Neurosciences Commons^™

Sciatic Nerve Cut And Repair Using Fibrin Glue In Adult Mice, Erica T. Akhter, Travis M. Rotterman, Arthur W. English, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injury (PNI) is an excellent model for studying neural responses to injury and elucidating the mechanisms that can facilitate axon regeneration. As such, several animal models have been employed to study regenerative mechanisms after PNI, including Aplysia, zebrafish, rabbits, cats and rodents. This protocol describes how to perform a sciatic nerve injury and repair in mice, one of the most frequently used models to study mechanisms that facilitate recovery after PNI, and that takes advantage of the availability of many genetic models. In this protocol, we describe a method for using fibrin glue to secure the proximal …

Autophagy Modulation As A Treatment Of Amyloid Diseases, Zoe Mputhia, Eugene Hone, Timir Tripathi, Tim Sargeant, Ralph Martins, Prashant Bharadwaj

Research outputs 2014 to 2021

Amyloids are fibrous proteins aggregated into toxic forms that are implicated in several chronic disorders. More than 30 diseases show deposition of fibrous amyloid proteins associated with cell loss and degeneration in the affected tissues. Evidence demonstrates that amyloid diseases result from protein aggregation or impaired amyloid clearance, but the connection between amyloid accumulation and tissue degeneration is not clear. Common examples of amyloid diseases are Alzheimer's disease (AD), Parkinson's disease (PD) and tauopathies, which are the most common forms of neurodegenerative diseases, as well as polyglutamine disorders and certain peripheral metabolic diseases. In these diseases, increased accumulation of toxic …

Map7 Prevents Axonal Branch Retraction By Creating A Stable Microtubule Boundary To Rescue Polymerization., Stephen R. Tymanskyj, Le Ma

Farber Institute for Neuroscience Faculty Papers

Complex neural circuits are built from axonal branches that allow each neuron to connect with multiple targets. During development, maturation of nascent branches depends on stabilization of newly assembled or transported microtubules, which are thought to be regulated by microtubule-associated proteins (MAPs). However, because many known MAPs inhibit branch formation, it is not clear which MAP is responsible for regulating microtubule stability during branch development. Here, we show that MAP7, a less-well understood MAP that is localized to branch junctions, provides a key molecular mechanism to regulate microtubule stability during branch formation. In developing rodent sensory neurons of mixed sex, …

Stimulus-Locked Responses On Human Upper Limb Muscles And Corrective Reaches Are Preferentially Evoked By Low Spatial Frequencies, Rebecca A. Kozak, Philipp Kreyenmeier, Chao Gu, Kevin Johnston, Brian D. Corneil

Brain and Mind Institute Researchers' Publications

© 2019 Kozak et al. In situations requiring immediate action, humans can generate visually-guided responses at remarkably short latencies. Here, to better understand the visual attributes that best evoke such rapid responses, we recorded upper limb muscle activity while participants performed visually-guided reaches towards Gabor patches composed of differing spatial frequencies (SFs). We studied reaches initiated from a stable posture (experiment 1, a static condition), or during on-line reach corrections to an abruptly displaced target (experiment 2, a dynamic condition). In both experiments, we detail the latency and prevalence of stimulus-locked responses (SLRs), which are brief bursts of EMG activity …

Thirty-Five Years Of Computerized Cognitive Assessment Of Aging — Where Are We Now?, Avital Sternin, Alistair Burns, Adrian M. Owen

Brain and Mind Institute Researchers' Publications

Over the past 35 years, the proliferation of technology and the advent of the internet have resulted in many reliable and easy to administer batteries for assessing cognitive function. These approaches have great potential for affecting how the health care system monitors and screens for cognitive changes in the aging population. Here, we review these new technologies with a specific emphasis on what they offer over and above traditional ‘paper-and-pencil’ approaches to assessing cognitive function. Key advantages include fully automated administration and scoring, the interpretation of individual scores within the context of thousands of normative data points, the inclusion of …

Utilization, Safety, And Tolerability Of Ocrelizumab: Year 2 Data From The Providence Ocrelizumab Registry, Kyle E Smoot

Articles, Abstracts, and Reports

Background: Ocrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, was approved in the US in 2017 for the treatment of relapsing MS (RMS) and primary progressive MS (PPMS). The Providence OCR Registry was established to monitor long-term treatment and safety outcomes.

Objective: To evaluate OCR treatment outcomes using real-world data from a diverse, community-based MS population.

Methods: Adult MS patients who have been prescribed OCR were eligible. Chart reviews at OCR start date and then every 6 months were done by a trained RN. Expanded Disability Status Scale (EDSS) scores were determined by the treating provider on the start date and …

Electroencephalographic Asymmetry, Emotion Regulation, And Their Relationships With Depression Risk, Aliza Jacob

Dissertations, Theses, and Capstone Projects

Background: Research investigating patterns of electroencephalographic (EEG) brain asymmetry aids our understanding of neural systems involved in the processing of emotion, motivation, and psychopathology. Withdrawal-motivated negative emotions characteristic of depression are associated with relative right prefrontal cortex (PFC) activity, whereas approach- motivated positive emotions are associated with relative left PFC activity. Styles of emotion regulation (ER), or modulation of the intensity and duration of emotional responses, are also associated with presence (e.g., suppression, or maladaptive ER) versus absence (e.g., cognitive reappraisal, or adaptive ER) of depression vulnerability. Most PFC asymmetry studies of emotion, depression, and/or ER rely upon EEG recorded …

Long-Distance Axon Regeneration Promotes Recovery Of Diaphragmatic Respiratory Function After Spinal Cord Injury., Mark W. Urban, Biswarup Ghosh, Cole G. Block, Laura R. Strojny, Brittany A. Charsar, Miguel Goulão, Sreeya S. Komaravolu, George M. Smith, Megan C. Wright, Shuxin Li, Angelo C. Lepore

Farber Institute for Neuroscience Faculty Papers

Compromise in inspiratory breathing following cervical spinal cord injury (SCI) is caused by damage to descending bulbospinal axons originating in the rostral ventral respiratory group (rVRG) and consequent denervation and silencing of phrenic motor neurons (PhMNs) that directly control diaphragm activation. In a rat model of high-cervical hemisection SCI, we performed systemic administration of an antagonist peptide directed against phosphatase and tensin homolog (PTEN), a central inhibitor of neuron-intrinsic axon growth potential. PTEN antagonist peptide (PAP4) robustly restored diaphragm function, as determined with electromyography (EMG) recordings in living SCI animals. PAP4 promoted substantial, long-distance regeneration of injured rVRG axons through …

Inference Of Language Functional Network In Healthy, Cancerous And Bilingual Brains By Fmri And Network Modeling, Qiongge Li

Dissertations, Theses, and Capstone Projects

We study the underlying mechanism by which language processing occurs in the human brain using inference methods on functional magnetic resonance imaging data. The data analyzed stems from several cohorts of subjects; a monolingual group, a bilingual group, a healthy control group and one diseased case. We applied a complex statistical inference pipeline to determine the network structure of brain components involved with language. This healthy network reveals a fully connected triangular relationship between the pre-Supplementary Motor Area (pre-SMA), the Broca's Area (BA), and the ventral Pre-Motor Area (PreMA) in the left hemisphere. This "triangle'' shows consistently in all the …

Assessing General Cognitive And Adaptive Abilities In Adults With Down Syndrome: A Systematic Review, Sarah Hamburg, Bryony Lowe, Carla Marie Startin, Concepcion Padilla, Antonia Coppus, Wayne Silverman, Juan Fortea, Shahid Zaman, Elizabeth Head, Benjamin L. Handen, Ira Lott, Weihong Song, André Strydom

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different ability measures used previously, focusing on tests of intelligence quotient (IQ) and adaptive behaviour (AB), and where possible examines floor effects and differences between DS subpopulations. We aimed to use information regarding existing measures to provide recommendations for individual researchers and the DS research community.

RESULTS: Nineteen studies reporting IQ test data met inclusion for this review, with 17 different IQ tests used. Twelve of these IQ tests were used in only one study while …

Binding During Sequence Learning Does Not Alter Cortical Representations Of Individual Actions, Patrick Beukema, Jörn Diedrichsen, Timothy D. Verstynen

Brain and Mind Institute Researchers' Publications

Copyright © 2019 the authors. As a sequence of movements is learned, serially ordered actions get bound together into sets to reduce computational complexity during planning and execution. Here, we investigated how actions become naturally bound over the course of learning and how this learning affects cortical representations of individual actions. Across 5 weeks of practice, neurologically healthy human subjects learned either a complex 32-item sequence of finger movements (trained group, n = 9; 3 female) or randomly ordered actions (control group, n = 9; 3 female). Over the course of practice, responses during sequence production in the trained group …

Experimental Neuroscience Neu 410, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Neuroscience Research Seminar Neu 110, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Neuroethics And Diversity Neu 210, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Foundations In Neuroscience Neu 101, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Clinical Neurosciences Neu 320, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Developing Drug Therapies: Cognitive Damage In Mice Following Brain Radiation, Rachel Yuska

The Journal of Purdue Undergraduate Research

Pediatric brain cancer patients are at a high risk for radiation-induced cognitive impairment due to white matter changes in the brain. Half of six-month radiotherapy survivors develop significant changes in white matter. Previous research has shown that a mouse model can be used to show similar cognitive and behavioral deficits in human patients. The purpose of this work is to evaluate the effectiveness of two drug therapies, Donepezil and 3,3-Diindolylmethane (DIM), that could be used to either protect the brain from radiation injury or cure the cognitive injury and behavioral deficits that result from whole-brain irradiation. This project consisted of …

Advances In Management Of Neuropsychiatric Syndromes In Neurodegenerative Diseases, Jeffrey Cummings, Aaron Ritter, Kasia Rothenberg

School of Medicine Faculty Research

Purpose of Review Neuropsychiatric syndromes (NPS) are common in neurodegenerative disorders (NDD). This review describes the role of NPS in the diagnosis of NDD, criteria for the diagnosis of NPS, management of NPS, and agents in clinical trials for NPS. Recent Findings NPS play an increasingly important role in the diagnosis of NDD. Consensus diagnostic criteria have evolved for psychosis, depression, agitation, and apathy in NDD. With one exception—pimavanserin is approved for the treatment of hallucinations and delusions in Parkinson’s disease—there are no drugs approved by the FDA for treatment of NPS in NDD. Trials show that atypical antipsychotics reduce …

Further Analyses Of The Safety Of Verubecestat In The Phase 3 Epoch Trial Of Mild-To-Moderate Alzheimer’S Disease, Michael F. Egan, Yuki Mukai, Tiffini Voss, James Kost, Julie Stone, Christine Furtek, Erin Mahoney, Jeffrey L. Cummings, Pierre N. Tariot, Paul S. Aisen, Bruno Vellas, Christopher Lines, David Michaelson

Integrated Health Sciences Faculty Research

Background: Verubecestat, a BACE1 inhibitor that reduces Aβ levels in the cerebrospinal fluid of humans, was not effective in a phase 3 trial (EPOCH) of mild-to-moderate AD and was associated with adverse events. To assist in the development of BACE1 inhibitors, we report detailed safety findings from EPOCH. Methods: EPOCH was a randomized, double-blind, placebo-controlled 78-week trial evaluating verubecestat 12 mg and 40 mg in participants with mild-to-moderate AD diagnosed clinically. The trial was terminated due to futility close to its scheduled completion. Of 1957 participants who were randomized and took treatment, 652 were assigned to verubecestat 12 mg, 652 …

Understanding The Axonal Response To Injury By In Vivo Imaging In The Mouse Spinal Cord: A Tale Of Two Branches., Binhai Zheng, Ariana O Lorenzana, Le Ma

Department of Neuroscience Faculty Papers

Understanding the basic properties of how axons respond to injury in the mammalian central nervous system (CNS) is of fundamental value for developing strategies to promote neural repair. Axons possess complex morphologies with stereotypical branching patterns. However, current knowledge of the axonal response to injury gives little consideration to axonal branches, nor do strategies to promote axon regeneration. This article reviews evidence from in vivo spinal cord imaging that axonal branches markedly impact the degenerative and regenerative responses to injury. At a major bifurcation point, depending on whether one or both axonal branches are injured, neurons may choose either a …

The Effect Of Spinal Cord Injury On Sexual Function., Casey J. Steadman

Electronic Theses and Dissertations

Spinal cord injury (SCI) causes severe neurological impairment with widespread motor, autonomic and sensory deficits, leading to a substantial quality of life impairment. The number of individuals with SCI increases by approximately 12,500 annually, and over 80% of individuals with SCI are males. SCI individuals rate sexual function as a top priority quality of life issue, and men with SCI likely suffer from sexual dysfunction, such as erectile and ejaculatory dysfunction, as well as infertility. Regardless of the high status of importance of sexual function, limited numbers of experimental studies in SCI animal models have focused on sexual function after …

Reduced Gabaergic Signaling At The Axon Initial Segment Decreases Vigilance State Transitioning, Austin John Boren

UNLV Theses, Dissertations, Professional Papers, and Capstones

Sleep is a highly regulated homeostatic process that is disrupted in an estimated 50-70 million Americans. Regulation of sleep depends upon coordinated signaling of multiple neurotransmitter systems. In particular, inhibitory gamma-aminobutyric acid (GABA) signaling is required to suppress wake-active brain regions in order to initiate and maintain sleep states. GABA type A receptors (GABAARs) are ionotropic receptors with subunit compositions uniquely enriched on subcellular domains of target cells. α2 subunit-containing GABAARs are the primary target of GABA released onto the axon initial segment (AIS), a site critical for phasing the oscillatory activity of cortical cells. α2-containing GABAARs have previously been …

Fear Learning And The Olfactory Bulb: Neural Correlates Of Behavioral Fear Generalization, Jordan Marie Ross

Theses and Dissertations (ETD)

The exploration of how learning alters neural coding to guide behaviors remains fundamental to neuroscience. At the most basic level, the ability for organisms to flexibly adapt to changing environments and situations is paramount to biological success and often manifests in behavioral responses controlled by neural activity. For example, organisms must modify their behavior to defensive responses in the face of biological threat. Neural circuitry is involved in coordinating an initial defensive behavioral response but must undergo reorganization in order to reliably employ defensive responses in subsequent encounters based on a cue that signals imminent danger. One such form of …

Developmental Neurobiology Neu 201, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Neuroscience Professional Development Neu 230, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY …

Anti-N-Methyl-D-Aspartate Receptor Encephalitis., Gregory Tanquary, William Fraser, Kaitlin M Bowers

Neuroscience Articles

Anti-N-methyl-D-aspartate receptor (NMDA) encephalitis is an underrecognized encephalitis that may be mistaken for a wide variety of mental illnesses and causes of delirium. This syndrome is predominantly present in young females presenting with acute psychotic episodes, autonomic instability, and neurologic abnormalities. It is commonly associated with ovarian teratoma. Our case illustrates anti-NMDA encephalitis presenting in a young female with progressive mental status changes and neurologic abnormalities throughout her emergency department course. We review the investigative approach, diagnostic modalities, and treatment options in patient management. This case emphasizes the need for a high index of suspicion of anti-NMDA receptor encephalitis when …

Cortical Beta Oscillations Are Associated With Motor Performance Following Visuomotor Learning, Svenja Espenhahn, Bernadette C.M. Van Wijk, Holly E. Rossiter, Archy O. De Berker, Nell D. Redman, Jane Rondina, Joern Diedrichsen, Nick S. Ward

Brain and Mind Institute Researchers' Publications

© 2019 The Authors People vary in their capacity to learn and retain new motor skills. Although the relationship between neuronal oscillations in the beta frequency range (15–30 Hz) and motor behaviour is well established, the electrophysiological mechanisms underlying individual differences in motor learning are incompletely understood. Here, we investigated the degree to which measures of resting and movement-related beta power from sensorimotor cortex account for inter-individual differences in motor learning behaviour in the young and elderly. Twenty young (18–30 years) and twenty elderly (62–77 years) healthy adults were trained on a novel wrist flexion/extension tracking task and subsequently retested …

Self-Directed Down-Regulation Of Auditory Cortex Activity Mediated By Real-Time Fmri Neurofeedback Augments Attentional Processes, Resting Cerebral Perfusion, And Auditory Activation, Matthew Sherwood, Jason G. Parker, Emily E. Diller, Subhashini Ganapathy, Kevin B. Bennett, Carlos R. Esquivel, Jeremy T. Nelson

Neuroscience, Cell Biology & Physiology Faculty Publications

In this work, we investigated the use of real-time functional magnetic resonance imaging (fMRI) with neurofeedback training (NFT) to teach volitional down-regulation of the auditory cortex (AC) using directed attention strategies as there is a growing interest in the application of fMRI-NFT to treat neurologic disorders. Healthy participants were separated into two groups: the experimental group received real feedback regarding activity in the AC; the control group was supplied sham feedback yoked from a random participant in the experimental group and matched for fMRI-NFT experience. Each participant underwent five fMRI-NFT sessions. Each session contained 2 neurofeedback runs where participants completed …

Glucocorticoids And “Stress” Are Not Synonymous, Scott Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

Synopsis

Reference to glucocorticoids as “stress hormones” has been growing in prevalence in the literature, including in comparative and environmental endocrinology. Although glucocorticoids are elevated in response to a variety of stressors in vertebrate animals, the primary functions of glucocorticoids are not responding to stressors and they are only one component of complex suite of physiological and behavioral responses to stressors. Thus, the use of the short-hand phrase “stress hormone” can be misleading. Further, simply measuring glucocorticoids is not equivalent to measuring a stress response, nor is manipulating glucocorticoids equivalent to exposing an animal to a stressor. In this commentary …