively). Overall symptom severity and performance on a battery of motor tasks - gait, postural control, single-joint flexion-extension, postural tremor, and tapping - were assessed at each condition using the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and quantitative measures. Data were analyzed to determine whether subjects demonstrated a threshold response (one decrement in stimulation resulted in ≥ 70% of the maximum change) or a graded response to reduced stimulation. Day-to-day variability was assessed using the CDS data from the three testing sessions. Although the cohort as a whole demonstrated a graded response on several measures, there was high variability across subjects, with subsets exhibiting graded, threshold, or minimal responses. Some subjects experienced greater variability in their CDS performance across the three days than the change induced by reducing stimulation. For several tasks, a subset of subjects exhibited improved performance at one or more of the reduced conditions. Reducing stimulation did not affect all subjects equally, nor did it uniformly affect each subject's performance across tasks. These results indicate that altered recruitment of neural structures can differentially affect motor capabilities and demonstrate the need for clinical consideration of the effects on multiple symptoms across several days when selecting DBS parameters.
ContributorsConovaloff, Alison (Author) / Abbas, James (Thesis advisor) / Krishnamurthi, Narayanan (Committee member) / Mahant, Padma (Committee member) / Jung, Ranu (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Parkinson's disease, the most prevalent movement disorder of the central nervous system, is a chronic condition that affects more than 1000,000 U.S. residents and about 3% of the population over the age of 65. The characteristic symptoms include tremors, bradykinesia, rigidity and impaired postural stability. Current therapy based on augmentation or replacement of dopamine is designed to improve patients' motor performance but often leads to levodopa-induced complications, such as dyskinesia and motor fluctuation. With the disease progress, clinicians must closely monitor patients' progress in order to identify any complications or decline in motor function as soon as possible in PD management. Unfortunately, current clinical assessment for Parkinson's is subjective and mostly influenced by brief observations during patient visits. Thus improvement or decline in patients' motor function in between visits is extremely difficult to assess. This may hamper clinicians while making informed decisions about the course of therapy for Parkinson's patients and could negatively impact clinical care. In this study we explored new approaches for PD assessment that aim to provide home-based PD assessment and monitoring. By extending the disease assessment to home, the healthcare burden on patients and their family can be reduced, and the disease progress can be more closely monitored by physicians. To achieve these aims, two novel approaches have been designed, developed and validated. The first approach is a questionnaire based self-evaluation metric, which estimate the PD severity through using self-evaluation score on pre-designed questions. Based on the results of the first approach, a smart phone based approach was invented. The approach takes advantage of the mobile computing technology and clinical decision support approach to evaluate the motor performance of patient daily activity and provide the longitudinal disease assessment and monitoring. Both approaches have been validated on recruited PD patients at the movement disorder program of Barrow Neurological Clinic (BNC) at St Joseph's Hospital and Medical Center. The results of validation tests showed favorable accuracy on detecting and assessing critical symptoms of PD, and shed light on promising future of implementing mobile platform based PD evaluation and monitoring tools to facilitate PD management.
ContributorsPan, Di (Author) / Petitti, Diana (Thesis advisor) / Greenes, Robert (Committee member) / Johnson, William (Committee member) / Dhall, Rohit (Committee member) / Arizona State University (Publisher)
Created2013
Description
The present study aimed to compare brain activity changes related to proactive and reactive control strategies in patients with Parkinson’s disease during “On” levodopa and “Off” levodopa conditions. The study consisted of two participants who had received a prior diagnosis of Parkinson’s Disease. The participants completed AX-CPT task as a measure of attention control in two sessions: a) “On Levodopa” and b) “Off Levodopa” while they were in the fMRI scanner. Prior to the analysis, the T1- weighted anatomical scan images and the BOLD multiband functional images of both the participants were BIDS (Brain Imaging Data Structure) validated and preprocessed using the standard FMRIPrep pipeline. The imaging data was then analyzed using SPM12 (Statistical parametric mapping) software. Individual-level analysis of the imaging data was conducted by creating General Linear models for both the participants on “ON” and “OFF” levodopa conditions. The BOLD responses were compared using AY>BY and BX > BY contrasts. Where BX >, BY contrast, measured BOLD activity related to reactive control strategy and AY> BY contrast measured BOLD activity related to the proactive control strategy. It was observed that participants tended towards reactive control strategy in both “On” and “Off” levodopa conditions.
ContributorsDatta, Kalyani (Author) / Brewer, Gene (Thesis advisor) / Braden, B. Blair (Committee member) / Peterson, Daniel (Committee member) / Arizona State University (Publisher)
Created2022
Description
Information processing in the brain is mediated by network interactions between anatomically distant (centimeters apart) regions of cortex and network action is fundamental to human behavior. Disruptive activity of these networks may allow a variety of diseases to develop. Degradation or loss of network function in the brain can affect many aspects of the human experience; motor disorder, language difficulties, memory loss, mood swings, and more. The cortico-basal ganglia loop is a system of networks in the brain between the cortex, basal ganglia, the thalamus, and back to the cortex. It is not one singular circuit, but rather a series of parallel circuits that are relevant towards motor output, motor planning, and motivation and reward. Studying the relationship between basal ganglia neurons and cortical local field potentials may lead to insights about neurodegenerative diseases and how these diseases change the cortico-basal ganglia circuit. Speech and language are uniquely human and require the coactivation of several brain regions. The various aspects of language are spread over the temporal lobe and parts of the occipital, parietal, and frontal lobe. However, the core network for speech production involves collaboration between phonologic retrieval (encoding ideas into syllabic representations) from Wernicke’s area, and phonemic encoding (translating syllables into motor articulations) from Broca’s area. Studying the coactivation of these brain regions during a repetitive speech production task may lead to a greater understanding of their electrophysiological functional connectivity. The primary purpose of the work presented in this document is to validate the use of subdural microelectrodes in electrophysiological functional connectivity research as these devices best match the spatial and temporal scales of brain activity. Neuron populations in the cortex are organized into functional units called cortical columns. These cortical columns operate on the sub-millisecond temporal and millimeter spatial scale. The study of brain networks, both in healthy and unwell individuals, may reveal new methodologies of treatment or management for disease and injury, as well as contribute to our scientific understanding of how the brain works.
ContributorsO'Neill, Kevin John (Author) / Greger, Bradley (Thesis advisor) / Santello, Marco (Committee member) / Helms Tillery, Stephen (Committee member) / Papandreou-Suppapola, Antonia (Committee member) / Kleim, Jeffery (Committee member) / Arizona State University (Publisher)
Created2021
Description
Cannabis use is increasing both medically and recreationally. Over the last decade studies have investigated sex differences associated with Parkinson’s disease (PD) diagnosis and degenerative symptoms. Previous research has shown that cannabis use has had either a beneficial or deleterious effect on PD symptoms. This research will examine whether sex differences exist among the positive or negative effects of cannabis use in PD. In this paper, an analysis of sex-based differences between male and female cohorts categorized across 2,700 participants is completed under the Fox Insight data set. Each cohort will be compared to 14 nonmotor symptoms and 8 motor symptoms commonly associated with PD. In each cohort mean age, cannabis intake, cannabis dose, cannabis type, and PD diagnosis are analyzed within groups. Each symptom (motor and nonmotor) was analyzed between cohort responses to indicate if there was beneficial or worsening effect within cannabis. Results indicated that the designated female cohort reported both beneficial and worsening effects of cannabis use regarding both motor and nonmotor symptoms. The positive symptoms primarily consisted of individual motor functioning (e.g. dyskinesia, stiffness, back pain, etc.) while the worsening symptoms primarily consisted of nonmotor functioning (e.g. anxiety and apathy). Meanwhile, the male cohort only reported beneficial effects towards nonmotor symptoms (e.g. dystonia, muscle cramps, heart rate). These findings suggest the need for further examination of nigrostriatal pathways and hypothalamic integrity in PD, as it may provide more information into the effects of cannabis use based on sex differences.
ContributorsHooten, Madeline Loraine (Author) / Ofori, Edward (Thesis advisor) / Daniulaityte, Raminta (Committee member) / Peterson, Daniel (Committee member) / Arizona State University (Publisher)
Created2022
Description
Diffusion Tensor Imaging may be used to understand brain differences within PD. Within the last couple of decades there has been an explosion of learning and development in neuroimaging techniques. Today, it is possible to monitor and track where a brain is needing blood during a specific task without much delay such as when using functional Magnetic Resonance Imaging (fMRI). It is also possible to track and visualize where and at which orientation water molecules in the brain are moving like in Diffusion Tensor Imaging (DTI). Data on certain diseases such as Parkinson’s Disease (PD) has grown considerably, and it is now known that people with PD can be assessed with cognitive tests in combination with neuroimaging to diagnose whether people with PD have cognitive decline in addition to any motor ability decline. The Montreal Cognitive Assessment (MoCA), Modified Semantic Fluency Test (MSF) and Mini-Mental State Exam (MMSE) are the primary tools and are often combined with fMRI or DTI for diagnosing if people with PD also have a mild cognitive impairment (MCI). The current thesis explored a group of cohort of PD patients and classified based on their MoCA, MSF, and Lexical Fluency (LF) scores. The results indicate specific brain differences in whether PD patients were low or high scorers on LF and MoCA scores. The current study’s findings adds to the existing literature that DTI may be more sensitive in detecting differences based on clinical scores.
ContributorsAndrade, Eric (Author) / Oforoi, Edward (Thesis advisor) / Zhou, Yi (Committee member) / Liss, Julie (Committee member) / Arizona State University (Publisher)
Created2022
Description
Parkinson's Disease (PD) is a progressive neurodegenerative disorder that affects movement and balance control. Falls are a common and often debilitating consequence of PD, and reactive balance control is critical in preventing falls. This dissertation aimed to determine the adaptability and neural control of reactive balance responses in people with PD. Aim 1 investigated whether people with PD at risk for falls can improve their reactive balance responses through a 2-week, 6-session training protocol. The study found that reactive step training resulted in immediate and retained improvements in stepping, as measured by the anterior-posterior margin of stability (MOS), step length, and step latency during backward stepping. The second aim explored the neural mechanisms behind eliciting and learning reactive balance responses in PD. The study investigated the white matter (WM) correlates of reactive stepping and responsiveness to step training in PD. White matter was not significantly correlated with any baseline stepping outcomes. However, greater retention of step length was associated with increased fractional anisotropy (FA) within the left anterior corona radiata, left posterior thalamic radiation, and right and left superior longitudinal fasciculi. Lower radial diffusivity (RD) within the left posterior and anterior corona radiata were associated with retention of step latency improvements. These findings highlight the importance of WM microstructural integrity in motor learning and retention processes in PD. The third aim examined the role of the somatosensory system in reactive balance control in people with PD. The tactile and proprioceptive systems were perturbed using vibrotactile stimulation during backward feet-in-place balance responses. The results showed that tactile and proprioceptive stimulation had minimal impact on reactive balance responses. Small effects were observed for delayed tibialis anterior (TA) onsets with proprioceptive stimulation at a medium intensity. Overall, this dissertation provides insights into improving reactive balance responses and the underlying neural mechanisms in PD, which can potentially inform the development of targeted interventions to reduce falls in people with PD.
ContributorsMonaghan, Andrew S (Author) / Peterson, Daniel S (Thesis advisor) / Ofori, Edward (Committee member) / Daliri, Ayoub (Committee member) / Buman, Matthew P (Committee member) / Fling, Brett W (Committee member) / Arizona State University (Publisher)
Created2023
Description
Parkinson’s disease (PD) is a progressive neurodegenerative disorder, diagnosed late in
the disease by a series of motor deficits that manifest over years or decades. It is characterized by degeneration of mid-brain dopaminergic neurons with a high prevalence of dementia associated with the spread of pathology to cortical regions. Patients exhibiting symptoms have already undergone significant neuronal loss without chance for recovery. Analysis of disease specific changes in gene expression directly from human patients can uncover invaluable clues about a still unknown etiology, the potential of which grows exponentially as additional gene regulatory measures are questioned. Epigenetic mechanisms are emerging as important components of neurodegeneration, including PD; the extent to which methylation changes correlate with disease progression has not yet been reported. This collection of work aims to define multiple layers of PD that will work toward developing biomarkers that not only could improve diagnostic accuracy, but also push the boundaries of the disease detection timeline. I examined changes in gene expression, alternative splicing of those gene products, and the regulatory mechanism of DNA methylation in the Parkinson’s disease system, as well as the pathologically related Alzheimer’s disease (AD). I first used RNA sequencing (RNAseq) to evaluate differential gene expression and alternative splicing in the posterior cingulate cortex of patients with PD and PD with dementia (PDD). Next, I performed a longitudinal genome-wide methylation study surveying ~850K CpG methylation sites in whole blood from 189 PD patients and 191 control individuals obtained at both a baseline and at a follow-up visit after 2 years. I also considered how symptom management medications could affect the regulatory mechanism of DNA methylation. In the last chapter of this work, I intersected RNAseq and DNA methylation array datasets from whole blood patient samples for integrated differential analyses of both PD and AD. Changes in gene expression and DNA methylation reveal clear patterns of pathway dysregulation that can be seen across brain and blood, from one study to the next. I present a thorough survey of molecular changes occurring within the idiopathic Parkinson’s disease patient and propose candidate targets for potential molecular biomarkers.
the disease by a series of motor deficits that manifest over years or decades. It is characterized by degeneration of mid-brain dopaminergic neurons with a high prevalence of dementia associated with the spread of pathology to cortical regions. Patients exhibiting symptoms have already undergone significant neuronal loss without chance for recovery. Analysis of disease specific changes in gene expression directly from human patients can uncover invaluable clues about a still unknown etiology, the potential of which grows exponentially as additional gene regulatory measures are questioned. Epigenetic mechanisms are emerging as important components of neurodegeneration, including PD; the extent to which methylation changes correlate with disease progression has not yet been reported. This collection of work aims to define multiple layers of PD that will work toward developing biomarkers that not only could improve diagnostic accuracy, but also push the boundaries of the disease detection timeline. I examined changes in gene expression, alternative splicing of those gene products, and the regulatory mechanism of DNA methylation in the Parkinson’s disease system, as well as the pathologically related Alzheimer’s disease (AD). I first used RNA sequencing (RNAseq) to evaluate differential gene expression and alternative splicing in the posterior cingulate cortex of patients with PD and PD with dementia (PDD). Next, I performed a longitudinal genome-wide methylation study surveying ~850K CpG methylation sites in whole blood from 189 PD patients and 191 control individuals obtained at both a baseline and at a follow-up visit after 2 years. I also considered how symptom management medications could affect the regulatory mechanism of DNA methylation. In the last chapter of this work, I intersected RNAseq and DNA methylation array datasets from whole blood patient samples for integrated differential analyses of both PD and AD. Changes in gene expression and DNA methylation reveal clear patterns of pathway dysregulation that can be seen across brain and blood, from one study to the next. I present a thorough survey of molecular changes occurring within the idiopathic Parkinson’s disease patient and propose candidate targets for potential molecular biomarkers.
ContributorsHenderson, Adrienne Rose (Author) / Huentelman, Matthew J (Thesis advisor) / Newbern, Jason (Thesis advisor) / Dunckley, Travis L (Committee member) / Jensen, Kendall (Committee member) / Wilson, Melissa (Committee member) / Arizona State University (Publisher)
Created2019
Description
Injuries and death associated with fall incidences pose a significant burden to society, both in terms of human suffering and economic losses. The main aim of this dissertation is to study approaches that can reduce the risk of falls. One major subset of falls is falls due to neurodegenerative disorders such as Parkinson’s disease (PD). Freezing of gait (FOG) is a major cause of falls in this population. Therefore, a new FOG detection method using wavelet transform technique employing optimal sampling window size, update time, and sensor placements for identification of FOG events is created and validated in this dissertation. Another approach to reduce the risk of falls in PD patients is to correctly diagnose PD motor subtypes. PD can be further divided into two subtypes based on clinical features: tremor dominant (TD), and postural instability and gait difficulty (PIGD). PIGD subtype can place PD patients at a higher risk for falls compared to TD patients and, they have worse postural control in comparison to TD patients. Accordingly, correctly diagnosing subtypes can help caregivers to initiate early amenable interventions to reduce the risk of falls in PIGD patients. As such, a method using the standing center-of-pressure time series data has been developed to identify PD motor subtypes in this dissertation. Finally, an intervention method to improve dynamic stability was tested and validated. Unexpected perturbation-based training (PBT) is an intervention method which has shown promising results in regard to improving balance and reducing falls. Although PBT has shown promising results, the efficacy of such interventions is not well understood and evaluated. In other words, there is paucity of data revealing the effects of PBT on improving dynamic stability of walking and flexible gait adaptability. Therefore, the effects
of three types of perturbation methods on improving dynamics stability was assessed. Treadmill delivered translational perturbations training improved dynamic stability, and adaptability of locomotor system in resisting perturbations while walking.
of three types of perturbation methods on improving dynamics stability was assessed. Treadmill delivered translational perturbations training improved dynamic stability, and adaptability of locomotor system in resisting perturbations while walking.
ContributorsRezvanian, Saba (Author) / Lockhart, Thurmon (Thesis advisor) / Buneo, Christopher (Committee member) / Lieberman, Abraham (Committee member) / Abbas, James (Committee member) / Deep, Aman (Committee member) / Arizona State University (Publisher)
Created2019
How Does Technology Development Influence the Assessment of Parkinson’s Disease? A Systematic Review
Description
Parkinson’s disease (PD) is a neurological disorder with complicated and disabling motor and non-motor symptoms. The pathology for PD is difficult and expensive. Furthermore, it depends on patient diaries and the neurologist’s subjective assessment of clinical scales. Objective, accurate, and continuous patient monitoring have become possible with the advancement in mobile and portable equipment. Consequently, a significant amount of work has been done to explore new cost-effective and subjective assessment methods or PD symptoms. For example, smart technologies, such as wearable sensors and optical motion capturing systems, have been used to analyze the symptoms of a PD patient to assess their disease progression and even to detect signs in their nascent stage for early diagnosis of PD.
This review focuses on the use of modern equipment for PD applications that were developed in the last decade. Four significant fields of research were identified: Assistance diagnosis, Prognosis or Monitoring of Symptoms and their Severity, Predicting Response to Treatment, and Assistance to Therapy or Rehabilitation. This study reviews the papers published between January 2008 and December 2018 in the following four databases: Pubmed Central, Science Direct, IEEE Xplore and MDPI. After removing unrelated articles, ones published in languages other than English, duplicate entries and other articles that did not fulfill the selection criteria, 778 papers were manually investigated and included in this review. A general overview of PD applications, devices used and aspects monitored for PD management is provided in this systematic review.
This review focuses on the use of modern equipment for PD applications that were developed in the last decade. Four significant fields of research were identified: Assistance diagnosis, Prognosis or Monitoring of Symptoms and their Severity, Predicting Response to Treatment, and Assistance to Therapy or Rehabilitation. This study reviews the papers published between January 2008 and December 2018 in the following four databases: Pubmed Central, Science Direct, IEEE Xplore and MDPI. After removing unrelated articles, ones published in languages other than English, duplicate entries and other articles that did not fulfill the selection criteria, 778 papers were manually investigated and included in this review. A general overview of PD applications, devices used and aspects monitored for PD management is provided in this systematic review.
ContributorsDeb, Ranadeep (Author) / Ogras, Umit Y. (Thesis advisor) / Shill, Holly (Committee member) / Chakrabarti, Chaitali (Committee member) / Arizona State University (Publisher)
Created2019