Neurosciences Commons^™

Schrödinger Filtering: A Precise Eeg Despiking Technique For Eeg-Fmri Gradient Artifact, Gabriel B. Benigno, Ravi S. Menon, Hacene Serrai

Brain and Mind Institute Researchers' Publications

In EEG data acquired in the presence of fMRI, gradient-related spike artifacts contaminate the signal following the common preprocessing step of average artifact subtraction. Spike artifacts compromise EEG data quality since they overlap with the EEG signal in frequency, thereby confounding frequency-based inferences on activity. As well, spike artifacts can inflate or deflate correlations among time series, thereby confounding inferences on functional connectivity. We present Schrödinger filtering, which uses the Schrödinger equation to decompose the spike-containing input. The basis functions of the decomposition are localized and pulse-shaped, and selectively capture the various input peaks, with the spike components clustered at …

Cracking The Code Of Place Value: The Relationship Between Place And Value Takes Years To Master, Pierina Cheung, Daniel Ansari

Brain and Mind Institute Researchers' Publications

Place value, which underlies the meanings of multidigits, encompasses the principle of position and base-10 rules. To understand 65, one needs to know that the digits 6 and 5 occupy different positions and thus represent ordered values of different magnitudes (i.e., the principle of position) and that the value of each position is determined by base-10 rules (i.e., the rightmost position is 100, followed by 101, 102, etc.). Without the principle of position, children cannot construct meanings for multidigits. Previous studies have shown that children do not know the exact value of digit positions until the early elementary school years, …

Rapid Decline In Telestroke Consults In The Setting Of Covid-19., Syed O. Shah., Robin Dharia, Jaime Stazi, Maureen Deprince, Robert H. Rosenwasswer

Farber Institute for Neuroscience Faculty Papers

Background and Purpose: As coronavirus disease 2019 (COVID-19) continues to be a global pandemic, there is a growing body of evidence suggesting that incidence of diseases that require emergent care, particularly myocardial infarction and ischemic stroke, has declined rapidly. The objective of this study is to quantify our experience of telestroke (TS) consults at a large tertiary comprehensive stroke center during the COVID-19 pandemic.

Methods: We retrospectively reviewed TS consults of patients presenting to our neuroscience network. Those with a confirmed diagnosis of acute ischemic stroke or transient ischemia attack were included. Data were compared from April 1, 2019, to …

Infection And Risk Of Parkinson's Disease, Richard Jay Smeyne, Alastair J Noyce, Matthew D. Byrne, Rodolfo Savica, Connie Marras

Department of Neuroscience Faculty Papers

Parkinson's disease (PD) is thought to be caused by a combination of genetic and environmental factors. Bacterial or viral infection has been proposed as a potential risk factor, and there is supporting although not entirely consistent epidemiologic and basic science evidence to support its role. Encephalitis caused by influenza has included parkinsonian features. Epidemiological evidence is most compelling for an association between PD and hepatitis C virus. Infection with Helicobacter pylori may be associated not only with PD risk but also response to levodopa. Rapidly evolving knowledge regarding the role of the microbiome also suggests a role of resident bacteria …

Development Of A Method Using Retrograde Neuronal Tracers To Neuroanatomically Characterize Respiratory Neural Circuitry, Samantha Thomas, Angelo Lepore

Phase 1

Introduction:

Loss of respiratory function is one of the leading causes of death following spinal cord injury (SCI). Existing studies have demonstrated that pre-phrenic interneurons (PPIN’s) can be recruited into the phrenic motor neuron (PhMN) pathway following cervical SCI and may contribute to respiratory recovery, but there is still a lack of information detailing the nature of these changes and the extent they may improve diaphragm function. This project aims to validate a method of utilizing neuronal tracers to further characterize the intact respiratory circuitry.

Methods:

This study was carried out using a rat model. A fluorophore-conjugated retrograde neuronal …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Characterization Of Abin-1 In The Traumatically Injured Brain, Aaron Orellana, Alana C. Conti

Medical Student Research Symposium

Traumatic brain injury (TBI) is associated with chronic pain and persistent neuroinflammation. Opioids are often prescribed in order to relieve pain symptoms, but recent evidence suggests that their use negatively impacts the neuropathology of TBI leading to behavioral impairments and exacerbated neuroinflammation. The de-ubiquinating enzyme tumor necrosis factor alpha-induced protein (TNFAIP)3 or A20, inhibits the inflammatory signaling transcription factor nuclear factor (NF)-kB leading to attenuation of the inflammatory response. A20-binding inhibitor of nuclear factor kB (ABIN-1), which physically interacts with A20, also plays a role in the inhibition of NF-kB and is poorly researched in the central nervous system (CNS). …

Sex, Diabetes Status And Cognition: Findings From The Study Of Longevity In Diabetes, Chris Moran, Paola Gilsanz, Michal S. Beeri, Rachel A. Whitmer, Mary E. Lacy

Epidemiology and Environmental Health Faculty Publications

INTRODUCTION: Women comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk.

RESEARCH DESIGN AND METHODS: We examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D …

L-Theanine Prevents Long-Term Affective And Cognitive Side Effects Of Adolescent Δ-9-Tetrahydrocannabinol Exposure And Blocks Associated Molecular And Neuronal Abnormalities In The Mesocorticolimbic Circuitry, Marta De Felice, Justine Renard, Roger Hudson, Hanna J. Szkudlarek, Brian J. Pereira, Susanne Schmid, Walter J. Rushlow, Steven R. Laviolette

Brain and Mind Institute Researchers' Publications

Chronic adolescent exposure to Δ-9-tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioral abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathologic alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations. L-Theanine is an amino acid analog of L-glutamate and L-glutamine derived from various plant sources, including green tea leaves. L-Theanine has previously been …

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction In Tauopathy, Shon A. Koren, Matthew J. Hamm, Ryan Cloyd, Sarah N. Fontaine, Emad Chishti, Chiara Lanzillotta, Jennifer Rodriguez-Rivera, Alexandria Ingram, Michelle Bell, Sara M. Galvis-Escobar, Nicholas Zulia, Fabio Di Domenico, Duc Duong, Nicholas T. Seyfried, David K. Powell, Moriel Vandsburger, Tal Frolinger, Anika M. S. Hartz, John Koren Iii, Jeffrey M. Axten, Nicholas J. Laping, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging …

Intracellular Β1-Adrenergic Receptors And Organic Cation Transporter 3 Mediate Phospholamban Phosphorylation To Enhance Cardiac Contractility, Ying Wang, Qian Shi, Minghui Li, Meimi Zhao, Raghavender Reddy Gopireddy, Jian-Peng Teoh, Bing Xu, Chaoqun Zhu, Kyle E. Ireton, Sanghavi Srinivasan, Shaoliang Chen, Paul J. Gasser, Julie Bossuyt, Johannes W. Hell, Donald M. Bers, Yang K. Xiang

Biomedical Sciences Faculty Research and Publications

Rationale:

β₁ARs (β₁-adrenoceptors) exist at intracellular membranes and OCT3 (organic cation transporter 3) mediates norepinephrine entry into cardiomyocytes. However, the functional role of intracellular β₁AR in cardiac contractility remains to be elucidated.

Objective:

Test localization and function of intracellular β₁AR on cardiac contractility.

Methods and Results:

Membrane fractionation, super-resolution imaging, proximity ligation, coimmunoprecipitation, and single-molecule pull-down demonstrated a pool of β₁ARs in mouse hearts that were associated with sarco/endoplasmic reticulum Ca²⁺-ATPase at the sarcoplasmic reticulum (SR). Local PKA (protein kinase A) activation was measured using a PKA biosensor …

Genetic Approach To Elucidate The Role Of Cyclophilin D In Traumatic Brain Injury Pathology, Ryan D. Readnower, W. Brad Hubbard, Olivia J. Kalimon, James W. Geddes, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Cyclophilin D (CypD) has been shown to play a critical role in mitochondrial permeability transition pore (mPTP) opening and the subsequent cell death cascade. Studies consistently demonstrate that mitochondrial dysfunction, including mitochondrial calcium overload and mPTP opening, is essential to the pathobiology of cell death after a traumatic brain injury (TBI). CypD inhibitors, such as cyclosporin A (CsA) or NIM811, administered following TBI, are neuroprotective and quell neurological deficits. However, some pharmacological inhibitors of CypD have multiple biological targets and, as such, do not directly implicate a role for CypD in arbitrating cell death after TBI. Here, we reviewed the …

Self-Administered Behavioral Skills-Based At-Home Virtual Reality Therapy For Chronic Low Back Pain: Protocol For A Randomized Controlled Trial., Laura Garcia, Beth Darnall, Parthasarathy Krishnamurthy, Ian Mackey, Josh Sackman, Robert Louis, Todd Maddox, Brandon Birckhead

Articles, Abstracts, and Reports

BACKGROUND: Chronic pain is one of the most common and debilitating health conditions. Treatments for chronic low back pain typically focus on biomedical treatment approaches. While psychosocial treatments exist, multiple barriers prevent broad access. There is a significant unmet need for integrative, easily accessible, non-opioid solutions for chronic pain. Virtual reality (VR) is an immersive technology allowing innovation in the delivery of behavioral pain treatments. Behavioral skills-based VR is effective at facilitating pain management and reducing pain-related concerns. Continued research on these emerging approaches is needed.

OBJECTIVE: In this randomized controlled trial, we seek to test the efficacy of a …

The Multiplicity Of Caregiving Burden: A Qualitative Analysis Of Families With Prolonged Disorders Of Consciousness., Laura E Gonzalez-Lara, Sarah Munce, Jennifer Christian, Adrian M Owen, Charles Weijer, Fiona Webster

Brain and Mind Institute Researchers' Publications

Objective: To understand the multiple and sometimes conflicting roles substitute decision makers (SDMs) of individuals in a vegetative state (VS), minimally conscious state (MCS), or with locked-in syndrome (LIS) perform while caring for a loved one and the competing priorities derived from these roles.Methods: We conducted semi-structured qualitative interviews using a constructive-grounded theory design. Twelve SDMs, who were also family members for 11 patients, were interviewed at two time points (except one) for a total of 21 in-depth interviews.Results: Participants described that caregiving is often the central role which they identify as their top priority …

A High Affinity, Partial Antagonist Effect Of 3,4-Diaminopyridine Mediates Action Potential Broadening And Enhancement Of Transmitter Release At Nmjs, Kristine S Ojala, Scott P Ginebaugh, Man Wu, Evan W Miller, Gloria Ortiz, Manuel Covarrubias, Stephen D Meriney

Department of Neuroscience Faculty Papers

3,4-Diaminopyridine (3,4-DAP) increases transmitter release from neuromuscular junctions (NMJs), and low doses of 3,4-DAP (estimated to reach ∼1 μM in serum) are the Food and Drug Administration (FDA)-Approved treatment for neuro muscular weakness caused by Lambert-Eaton myasthenic syn drome. Canonically, 3,4-DAP is thought to block voltage-gated potassium (Kv) channels, resulting in prolongation of the pre synaptic action potential (AP). However, recent reports have shown that low millimolar concentrations of 3,4-DAP have an off-Target agonist effect on the Cav1 subtype ("L-Type") of voltage-gated calcium (Cav) channels and have speculated that this agonist effect might contribute to 3,4-DAP effects on transmitter release …

Sharing Voxelwise Neuroimaging Results From Rhesus Monkeys And Other Species With Neurovault, Andrew S. Fox, Daniel Holley, Peter Christiaan Klink, Spencer A. Arbuckle, Carol A. Barnes, Jörn Diedrichsen, Sze Chai Kwok, Colin Kyle, J. Andrew Pruszynski, Jakob Seidlitz, Xu Feng Zhou, Russell A. Poldrack, Krzysztof J. Gorgolewski

Brain and Mind Institute Researchers' Publications

© 2020 The Authors Animal neuroimaging studies can provide unique insights into brain structure and function, and can be leveraged to bridge the gap between animal and human neuroscience. In part, this power comes from the ability to combine mechanistic interventions with brain-wide neuroimaging. Due to their phylogenetic proximity to humans, nonhuman primate neuroimaging holds particular promise. Because nonhuman primate neuroimaging studies are often underpowered, there is a great need to share data amongst translational researchers. Data sharing efforts have been limited, however, by the lack of standardized tools and repositories through which nonhuman neuroimaging data can easily be archived …

Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1 …

Abnormal Nutritive Sucking As An Indicator Of Neonatal Brain Injury, Sabrina Shandley, Gilson J. Capilouto, Eleonora Tamilia, David M. Riley, Yvette R. Johnson, Christos Papadelis

Communication Sciences and Disorders Faculty Publications

A term neonate is born with the ability to suck; this neuronal network is already formed and functional by 28 weeks gestational age and continues to evolve into adulthood. Because of the necessity of acquiring nutrition, the complexity of the neuronal network needed to suck, and neuroplasticity in infancy, the skill of sucking has the unique ability to give insight into areas of the brain that may be damaged either during or before birth. Interpretation of the behaviors during sucking shows promise in guiding therapies and how to potentially repair the damage early in life, when neuroplasticity is high. Sucking …

Encephalopathy And Complex Hyperkinesia In A Patient With Severe Acute Respiratory Syndrome Coronavirus-2 Infection, Wenyang Li, Elif Pinar Coskun, Rolando Berger, John T. Slevin, L. Creed Pettigrew

Neurology Faculty Publications

No abstract provided.

Dystrophic Microglia Are Associated With Neurodegenerative Disease And Not Healthy Aging In The Human Brain, Ryan K. Shahidehpour, Rebecca E. Higdon, Nicole G. Crawford, Janna H. Neltner, Eseosa T. Ighodaro, Ela Patel, Douglas Price, Peter T. Nelson, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could …