Neurosciences Commons^™

Genomic Copy Number Variation In Mus Musculus., M Elizabeth O Locke, Maja Milojevic, Susan T Eitutis, Nisha Patel, Andrea E Wishart, Mark Daley, Kathleen A. Hill

Brain and Mind Institute Researchers' Publications

BACKGROUND: Copy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.

RESULTS: We found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of …

Plastin 3 Expression Does Not Modify Spinal Muscular Atrophy Severity In The ∆7 Sma Mouse, Vicki L. Mcgovern, Aurelie Massoni-Laporte, Xueyong Wang, Thanh T. Le, Hao T. Le, Mark M. Rich, Arthur H. M. Burghes

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal muscular atrophy is caused by loss of the SMN1 gene and retention of SMN2. TheSMN2 copy number inversely correlates with phenotypic severity and is a modifier of disease outcome. The SMN2 gene essentially differs from SMN1 by a single nucleotide in exon 7 that modulates the incorporation of exon 7 into the final SMN transcript. The majority of the SMN2transcripts lack exon 7 and this leads to a SMN protein that does not effectively oligomerize and is rapidly degraded. However theSMN2 gene does produce some full-length SMN and theSMN2 copy number along with how …

Hand Use Predicts The Structure Of Representations In Sensorimotor Cortex., Naveed Ejaz, Masashi Hamada, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Fine finger movements are controlled by the population activity of neurons in the hand area of primary motor cortex. Experiments using microstimulation and single-neuron electrophysiology suggest that this area represents coordinated multi-joint, rather than single-finger movements. However, the principle by which these representations are organized remains unclear. We analyzed activity patterns during individuated finger movements using functional magnetic resonance imaging (fMRI). Although the spatial layout of finger-specific activity patterns was variable across participants, the relative similarity between any pair of activity patterns was well preserved. This invariant organization was better explained by the correlation structure of everyday hand movements than …

Changes In Visual And Sensory-Motor Resting-State Functional Connectivity Support Motor Learning By Observing., Heather R Mcgregor, Paul L Gribble

Brain and Mind Institute Researchers' Publications

Motor learning occurs not only through direct first-hand experience but also through observation (Mattar AA, Gribble PL. Neuron 46: 153-160, 2005). When observing the actions of others, we activate many of the same brain regions involved in performing those actions ourselves (Malfait N, Valyear KF, Culham JC, Anton JL, Brown LE, Gribble PL. J Cogn Neurosci 22: 1493-1503, 2010). Links between neural systems for vision and action have been reported in neurophysiological (Strafella AP, Paus T. Neuroreport 11: 2289-2292, 2000; Watkins KE, Strafella AP, Paus T. Neuropsychologia 41: 989-994, 2003), brain imaging (Buccino G, Binkofski F, Fink GR, Fadiga L, …

Dualism And Doctrine, Dov Fox, Alex Stein

Indiana Law Journal

What kinds of harm among those that tortfeasors inflict are worthy of compensation? Which forms of self-incriminating evidence are privileged against government compulsion? What sorts of facts constitute a criminal defendant’s intent? Existing doctrine pins the answer to all of these questions on whether the injury, facts, or evidence at stake are “mental” or “physical.” The assumption that operations of the mind are meaningfully distinct from those of the body animates fundamental rules in our law.

A tort victim cannot recover for mental harm on its own because the law presumes that he is able to unfeel any suffering arising …

Clinical Spectrum And Radiographic Features Of The Syndrome Of The Trephined, Cara L. Sedney, William Dillen, Terrence Julien

Neurosurgery Faculty Publications

OBJECT: Craniectomy is a common neurosurgical procedure. Syndrome of the trephined (ST) occurring after craniectomy results in neurologic symptoms that are reversible with cranioplasty. While well-documented, previous literature consisted of case reports, symptom spectrum and risk factors have not been well characterized.

MATERIALS AND METHODS: A retrospective review of 29 consecutive cases who underwent decompressive craniectomy within a 30-month period was performed. Patients were considered affected by ST if a previously stable neurological deficit improved within 3 weeks after cranioplasty. Prevalence of ST was measured and association with demographic information, clinical symptoms patterns, indication for and size of craniectomy, as …

Neural Plasticity In Response To Intervention In Adolescents With Autism Spectrum Disorders, Sheryl Jayne Stevens

Dissertations (1934 -)

Current theories of Autism Spectrum Disorders (ASD) suggest that they may develop from the transactional interaction between biological risk factors and environmental processes (Dawson et al., 2009). Due to the brain’s experience-expectant nature, one’s degree of social exposure may have a significant impact on their brain development and behavioral presentation. In addition to the primary critical neurodevelopmental period identified in early childhood, recent research has demonstrated a second period of substantial neurodevelopment during the adolescent period (Sisk & Foster, 2004). This study investigated the neural and behavioral impact of participation in an empirically validated behavioral intervention (The Program for the …

Effects Of Cocaine Sensitization On Drug Self-Administration, Mesocorticolimbic Sapap Levels, And Prefrontal Ionotropic Glutamate Receptors, Kyle Christopher Summers

Theses and Dissertations (ETD)

Towards the goal of improving the knowledge base of how drugs of abuse function to create addicts and using currently uninvestigated areas of this knowledge base, we focused our research studies the male albino rat, and strived to explain how cocaine sensitization alters particular molecular mechanisms in the mesocorticolimbic system related to glutamate receptors, SAPAPs, and affects drug self-administration. Taking all the previously discussed research studies into consideration, we hypothesized that low-dose cocaine self-administration would yield a significant elevation in drug seeking behavior for psychostimulant sensitized animals. For specific changes at the PSD, we hypothesized that acute cocaine exposure and/or …

Embracing Multiple Definitions Of Learning, Andrew B. Barron, Eileen A. Hebets, Thomas A. Cleland, Courtney L. Fitzpatrick, Mark E. Hauber, Jeffrey R. Stevens

Eileen Hebets Publications

Definitions of learning vary widely across disciplines, driven largely by different approaches used to assess its occurrence. These definitions can be better reconciled with each other if each is recognized as coherent with a common conceptualization of learning, while appreciating the practical utility of different learning definitions in different contexts.

Learning is a major focus of research in psychology, neuro- science, behavioral ecology, evolutionary theory, and computer science, as well as in many other disciplines. Despite its conceptual prevalence, definitions of learning differ enormously both within and between these disciplines, and new definitions continue to be proposed [1]. Ongoing disputes …

Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh

Department of Neuroscience Faculty Papers

Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically …

Concordance Of The Montreal Cognitive Assessment With Standard Neuropsychological Measures, Sally J. Vogel, Sarah J. Banks, Jeffrey Cummings, Justin B. Miller

School of Medicine Faculty Research

Introduction: The concordance of the Montreal cognitive assessment (MoCA) with more comprehensive neuropsychological measures remains unclear. This study examined the individual MoCA domains with more comprehensive and commonly used neuropsychological measures to determine the degree of overlap. Methods: Data included individuals seen in an outpatient neurology clinic specializing in neurodegenerative disease who were administered the MoCA and also underwent neuropsychological assessment (n = 471). A principal component analysis with varimax rotation was completed using the MoCA domain scores and comprehensive neuropsychological evaluation measures. Results: Four factors emerged accounting for 55.6% of the variance: (1) visuospatial/executive functioning; (2) memory; (3) attention; …

Visual Feedback Dominates The Sense Of Agency For Brain-Machine Actions, Nathan Evans, Steven Gale, Aaron Schurger, Olaf Blanke

Psychology Faculty Articles and Research

Recent advances in neuroscience and engineering have led to the development of technologies that permit the control of external devices through real-time decoding of brain activity (brain-machine interfaces; BMI). Though the feeling of controlling bodily movements (sense of agency; SOA) has been well studied and a number of well-defined sensorimotor and cognitive mechanisms have been put forth, very little is known about the SOA for BMI-actions. Using an on-line BMI, and verifying that our subjects achieved a reasonable level of control, we sought to describe the SOA for BMI-mediated actions. Our results demonstrate that discrepancies between decoded neural activity and …

Connectivity Measures Are Robust Biomarkers Of Cortical Function And Plasticity After Stroke, Jennifer Wu, Erin Burke Quinlan, Lucy Dodakian, Alison Mckenzie, Nikhita Kathuria, Robert J. Zhou, Renee Augsburger, Jill See, Vu H. Lee, Ramesh Srinivasan, Steven C. Cramer

Physical Therapy Faculty Articles and Research

Valid biomarkers of motor system function after stroke could improve clinical decision-making. Electroencephalography-based measures are safe, inexpensive, and accessible in complex medical settings and so are attractive candidates. This study examined specific electroencephalography cortical connectivity measures as biomarkers by assessing their relationship with motor deficits across 28 days of intensive therapy. Resting-state connectivity measures were acquired four times using dense array (256 leads) electroencephalography in 12 hemiparetic patients (7.3 ± 4.0 months post-stroke, age 26–75 years, six male/six female) across 28 days of intensive therapy targeting arm motor deficits. Structural magnetic resonance imaging measured corticospinal tract injury and infarct volume. …

Magnetic Resonance Imaging Of Folic Acid-Coated Magnetite Nanoparticles Reflects Tissue Biodistribution Of Long-Acting Antiretroviral Therapy., Tianyuzi Li, Howard Gendelman, Gang Zhang, Pavan Puligujja, Joellyn Mcmillan, Tatiana K. Bronich, Benson Edagwa, Xin-Ming Liu, Michael D. Boska

Journal Articles: Pharmacology & Experimental Neuroscience

Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory's development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite …

Fusion Analysis Of Functional Mri Data For Classification Of Individuals Based On Patterns Of Activation., Mahdi Ramezani, Purang Abolmaesumi, Kris Marble, Heather Trang, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

Classification of individuals based on patterns of brain activity observed in functional MRI contrasts may be helpful for diagnosis of neurological disorders. Prior work for classification based on these patterns have primarily focused on using a single contrast, which does not take advantage of complementary information that may be available in multiple contrasts. Where multiple contrasts are used, the objective has been only to identify the joint, distinct brain activity patterns that differ between groups of subjects; not to use the information to classify individuals. Here, we use joint Independent Component Analysis (jICA) within a Support Vector Machine (SVM) classification …

Astrocyte Morphology, Heterogeneity, And Density In The Developing African Giant Rat (Cricetomys Gambianus), Matthew A. Olude, Oluwaseun A. Mustapha, Oluwatunde A. Aderounmu, James O. Olopade, Amadi O. Ihunwo

Brain and Mind Institute

Astrocyte morphologies and heterogeneity were described in male African giant rats (AGR; Cricetomys gambianus, Waterhouse) across three age groups (five neonates, five juveniles, and five adults) using Silver impregnation method and immunohistochemistry against glial fibrillary acidic protein. Immunopositive cell signaling, cell size and population were least in neonates, followed by adults and juveniles, respectively. In neonates, astrocyte processes were mostly detected within the glia limitans of the mid and hind brain; their cell bodies measuring 32 ± 4.8 μm in diameter against 91 ± 5.4 μm and 75 ± 1.9 μm in juveniles and adults, respectively. Astrocyte heterogeneity in …

Novel Advances In Alzheimer's Disease, Jacob P. Naumann

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

Alzheimer’s disease, the most common form of dementia in adults, is a progressive degenerative neurological disease that affects memory, cognition, and behavior. Dr. Alois Alzheimer discovered and diagnosed the irreversible disease in 1906 after documenting the famous case of Auguste Deter.¹ Since the discovery of the disease, numerous advances have made it possible to not only better understand the causal factors, but also to improve the medical diagnosis and preventative measures that healthcare providers can implement. For the first time since 1984, the National Institute on Aging (NIAA) and the Alzheimer’s Association (AA) proposed and published new diagnostic guideline …

Drug Predictive Cues Activate Aversion-Sensitive Striatal Neurons That Encode Drug Seeking, Daniel S. Wheeler, Mykel A. Robble, Emily M. Hebron, Matthew J. Dupont, Amanda L. Ebben, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Drug-associated cues have profound effects on an addict’s emotional state and drug-seeking behavior. Although this influence must involve the motivational neural system that initiates and encodes the drug-seeking act, surprisingly little is known about the nature of such physiological events and their motivational consequences. Three experiments investigated the effect of a cocaine-predictive stimulus on dopamine signaling, neuronal activity, and reinstatement of cocaine seeking. In all experiments, rats were divided into two groups (paired and unpaired), and trained to self-administer cocaine in the presence of a tone that signaled the immediate availability of the drug. For rats in the paired group, …

Connectionist Perspectives On Language Learning, Representation And Processing., Marc F Joanisse, James L Mcclelland

Brain and Mind Institute Researchers' Publications

The field of formal linguistics was founded on the premise that language is mentally represented as a deterministic symbolic grammar. While this approach has captured many important characteristics of the world's languages, it has also led to a tendency to focus theoretical questions on the correct formalization of grammatical rules while also de-emphasizing the role of learning and statistics in language development and processing. In this review we present a different approach to language research that has emerged from the parallel distributed processing or 'connectionist' enterprise. In the connectionist framework, mental operations are studied by simulating learning and processing within …

Estrodial Effects On Age-Related Shifts In Learning And Memory: A Multiple Memory Systems Approach, Luis Castelan

Renée Crown University Honors Thesis Projects - All

Many findings from our lab and others suggest that circulating estrogens as well as estrogen replacement after ovariectomy influence cognitive performance. Young female rats trained during proestrus, when estrogens are high, or with acute estradiol (E2) administration after ovariectomy perform better on the hippocampus-sensitive place task but worse on the striatum-sensitive response task (Korol et al., 2004; Korol and Kolo, 2002). Behavioral neuroscience studies tend to use male rodent models to avoid the complexities of the female reproductive cycle, producing a gap in our knowledge about neural mechanisms of learning and memory in females. As a consequence, age-related effects of …

Functional Capacity In Schizophrenia: Relationship Among Effort, Reinforcement Learning And Self-Beliefs, Sally J. Vogel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Individuals with schizophrenia exhibit a wide range of complex neurocognitive, psychiatric and behavioral impairments. Recent research suggests that this complex array of symptoms can be at least partially accounted for by dysfunction in more basic mechanisms, such as the ability to learn from positive and negative reinforcement, or the ability to exert adequate effort when completing simple tasks. Evidence also suggests that deficits in these basic mechanisms may contribute to more complex symptoms, such as functional impairment. Also, the relationship between neurocognitive deficits and functional impairment has been found to be mediated by defeatist performance beliefs. However, studies have not …

Integration Of Atm, Atr, And Dna-Pkcs Signaling Maintains Genome Integrity During Neurogenesis, Vanessa D. Enriquez-Rios

Theses and Dissertations (ETD)

The DNA damage response (DDR) orchestrates a network of cellular processes such as cell cycle progression, DNA repair, and apoptosis when complex DNA lesions arise to maintain genomic integrity. ATM, ATR, and DNA-PKcs (encoded by PRKDC) are related phosphatidylinositol-3-kinase like serine/threonine kinases (PIKK) that collectively regulate the DDR network. Studies have demonstrated these kinases can phosphorylate many of the same substrates, suggesting a significant potential for functional redundancy. However, deficiencies in these kinases have been linked to distinct neural degenerative and developmental disorders, underscoring their unique functions for maintain genomic integrity during nervous system development.

Here we utilized mouse genetic …

Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski

Honors Scholar Theses

Each year, nearly 800,000 individuals residing in the United States will have a stroke. Of these, about 130,000 cases will prove fatal while many of the survivors will be forced to live with disability for the remainder of their lives. Out of all strokes over 87% are ischemic strokes. The widespread incidence of this debilitating condition costs the United States an estimated $36.5 billion dollars every single year. Despite this, clinicians are armed with very little to combat the disease. Recent research developments have brought about the rise in awareness about the importance of the microbiome, the various gut flora …

Connecticut's Elderly Population: An In-Depth Analysis Of Current And Future Trends In Elder Care, With A Focus On Dementia And Cognitive Decline, Emily J. Snodgrass

Honors Scholar Theses

The aging population in Connecticut currently represents ~15% of the state’s population but is anticipated to rapidly increase over the next 20 years. My thesis is an examination of the types of interventions and programs currently available for elderly persons with memory impairment and cognitive decline, as well as the challenges associated with caring for a larger elderly population. Data collected from interviews with CT healthcare and research professionals representative of the diverse specialties of aging together with an analysis of current research literature are used to demonstrate the importance of continued research and expansion of appropriate and accessible services …

A Comparison Of The Effects Of Different Doses Of Gabab Receptor Ligands On Spatial Learning And Memory And Memory Flexibility, Chelcie Heaney

UNLV Theses, Dissertations, Professional Papers, and Capstones

The principal inhibitory neurotransmitter in the brain, gamma amino-butyric acid (GABA), mediates several types of learning and memory. Of the two main receptor subtypes for GABA, the in vivo role of GABAB receptor in learning and memory is less well characterized and the current data often conflict. Based on the current literature, it is unclear, for instance, whether enhancing GABAergic activity via the GABAB receptor could be beneficial for or detrimental to learning and memory. Hippocampally-dependent learning and memory tasks are of particular interest due to their clinical relevance to patients with schizophrenia or Alzheimer’s disease, who exhibit impaired performance …

The Plight Of The Lucluc: Examining The Deadly Mystery Of Nodding Syndrome, Ethan K. Mcgann

Senior Honors Theses

Nodding syndrome (NS) is an emerging epidemic neurological disease that is shrouded in mystery. It is currently only found in the post-conflict regions of South Sudan, northern Uganda, and Tanzania. NS occurs in children from the ages of five to fifteen and is characterized by a loss of motor control in the neck muscles. Seizure episodes can range in intensity from atonic to tonic-clonic, and the onset of the first episode generally marks the beginning of a decline in the child’s physical and mental health. NS is a progressive disease that generally results in physical wasting, stunted growth, behavioral difficulties, …

Direct Reprogramming Of Induced Neural Progenitors: A New Promising Strategy For Ad Treatment., Siqiang Lai, Min Zhang, Dongsheng Xu, Yiying Zhang, Lisha Qiu, Changhai Tian, Jialin Charlie Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

Alzheimer's disease (AD) is a prominent form of dementia, characterized by aggregation of the amyloid β-peptide (Aβ) plaques and neurofibrillary tangles, loss of synapses and neurons, and degeneration of cognitive functions. Currently, although a variety of medications can relieve some of the symptoms, there is no cure for AD. Recent breakthroughs in the stem cell field provide promising strategies for AD treatment. Stem cells including embryonic stem cells (ESCs), neural stem cells (NSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) are potentials for AD treatment. However, the limitation of cell sources, safety issues, and ethical issues restrict …

Is It Ethical To Hold A Person Culpable For His Actions If He Cannot Recognize Right And Wrong, Tabitha E.H. Moses

Student Works

The field of neuroscience has opened up a proverbial can of worms when it comes to questions of free will and culpability. The more we know about the mind the more it appears that no one has any real choice in their actions. The ethical implications of this assumption are astronomical. Guilt and culpability come into question; it would seem unjust to punish a person for a crime if he had no choice but to commit it. While these are interesting questions for an ethicist they are impractical for society as they might affect how society functions. As such, the …

Live Imaging Of The Ependymal Cilia In The Lateral Ventricles Of The Mouse Brain, Alzahra J. Al Omran, Hannah C. Saternos, Tongyu Liu, Surya M. Nauli, Wissam A. Aboualaiwi

Pharmacy Faculty Articles and Research

Multiciliated ependymal cells line the ventricles in the adult brain. Abnormal function or structure of ependymal cilia is associated with various neurological deficits. The current ex vivo live imaging of motile ependymal cilia technique allows for a detailed study of ciliary dynamics following several steps. These steps include: mice euthanasia with carbon dioxide according to protocols of The University of Toledo’s Institutional Animal Care and Use Committee (IACUC); craniectomy followed by brain removal and sagittal brain dissection with a vibratome or sharp blade to obtain very thin sections through the brain lateral ventricles, where the ependymal cilia can be visualized. …

Motor Skill Learning Between Selection And Execution., Jörn Diedrichsen, Katja Kornysheva

Brain and Mind Institute Researchers' Publications

Learning motor skills evolves from the effortful selection of single movement elements to their combined fast and accurate production. We review recent trends in the study of skill learning which suggest a hierarchical organization of the representations that underlie such expert performance, with premotor areas encoding short sequential movement elements (chunks) or particular component features (timing/spatial organization). This hierarchical representation allows the system to utilize elements of well-learned skills in a flexible manner. One neural correlate of skill development is the emergence of specialized neural circuits that can produce the required elements in a stable and invariant fashion. We discuss …