Neuroscience and Neurobiology Commons^™

Optical Perturbation Of Protein Kinase A Activity Via Photoactivatable Inhibitor Peptides, Peter Chen

McKelvey School of Engineering Theses & Dissertations

Protein Kinase A (PKA) plays important roles in diverse biological processes such as sleep, long term memory, and synaptic plasticity. In addition, PKA also acts as an integrator of neuromodulator signaling though G protein-coupled receptor activation. However, despite genetic knockout and pharmacological inhibition experiments that demonstrate the importance of PKA, it is unclear where, when, or how PKA plays these roles in cellular physiology and behavior. In order to better understand the function of PKA in these processes, and how neuromodulator signaling drives complex behavioral changes, there exists a need for a method to selectively activate/inactivate PKA with high spatial …

Preparing Non-Human Primates To Study Hand-Eye Coordination In Frontal Eye Fields (Fef) During Delayed Movement Task, Juliusz Cydzik

McKelvey School of Engineering Theses & Dissertations

ABSTRACT OF THE THESIS Preparing Non-Human Primates to Study Hand-Eye Coordination in Frontal Eye Fields (FEF) During Delayed Movement Task by Juliusz Cydzik Master of Science in Biomedical Engineering Washington University in St. Louis, 2023 Professor Lawrence Snyder, Chair Hand-eye coordination enables humans and non-human primates to use their hands and eyes to perform various tasks. We are interested in coordination at the systems level, where saccades and reaches are encoded. The parietal reach region (PRR), situated at the posterior end of the intraparietal sulcus (IPS) and overlapping portions of the medial intraparietal area (MIP) and V6a, is commonly attributed …

Mechanisms Of Primate Working Memory, Charles Damian Holmes

McKelvey School of Engineering Theses & Dissertations

One of the defining features of the behavior of many animal species is the ability to retain and utilize information from the environment even after it is gone. The encoding and utilization of information on short time scales is referred to as working memory. It is not yet fully understood how the brain accomplishes working memory.

This dissertation presents three studies that help to characterize the working memory system of primates. All three studies involve primates performing saccades during a spatial memory task. The first study demonstrates that while the local field potential power is contralaterally tuned (i.e., power is …

Development Of Noninvasive Biomarkers For Cervical Spondylotic Myelopathy, Dinal Jayasekera

McKelvey School of Engineering Theses & Dissertations

Cervical spondylotic myelopathy (CSM) represents the most common cause of chronic spinal cord injury (SCI) in adults. Many patients with symptomatic CSM will experience a decline in neurological function and consequently undergo surgical decompression. Unfortunately, surgeons are unable to adequately counsel patients about the benefits of surgery because the natural history of disease and outcome after decompression vary widely among patients. This can hinder the decision-making capacity of patients and physicians. Therefore, we require additional tools to help guide therapy and counsel patients with CSM. Noninvasive biomarkers present valuable potential as predictors of a patient’s recovery in the long term. …

Anti-Amyloid Chimeric Antigen Receptor Macrophages For Alzheimer's Disease Immunotherapy, Qiuyun Pan

McKelvey School of Engineering Theses & Dissertations

Alzheimer’s disease is the most common cause of dementia. None of the available drugs can cure the disease. Chimeric Antigen Receptor (CAR) macrophages, because of their phagocytic activity, have potential as a cellular treatment for amyloid aggregation. In this study, we generated an anti-amyloid CAR hematopoietic progenitor cell line. By inducing the progenitor cell line to differentiate into macrophages, we show that the anti-amyloid CAR-Macrophage has enhanced specific phagocytic activity towards amyloid in in vitro experiments. In addition, in ex vivo experiments, anti-amyloid CAR significantly reduces the plaque load on brain slice from APP/PS1 mice when compared to a non-targeted …

Towards The Discovery Of Prognostic Biomarkers For Glioblastoma Using Resting-State Functional Connectivity, Andy G. S. Daniel

McKelvey School of Engineering Theses & Dissertations

Gliomas are highly diffusive, primary brain tumors. The most malignant form, glioblastoma, has a dismal survival rate: 14-17 months following the current standard of care, which consists of surgery, radiation, and chemotherapy. Insights into the molecular, cellular, and microenvironmental components of glioblastoma have revealed a vast array of factors utilized to support its proliferation, infiltration, and resistance to treatment. Recent advancements have also identified diagnostic and prognostic biomarkers that are now being used to guide treatment planning. However, survival has improved only marginally, thus emphasizing the continued need for novel biomarkers and treatment strategies. Given its delicate location in the …

Elucidating And Leveraging Dynamics-Function Relationships In Neural Circuits Through Modeling And Optimal Control, Sruti Mallik

McKelvey School of Engineering Theses & Dissertations

A fundamental research question in neuroscience pertains to understanding how neural networks through their activity encode and decode information. In this research, we build on methods from theoretical domains such as control theory, dynamical systems analysis and reinforcement learning to investigate such questions. Our objective is two-fold: first, to use methods from engineering to identify specific objectives that neural circuits might be optimizing through their spatiotemporal activity patterns, and second, to draw motivation from neuroscience to formulate new engineering principles such as synthesis of dynamical networks for decentralized control applications. We specifically take a top-down, optimization driven approach in our …

Long-Term Neural Activity Recorders Using Energy-Based Sensing, Compressive Computation And Data Logging, Darshit Mehta

McKelvey School of Engineering Theses & Dissertations

Insects are ideal candidates for developing bio-robotic systems owing to their ability to thrive in almost any environment. For example, neurons in their exquisite olfactory sensory systems can be tapped to create a sensing platform for standoff chemical monitoring. However, for enabling such cyborg systems, it is vital that the neural activity of a freely behaving organism can be measured for long periods of time. The current state-of-the-art neural recording techniques are power-intensive and they either need batteries, which make them too bulky for insects, or they have to maintain a continuous telemetry link to an external power source which …

Cortical Organization In Humans And Nonhuman Primates: The Evolution Of Cognitive Areas And Circuits, Chad Joseph Donahue

McKelvey School of Engineering Theses & Dissertations

Similarities in organization of cerebral cortex in humans and nonhuman primates offer the promise of leveraging data from invasive animal studies to better understand the complexities of the human brain, particularly those related to higher cognitive function (e.g. attention, working memory, language). Such comparisons necessitate the identification of convincing cortical homologues (areas or regions presumed to have derived from a common ancestor), requiring an accurate interspecies mapping of cortical areas and features. To this end, I describe (i) a survey of connectivity and its measures across primate species, particularly retrograde tracing and diffusion tractography, (ii) a morphometric analysis of cognitive …

Neural Dynamics, Adaptive Computations, And Sensory Invariance In An Olfactory System, Srinath Nizampatnam

McKelvey School of Engineering Theses & Dissertations

Sensory stimuli evoke spiking activities that are patterned across neurons and time in the early processing stages of olfactory systems. What features of these spatiotemporal neural response patterns encode stimulus-specific information (i.e. ‘neural code’), and how they are translated to generate behavioral output are fundamental questions in systems neuroscience. The objective of this dissertation is to examine this issue in the locust olfactory system. In the locust antennal lobe (analogous to the vertebrate olfactory bulb), a neural circuit directly downstream to the olfactory sensory neurons, even simple stimuli evoke neural responses that are complex and dynamic. We found each odorant …

Neural Coding And Organization Principles In The Drosophila Olfactory System, Haoyang Rong

McKelvey School of Engineering Theses & Dissertations

Sensory systems receive and process external stimuli to allow an organism to perceive and react to the environment. How is sensory information subsequently represented, transformed, and interpreted in the neural system? In this dissertation, I have investigated this fundamental question using the fruit fly (Drosophila melanogaster) olfactory system.Chemical cues are transduced into neural signals in the insect antenna by the olfactory receptor neurons (ORNs). The ORNs send their axons to the antennal lobe (AL), with each ORN type innervating a specific neuropil (glomerulus), where they synapse onto excitatory and inhibitory projection neurons (ePNs and iPNs). The ePNs project their axons …

Constructing And Analyzing Neural Network Dynamics For Information Objectives And Working Memory, Elham Ghazizadeh Ahsaei

McKelvey School of Engineering Theses & Dissertations

Creation of quantitative models of neural functions and discovery of underlying principles of how neural circuits learn and compute are long-standing challenges in the field of neuroscience. In this work, we blend ideas from computational neuroscience, information and control theories with machine learning to shed light on how certain key functions are encoded through the dynamics of neural circuits. In this regard, we pursue the ‘top-down’ modeling approach of engineering neuroscience to relate brain functions to basic generative dynamical mechanisms. Our approach encapsulates two distinct paradigms in which ‘function’ is understood. In the first part of this research, we explore …

Transdiagnostic Multimodal Neural Correlates Of Psychosis Dimensions, Dov Bernard Lerman-Sinkoff

McKelvey School of Engineering Theses & Dissertations

Psychosis refers to a debilitating set of symptoms that impacts individuals, their communities, and society at large. Current psychiatric nosology treats psychosis as a categorical construct. However, recent evidence suggests that a dimensional approach that cuts across extant nosological boundaries may more accurately represent the underlying phenomena contributing to dysfunction in psychosis. One putative domain of transdiagnostic variation is cognitive control, a construct that refers to the set of functions that enable and support goal-directed behavior and regulation of one’s thoughts and actions. Previous analyses in both healthy individuals and individuals with psychosis have led to a number of findings …

A Microfluidic Platform To Investigate The Mechanism By Which Gdnf Overexpression In Schwann Cells Causes Neuronal Axon Entrapment, Ze Zhong Wang

McKelvey School of Engineering Theses & Dissertations

Twenty million Americans suffer from peripheral nerve injury (PNI) caused by trauma and medical disorders, with approximately $150 billion spent in annual health-care dollars in the United States. Even with proper surgical reconstruction, less than 50% of the patients achieve satisfactory functional recovery. The gold standard surgical repair for long gaps (>3cm) is the autologous nerve graft, despite its disadvantages such as donor site morbidity, risk of infection, and increased cost. Alternative methods, such as acellular nerve grafts (ANA), are ineffective for large lesion gaps because of the lack of cells and regeneration factors. Recent efforts have been focused …

Dynamics And Control In Spiking Neural Networks, Fuqiang Huang

McKelvey School of Engineering Theses & Dissertations

In the brain, neurons (brain cells) produce electrical impulses, or spikes, that are thought to be the substrate of information processing and computation. Through enigmatic processes, these spikes are ultimately decoded into perceptions and actions. The nature of this encoding and decoding is one of the most pervasive questions in theoretical neuroscience. In other words, what are the specific functions enacted by neural circuits, through their biophysics and dynamics? This thesis examines the dynamics of neural networks from the perspective of control theory and engineering. The pivotal concept is that of the normative synthesis of neural circuits, wherein neural dynamics …

Approaches To Understanding The Function Of Intrinsic Activity And Its Relationship To Task-Evoked Activity In The Human Brain, Dohyun Kim

McKelvey School of Engineering Theses & Dissertations

Traditionally neuroscience research has focused on characterizing the topography and patterns of brain activation evoked by specific cognitive or behavioral tasks to understand human brain functions. This activation-based paradigm treated underlying spontaneous brain activity, a.k.a. intrinsic activity, as noise hence irrelevant to cognitive or behavioral functions. This view, however, has been profoundly modified by the discovery that intrinsic activity is not random, but temporally correlated at rest in widely distributed spatiotemporal patterns, so called resting state networks (RSN). Studies of temporal correlation of spontaneous activity among brain regions, or functional connectivity (FC), have yielded important insights into the network organization …

Elucidating The Roles Of Astrocyte-Derived Factors In Recovery And Regeneration Following Spinal Cord Injury, Russell E. Thompson

McKelvey School of Engineering Theses & Dissertations

Central nervous system (CNS) injury often causes some level of long-term functional deficit, due to the limited regenerative potential of the CNS, that results in a decreased quality of life for patients. CNS regeneration is inhibited partly by the development of a glial scar following insult that is inhibitory to axonal growth. The major cell population responsible for the formation this glial scar are astrocytes, which has led to the belief that astrocytes are primarily inhibitory following injury. Recent work has challenged this conclusion, finding that astrocyte reactivity is heterogeneous and that some astrocytes are pro-regenerative following injury. Astrocyte transplantation …

Coupled Correlates Of Attention And Consciousness, Ravi Varkki Chacko

McKelvey School of Engineering Theses & Dissertations

Introduction: Brain Computer Interfaces (BCIs) have been shown to restore lost motor function that occurs in stroke using electrophysiological signals. However, little evidence exists for the use of BCIs to restore non-motor stroke deficits, such as the attention deficits seen in hemineglect. Attention is a cognitive function that selects objects or ideas for further neural processing, presumably to facilitate optimal behavior. Developing BCIs for attention is different from developing motor BCIs because attention networks in the brain are more distributed and associative than motor networks. For example, hemineglect patients have reduced levels of arousal, which exacerbates their attentional deficits. More …

Exploiting Click-Chemistry And Microfluidics To Map The Neuronal Itinerary Of App Processing And Amyloid-Beta Generation, Namratha Srinivas

McKelvey School of Engineering Theses & Dissertations

Alzheimer’s disease (AD) is a chronic neurodegenerative disease and is the sixth leading cause of death in the United States with approximately 5.5 million Americans diagnosed with it. The neuropathological hallmark includes extracellular senile plaques and intraneuronal neurofibrillary tangles. Recent GWAS studies have identified genes associated with AD, and have revealed several classes of genes implicated in disease pathogenesis. In particular, three general pathways associated with an increased risk of AD included: 1) cholesterol metabolism, innate immune system, and the membrane trafficking. Our lab has focused on intracellular trafficking as it relates to the processing of amyloid precursor protein (APP), …

Functional Electrical Stimulation Of Peripheral Nerve Tissue Via Regenerative Sieve Microelectrodes, Matthew Reagan Macewan

McKelvey School of Engineering Theses & Dissertations

Functional electrical stimulation (FES) of peripheral nervous tissue offers a promising method for restoring motor function in patients suffering from complex neurological injuries. However, existing microelectrodes designed to stimulate peripheral nerve are unable to provide the type of stable, selective interface required to achieve near-physiologic control of peripheral motor axons and distal musculature. Regenerative sieve electrodes offer a unique alternative to such devices, achieving a highly stable, selective electrical interface with independent groups of regenerated nerve fibers integrated into the electrode. Yet, the capability of sieve electrodes to functionally recruit regenerated motor axons for the purpose of muscle activation remains …

Multiscale Imaging Of The Mouse Cortex Using Two-Photon Microscopy And Wide-Field Illumination, Jonathan Richard Bumstead

McKelvey School of Engineering Theses & Dissertations

The mouse brain can be studied over vast spatial scales ranging from microscopic imaging of single neurons to macroscopic measurements of hemodynamics acquired over the majority of the mouse cortex. However, most neuroimaging modalities are limited by a fundamental trade-off between the spatial resolution and the field-of-view (FOV) over which the brain can be imaged, making it difficult to fully understand the functional and structural architecture of the healthy mouse brain and its disruption in disease. My dissertation has focused on developing multiscale optical systems capable of imaging the mouse brain at both microscopic and mesoscopic spatial scales, specifically addressing …

Mechanics Of The Developing Brain: From Smooth-Walled Tube To The Folded Cortex, Kara Ellspermann Garcia

McKelvey School of Engineering Theses & Dissertations

Over the course of human development, the brain undergoes dramatic physical changes to achieve its final, convoluted shape. However, the forces underlying every cinch, bulge, and fold remain poorly understood. This doctoral research focuses on the mechanical processes responsible for early (embryonic) and late (preterm) brain development.

First, we examine early brain development in the chicken embryo, which is similar to human at these stages. Research has primarily focused on molecular signals to describe morphogenesis, but mechanical analysis can also provide important insights. Using a combination of experiments and finite element modeling, we find that actomyosin contraction is responsible for …

Characterization Of Structural Dynamics Of The Human Head Using Magnetic Resonance Elastography, Andrew Arun Badachhape

McKelvey School of Engineering Theses & Dissertations

In traumatic brain injury (TBI), the skull-brain interface, composed of three meningeal layers: the dura mater, arachnoid mater, and pia mater, along with cerebrospinal fluid (CSF) between the layers, plays a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is a noninvasive imaging modality capable of providing in vivo estimates of tissue motion and material properties. The objective of this work is to augment human and phantom MRE studies to better characterize the mechanical contributions of the skull-brain interface to improve the parameterization and validation of computational models of TBI. Three specific aims …

Extrinsic And Intrinsic Control Of Integrative Processes In Neural Systems, Anirban Nandi

McKelvey School of Engineering Theses & Dissertations

At the simplest dynamical level, neurons can be understood as integrators. That is, neurons accumulate excitation from afferent neurons until, eventually, a threshold is reached and they produce a spike. Here, we consider the control of integrative processes in neural circuits in two contexts. First, we consider the problem of extrinsic neurocontrol, or modulating the spiking activity of neural circuits using stimulation, as is desired in a wide range of neural engineering applications. From a control-theoretic standpoint, such a problem presents several interesting nuances, including discontinuity in the dynamics due to the spiking process, and the technological limitations associated with …

Robust Odorant Recognition In Biological And Artificial Olfaction, Nalin Katta

McKelvey School of Engineering Theses & Dissertations

Accurate detection and identification of gases pose a number of challenges for chemical sensory systems. The stimulus space is enormous; volatile compounds vary in size, charge, functional groups, and isomerization among others. Furthermore, variability arises from intrinsic (poisoning of the sensors or degradation due to aging) and extrinsic (environmental: humidity, temperature, flow patterns) sources. Nonetheless, biological olfactory systems have been refined over time to overcome these challenges. The main objective of this work is to understand how the biological olfactory system deals with these challenges, and translate them to artificial olfaction to achieve comparable capabilities. In particular, this thesis focuses …

Developing An In Vitro Assay For Detection And Characterization Of Functional Connectivity Within Transplantation Candidate Embryonic Stem Cell-Derived V2a Interneuron Networks, Jeffrey Robert Gamble

McKelvey School of Engineering Theses & Dissertations

Facilitating plasticity after spinal cord injury tends to be the focus of most modern interventions for this condition. In particular, stem cell therapies attempt to both modulate and mimic some of the native plasticity after injury through multiple mechanisms. One such mechanism, the creation of new exogenous relay circuits bridging the injury, has been explored extensively, revealing serious impediments to its optimization and adoption for clinical settings. Our collaborator, the Sakiyama-Elbert group, has spent years addressing the first limitation, the variability of cellular graft composition, by perfecting protocols to generate embryonic stem cell (ESC)-derived populations of neurons with pre-determined genetic …

Development And Investigation Of Sparse Co-Adaptive Algorithms In Ecog Based Closed-Loop Brain Computer Interface, Piyush Karande

McKelvey School of Engineering Theses & Dissertations

Electrocorticography (ECoG) has gained a lot of momentum and has become a serious contender as a recording modality for the implementation of Brain-Computer Interface (BCI) systems in the last few years. ECoG signals provide the right balance between minimal invasiveness and robust spectral information to accomplish a BCI task. However, all the BCI studies until now have used signals recorded from a large number of implanted electrodes and a larger number of spectral features. The recording and processing of these signals uses a lot of electrical power and thus hinders its use outside the research setting. To translate this research …

Lesion Identification And The Effect Of Lesion On Motor Mapping After Stroke, Ruixi Zhou

McKelvey School of Engineering Theses & Dissertations

Stroke is the most common cause of long-term severe disability and the motor system that is most commonly affected in stroke. One of the mechanisms that underlies recovery of motor deficits is reorganization or remapping of functional representations around the motor cortex. This mechanism has been shown in monkeys, but results in human subjects have been variable. In this thesis, I used a database that includes longitudinal behavioral and multimodal imaging data in both stroke patients and healthy controls for two research projects. Firstly, I improved an automatic lesion segmentation method to aid in the identification of the location and …