Neurosciences Commons^™

Equal-Magnitude Size-Weight Illusions Experienced Within And Between Object Categories., Gavin Buckingham, Melvyn A Goodale, Justin A White, David A Westwood

Brain and Mind Institute Researchers' Publications

In the size-weight illusion (SWI), small objects feel heavier than larger objects of the same mass. This effect is typically thought to be a consequence of the lifter's expectation that the large object will outweigh the small object, because objects of the same type typically get heavier as they get larger. Here, we show that this perceptual effect can occur across object category, where there are no strong expectations about the correspondence between size and mass. One group of participants lifted same-colored large and small cubes with the same mass as one another, while another group lifted differently-colored large and …

Working Memory Training And Speech In Noise Comprehension In Older Adults., Rachel V Wayne, Cheryl Hamilton, Julia Jones Huyck, Ingrid S Johnsrude

Brain and Mind Institute Researchers' Publications

Understanding speech in the presence of background sound can be challenging for older adults. Speech comprehension in noise appears to depend on working memory and executive-control processes (e.g., Heald and Nusbaum, 2014), and their augmentation through training may have rehabilitative potential for age-related hearing loss. We examined the efficacy of adaptive working-memory training (Cogmed; Klingberg et al., 2002) in 24 older adults, assessing generalization to other working-memory tasks (near-transfer) and to other cognitive domains (far-transfer) using a cognitive test battery, including the Reading Span test, sensitive to working memory (e.g., Daneman and Carpenter, 1980). We also assessed far transfer to …

Medial Prefrontal And Anterior Insular Connectivity In Early Schizophrenia And Major Depressive Disorder: A Resting Functional Mri Evaluation Of Large-Scale Brain Network Models., Jacob Penner, Kristen A Ford, Reggie Taylor, Betsy Schaefer, Jean Théberge, Richard W J Neufeld, Elizabeth A Osuch, Ravi S Menon, Nagalingam Rajakumar, John M Allman, Peter C Williamson

Brain and Mind Institute Researchers' Publications

Anomalies in the medial prefrontal cortex, anterior insulae, and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD). In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed-based resting state functional magnetic resonance imaging analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients with …

The Semantic Memory Imaging In Late Life Pilot Study, Michael Adam Sugarman

Wayne State University Dissertations

Introduction: Several functional magnetic resonance imaging (fMRI) studies have analyzed the famous name discrimination task (FNDT), an uncontrolled semantic memory probe requiring discrimination between famous and unfamiliar individuals. Completion of this simple task recruits a semantic memory network that has shown utility in determining risk for Alzheimer's disease (AD). Specific semantic memory probes using biographical information associated with famous individuals may build on previous findings and yield superior information regarding risk for AD.

Method: Sixteen cognitively intact elders completed the FNDT and two novel tasks during fMRI: Categories (matching famous individuals to occupational categories) and Attributes (matching famous individuals to …

Cognitive, Psychiatric, And Neuropathological Manifestations Of Repetitive Mild Traumatic Brain Injury, Denise Briggs

Wayne State University Dissertations

Millions of athletes participate in contact sports that involve repeated head impacts (e.g., football, ice hockey, boxing), often from a very young age, and it is feared that subsequent impacts can synergize with previous ones so that their effects on the brain become magnified. Repetitive mild traumatic brain injury (rmTBI) has been linked to the development of chronic traumatic encephalopathy (CTE). The neurodegeneration accompanying CTE occurs over many years following repeated head impacts and is characterized by progressive brain atrophy, accumulation of hyper-phosphorylated tau and aggregates of TDP-43, myelinated axonopathy, neuroinflammation and degeneration of white matter tracts. The relationship between …

An Analysis Of Virtual Place Learning/Navigation In Children And Young Adults Prenatally Exposed To Alcohol, Neil Christopher Dodge

Wayne State University Dissertations

Fetal alcohol spectrum disorder refers to the spectrum of disorders resulting from prenatal alcohol exposure and is the leading cause of preventable mental retardation. Rodent studies have found that prenatal alcohol exposure impairs performance on the Morris water maze. This task requires the rodent to use distal room cues to locate a hidden platform in a pool of opaque water. Successful performance on this task is dependent upon hippocampal function. Rodents prenatally exposed to alcohol are impaired on the Morris water maze and show damage to hippocampal neurons. A human analogue of the Morris water maze, the virtual water maze …

Childhood Trauma And Emotion Processing Neurocircuitry, Hilary A. Marusak

Wayne State University Dissertations

Childhood trauma is one of the strongest risk factors for a range of common and debilitating neuropsychiatric disorders, including anxiety, depression, and posttraumatic stress disorder (PTSD). These emotion-related disorders have their roots in childhood and adolescence, underscoring a critical need to understand their biological bases in early life. In this dissertation, we evaluate how childhood trauma impacts emotion processing neurocircuitry in a sample of high-risk urban youth, ages 7-15. In four inter-related studies, we test neural function and functional connectivity of core emotion processing regions, including the amygdala, insula, and pregenual/subgenual anterior cingulate cortex (pgACC/sgACC). To examine the relevance of …

Identification Of Metabolite Biomarkers In Epilepsy Using 1h Mrs, Helen Wu

Wayne State University Dissertations

Epilepsy is a serious neurological disorder that affects 1% percent of the global population. Despite its status as one of the oldest neurological disorders known to man, its mechanisms remain poorly understood. Available medications are not curative but provide symptomatic management and do not work for well for more than 30 percent of patients. Because it is nearly impossible to predict on an individual level who will eventually develop epilepsy, it is also a disorder that can only be diagnosed after the patient has experienced established seizure activity, eliminating any possibility of stopping the disorder in its prodromal phase, before …

A Urinary Metabolic Signature For Multiple Sclerosis And Neuromyelitis Optica, Teklab Gebregiworgis, Helle H. Nielsen, Chandirasegara Massilamany, Arunakumar Gangaplara, Jay Reddy, Zsolt Illes, Robert Powers

Jay Reddy Publications

Urine is a metabolite-rich biofluid that reflects the body’s effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. For illustration of the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses, 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum …

The Mixed Lineage Kinase-3 Inhibitor Urmc-099 Improves Therapeutic Outcomes For Long-Acting Antiretroviral Therapy., Gang Zhang, Dongwei Guo, Prasanta Dash, Mariluz Araínga, Jayme Wiederin, Nicole A. Haverland, Jaclyn Knibbe-Hollinger, Andrea Martinez-Skinner, Pawel Ciborowski, Val S. Goodfellow, Tadeusz A. Wysocki, Beata J. Wysocki, Larisa Y. Poluektova, Xin-Ming Liu, Joellyn Mcmillan, Santhi Gorantla, Harris A. Gelbard, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

During studies to extend the half-life of crystalline nanoformulated antiretroviral therapy (nanoART) the mixed lineage kinase-3 inhibitor URMC-099, developed as an adjunctive neuroprotective agent was shown to facilitate antiviral responses. Long-acting ritonavir-boosted atazanavir (nanoATV/r) nanoformulations co-administered with URMC-099 reduced viral load and the numbers of HIV-1 infected CD4+ T-cells in lymphoid tissues more than either drug alone in infected humanized NOD/SCID/IL2Rγc-/- mice. The drug effects were associated with sustained ART depots. Proteomics analyses demonstrated that the antiretroviral responses were linked to affected phagolysosomal storage pathways leading to sequestration of nanoATV/r in Rab-associated recycling and late endosomes; sites associated with viral …

Vitamin D Clinical Relevance In The Recovery From Traumatic Brain Injury Among The Military Population, Yuisa M. Colón

Honors Undergraduate Theses

Background: Traumatic brain injury (TBI) still remains a difficult disorder to treat. TBI has been associated to chronic neuroinflammation and a high risk for neurodegenerative disorders. Since 2001 between ten to twenty percent of all deployed military members have suffered a combat-related TBI. Nearly twenty to thirty percent of those will experience chronic cognitive, behavioral and somatic symptoms after suffering a TBI.
Methods: The objective of this review is to evaluate current literature examining vitamin D as a neurosteroid with protective properties and its clinical relevance after traumatic brain injury. Vitamin D is known to participate in neurobiological …

Consequences Of Estrogen Receptor Beta Phosphorylation In The Aged Female Brain And Heart, Elena Pinceti

Dissertations

Female life expectancy in the United States has steadily increased and now averages 81 years. Meanwhile, the age at which women reach menopause remains constant at 51 years. Both neurological and cardiovascular disorders increase following menopause, affecting women’s quality of life and leading to large health care costs. Estrogens are neuroprotective and cardioprotective for women, however when administered long after menopause, they fail to improve their health.

The effects of estrogen are mediated by Estrogen Receptor α (ERα) and Estrogen Receptor β (ERβ). Evidence supports that ERβ plays an important role in neuroprotection and cardioprotection, but aspects of ERβ molecular …

Potential Treatments For Malformation Associated Epilepsy, Olivia M. Bowles

Theses and Dissertations

Epilepsy has been previously attributed to either increased excitation or decreased inhibition. With this closed frame of mind, modern medicine has been unable to develop a permanent treatment against the mechanisms of epilepsy. In order to treat patients with intractable seizures, especially those caused by developmental malformations, it is essential to understand the entirety of mechanisms that could possibly play a role in the abnormal cortical function. One such developmental malformation is known as polymicrogyria. Epileptogenesis occurs in an area laterally adjacent to this malformation known as the paramicrogyral region (PMR). Past studies have narrowed down the potential cause of …

Bisphenol-A And Sleep Adequacy Among Adults In The National Health And Nutrition Examination Surveys, Hind A. Beydoun, May A. Beydoun, Hueiwang Anna Jeng, Alan B. Zonderman, Shaker M. Eid

Community & Environmental Health Faculty Publications

Study Objectives: To evaluate bisphenol-A (BPA) level and its relationship to sleep adequacy in a nationally representative sample of U.S. adults.
Methods: A population-based cross-sectional study was conducted using 2005-2010 National Health and Nutrition Examination Survey whereby data were collected using in-person interviews, physical examination and laboratory testing. BPA level was measured in urine samples and analyzed as loge-transformed variable and in quartiles (< 0.9 ng/mL; 0.9 to < 1.9 ng/mL; 1.9 to < 3.7 ng/mL; 3.7+ ng/mL). Sleep adequacy was operationalized with three questions: "How much sleep do you usually get at night on weekdays or workdays?", "Have you ever told a doctor or other health professionals that you have trouble sleeping?" and "Have you ever been told by a doctor or other health professional that you have a sleep disorder?" Sleep duration was further categorized as (< 6 h, ≥ 6 h); (< 7 h, 7-8 h, > 8 h); (< 5 h, 5-6 h, 7-8 h, ≥ 9 h). Linear, binary, and ordinal logistic regression models were constructed.
Results: Loge-transformed BPA level was inversely related to sleep duration defined, in hours, as a continuous variable, a dichotomous variable (≥ 6, < 6), or an ordinal variable (≥ 9, 7-8, 5-6, < 5), after adjustment for confounders. Help-seeking behavior for sleep problems and diagnosis with sleep disorders were not significantly associated with loge-transformed BPA level in fully adjusted models.
Conclusions: Loge-transformed BPA level may be associated with fewer hours of …

The Effects Of 7,8-Dihydroxyflavone On Hippocampal Neurogenesis Following Traumatic Brain Injury, Mary K. Wurzelmann

Theses and Dissertations

Following traumatic brain injury (TBI), the hippocampus is particularly vulnerable to damage, and BDNF, an endogenous neurotrophin that activates the TrkB receptor, has been shown to play a key role in the brain’s neuroprotective response. Activation of the TrkB signaling pathway by BDNF in the CNS promotes cell survival and aids in cell growth. However, due to its inability to cross the blood brain barrier (BBB), the therapeutic advantages of BDNF treatment following TBI are limited. 7,8-Dihydroxyflavone (7,8-DHF) is a flavonoid that mimics the effects of BDNF, is a potent TrkB receptor agonist, and can successfully cross the BBB. Our …

Stress-Induced Reinstatement Of Drug Seeking: 20 Years Of Progress, John R. Mantsch, David A. Baker, Douglas Funk, Anh D. Lê, Yavin Shaham

Biomedical Sciences Faculty Research and Publications

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, …

Analgesia Followed By Long-Term Hyperalgesia Generated By Disinhibition Of The Basolateral Amygdala, Derek Atchley

Wayne State University Theses

Stress produces bimodal effects on pain peception. During exposure to a stressor pain responses are inibited (i.e. stress-induced analgesia). However, following long-term exposure to a stressor increases in responsiveness to painful stimuli may develop (i.e. stress-induced hyperalgesia). Here I evaluated how a key component of the subcortical defense circuit and target of stress hormones contributes to the development of both stress-induced analgesia and hyperalgesia. Bicuculline methiodide, a GABAA antagonist, injected into the basolateral amygdala was used to mimic the neural effects of a stressor or threat exposure. Immediately following injection pain responsiveness was decreased as measured by vocalizations after discharge …

The Effect Of Caffeine On Migraine Headaches, Deborah Shimshoni

Honors Undergraduate Theses

As the most widely consumed drug around the globe, there is a vast array of contradicting research available on caffeine. One of the most debated and researched topics on caffeine is its effect on the brain. Meanwhile, the data on the neurological condition of migraine has information scattered throughout countless research articles and experiments.

Although neither migraine or caffeine are completely understood by the medical world, this analysis attempts to give a more coherent understanding of the relationship between the two. This is done by first understanding the known and theorized mechanisms of caffeine as well as the pathologies of …

Cerebrovascular Risk Factors, Arteriolar Sclerosis, And Cognitive Decline In The Kentucky Appalachian “Stroke-Belt”, Omar M. Al-Janabi

Theses and Dissertations--Medical Sciences

The relationship between cerebrovascular disease (CVD) risk factors and cognitive impairment or dementia has been widely studied with significant variability in findings between groups. We hypothesized that chronic small vessel injury in the form of arteriolar sclerosis, measured quantitatively using MRI to measure total white matter hyperintensity (WMH) volumes, would identify specific association of CVD risk factors and patterns of cognitive decline, associated with mild cognitive impairment of the cerebrovascular type, that represent the core features of vascular cognitive impairment in our cohort.

A Cross-sectional analysis of clinical and quantitative MRI data on 114 subjects with normal cognitive function (n=52) …

Novel Targets For Mitochondrial Dysfunction Following Traumatic Brain Injury, Heather M. Yonutas

Theses and Dissertations--Neuroscience

Mitochondrial dysfunction is a phenomenon observed in models of Traumatic Brain Injury (TBI). Loss of mitochondrial bioenergetics can result in diminished cellular homeostasis leading to cellular dysfunction and possible cellular death. Consequently, the resultant tissue damage can manifest as functional deficits and/or disease states. Therapeutic strategies to target this mitochondrial dysfunction have been investigated for models TBI and have shown promising effects.

For this project, we tested the hypothesis that mitoNEET, a novel mitochondrial membrane protein, is a target for pioglitazone mediated neuroprotection. To test this, we used a severe Controlled Cortical Impact (CCI) injury model in mitoNEET null and …

Effects Of Mammalian Target Of Rapamycin Inhibition On Circuitry Changes In The Dentate Gyrus Of Mice After Focal Brain Injury, Corwin R. Butler

Theses and Dissertations--Physiology

Post-traumatic epilepsy is a common outcome of severe traumatic brain injury (TBI). The development of spontaneous seizures after traumatic brain injury generally follows a latent period of little to no symptoms. The series of events occurring in this latent period are not well understood. Additionally, there is no current treatment to prevent the development of epilepsy after TBI (i.e. antiepileptogenics). One cell signaling pathway activated in models of TBI and in models of epilepsy is the mammalian target of rapamycin (mTOR). mTOR activity is sustained for weeks after the initial insult in models of TBI, and the inhibition of mTOR …

Protein Kinase A And Epac Mediate Chronic Pain After Injury: Prolonged Inhibition By Endogenous Y1 Receptors In Dorsal Horn, Weisi Fu

Theses and Dissertations--Physiology

Inflammation or nerve injury sensitizes several populations of nociceptive neurons in the dorsal horn of the spinal cord, including those that express the neuropeptide Y (NPY) Y1 receptor (Y1R). Our overall hypothesis is that after tissue or nerve injury, these Y1R-expressing neurons enter a state of latent sensitization (LS) that contributes to vulnerability to the development of chronic pain; furthermore, LS is under the tonic inhibitory control of endogenous Y1R signaling. First, we evaluated the intracellular signaling pathways that become activated in Y1R-expressing neurons and participate in LS. To do this, we established behavioral models of inflammatory or neuropathic pain, …

Histological And Behavioral Consequences Of Repeated Mild Traumatic Brain Injury In Mice, Amanda Nicholle Bolton Hall

Theses and Dissertations--Physiology

The majority of the estimated three million traumatic brain injuries that occur each year are classified as “mild” and do not require surgical intervention. However, debilitating symptoms such as difficulties focusing on tasks, anxiety, depression, and visual deficits can persist chronically after a mild traumatic brain injury (TBI) even if an individual appears “fine”. These symptoms have been observed to worsen or be prolonged when an individual has suffered multiple mild TBIs. To test the hypothesis that increasing the amount of time between head injuries can reduce the histopathological and behavioral consequences of repeated mild TBI, a mouse model of …

Neural Circuitry Deficits Associated With Dysfunctional Myelin, Kathleen June Maheras

Wayne State University Dissertations

In the current study, we have generated mutant mice that lack Claudin 11 (Cldn11) tight junctions in CNS myelin sheaths. In myelin sheaths, Cldn11 forms tight junctions located along the outer and inner edges of the membrane spiral, preventing ions and small molecules from entering the intramyelinic space. The function of Cldn11 tight junctions is to improve the passive properties of the myelin membrane, by increasing membrane resistance and reducing capacitance, thereby improving the speed of saltatory conduction. In the absence of Cldn11, conduction velocity is slowed, most dramatically in small diameter myelinated fibers, somewhat analogous to reducing myelin thickness. …

Role Of Secretory Granule Heterogeneity In Calcium-Triggered Exocytosis, Tejeshwar Rao

Wayne State University Dissertations

The sympathetic nervous system is activated by a variety of threats to organismal homeostasis. The adrenomedullary chromaffin cell is the core effector of sympathetic activity in the peripheral nervous system. By design, the chromaffin cell secretory response is mutable so that release can be rapidly tuned to drive context-dependent changes in physiological function. However, the mechanisms by which this tuning is achieved with such high temporal fidelity and context specificity remain unclear. This represents a major gap in our understanding of the sympatho-adrenal system since it is known to modify the function of nearly every organ system in the body. …

Autotaxin In Central Nervous System Development And Disease, Natalie A. Wheeler

Theses and Dissertations

During development, oligodendrocytes (OLGs), the myelinating cells of the central nervous system (CNS), undergo a stepwise progression during which OLG progenitors, specified from neural stem/progenitor cells, differentiate into fully mature myelinating OLGs. This progression along the OLG lineage is characterized by well-synchronized changes in morphology and gene expression patterns. The studies presented in this dissertation identified the extracellular factor Autotaxin (ATX) as a novel upstream signal modulating HDAC1/2 activity and gene expression in cells of the OLG lineage. Using the zebrafish as an in vivo model system, as well as rodent primary OLG cultures, this functional property of ATX was …

The Effects Of External Focus Of Attention Exercise Rehabilitation On Dual Task Walking In Parkinson's Disease, Eric N. Beck

Theses and Dissertations (Comprehensive)

Parkinson’s disease impairs control of well-learned movements, and therefore, individuals with Parkinson’s disease are forced to walk with greater conscious control. This causes difficulties while walking and completing a secondary task simultaneously (dual tasking), in that distractions from conscious control of walking increase the risk of falls and injury. Although, attention-based exercise may be a potential avenue to decrease the demands associated with walking in Parkinson’s disease. For example, an external focus of attention (on manipulated objects) has been found to recruit the networks that are important for walking with little conscious control (automatic control networks). In contrast, an internal …

Modulation Of Gamma And Alpha Spinal Motor Neurons Activity By Trans-Spinal Direct Current Stimulation: Effects On Reflexive Actions And Locomotor Activity, Zaghloul Ahmed

Publications and Research

Spontaneous and evoked spinal activities interact to set the characteristics of emergent motor responses. Gamma motor neurons have feedforward and feedback functions in motor control, which are crucial for transforming motor commands into action. Meanwhile, the intrinsic excitability and functional connectivity of alpha motor neurons determine the accuracy of actions. In this study, we investigated the effects of trans-spinal direct current stimulation (tsDCS) on spontaneous and cortically evoked activity of well-isolated single units of gamma and alpha motor neurons in mice. We also investigated the effects of tsDCS on reflexive and locomotor actions. In general, motor neurons showed increased responses …

An Analysis Of Plasticity In The Rat Respiratory System Following Cervical Spinal Cord Injury And The Application Of Nanotechnology To Induce Or Enhance Recovery Of Diaphragm Function, Janelle Lorien Walker

Wayne State University Dissertations

Second cervical segment spinal cord hemisection (C2Hx) results in ipsilateral hemidiaphragm paralysis. However, the intact latent crossed phrenic pathway can restore function spontaneously over time or immediately following drug administration.

WGA bound fluorochromes were administered to identify nuclei associated with diaphragm function in both the acute and chronic C2Hx models. WGA is unique in that it undergoes receptor mediated endocytosis and is transsynaptically transported across select physiologically active synapses. Comparison of labeling in the acutely injured to the chronically injured rat provided an anatomical map of spinal and supraspinal injury induced synaptic plasticity. The plasticity occurs over time in the …

The Level Of Nmda Receptor In The Membrane Modulates Amyloid-Β Association And Perforation, Christian Peters, Fernando J. Sepúlveda, Eduardo Fernández-Pérez, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

Alzheimer’s disease is a neurodegenerative disorder that affects mostly the elderly. The main histopathological markers are the senile plaques formed by amyloid-β peptide (Aβ) aggregates that can perforate the plasma membrane of cells, increasing the intracellular calcium levels and releasing synaptic vesicles that finally lead to a delayed synaptic failure. Several membrane proteins and lipids interact with Aβ affecting its toxicity in neurons. Here, we focus on NMDA receptors (NMDARs) as proteins that could be modulating the association and neurotoxic perforation induced by Aβ on the plasma membrane. In fact, our results showed that decreasing NMDARs, using enzymatic or siRNA …