Neuroscience and Neurobiology Commons^™

Editorial: Roles Of Sleep Disruption And Circadian Rhythm Alterations On Neurodegeneration And Alzheimer's Disease, Marilyn J. Duncan, Sigrid C. Veasey, Phyllis Zee

Neuroscience Faculty Publications

No abstract provided.

Altered Theta Rhythm And Hippocampal-Cortical Interactions Underlie Working Memory Deficits In A Hyperglycemia Risk Factor Model Of Alzheimer’S Disease, Ryan A. Wirt, Lauren A. Crew, Andrew A. Ortiz, Adam M. Mcneela, Emmanuel Flores, Jefferson W. Kinney, James M. Hyman

Integrated Health Sciences Faculty Research

Diabetes mellitus is a metabolic disease associated with dysregulated glucose and insulin levels and an increased risk of developing Alzheimer’s disease (AD) later in life. It is thought that chronic hyperglycemia leads to neuroinflammation and tau hyperphosphorylation in the hippocampus leading to cognitive decline, but effects on hippocampal network activity are unknown. A sustained hyperglycemic state was induced in otherwise healthy animals and subjects were then tested on a spatial delayed alternation task while recording from the hippocampus and anterior cingulate cortex (ACC). Hyperglycemic animals performed worse on long delay trials and had multiple electrophysiological differences throughout the task. We …

Anti-Angiogenic Effects Of Chemotherapeutic Agents And Their Enhancement With Ot-515 And S-Nach, Shimaa Adel Heikal

Theses and Dissertations

Chemotherapeutic agents have been used for the treatment of numerous types of tumors with great success. Cisplatin and Doxorubicin are among the well-known chemotherapeutic drugs that showed efficacy against various types of cancers. However, cell resistance and major side effects like chemotherapy-induced peripheral neuropathy (CIPN) are limiting factors in using these compounds. Using a combination or adjuvant compounds with anti-angiogenic effects is one of the strategies suggested to decrease resistance or ameliorate chemotherapeutic toxicity. The present study investigated the anti-angiogenic effects of Cisplatin and Doxorubicin alone and combined with Sulfated non-anticoagulant heparin (S-NACH), a low molecular weight heparin LMWH that …

Distress Tolerance As A Mechanism Linking Violence Exposure To Problematic Alcohol Use In Adolescence, Charlotte Heleniak, China R. Bolden, Connor J. Mccabe, Hilary K. Lambert, Maya L. Rosen, Kevin M. King, Kathryn C. Monahan, Katie A. Mclaughlin

Neuroscience: Faculty Publications

Adolescents exposed to violence are at elevated risk of developing most forms of psychopathology, including depression, anxiety, and alcohol abuse. Prior research has identified emotional reactivity and difficulties with emotion regulation as core mechanisms linking violence exposure with psychopathology. Scant research has examined behavioral responses to distress as a mechanism in this association. This study examined the association of violence exposure with distress tolerance—the ability to persist in the face of distress—and whether lower distress tolerance linked violence exposure with subsequent increases in depression, anxiety, and alcohol abuse problems during adolescence. Data were collected prospectively in a sample of 287 …

Odor-Evoked Increases In Olfactory Bulb Mitral Cell Spiking Variability, Cheng Ly, Andrea K. Barreiro, Shree Hari Gautam, Woodrow L. Shew

Physics Faculty Publications and Presentations

The spiking variability of neural networks has important implications for how information is encoded to higher brain regions. It has been well documented by numerous labs in many cortical and motor regions that spiking variability decreases with stimulus onset, yet whether this principle holds in the OB has not been tested. In stark contrast to this common view, we demonstrate that the onset of sensory input can cause an increase in the variability of neural activity in the mammalian OB. We show this in both anesthetized and awake rodents. Furthermore, we use computational models to describe the mechanisms of this …

Validation Of A Single Channel Eeg For The Athlete: A Machine Learning Protocol To Accurately Detect Sleep Stages, Kayla Thompson, Kamil Celoch, Frankie Pizzo, Ana I. Fins, Jaime Tartar

Journal for Sports Neuroscience

There is a large and growing movement towards the use of wearable technologies for sleep assessment. This trend is largely due to the desire for comfortable, burden free, and inexpensive technology. In tandem, given the competitive nature of professional athletes enduring high training load, sleep is often jeopardized which can result in adverse outcomes. Wearable devices hold the promise of increasing the ease of monitoring sleep in athletes which can inform health and recovery status, as well as aid performance optimization. However, wearable devices typically lack sufficient validity to assess sleep – and especially sleep stages. To address this concern, …

Investigating The Computations Underlying Complex Motor Skill Learning, Christopher S. Yang

Link Foundation Modeling, Simulation and Training Fellowship Reports

In order for a person to learn a new skill from scratch such as riding a bike or playing the piano, their brain must generate a new motor controller (a policy which maps one’s goal and current state to movements) that can perform this task, a process known as de novo learning. Despite the important role that de novo learning plays in acquiring motor skills, very little is understood about this learning process as the motor learning community has largely focused on investigating how existing skills are recalibrated, a process known as adaptation. In the present project, I designed an …

Estrogen Modulation Of Vta Dopamine Neuron Physiology And Behavioral Responsivity To Variable Social Stressors, Mary R. Shanley

Dissertations, Theses, and Capstone Projects

The behavioral output of different animals, or even the same animal in different contexts, is remarkably variable in response to the same external stimulus. This behavioral diversity is due to the complex integration of external and internal stimuli, through both neuronal and hormonal signals that selects the best behavioral response. By their nature as long-distance signaling molecules, hormones play a critical role in communicating information about internal states across the organism. Many hormones produced in the periphery target the central nervous system to modulate animal behavior, selecting for behaviors that are appropriate over behaviors that are maladaptive in that specific …

Apathy And Brain Atrophy During The First Year Of Moderate-Severe Traumatic Brain Injury: A Longitudinal Study, Gulnaz Kudoiarova

Dissertations, Theses, and Capstone Projects

Apathy, defined as disinterest and loss of motivation, is a common complication after moderate-severe traumatic brain injury (msTBI). The existing body of research in various neurological and neurodegenerative disorders suggests that apathetic symptoms may be associated with variation in the volume of the brain regions such as dorsal anterior cingulate cortex and ventral striatum. However, the longitudinal pattern of TBI-induced atrophy in these key regions and its relationship with apathy symptoms remain to be demonstrated. The current study aimed to describe the atrophy pattern in the anterior cingulate gyrus (ACG) and the nucleus accumbens (NAc; part of ventral striatum) after …

Analysis Of Transplantable Photoreceptor Replacement Cell Chemotactic Mechanisms In Retinal Biomimetic Ligand Gradients, Onyekwere Onwumere

Dissertations, Theses, and Capstone Projects

Disease or trauma induced loss of rod and cone photoreceptors is a major cause of vision loss worldwide. To replace lost photoreceptors and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal injection of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). A major obstacle in the field is that transplanted photoreceptor replacement cells exhibit extremely limited migration into host retina following injection into the subretinal space. In this work, we show that PPCs and host retinal interaction bioinformatics modeling can identify key pathways involved in photoreceptor replacement cell migration and invasion behaviors. In addition, …

A Randomized Controlled Trial Of Psychological Outcomes Of Mobile Guided Resonant Frequency Breathing In Young Adults With Elevated Stress During The Covid-19 Pandemic, Al Amira Safa Shehab

Dissertations, Theses, and Capstone Projects

Deep breathing practices have shown promise in reducing stress, anxiety, and depression in different populations, including young adults. Specifically, resonant frequency breathing can exert an impact on stress response systems through the vagus nerve and the hypothalamo-pituitary-adrenal (HPA) axis. This may induce reductions in stress and improvement in emotion regulation. Young adults, including college students, tend to be at a higher risk for psychological distress, as they face several psychosocial challenges. The COVID-19 pandemic has imposed new and unique stressors that resulted in higher levels of stress and emotional symptoms and it has been shown that this may have placed …

Working Memory Task Performance In Children With Sli: A Behavioral And Erp Study, Megan V. Mcveety

Dissertations, Theses, and Capstone Projects

In addition to language deficits, children with Specific Language Impairment often show deficits in tests of various aspects of working memory, including capacity, updating, and selective attention. The purpose of the present study is to examine the specific drivers of differences in working memory processing in 8–11 year-old children with and without SLI using behavioral and electrophysiological measures. Participants completed an n-back task with three working memory load conditions (0-back, 1-back, 2-back), with the addition of distractor trials at the 1-back and 2-back levels. The SLI group performed significantly less accurately across all task conditions. The children with SLI also …

Contributions Of Reward Identity And Time Prediction Errors To Pavlovian Learning, Daniel B. Siegel

Dissertations, Theses, and Capstone Projects

Some models of associative learning attempt to explain effects such as blocking and unblocking as reflecting a prediction error (PE): Associative strength, and thereby learning, are said to be greater when the unconditioned stimulus (US) received following a cue deviates from one’s expectations. Some models of PE-motivated behavior and PE-relevant brain activity represent the US as a single quantitative variable for outcome value, and that learning therefore only occurs when outcome value differs from expectations. There is growing evidence to suggest that changes in other dimensions of reward, such as identity and timing, also contribute to learning. In Experiment 1, …

Desire, Culture, And The Body, Zoey Lavallee

Dissertations, Theses, and Capstone Projects

What is the nature of desire? In this dissertation I develop a theory of desire according to which desires are essentially enculturated states that play the role of presenting favorable outcomes that act as inputs to intention formation, and thereby intentional action. This analysis of desire debunks a common assumption shared by prominent accounts of desire in philosophy of mind, what can be called the dualist assumption: that bodily desires such as urges and appetites differ in kind from conceptual desires that are typically described as higher cognitive attitudes. I argue that the desires traditionally understood as bodily or appetitive …

Investigation Of Notch Signaling In Cone Fate Specification In Vertebrate Retina, Xueqing Chen

Dissertations, Theses, and Capstone Projects

In the vertebrate retina, cone photoreceptors are crucial for high acuity color vision. Several retinal diseases lead to loss of cones and there is a need to identify the normal developmental genesis of these cells to inform the development of stem cell-based therapies. Cone genesis has previously been shown to be repressed by Notch signaling, however, the mechanism by which Notch signaling controls cone fate determination is still unclear. It has been identified that cone photoreceptors are formed from multipotent retinal progenitor cells (RPCs) that first generate genetically-defined, restricted RPCs with limited mitotic and fate potential to preferentially form cones …

The New Age Of Christian Healing Ministry And Spirituality: A Meta-Synthesis Exploring The Efficacy Of Christian-Adapted Complementary Therapies For Adult Survivors Of Familial Trauma, Amanda Lynne Brees

Doctoral Dissertations and Projects

Adult survivors of familial trauma present with many seemingly unrelated psychiatric and relational issues well into adulthood. Developmental and familial trauma is emerging in the research as a subset of complex posttraumatic stress disorder (C-PTSD). This specific type of trauma is rooted in attachment and family systems theory. Issues such as divorce, parental substance abuse, mental illness, enmeshment, parentification, abandonment, and abuse get passed down intergenerationally in vicious cycles until someone finds the courage to heal. Pastoral counselors are uniquely equipped to lead the third wave of cognitive-behavioral therapies proving effective in treating complex trauma includes mindfulness and complementary therapies …

Do Environmental Toxins Predict Violent Crimes?, Tyler Stahl

Symposium of Student Scholars

Do chemical pollutants that persistent in the environment and bioaccumulate in the body affect human health and behavior? Could these Persistent, Bioaccumulative, and Toxic (PBT) chemicals play a role in the cause of violent crimes due to deterioration of mental and cognitive functions? In the past, Mercury, a PBT chemical, has been shown in salmon to be associated with aggression. Could similar aggression occur in humans exposed to mercury through a toxic spill? Two sources of data are utilized in this analysis. The Environmental Protection Agency’s (EPA) Annual Toxic Release Inventory publishes data on toxic releases into the environment and …

Towards Understanding The Role Of Central Processing In Release From Masking, Nima Alamatsaz

Dissertations

People with normal hearing have the ability to listen to a desired target sound while filtering out unwanted sounds in the background. However, most patients with hearing impairment struggle in noisy environments, a perceptual deficit which current hearing aids and cochlear implants cannot resolve. Even though peripheral dysfunction of the ears undoubtedly contribute to this deficit, surmounting evidence has implicated central processing in the inability to detect sounds in background noise. Therefore, it is essential to better understand the underlying neural mechanisms by which target sounds are dissociated from competing maskers. This research focuses on two phenomena that help suppress …

Alcohol As A Catalyst For Hiv-Associated Neuroinflammation And Tbi-Induced Iron Toxicity, Agnieszka Agas

Dissertations

Alcohol has long been considered an exacerbator of diseases, disorders, and injuries as well as many of the accompanying symptoms. As an alternative approach, this dissertation explores alcohol as a catalyst for two different human disease conditions, human immunodeficiency virus (HIV)-associated neuroinflammation and traumatic brain injury (TBI)-induced iron toxicity. In HIV-1 infection, this dissertation presents a novel anti-viral drug, called Drug-S, for a possible inhibition and treatment of HIV-1 disease progression.

The first aim explores the influence of alcohol with HIV-associated neuroinflammation on macrophage migration across an in vitro model of the blood brain barrier. There is a gap in …

The Amyloid-Β Pathway In Alzheimer’S Disease, Harald Hampel, John Hardy, Kaj Blennow, Christopher Chen, George Perry, Seung Hyun Kim, Victor L. Villemagne, Paul Aisen, Michele Vendruscolo, Takeshi Iwatsubo, Colin L. Masters, Min Cho, Lars Lannfelt, Jeffrey L. Cummings, Andrea Vergallo

School of Medicine Faculty Research

Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer’s disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-temporal dynamics leading to synaptic failure, neurodegeneration, and clinical onset are still under intense investigation, the established biochemical alterations of the Aβ cycle remain the core biological hallmark of AD and are promising targets for the development of disease-modifying therapies. Here, we systematically review and update the vast state-of-the-art literature of Aβ science with evidence from basic research studies to human genetic and multi-modal biomarker investigations, which supports a crucial role of …

A Compact 1200 V, 700 A, Igbt-Based Pulse Generator For Repetitive Transcranial Magnetic Stimulation In Vivo Laboratory Experiments On Small Animals, Daniel Senda, Haley Strong, Dustin Hines, Rochelle Hines, R. Jacob Baker

Psychology Faculty Research

An insulated-gate bipolar transistor (IGBT) pulse generator for repetitive transcranial magnetic stimulation used for in vivo laboratory experiments on small animals, such as mice, is reported. The pulse generator is based upon an IGBT that can switch 700 A of current for 1 ms and that has a DC breakdown voltage of 1200 V. The duration of the design’s output pulse is controlled by, and follows, an input trigger pulse. The voltage amplitude of the output pulses is determined by an external high-voltage power supply and the energy stored in a 330 µF capacitor bank. The approach enables the amplitude …

Blood–Brain Barrier Breakdown And Astrocyte Reactivity Evident In The Absence Of Behavioral Changes After Repeated Traumatic Brain Injury, Celeste Dunn, Nasya Sturdivant, Sara Venier, Syed Ali, Jeffery Wolchok, Kartik Balachandran

Biomedical Engineering Faculty Publications and Presentations

Repeated traumatic brain injuries (TBIs) cause debilitating effects. Without understanding the acute effects of repeated TBIs, treatment options to halt further degeneration and damage cannot be developed. This study sought to examine the acute effects of blood–brain barrier (BBB) dysfunction, edema, inflammation and behavioral changes after either a single or double TBI using a C57BL/6 mouse model. We examined the effects of one or two TBIs, of either a mild or moderate severity. Double injuries were spaced 7 days apart, and all analysis was performed 24 h post-injury. To examine edema and inflammation, protein levels of glial fibrillary acidic protein …

Vitamin D Modulates Rett Syndrome Phenotypes And Underlying Cellular Pathways In An Mecp2-Mutant Mouse Model, Mayara De Cassia Ribeiro

Dissertations - ALL

Rett syndrome (RTT) is a progressive and severe X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MECP2. There is currently no effective treatment for RTT. Female RTT patients develop relatively normally during the first 6-18 months of life, after which they undergo a period of rapid regression, losing the ability to talk, walk and purposefully use their hands, in addition to suffering from deceleration of head growth, and onset of repetitive, autistic behaviors. RTT symptoms can be partially reversed by the re-expression of Mecp2 in adult mice, suggesting the potential for post-symptomatic therapeutic intervention. Among the many dysfunctions …

Estimating Progression Rates Across The Spectrum Of Alzheimer’S Disease For Amyloid-Positive Individuals Using National Alzheimer’S Coordinating Center Data, Michele Potashman, Marric Buessing, Mihaela Levitchi Benea, Jeffrey Cummings, Soo Borson, Peter Pemberton-Ross, Andrew J. Epstein

School of Medicine Faculty Research

Introduction: Published estimates of Alzheimer’s disease (AD) progression do not capture the full disease continuum. This study provides transition probabilities of individuals with amyloid-β (Aβ+) pathology across the disease continuum. Methods: Patient-level longitudinal data from the National Alzheimer’s Coordinating Center were used to estimate progression rates. Progression rates through five clinically defined AD stages—asymptomatic, mild cognitive impairment due to AD (MCI-AD), mild AD dementia, moderate AD dementia, severe AD dementia—and death were measured as transition probabilities. Rates were assessed in “incident” patients who recently entered the stage, controlling for covariates. Transition probabilities were generated from multinomial logit regression models that …

Virtual Reality (Vr)-Based Environmental Enrichment In Older Adults With Mild Cognitive Impairment (Mci) And Mild Dementia, Waleed Riaz, Zain Yar Khan, Ali Jawaid, Suleman Shahid

Medical College Documents

Background: Despite an alarming rise in the global prevalence of dementia, the available modalities for improving cognition and mental wellbeing of dementia patients remain limited. Environmental enrichment is an experimental paradigm that has shown promising anti-depressive and memory-enhancing effects in pre-clinical studies. However, its clinical utility has remained limited due to the lack of effective implementation strategies.
Objective: The primary objective of this study was to evaluate the usability (tolerability and interactivity) of a long-term virtual reality (VR)- based environmental enrichment training program in older adults with mild cognitive impairment (MCI) and mild dementia. A secondary objective was to assess …

Altering Sensory Learning By Chronic Inactivation Of Vip Interneurons, Christopher Alba, Hannah Selwyn, Katie Ferguson, Jessica Cardin

The Yale Undergraduate Research Journal

Vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) play a key role in the regulation of cortical circuits and are implicated in perceptual function and psychiatric disease. However, their role in perceptual augmentation and learning remains understudied. We performed chronic, localized ablation of VIP-INs in the primary visual cortex of adult mice using caspase-induced apoptosis to better understand how VIP-INs contribute to visual perception and the ability to learn a visual detection task. We find that chronic VIP-IN ablation does not affect naïve performance on a full-screen visual contrast detection task. However, mice with suppressed levels of VIP-INs achieved their final expert state …

Dimensionality Reduction For Classification Of Object Weight From Electromyography, Elnaz Lashgari, Uri Maoz

Psychology Faculty Articles and Research

Electromyography (EMG) is a simple, non-invasive, and cost-effective technology for measuring muscle activity. However, multi-muscle EMG is also a noisy, complex, and high-dimensional signal. It has nevertheless been widely used in a host of human-machine-interface applications (electrical wheelchairs, virtual computer mice, prosthesis, robotic fingers, etc.) and, in particular, to measure the reach-and-grasp motions of the human hand. Here, we developed an automated pipeline to predict object weight in a reach-grasp-lift task from an open dataset, relying only on EMG data. In doing so, we shifted the focus from manual feature-engineering to automated feature-extraction by using pre-processed EMG signals and thus …

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

McKelvey School of Engineering Graduate Student 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 …

Positron Emission Tomography From 1930 To 1990: The Epistemology And Process Of Scientific Instrumentation, Rick Shang

Arts & Sciences Graduate Student Theses and Dissertations

Positron Emission Tomography (PET) is a groundbreaking detection system that, among many other applications, enabled neuroscience researchers to detect and image physiological changes in the brain associated with cognitive operations as subjects perform a task. This technology helped researchers learn to explore the physiological basis of human cognition in new ways and was the immediate forerunner of functional Magnetic Resonance Imaging (fMRI), a technology that continues to dominate the neurosciences. PET was also the founding invention of a new field of cognitive science: human functional neuroimaging. Indeed, some would say that PET encouraged a particular way of understanding the brain …

The Disunity Of Perception, Benjamin Austin Henke

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation argues for disunity in perceptual processing: rather than outputting to a single ‘centralized’ cognitive system, separate perceptual processing pathways produce different person-level representations for different purposes. I argue that this disunity has important implications for abstract theorizing in the philosophy and cognitive science of perception, for experimental methodology, and for our understanding of the normative role of perception itself. The first three chapters explore models in cognitive neuroscience which support perceptual disunity. In Chapter 1, I argue that a version of Milner and Goodale’s (2006) influential ‘two visual streams hypothesis’ survives its recent empirical challenges. In Chapter 2, …