This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Using PET-CT to target and validate low-frequency TMS as treatment for Tinnitus Aim 1. Determine if low-frequency rTMS improves tinnitus by decreasing cortical activity in the primary auditory cortex. If increased cortical activity contributes to the perception of tinnitus, then decreasing activity should alleviate tinnitus. PET-CT scans will be used to visualize increased cortical activity in patients with tinnitus and guide the application of rTMS. rTMS will then be optimized by identifying the area of maximal tinnitus suppression during repeated 1-Hz rTMS stimulation of the area localized on PET-CT and applying treatment to this more targeted area. Repeat scans following a course of rTMS will be used to determine if treatment response (perceived tinnitus) relates to change in cortical activation. We also propose to develop an electrical scalp stimulation technique to mimic muscle twitching during low-frequency sham rTMS to more accurately simulate a placebo control.
Aim 2. Determine if asymmetric cortical activation promotes attentional disturbance (variability) in patients with tinnitus. If asymmetric activation promotes response variability, restoring symmetry via rTMS should reduce variability. The classic method for assessing attentional processes is a simple, not choice, RT task. The Psychomotor Vigilance Task (PVT), used in our preliminary work, provides quantitative assessment of multiple factors in RT tasks. RT measures will be used to assess change in attentional vigilance before and after rTMS. Cortical asymmetries on PET will be correlated with response time variability and perceived tinnitus.
Aim 3. Determine if rTMS treatment promotes lasting improvement in tinnitus patients. All patients will be reassessed at 3 and 6 months post-rTMS on behavioral measures (RT) and questionnaires. In addition, the 5 best and 5 worst responders, based on perceived tinnitus at 6 months, will also have a repeat PET-CT at 6 months and a repeat of all assessments, including PET-CT, at 12 months.Novel Studies on Sites of Action and Mechanisms in Balance DysfunctionSpecific Aim 1. Investigate the role of the ascending Reticular Activating System (RAS). We will measure the output of the RAS, i.e. pre-attentional/arousal processes, using the sleep state-dependent P50 midlatency auditory evoked potential, whose amplitude is a measure of level of arousal, and whose habituation to repetitive stimuli is a measure of sensory gating, the process behind distractibility.
Specific Aim 2. Investigate thalamo-cortical processing. We will assess attentional processing using the Psychomotor Vigilance Task (PVT), a measure of simple (not choice) reaction time, and evaluate the patients ability to sustain attention and respond in a timely manner to salient signals. We will test the participants ability to select a specified stimulus from two or more choice stimuli presented by using the Continuous Performance Task (CPT) which is a standardized clinical measure of attention, reaction time, and distractibility.
Specific Aim 3. Investigate cortical function. We will measure relative frontal lobe blood flow using Near Infrared Spectroscopy (NIRS) before and during performance of the P50 and PVT tasks to assess changes in relative blood flow to cortical regions involved in critical judgment, which are impaired in depression and other psychiatric disorders. Additionally, we will administer the Wisconsin Card Sorting Task (WCST) to access human frontal lobe function and to measure the participants ability to shift attention from one category to another (set-shifting) with no warning using a trial and error paradigm. We will use the Operant Test Battery (OTB) to evaluate the higher cognitive functions of short-term memory, time estimation, and learning.This design will allow us to determine at which level of the neuraxis (brainstem-thalamus, thalamo-cortical, and/or cortical) patients with balance disorders manifest quantitative physiological deficits. By localizing the level of the neuraxis affected, we can develop more informed therapies that may selectively alleviate pre-attentional, attentional, and/or cognitive deficits. The proposed research will provide answers to the following questions: Do patients with balance disorders show differential changes in P50 potential amplitude, i.e. level of arousal? Do these patients show differential changes in P50 potential habituation, i.e. sensory gating? Do they show differences in mean reaction time, number of lapses, or other measures of simple attentional mechanisms? Do they show differences in higher cognitive function as evidenced by performance accuracies and latencies in short-term memory, time perception, and learning tasks? Do they show differences in relative frontal lobe blood flow before (i.e. continuous hypofrontality) and/or during (i.e. task-related) the performance of an attentional task? Quantitative physiological investigation of these potential neurological substrates for balance disorders represents a novel, comprehensive program of research with great promise for developing innovative therapies for this condition.
|Odle, Angela; Allensworth-James, Melody; Childs, Gwen V (2018) The War on the Placenta: The Differing Battles of High-Fat Diet and Obesity. Endocrinology 159:1642-1643|
|MacNicol, Melanie C; Cragle, Chad E; McDaniel, F Kennedy et al. (2017) Evasion of regulatory phosphorylation by an alternatively spliced isoform of Musashi2. Sci Rep 7:11503|
|Rhee, Christopher J; Kaiser, Jeffrey R; Rios, Danielle R et al. (2016) Elevated Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants. J Pediatr 174:52-6|
|Odle, Angela Katherine; Allensworth-James, Melody; Haney, Anessa et al. (2016) Adipocyte Versus Somatotrope Leptin: Regulation of Metabolic Functions in the Mouse. Endocrinology 157:1443-56|
|Gannon, Brenda M; Williamson, Adrian; Suzuki, Masaki et al. (2016) Stereoselective Effects of Abused ""Bath Salt"" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation. J Pharmacol Exp Ther 356:615-23|
|Rhee, Christopher J; Kibler, Kathleen K; Easley, R Blaine et al. (2016) The Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants. Acta Neurochir Suppl 122:147-50|
|Odle, Angela K; Allensworth-James, Melody L; Akhter, Noor et al. (2016) A Sex-Dependent, Tropic Role for Leptin in the Somatotrope as a Regulator of POU1F1 and POU1F1-Dependent Hormones. Endocrinology 157:3958-3971|
|Rhee, Christopher J; Fraser 3rd, Charles D; Kibler, Kathleen et al. (2015) Ontogeny of cerebrovascular critical closing pressure. Pediatr Res 78:71-5|
|Odle, Angela K; Drew, Paul D; Childs, Gwen V (2015) Giant mice reveal new roles for GH in regulating the adipose immune microenvironment. Endocrinology 156:1613-5|
|MacNicol, Angus M; Hardy, Linda L; Spencer, Horace J et al. (2015) Neural stem and progenitor cell fate transition requires regulation of Musashi1 function. BMC Dev Biol 15:15|
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