Matching Items (17)

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Do Pupillometry and the P3 Event-Related Potential Reflect Locus Coeruleus-Norepinephrine System Activity in Humans?

Description

The locus coeruleus-norepinephrine system (LC-NE) has been argued to play a vital role in task engagement and attention control by the adaptive gain theory (Aston-Jones & Cohen, 2005). One of

The locus coeruleus-norepinephrine system (LC-NE) has been argued to play a vital role in task engagement and attention control by the adaptive gain theory (Aston-Jones & Cohen, 2005). One of the central claims of this theory is that tonic LC activity exhibits a quadratic relationship with task performance. Pupil dynamics have been correlated to LC-NE activity via primate intracranial recordings in ways that provide evidence for the adaptive gain theory. Due to the small size and location of the LC, less is known about LC functioning in humans, leading to a desire to find valid, noninvasive psychophysiological proxies to study this structure. In this paper we performed a replication of Murphy, Robertson, Balsters, & O’Connell (2011) to gather evidence on whether pupil fluctuations and the P3 event-related potential are viable markers for measuring tonic and phasic LC-NE activity in humans. A sample of 33 subjects from the Arizona State University human subjects pool provided usable electroencephalogram and pupillometry data collected during an auditory oddball task. Our analyses largely correspond with those found in Murphy et al. (2011) showing some evidence that pupillometry and P3 can be utilized when studying the LC. Moving forward we will reproduce the full set of analyses from Murphy et al. (2011) with our dataset.

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Date Created
  • 2020-05

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Specificity of Auditory Modulation during Speech Planning

Description

Previous research has showed that auditory modulation may be affected by pure tone
stimuli played prior to the onset of speech production. In this experiment, we are examining the
specificity

Previous research has showed that auditory modulation may be affected by pure tone
stimuli played prior to the onset of speech production. In this experiment, we are examining the
specificity of the auditory stimulus by implementing congruent and incongruent speech sounds in
addition to non-speech sound. Electroencephalography (EEG) data was recorded for eleven adult
subjects in both speaking (speech planning) and silent reading (no speech planning) conditions.
Data analysis was accomplished manually as well as via generation of a MATLAB code to
combine data sets and calculate auditory modulation (suppression). Results of the P200
modulation showed that modulation was larger for incongruent stimuli than congruent stimuli.
However, this was not the case for the N100 modulation. The data for pure tone could not be
analyzed because the intensity of this stimulus was substantially lower than that of the speech
stimuli. Overall, the results indicated that the P200 component plays a significant role in
processing stimuli and determining the relevance of stimuli; this result is consistent with role of
P200 component in high-level analysis of speech and perceptual processing. This experiment is
ongoing, and we hope to obtain data from more subjects to support the current findings.

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Date Created
  • 2020-05

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White Matter Integrity After Traumatic Brain Injury: Corpus Callosum

Description

Abstract White matter thickness correlates with various mental illness. Commissure white matter tracts are responsible for interconnecting the same cortical area in both hemispheres. Injury to the brain can result

Abstract White matter thickness correlates with various mental illness. Commissure white matter tracts are responsible for interconnecting the same cortical area in both hemispheres. Injury to the brain can result in thinning and shrinkage even collapsing and detachment of the white matter tracts' myelin sheaths. Injury can affect cognitive function and time points are essential for therapeutic intervention. Research is beginning to identify gradual long-term neurodegenerative effects. With the advancement of brain imaging technology, we know that Wallerian degeneration has a significant negative impact on the white matter tracts throughout the brain (Johnson, Stewart, & Smith, 2013). If major tracts become injured like, the corpus callosum, then it can affect interhemispheric communication. Once myelin is damaged the axon becomes vulnerable, and the mechanisms of nerve recovery are not well known. Myelin sheath recovery has been studied in hopes to proliferate the oligodendrocytes that make up for the atrophied myelin. Neurotoxic chemicals released at activation of macrophages which hinders the brains ability to proliferate myelin protein needed for myelin differentiation adequately. In the central nervous system myelin has mechanisms to recover. Neurogenesis is a naturally occurring recovery mechanism seen after brain injury. Understanding the time points in which brain recovery occurs is important for treatment of diffuse injuries that cannot be identified through some imaging techniques. To better understand critical timepoints of natural recovery after brain injury can allow further investigation for early intervention to promote adequate recovery.

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Date Created
  • 2018-12

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Time-Lapse Visualization of Microglia Cell Processes using Fluorescent Miniature (Miniscope) Imaging

Description

In the United States, an estimated 2 million cases of traumatic brain injury (TBI) resulting in more than 50,000 deaths occur every year. TBI induces an immediate primary injury resulting

In the United States, an estimated 2 million cases of traumatic brain injury (TBI) resulting in more than 50,000 deaths occur every year. TBI induces an immediate primary injury resulting in local or diffuse cell death in the brain. Then a secondary injury occurs through neuroinflammation from immune cells in response to primary injury. Microglia, the resident immune cell of the central nervous system, play a critical role in neuroinflammation following TBI. Microglia make up 10% of all cells in the nervous system and are the fastest moving cells in the brain, scanning the entire parenchyma every several hours. Microglia have roles in both the healthy and injured brain. In the healthy brain, microglia can produce neuroprotective factors, clear cellular debris, and organize neurorestorative processes to recover from TBI. However, microglia mediated neuroinflammation during secondary injury produces pro-inflammatory and cytotoxic mediators contributing to neuronal dysfunction, inhibition of CNS repair, and cell death. Furthermore, neuroinflammation is a prominent feature in many neurodegenerative diseases such as Alzheimer’s, and Parkinson’s disease, of which include overactive microglia function. Microglia cell morphology, activation, and response to TBI is poorly understood. Currently, imaging microglia can only be performed while the animal is stationary and under anesthesia. The Miniscope technology allows for real-time visualization of microglia in awake behaving animals. The Miniscope is a miniature fluorescent microscope that can be implanted over a craniectomy to image microglia. Currently, the goals of Miniscope imaging are to improve image quality and develop time-lapse imaging capabilities. There were five main sub-projects that focused on these goals including surgical nose cone design, surgical holder design, improved GRIN lens setup, improved magnification through achromatic lenses, and time-lapse imaging hardware development. Completing these goals would allow for the visualization of microglia function in the healthy and injured brain, elucidating important immune functions that could provide new strategies for treating brain diseases.

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Date Created
  • 2019-05

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Understanding the processing of degraded speech: electroencephalographic measures as a surrogate for recovery from concussion

Description

The recent spotlight on concussion has illuminated deficits in the current standard of care with regard to addressing acute and persistent cognitive signs and symptoms of mild brain injury. This

The recent spotlight on concussion has illuminated deficits in the current standard of care with regard to addressing acute and persistent cognitive signs and symptoms of mild brain injury. This stems, in part, from the diffuse nature of the injury, which tends not to produce focal cognitive or behavioral deficits that are easily identified or tracked. Indeed it has been shown that patients with enduring symptoms have difficulty describing their problems; therefore, there is an urgent need for a sensitive measure of brain activity that corresponds with higher order cognitive processing. The development of a neurophysiological metric that maps to clinical resolution would inform decisions about diagnosis and prognosis, including the need for clinical intervention to address cognitive deficits. The literature suggests the need for assessment of concussion under cognitively demanding tasks. Here, a joint behavioral- high-density electroencephalography (EEG) paradigm was employed. This allows for the examination of cortical activity patterns during speech comprehension at various levels of degradation in a sentence verification task, imposing the need for higher-order cognitive processes. Eight participants with concussion listened to true-false sentences produced with either moderately to highly intelligible noise-vocoders. Behavioral data were simultaneously collected. The analysis of cortical activation patterns included 1) the examination of event-related potentials, including latency and source localization, and 2) measures of frequency spectra and associated power. Individual performance patterns were assessed during acute injury and a return visit several months following injury. Results demonstrate a combination of task-related electrophysiology measures correspond to changes in task performance during the course of recovery. Further, a discriminant function analysis suggests EEG measures are more sensitive than behavioral measures in distinguishing between individuals with concussion and healthy controls at both injury and recovery, suggesting the robustness of neurophysiological measures during a cognitively demanding task to both injury and persisting pathophysiology.

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Created

Date Created
  • 2014

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Practical therapies for diffuse traumatic brain injury in the mouse: translational considerations

Description

Approximately 2.8 million Americans seek medical care for traumatic brain injury (TBI) each year. Of this population, the majority are sufferers of diffuse TBI, or concussion. It is unknown how

Approximately 2.8 million Americans seek medical care for traumatic brain injury (TBI) each year. Of this population, the majority are sufferers of diffuse TBI, or concussion. It is unknown how many more individuals decline to seek medical care following mild TBI. This likely sizeable population of un- or self-treated individuals combined with a lack of definitive biomarkers or objective post-injury diagnostics creates a unique need for practical therapies among diffuse TBI sufferers. Practical therapies stand to decrease the burden of TBI among those who would otherwise not seek treatment or do not meet clinical diagnostic criteria upon examination. For this unique treatment niche, practical therapies for TBI are defined as having one or more of the following qualities: common availability, easy administration, excellent safety profile, and cost-effectiveness. This dissertation identifies and critically examines the efficacy of four classes of practical treatments in improving rodent outcome from experimental diffuse traumatic brain injury.

Over-the-counter (OTC) analgesics, omega-3 fatty acids, specialized pro-resolving mediators (SPMs), and remote ischemic conditioning (RIC) were administered before or following midline fluid percussion injury. Behavioral, histological, and molecular analyses were used to assess treatment effects on functional outcome and secondary injury progression. Acute administration of common OTC analgesics had little effect on post-injury outcome in mice. Dietary supplementation with omega-3 fatty acid docosahexaenoic acid (DHA) prior to or following diffuse TBI significantly reduced injury-induced sensory sensitivity and markers of neuroinflammation with no effect on spatial learning. Intraperitoneal administration of omega-3 fatty acid-derived SPM resolvin E1 significantly increased post-injury sleep and suppressed microglial activation. Aspirin-triggered (AT) resolvin D1 administration improved both motor and cognitive outcome following diffuse TBI. RIC treatment in mice demonstrated little effect on functional outcome from diffuse TBI. Untargeted proteomic analysis of plasma samples from RIC-treated mice was used to identify candidate molecular correlates of RIC. Identification of these candidates represents a vital first step in elucidating the neuroprotective mechanisms underlying RIC. The overall findings suggest that omega-3 fatty acid supplementation, SPM administration, and RIC may serve as effective practical therapies to reduce the somatic, cognitive, and neurological burden of diffuse TBI felt by millions of Americans.

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Created

Date Created
  • 2017

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Manifestation of higher-order cognitive processing deficits resulting from concussion

Description

Concussion, a subset of mild traumatic brain injury (mTBI), has recently been brought to the forefront of the media due to a large lawsuit filed against the National Football League.

Concussion, a subset of mild traumatic brain injury (mTBI), has recently been brought to the forefront of the media due to a large lawsuit filed against the National Football League. Concussion resulting from injury varies in severity, duration, and type, based on many characteristics about the individual that research does not presently understand. Chronic fatigue, poor working memory, impaired self-awareness, and lack of attention to task are symptoms commonly present post-concussion. Currently, there is not a standard method of assessing concussion, nor is there a way to track an individual's recovery, resulting in misguided treatment for better prognosis. The aim of the following study was to determine patient specific higher-order cognitive processing deficits for clinical diagnosis and prognosis of concussion. Six individuals (N=6) were seen during the acute phase of concussion, two of whom were seen subsequently when their symptoms were deemed clinically resolved. Subjective information was collected from both the patient and from neurology testing. Each individual completed a task, in which they were presented with degraded speech, taxing their higher-order cognitive processing. Patient specific behavioral patterns are noted, creating a unique paradigm for mapping subjective and objective data for each patient's strategy to compensate for deficits and understand speech in a difficult listening situation. Keywords: concussion, cognitive processing

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Created

Date Created
  • 2013

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Fully passive wireless acquisition of neuropotentials

Description

The ability to monitor electrophysiological signals from the sentient brain is requisite to decipher its enormously complex workings and initiate remedial solutions for the vast amount of neurologically-based disorders. Despite

The ability to monitor electrophysiological signals from the sentient brain is requisite to decipher its enormously complex workings and initiate remedial solutions for the vast amount of neurologically-based disorders. Despite immense advancements in creating a variety of instruments to record signals from the brain, the translation of such neurorecording instrumentation to real clinical domains places heavy demands on their safety and reliability, both of which are not entirely portrayed by presently existing implantable recording solutions. In an attempt to lower these barriers, alternative wireless radar backscattering techniques are proposed to render the technical burdens of the implant chip to entirely passive neurorecording processes that transpire in the absence of formal integrated power sources or powering schemes along with any active circuitry. These radar-like wireless backscattering mechanisms are used to conceive of fully passive neurorecording operations of an implantable microsystem. The fully passive device potentially manifests inherent advantages over current wireless implantable and wired recording systems: negligible heat dissipation to reduce risks of brain tissue damage and minimal circuitry for long term reliability as a chronic implant. Fully passive neurorecording operations are realized via intrinsic nonlinear mixing properties of the varactor diode. These mixing and recording operations are directly activated by wirelessly interrogating the fully passive device with a microwave carrier signal. This fundamental carrier signal, acquired by the implant antenna, mixes through the varactor diode along with the internal targeted neuropotential brain signals to produce higher frequency harmonics containing the targeted neuropotential signals. These harmonics are backscattered wirelessly to the external interrogator that retrieves and recovers the original neuropotential brain signal. The passive approach removes the need for internal power sources and may alleviate heat trauma and reliability issues that limit practical implementation of existing implantable neurorecorders.

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Date Created
  • 2014

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Variations in Menopause Etiology Affect Cognitive Outcomes: How Age, Menopause Type, and Exogenous Ovarian Hormone Exposures Across the Lifespan Impact the Trajectory of Brain Aging

Description

Reproductive hormones are recognized for their diverse functions beyond reproduction itself, including a vital role in brain organization, structure, and function throughout the lifespan. From puberty to reproductive senescence, the

Reproductive hormones are recognized for their diverse functions beyond reproduction itself, including a vital role in brain organization, structure, and function throughout the lifespan. From puberty to reproductive senescence, the female is characterized by inherent responsiveness to hormonal cyclicity. For most women, a natural transition to menopause occurs in midlife, wherein the endogenous hormonal milieu undergoes significant changes and marks the end of the reproductive life stage. Although most women experience natural menopause, many women will undergo gynecological surgery during their lifetime, which can lead to an abrupt surgical menopause. It is of critical importance to better understand how endogenous and exogenous reproductive hormone exposures across the lifespan influence cognitive and brain aging, as women are at a greater risk for developing a variety of diseases after menopause, including dementia. Using rodent models, this dissertation explores how the etiology of reproductive senescence, that is, whether it is transitional or surgical, influences the female phenotype to result in divergent cognitive outcomes dependent upon a variety of factors, with an emphasis on age at the time of intervention playing a key role in brain outcomes. Furthermore, the impact of exogenous hormone therapy on cognition is evaluated in the context of surgical menopause. A novel rat model of hysterectomy is also presented, with results demonstrating for the first time that the nonpregnant uterus, which is typically considered to be a quiescent organ, may play a unique, direct role in modulating cognitive outcomes. Neurobiological mechanisms associated with reproductive hormones and aging are assessed to better recognize neural correlates underlying the observed behavior changes. The overarching goal of this dissertation was to elucidate novel factors contributing to cognitive aging outcomes in females. Collectively, the data presented herein indicate that the age at the onset of reproductive senescence has significant implications for learning and memory outcomes, and that variations in gynecological surgery can have unique, long-lasting effects on the brain and cognition. Translationally, this series of experiments moves the field forward toward the goal of improving the health and quality of life for women throughout the lifespan.

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Created

Date Created
  • 2019

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Multi-parametric MRI Study of Brain Insults (Traumatic Brain Injury and Brain Tumor) in Animal Models

Description

The objective of this small animal pre-clinical research project was to study quantitatively the long-term micro- and macro- structural brain changes employing multiparametric MRI (Magnetic Resonance Imaging) techniques. Two separate

The objective of this small animal pre-clinical research project was to study quantitatively the long-term micro- and macro- structural brain changes employing multiparametric MRI (Magnetic Resonance Imaging) techniques. Two separate projects make up the basis of this thesis. The first part focuses on obtaining prognostic information at early stages in the case of Traumatic Brain Injury (TBI) in rat animal model using imaging data acquired at 24-hours and 7-days post injury. The obtained parametric T2 and diffusion values from DTI (Diffusion Tensor Imaging) showed significant deviations in the signal intensities from the control and were potentially useful as an early indicator of the severity of post-traumatic injury damage. DTI was especially critical in distinguishing between the cytotoxic and vasogenic edema and in identification of injury regions resolving to normal control values by day-7. These results indicate the potential of quantitative MRI as a clinical marker in predicting prognosis following TBI. The second part of this thesis focuses on studying the effect of novel therapeutic strategies employing dendritic cell (DC) based vaccinations in mice glioma model. The treatment cohorts included comparing a single dose of Azacytidine drug vs. mice getting three doses of drug per week. Another cohort was used as an untreated control group. The MRI results did not show any significant changes in between the two treated cohorts with no reduction in tumor volumes compared to the control group. The future studies would be focused on issues regarding the optimal dose for the application of DC vaccine. Together, the quantitative MRI plays an important role in the prognosis and diagnosis of the above mentioned pathologies, providing essential information about the anatomical location, micro-structural tissue environment, lesion volume and treatment response.

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Created

Date Created
  • 2014