Doctor of Philosophy, Case Western Reserve University, 2023, Biomedical Engineering

Deep brain stimulation (DBS) has the potential to provide life-changing relief for people who have exhausted other therapeutic options for treating Parkinson's disease (PD). Even after the surgical procedure itself, however, patients must undergo multiple therapeutic programming sessions in an effort to identify the electrical stimulation parameters that maximize therapeutic benefit while minimizing stimulation-induced side effects. Current practice involves a subjective, time-consuming, manual exploration of the DBS parameter space by a clinical specialist. New techniques at titrating stimulation parameters may yield better outcomes for patients by replacing an inefficient and subjective system of optimizing therapeutic benefit with a data-driven approach based on biological feedback. The work presented in this dissertation provides the foundation for an objective and data-driven approach at titrating DBS for PD. We propose the use of DBS-cortical evoked potentials (DBS-CEPs) as a viable metric of therapeutic modulation of the basal-ganglia thalamocortical (BGTC) circuit that may serve as a tool to guide objective therapeutic programming efforts. The first two aims utilize a non-human primate (NHP) model of PD. First, this work addresses the issue of accurate surgical targeting in a NHP model by introducing a new frameless stereotactic approach for implanting DBS leads. Results demonstrate that this technique provides methodological improvements over existing approaches without sacrificing surgical precision. Having applied that approach to instrument a NHP, the second aim characterizes the features of the proposed physiological signal, the DB-CEP, as a function of time, disease state, and medication status. Findings support the overall reliability of the DBS-CEP a measure of therapeutic circuit modulation and, in turn, a potential tool to guide DBS programming. Having established its reliability, the third aim explored whether the response was sensitive to an (open full item for complete abstract)

Committee: Kenneth Baker (Advisor); Jeffrey Capadona (Committee Chair); Dawn Taylor (Committee Member); Kenneth Gustafson (Committee Member) Subjects: Biomedical Engineering; Neurology; Neurosciences

Doctor of Philosophy, The Ohio State University, 2021, Speech and Hearing Science

The three manuscripts presented here examine the role of acoustic and electrically evoked potentials to assess sensory and neural encoding processes by the peripheral auditory system in hearing-impaired listeners. The first manuscript defined how spectral and temporal properties of the phonemes /da/ and /ba/ were encoded in the peripheral auditory system using electrocochleography (ECochG) in normal and hearing-impaired listeners. Results suggest that the fundamental frequency of each phoneme is the dominant spectral content encoded by the peripheral auditory system. Additionally, spectral encoding by the sensory cells of the cochlea, as measured by the cochlear microphonic response, is strongly correlated with word recognition performance. In the second manuscript, acoustic click train stimulation was employed to study the impact of M%eacute;niere's disease on two temporal response properties of the auditory nerve: adaptation and recovery from adaptation. The findings of this study suggest little evidence of neural damage in Meniere's disease that exceeds that of other forms of sensorineural hearing loss. Finally, in the third manuscript, electrical stimulation of the auditory nerve was utilized to investigate the effect of aging on the response properties of the auditory nerve. The sensitivity of the auditory nerve to steady state pulse trains was not found to be significantly different between older and younger adult cochlear implant users, although trends of poorer function in older adults did exist, especially at higher pulse rates. Results suggest potential negative effects of aging on temporal response properties to electrical pulse train stimulation at high pulse rates. Overall, evoked potentials provide a robust technique to objectively study processing of the auditory system in normal and hearing-impaired listeners.

Committee: Eric Bielefeld PhD (Advisor); Aaron Moberly MD (Committee Member); Christina Roup PhD (Committee Member); Shuman He PhD (Committee Member) Subjects: Audiology

Doctor of Philosophy, The Ohio State University, 1987, Graduate School

Committee: Not Provided (Other) Subjects: Education

Doctor of Philosophy, The Ohio State University, 1986, Graduate School

Committee: Not Provided (Other) Subjects: Education

Doctor of Philosophy, The Ohio State University, 1981, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

MA, University of Cincinnati, 2001, Allied Health Sciences : Communication Sciences and Disorders

Purpose: Meniere's disease is a progressive inner ear disorder in which there is no gold standard for diagnosis, treatment, or cure. This disorder has been diagnosed based upon classic Meniere's disease symptoms and Electrocochleography results. Classic Meniere's disease symptoms include fluctuating hearing loss, roaring tinnitus, and aural pressure. The most common diagnosis for Meniere's disease with regards to Electrocochleography is an abnormal summating potential (SP) to action potential (AP) ratio (SP/AP ratio) due to an enlarged SP. However, Ferraro and Tibbils (1999) discovered that the sensitivity of the SP/AP lacked a strong clinical significance in that it only diagnosed 60% of existing Meniere's disease patients. The purpose of this study is to investigate the area under the SP/AP complex in relation to the final otologic diagnosis of Meniere's disease. Methodology: Each subject was administered the Electrocochleography test. The waveforms from each ear were measured from baseline to 2ms post-baseline. The area under the SP/AP complex was then calculated. Subjects: 16 subjects were evaluated in this study. 8 of these subjects were suspected of having Meniere's disease. The remaining 8 subjects were normal hearing individuals with a negative history of otologic disease. Interventions: Otoscopy, tympanometry, and Electrocochleography were administered for each ear of each subject. Main outcome measures: The waveforms were measured from baseline to 2ms post-baseline. Coordinates were recorded every .04 ms. The coordinates were entered into an integrated function to determine the area under the SP/AP complex. Results: There was no significant interaural difference between areas within the research group. There was no significant difference between the areas of the research and control groups. Conclusion: Due to the complexity and fluctuating nature of Meniere's disorder, it is hard to evaluate the disorder if symptoms are not active at the time of testing. F (open full item for complete abstract)

Committee: Dr. Robert W. Keith (Advisor) Subjects: Urban and Regional Planning

PhD, University of Cincinnati, 2010, Allied Health Sciences : Communication Science and Disorders

The overall aim of the present research was to perform an exploratory analysis of the relationship between the P1 auditory evoked potential response and residual auditory cortical function as shown by fMRI activation maps in moderate or severe to profoundly hearing impaired subjects. Electrophysiologic and functional neuroimaging evaluations using speech stimuli were conducted on fourteen subjects ages 9-24 months with residual hearing ranging from 85 dBHL to 100 dBHL pure tone average (PTA), in the .5 to 2 KHz range. Electrophysiological testing included evaluation of P1 cortical auditory evoked response with a hearing aid on using a Klatt generated /ba/ stimulus in the soundfield at 75 dBSPL. Subjects unable to wear an amplification device during the testing were stimulated using an Eartone 3A insert earphone at a minimum of 10 dB sensation level based on aided audiometric results. An fMRI paradigm consisting of Narrow Band Noise (NBN) and stories was administered under sedation at the end of a clinical scan in a 3 Tesla system using sound presentation levels of 10 dB sensation level based on audiometric results. Stimuli were interleaved with silence in a block-periodic counterbalanced fMRI design with 30-second on-off intervals. Results were subjected to a correlation analysis to search for a relationship between P1 characteristics and the number of activated fMRI pixels detected within specified regions of interest in the auditory cortex. In addition, a multiple regression analysis was conducted to assess the prediction of the P1 latency in our sample based on duration of hearing aid use and age at the time of the fitting. Results indicated that although fMRI activation patterns do not exhibit a predictive relationship with P1 latency (r(10) = .038, p = .456), the strength of the auditory BOLD response was inversely correlated with P1 amplitude (rS = -.85, p = .001), suggesting more localized regions of cortical responsivity in subjects with robust P1 waveforms. (open full item for complete abstract)

Committee: Robert Keith PhD (Committee Chair); David Brown PhD (Committee Member); Scott Holland PhD (Committee Member); Peter Scheifele PhD (Committee Member) Subjects: Audiology

Doctor of Philosophy, The Ohio State University, 2009, Neuroscience

Spinal cord injury (SCI) impairs sensory systems causing debilitating chronic allodynia, neuropathic pain elicited from an innocuous stimulus. While inflammation can cause allodynia under some conditions, no ameliorative cure exists. Our rat spinal cord contusion model emulates the pathology of human SCI but its validity as a model of allodynia remains debatable. Hence, our goals were: to validate and extend behavioral assessments of below-level allodynia for experimental SCI, to identify the anatomical and functional connections involved in processing sensation after SCI, and to characterize the patterns of glial activation and pro-inflammatory cytokine production in sensory processing centers of the lumbar spinal cord. To test for allodynia in experimental SCI, we validated current paradigms and developed a new assessment of sensation that did not rely on hindlimb or postural control. We validated these techniques in >150 rats with SCI and demonstrate that Up-Down methods provide a quantitative assessment of perceptual threshold. With the new sensory test, thresholds collected prior to recovery of hindlimb weight support predicted chronic thresholds with 75-89% accuracy. Subsequently, we showed that anatomical connections between L5 and supraspinal centers remain intact after moderate SCI. Mechanistically, the activation of microglia and p38 MAP kinase in L5 cord predicted allodynia. Tumor necrosis factor-α and interluekin-1β¿¿¿¿ increased in the L5 dorsal horn by 7 dpo and interleukin-6 was elevated chronically. These data suggest that remote microglial activation is pivotal in SCI-induced allodynia. Fractalkine, a microglial activator, and astrocytes were not primary modulators of pain. Finally, we showed supraspinal processing of below-level stimuli occurs after moderate SCI using functional MRI and somatosensory evoked potentials (SSEP). SSEPs delineated pain-specific delays in S1 cortical depolarization. Importantly, we show that fMRI captures cortic (open full item for complete abstract)

Committee: D. Michele Basso (Advisor); John A. Buford (Committee Member); Lyn B. Jakeman (Committee Member); Deborah S. Larsen (Committee Member); Phillip G. Popovich (Committee Member) Subjects: Behaviorial Sciences; Biomedical Research

Doctor of Philosophy, The Ohio State University, 2004, Biomedical Engineering

The purpose of the study was to design and engineer a novel microdevice, a microgrid electrode array, that can further biomedical engineering research in the areas of neuroscience and neurology. Microfabrication techniques were developed to create the microdevice, which is capable of measuring electrical activity on the surface of the cerebral cortex at a greater level of spatial resolution than currently available for surface electrode grids. The device has been designed to detect the activity of individual cortical columns. Although penetrating microelectrodes are capable of detecting this level of detail, their invasiveness limits their use to human cortical tissue destined for surgical resection or strictly to animal studies. The development of a less-invasive non-penetrating microgrid electrode array suitable for human use would provide medical scientists with a unique and powerful tool for detailed brain mapping, gaining a better understanding of human cortical column function, as well as for exploring diseases and therapy options associated with the cerebral cortex. The fabrication protocol included several standard photolithography steps and many novel chemical and encapsulation methods. Characterization of the fabrication protocol steps and testing of the electrical connection integrity was performed using Scanning Electron Microscopy (SEM), optical microscopy, profilometery, and a microprobe station. Cyto-compatibility testing of the microgrid electrode with mammalian and human cortical cells consisted of qualitative and quantitative analyses. Evaluation with a porcine animal model consisted of collecting Visual Evoked Potentials (VEPs) from the primary visual cortex. Results from characterization of the fabrication process revealed that the desired geometries of the device were achieved. The resulting microgrid consisted of an array of surface contacts (200-micron platinum squares with bi-directional pitch of 400 microns) suspended in an insulating polydi (open full item for complete abstract)

Committee: Derek Hansford (Advisor) Subjects: Engineering, Biomedical

Master of Arts, Miami University, 2008, Speech Pathology and Audiology

Over 800 athletes suffer from concussion in the United States each day, resulting in over 300,000 concussions each year. Recent data has revealed that the incidence of mild traumatic brain injury is on the rise for many different sports, placing athletes at higher risk. Damage is caused by the shearing of axons, which results in swelling and loss of limited function. Electrophysiologic techniques, specifically event-related potentials are one of the most frequently used cognitive assessments. Event-related potentials are a non-invasive method to gather a baseline of cognitive processes and to evaluate cognitive deficits. The current study investigated the sensitivity of event-related potentials in the identification of cognitive deficits following concussion in college athletes. Neuropsychological and electrophysiological measures were collected from two groups of participants allocated by injury versus non-injury. Results from the study found important differences between non-concussed and concussed athletes using electrophysiological measures and neuropsychological test measures.

Committee: Kathleen Hutchinson PhD (Committee Chair); Fofi Constantinidou PhD (Committee Member); J Brett Massie EdD (Committee Member) Subjects: Cognitive Therapy; Communication; Speech Therapy; Sports Medicine

Doctor of Philosophy (Ph.D.), Bowling Green State University, 2006, Psychology/Experimental

Medial prefrontal cortex (mPFC) is a crucial region involved in inhibitory processes. Damage to mPFC leads to loss of normal inhibitory control over motor, sensory, emotional and cognitive functions. The present study was designed to examine basic properties, influence of aversive conditioning, and neuropharmacology of inhibitory gating in mPFC. Inhibitory gating is a neurophysiological assay for sensory filters in higher brain regions that potentially enable or disable information throughput. This perspective has important clinical relevance due to findings that gating is dramatically impaired in individuals with emotional and cognitive impairments (i.e., in schizophrenia, PTSD, and drug abuse). In the present research, single-units and local field potentials (LFPs) were measured using chronic microwire arrays implanted in rat mPFC. The stability of gating was first examined using paired tone tests in short-term (within session) and long-term (between session) analyses of auditory gating. LFPs displayed reduction in amplitudes of tone responses and increase of gating over both short and long-term time windows. A variety of single-unit responses retained similar levels of auditory responsiveness and inhibition in both short and long-term analysis. Next, altering the interval between tones in each tone-pair influenced the potency of inhibition. Neural inhibition decreased monotonically related to the increase in intertone interval for both LFPs and single-units. The influence of fear conditioning was investigated by administering 30 footshock pairings with tones similar to those normally used to test gating. Inhibitory gating of LFPs weakened, and animals' orienting behavior to tones increased after, compared to before, the session of footshock and tone pairings. Systemic neuropharmacological manipulations were used to investigate effects of dopamine and GABA neurotransmitter systems on inhibitory gating of LFPs in mPFC. For effects of dopaminergic manipulations, the (open full item for complete abstract)

Committee: Howard Cromwell (Advisor) Subjects:

PhD, University of Cincinnati, 2013, Allied Health Sciences: Communication Sciences and Disorders

The field of Bioacoustics is an emerging field of science that investigates various aspects of animal audiology and communication. More recently, audiological means have been used to evaluate the cognitive abilities of animals using event related brain potentials (ERP's). The Mismatch Negativity (MMN) component of the ERP is considered a cognitive neuroelectric phenomenon since it is generated in the area of the cortex that is responsible for evaluating sound stimuli including the ability to discriminate. Such discrimination produces a negative-going waveform with a relative latency of about 150-250 msec when elicited with auditory stimuli in human adults. The MMN response is elicited by use of the oddball paradigm in which two different tones are presented in pseudo-random order. The purpose of this study was to determine if elicitation of the MMN is achievable in the horse by use of current equipment in a non-clinical setting such as a barn. During the course of this experiment, it became obvious that the major challenge was the excessive amount of noise that inundated the waveforms thereby making any specific waves even remotely discernible. Attempts were made to improve the signal-to-noise ratio (SNR) by modifications to the testing unit and the addition of several in-line and digital filters. However, even with these modifications, the MMN response still could not be identifiable within the noise of the waveforms. Therefore, the matter of whether or not the horse elicits a MMN response should be revised to if it is even feasible to elicit a MMN response in these animals.

Committee: Peter Scheifele Ph.D. (Committee Chair); Jennifer Wells DVM (Committee Member); John Clark Ph.D. (Committee Member) Subjects: Animals

Doctor of Philosophy (PhD), Ohio University, 2013, Biological Sciences (Arts and Sciences)

Fatigue is an expected and normal physiologic reaction to intense and to sustained activity. As fatigue develops during sustained isometric submaximal contractions, the amount of excitatory descending drive from supraspinal regions to the spinal motorneuron pool increases to compensate for the decline in spinal excitability by recruiting additional motor units in order to prolong task performance. However, despite the compensatory mechanisms from supraspinal inputs, task failure remains inevitable. Therefore, it remains largely unknown whether supraspinal mechanisms that could alter the amount of descending drive, including changes in motor cortex excitability and voluntary drive upstream to the motor cortex, also contribute to task failure. The focus of this dissertation research was to delineate the specific contributions that supraspinal circuits have in determining the time to task failure. Experiment 1 compared adjustments in multiple neurophysiologic measures of supraspinal and spinal excitability taken throughout the performance of two different fatigue tasks (i.e. force-matching and position-matching) to determine the functional significance of the changes to task duration. Although no task-specific differences were found, task failure occurred for both tasks after a similar mean decline in motorneuron excitability developed coupled with a similar mean increase in corticospinal excitability. Additionally, the amount of intracortical inhibition dropped while the amount of intracortical facilitation and upstream excitation of the motor cortex remained unchanged. Together the data for these two tasks indicate that, in general, the motor cortex is able to compensate for changes in spinal excitability until a critical amount of change in both regions develops. This suggests that unless more drive is provided to the motor cortex to sustain or strengthen the descending drive, failure occurs. Experiment 2 examined whether delivering anodal transcranial direct (open full item for complete abstract)

Committee: Brian Clark PhD (Advisor); Thad Wilson PhD (Committee Member); Robert Staron PhD (Committee Member); Roger Gilders PhD (Committee Chair) Subjects: Neurology; Neurosciences; Physiology; Rehabilitation