Neurosciences Commons^™

Rac-Maninoff And Rho-Vel: The Symphony Of Rho-Gtpase Signaling At Excitatory Synapses, Joseph G Duman, Francisco A Blanco, Christopher A Cronkite, Qin Ru, Kelly C Erikson, Shalaka Mulherkar, Ali Bin Saifullah, Karen Firozi, Kimberley F Tolias

Faculty, Staff and Students Publications

Synaptic connections between neurons are essential for every facet of human cognition and are thus regulated with extreme precision. Rho-family GTPases, molecular switches that cycle between an active GTP-bound state and an inactive GDP-bound state, comprise a critical feature of synaptic regulation. Rho-GTPases are exquisitely controlled by an extensive suite of activators (GEFs) and inhibitors (GAPs and GDIs) and interact with many different signalling pathways to fulfill their roles in orchestrating the development, maintenance, and plasticity of excitatory synapses of the central nervous system. Among the mechanisms that control Rho-GTPase activity and signalling are cell surface receptors, GEF/GAP complexes that …

A Precision Medicine Agenda In Traumatic Brain Injury, Jovany Cruz Navarro, Lucido L Ponce Mejia, Claudia Robertson

Faculty, Staff and Students Publications

Traumatic brain injury remains a leading cause of death and disability across the globe. Substantial uncertainty in outcome prediction continues to be the rule notwithstanding the existing prediction models. Additionally, despite very promising preclinical data, randomized clinical trials (RCTs) of neuroprotective strategies in moderate and severe TBI have failed to demonstrate significant treatment effects. Better predictive models are needed, as the existing validated ones are more useful in prognosticating poor outcome and do not include biomarkers, genomics, proteonomics, metabolomics, etc. Invasive neuromonitoring long believed to be a "game changer" in the care of TBI patients have shown mixed results, and …

Faces Of Pain In Dementia: Learnings From A Real-World Study Using A Technology-Enabled Pain Assessment Tool, Mustafa Atee, Kreshnik Hoti, Paola Chivers, Jeffery D. Hughes

Research outputs 2022 to 2026

Pain is common in people living with dementia (PLWD), including those with limited verbal skills. Facial expressions are key behavioral indicators of the pain experience in this group. However, there is a lack of real-world studies to report the prevalence and associations of pain-relevant facial micro-expressions in PLWD. In this observational retrospective study, pain-related facial features were studied in a sample of 3,144 PLWD [mean age 83.3 years (SD = 9.0); 59.0% female] using the Face domain of PainChek®, a point-of-care medical device application. Pain assessments were completed by 389 users from two national dementia-specific care programs and 34 Australian …

Transcranial Magnetic Stimulation To Assess Motor Neurophysiology After Acute Stroke In The United States: Feasibility, Lessons Learned, And Values For Future Research, Yi-Ling Kuo, David J. Lin, Isha Vora, Julie A. Dicarlo, Dylan J. Edwards, Teresa J. Kimberley

Research outputs 2022 to 2026

Transcranial magnetic stimulation (TMS) has been widely applied in both basic and clinical neuroscience since its introduction in 1985 . . .

Walking Improvement In Chronic Incomplete Spinal Cord Injury With Exoskeleton Robotic Training (Wise): A Randomized Controlled Trial, Dylan J. Edwards, Gail Forrest, Mar Cortes, Margaret M. Weightman, Cristina Sadowsky, Shuo-Hsiu Chang, Kimberly Furman, Amy Bialek, Sara Prokup, John Carlow, Leslie Vanhiel, Laura Kemp, Darrell Musick, Marc Campo, Arun Jayaraman

Research outputs 2022 to 2026

Study design:

Clinical trial.

Objective:

To demonstrate that a 12-week exoskeleton-based robotic gait training regimen can lead to a clinically meaningful improvement in independent gait speed, in community-dwelling participants with chronic incomplete spinal cord injury (iSCI).

Setting:

Outpatient rehabilitation or research institute.

Methods:

Multi-site (United States), randomized, controlled trial, comparing exoskeleton gait training (12 weeks, 36 sessions) with standard gait training or no gait training (2:2:1 randomization) in chronic iSCI ( > 1 year post injury, AIS-C, and D), with residual stepping ability. The primary outcome measure was change in robot-independent gait speed (10-meter walk test, 10MWT) post 12-week intervention. Secondary …

5-Ht2 Receptor Antagonism Reduces Human Motoneuron Output To Antidromic Activation But Not To Stimulation Of Corticospinal Axons, Jacob R. Thorstensen, Janet L. Taylor, Justin J. Kavanagh

Research outputs 2022 to 2026

The intrinsic electrical properties of motoneurons strongly affect motoneuron excitability to fast-acting excitatory ionotropic inputs. Serotonin (5-HT) is a neurochemical that alters the intrinsic properties of motoneurons, whereby animal models and in vitro experiments indicate that 5-HT increases motoneuron excitability by activating 5-HT2 receptors on the somato-dendritic compartment. In the current study, we examined how antagonism of the 5-HT2 receptor affects motoneuron excitability in humans. We hypothesised that motoneuron excitability would be reduced. The 5-HT2 antagonist cyproheptadine was administered to 10 healthy participants in a double-blinded, placebo-controlled, crossover trial. Electrical cervicomedullary stimulation was used to deliver a synchronised excitatory volley …

The Benefits Of Astaxanthin To Improve Pain Relief In Patients With Painful Diabetic Neuropathy: An Open-Label, Randomized Controlled Trial, Rizaldy Taslim Pinzon, Mary Rose Angelina Budi Harsana

Pharmaceutical Sciences and Research

Treatment of diabetic neuropathy is still carried out by providing symptomatic therapy, which only improves ± 50% of the total symptoms felt by patients, but does not tackle the underlying causes of the disease. Astaxanthin is a potent antioxidant, anti-inflammatory, and anti-diabetic carotenoid that could be an additional treatment option. We aimed to measure the effectiveness of administering astaxanthin as an additional therapy to improve the impact of pain and discomfort experienced daily by diabetes mellitus patients with painful diabetic neuropathy. We conducted a randomized experimental study with an open label design of 36 patients who had been diagnosed with …

Inhibition Of Bruton Tyrosine Kinase Reduces Neuroimmune Cascade And Promotes Recovery After Spinal Cord Injury, Chen Guang Yu, Vimala Bondada, Hina Iqbal, Kate L. Moore, John C. Gensel, Subbarao Bondada, James W. Geddes

Physiology Faculty Publications

Microglia/astrocyte and B cell neuroimmune responses are major contributors to the neurological deficits after traumatic spinal cord injury (SCI). Bruton tyrosine kinase (BTK) activation mechanistically links these neuroimmune mechanisms. Our objective is to use Ibrutinib, an FDA-approved BTK inhibitor, to inhibit the neuroimmune cascade thereby improving locomotor recovery after SCI. Rat models of contusive SCI, Western blot, immunofluorescence staining imaging, flow cytometry analysis, histological staining, and behavioral assessment were used to evaluate BTK activity, neuroimmune cascades, and functional outcomes. Both BTK expression and phosphorylation were increased at the lesion site at 2, 7, 14, and 28 days after SCI. Ibrutinib …

Treatment-Specific Hippocampal Subfield Volume Changes With Antidepressant Medication Or Cognitive-Behavior Therapy In Treatment-Naive Depression., Hua-Hsin Tai, Jungho Cha, Faezeh Vedaei, Boadie W Dunlop, W Edward Craighead, Helen S Mayberg, Ki Sueng Choi

Department of Neuroscience Faculty Papers

Background: Hippocampal atrophy has been consistently reported in major depressive disorder with more recent focus on subfields. However, literature on hippocampal volume changes after antidepressant treatment has been limited. The first-line treatments for depression include antidepressant medication (ADM) or cognitive-behavior therapy (CBT). To understand the differential effects of CBT and ADM on the hippocampus, we investigated the volume alterations of hippocampal subfields with treatment, outcome, and chronicity in treatment-naïve depression patients. Methods: Treatment-naïve depressed patients from the PReDICT study were included in this analysis. A total of 172 patients who completed 12 weeks of randomized treatment with CBT (n …

Levels Of Angiotensin-Converting Enzyme And Apolipoproteins Are Associated With Alzheimer’S Disease And Cardiovascular Diseases, Chun Xu, Debra Garcia, Yongke Lu, Kaysie Ozuna, Donald A. Adjeroh, Kesheng Wang

Health & Biomedical Sciences Faculty Publications

Angiotensin-converting enzyme-1 (ACE1) and apolipoproteins (APOs) may play important roles in the development of Alzheimer’s disease (AD) and cardiovascular diseases (CVDs). This study aimed to examine the associations of AD, CVD, and endocrine-metabolic diseases (EMDs) with the levels of ACE1 and 9 APO proteins (ApoAI, ApoAII, ApoAIV, ApoB, ApoCI, ApoCIII, ApoD, ApoE, and ApoH). Non-Hispanic white individuals including 109 patients with AD, 356 mild cognitive impairment (MCI), 373 CVD, 198 EMD and controls were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Multivariable general linear model (GLM) was used to examine the associations. ApoE ε4 allele was associated with …

Effects Of Subthalamic Deep Brain Stimulation On Treating Motor Symptoms In Early Parkinson's Disease, Emily Reale, Gina Legaluppi

Physician Assistant Capstones, 2020-current

Objective: Assess the efficacy of subthalamic nucleus deep brain stimulation (STN DBS) versus solely optimal pharmacological use in early Parkinson's Disease to improve motor dysfunction. Design: Systematic Literature Review. Methods: Searches were completed on PubMed utilizing the MeSH terms: “subthalamic, deep brain stimulation, and early parkinson.” Using PubMed the following limits and terms were used: published in the last 10 years, randomized controlled trial, English, human, and removing duplicates. A total of three studies resulted after the search. Results: All three studies showed statistically significant results in reduction in disease progressive motor symptoms. Additionally, at the end of each study …

Design And Development Of A Mobile Health (Mhealth) Platform For Dementia Prevention In The Prevention Of Dementia By Mobile Phone Applications (Prodemos) Project, Melanie Hafdi, Esmé Eggink, Marieke P. Hoevenaar-Blom, M. Patrick Witvliet, Sandrine Andrieu, Linda Barnes, Carol Brayne, Rachael Brooks, Nicola Coley, Jean Georges, Abraham Van Der Groep, Harm Van Marwijk, Mark Van Der Meijden, Libin Song, Manshu Song, Youxin Wang, Wenzhi Wang, Wei Wang, Anders Wimo, Xiaoyan Ye, Eric P. Moll Van Charante, Edo Richard, Prodemos Consortium

Research outputs 2014 to 2021

Background:

Mobile health (mHealth) has the potential to bring preventive healthcare within reach of populations with limited access to preventive services, by delivering personalized support at low cost. Although numerous mHealth interventions are available, very few have been developed following an evidence-based rationale or have been tested for efficacy. This article describes the systematic development of a coach-supported mHealth application to improve healthy lifestyles for the prevention of dementia and cardiovascular disease in the United Kingdom (UK) and China.

Methods:

Development of the Prevention of Dementia by Mobile Phone applications (PRODEMOS) platform built upon the experiences with the Healthy Aging …

An Investigation Of Sensory Percepts Elicited By Macro-Sieve Electrode Stimulation Of The Rat Sciatic Nerve, Nikhil Shiva Chandra

McKelvey School of Engineering Graduate Student Theses & Dissertations

Intuitive control of conventional prostheses is hampered by their inability to replicate the rich tactile and proprioceptive feedback afforded by natural sensory pathways. Electrical stimulation of residual nerve tissue is a promising means of reintroducing sensory feedback to the central nervous system. The macro-sieve electrode (MSE) is a candidate interface to amputees’ truncated peripheral nerves whose unique geometry enables selective control of the complete nerve cross-section. Unlike previously studied interfaces, the MSE’s implantation entails transection and subsequent regeneration of the target nerve. Therefore, a key determinant of the MSE’s suitability for this task is whether it can elicit sensations at …

Mapping Neural Responses Onto Innate And Acquired Behavior: From Insect Olfaction To Realizing A Bio-Hybrid Chemical Recognition System, Rishabh Chandak

McKelvey School of Engineering Graduate Student Theses & Dissertations

In many organisms, the sense of smell, driven by the olfactory system, serves as the primary sensory modality that guides a plethora of behaviors such as foraging for food, finding mates, and evading predators. Using an array of biological sensors, the olfactory system converts volatile chemical inputs from an organism’s environment into well-patterned neural responses that inform downstream motor neurons to drive appropriate behaviors (e.g., moving towards food or away from danger). For many external cues, the elicited neural responses are often determined by the genetic makeup of the organism, which assigns an innate preference, or valence, for these different …

Functional Differentiation In The Language Network Revealed By Lesion-Dymptom Mapping, William Matchin, Alexandra Basilakos, Dirk B. Den Ouden, Brielle C. Stark, Gregory Hickok, Julius Fridriksson

Communication Sciences and Disorders Faculty Articles and Research

Theories of language organization in the brain commonly posit that different regions underlie distinct linguistic mechanisms. However, such theories have been criticized on the grounds that many neuroimaging studies of language processing find similar effects across regions. Moreover, condition by region interaction effects, which provide the strongest evidence of functional differentiation between regions, have rarely been offered in support of these theories. Here we address this by using lesion-symptom mapping in three large, partially-overlapping groups of aphasia patients with left hemisphere brain damage due to stroke (N = 121, N = 92, N = 218). We identified multiple measure by …

Dementia Risk Reduction: Why Haven't The Pharmacological Risk Reduction Trials Worked? An In-Depth Exploration Of Seven Established Risk Factors, Ruth Peters, John Breitner, Sarah James, Gregory A. Jicha, Pierre-Francois Meyer, Marcus Richards, A. David Smith, Hussein N. Yassine, Erin L. Abner, Atticus H. Hainsworth, Patrick G. Kehoe, Nigel Beckett, Christopher Weber, Craig Anderson, Kaarin J. Anstey, Hiroko H. Dodge

Neurology Faculty Publications

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need …

Bi-Allelic Variants In Ogdhl Cause A Neurodevelopmental Spectrum Disease Featuring Epilepsy, Hearing Loss, Visual Impairment, And Ataxia, Zheng Yie Yap, Stephanie Efthymiou, Simone Seiffert, Karen Vargas Parra, Sukyeong Lee, Alessia Nasca, Reza Maroofian, Isabelle Schrauwen, Manuela Pendziwiat, Sunhee Jung, Elizabeth Bhoj, Pasquale Striano, Kshitij Mankad, Barbara Vona, Sanmati Cuddapah, Anja Wagner, Javeria Raza Alvi, Elham Davoudi-Dehaghani, Mohammad-Sadegh Fallah, Srinitya Gannavarapu, Costanza Lamperti, Andrea Legati, Bibi Nazia Murtaza, Muhammad Shahid Nadeem, Mujaddad Ur Rehman, Kolsoum Saeidi, Vincenzo Salpietro, Sarah Von Spiczak, Abigail Sandoval, Sirous Zeinali, Massimo Zeviani, Adi Reich, Synaps Study Group, University Of Washington Center For Mendelian Genomics, Cholsoon Jang, Ingo Helbig, Tahsin Stefan Barakat, Daniele Ghezzi, Suzanne M Leal, Yvonne Weber, Henry Houlden, Wan Hee Yoon

Faculty, Staff and Students Publications

The 2-oxoglutarate dehydrogenase-like (OGDHL) protein is a rate-limiting enzyme in the Krebs cycle that plays a pivotal role in mitochondrial metabolism. OGDHL expression is restricted mainly to the brain in humans. Here, we report nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum. The variants include three homozygous missense variants (p.Pro852Ala, p.Arg244Trp, and p.Arg299Gly), three compound heterozygous single-nucleotide variants (p.Arg673Gln/p.Val488Val, p.Phe734Ser/p.Ala327Val, and p.Trp220Cys/p.Asp491Val), one homozygous frameshift variant (p.Cys553Leufs∗16), and one homozygous stop-gain variant (p.Arg440Ter). To support the …

Early Protein Intake Predicts Functional Connectivity And Neurocognition In Preterm Born Children, Emma G. Duerden, Benjamin Thompson, Tanya Poppe, Jane Alsweiler, Greg Gamble, Yannan Jiang, Myra Leung, Anna C. Tottman, Trecia Wouldes, Steven P. Miller, Jane E. Harding, Jane M. Alsweiler, Janene B. Biggs, Coila Bevan, Joanna M. Black, Frank H. Bloomfield, Kelly Fredell, Greg D. Gamble, Jane E. Harding, Sabine Huth, Yannan Jiang, Christine Kevan, Myra Leung, Geraint Phillips, Tanya Poppe, Jennifer A. Rogers, Heather Stewart, Benjamin S. Thompson

Brain and Mind Institute Researchers' Publications

© 2021, The Author(s). Nutritional intake can promote early neonatal brain development in very preterm born neonates (< 32 weeks’ gestation). In a group of 7-year-old very preterm born children followed since birth, we examined whether early nutrient intake in the first weeks of life would be associated with long-term brain function and neurocognitive skills at school age. Children underwent resting-state functional MRI (fMRI), intelligence testing (Wechsler Intelligence Scale for Children, 5th Ed) and visual-motor processing (Beery-Buktenica, 5th Ed) at 7 years. Relationships were assessed between neonatal macronutrient intakes, functional connectivity strength between thalamic and default mode networks (DMN), and neuro-cognitive function using multivariable regression. Greater functional connectivity strength between thalamic networks and DMN was associated with greater intake of protein in the first week (β = 0.17; 95% CI 0.11, 0.23, p < 0.001) but lower intakes of fat (β = − 0.06; 95% CI − 0.09, − 0.02, p = 0.001) and carbohydrates (β = − 0.03; 95% CI − 0.04, − 0.01, p = 0.003). Connectivity strength was also associated with protein intake during the first month (β = 0.22; 95% CI 0.06, 0.37, p = 0.006). Importantly, greater thalamic-DMN connectivity strength was associated with higher processing speed indices (β = 26.9; 95% CI 4.21, 49.49, p = 0.02) and visual processing scores (β = 9.03; 95% CI 2.27, 15.79, p = 0.009). Optimizing early protein intake may contribute to promoting long-term brain health in preterm-born children.

Effects Of Chemosensory Experience And Context On Consummatory Behaviors., Saphira M. Chiu

Electronic Theses and Dissertations

Eating food generates associations between odors and tastes (i.e., flavor) that guide future choices. Experience with an odor-taste mixture links an odor with a taste’s quality and hedonic value, resulting in a preference for an odor paired with a palatable taste over an odor paired with an unpalatable taste. However, experience with a neutral stimulus (i.e., latent inhibition) or environment (i.e., context) can influence the formation of conditioned associations. Here, I used a two-bottle brief-access task to determine whether rats display an innate preference between unpaired odors (isoamyl acetate and benzaldehyde), how preexposure to the unpaired odors impacts mixture-dependent consummatory …

(R)-2,5-Dimethoxy-4-Iodoamphetamine [(R)-Doi] Influences Coping Strategies To An Escapable Social Stress, Kevin Thomas Krupp

Dissertations and Theses

Depressive mood disorders are a leading cause of disability worldwide and pharmacological treatments for these disorders are inadequate, requiring new compounds with greater efficacy be investigated. The etiology of depression is heterogeneous; however, it is well established that stress exposure, and the proinflammatory effects of stress have a major role. Psychedelic compounds have rapid and long-lasting anxiolytic and antidepressive effects in humans and animal models of stress induced affective behavior. However, it is not completely understood how these compounds produce such rapid effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT2A partial agonist with potent anti-inflammatory properties, …

Widening Spinal Injury Research To Consider All Supraspinal Cell Types: Why We Must And How We Can, Murray G. Blackmore, Eliazbeth Batsel, Pantelis Tsoulfas

Biomedical Sciences Faculty Research and Publications

The supraspinal connectome consists of dozens of neuronal populations that project axons from the brain to the spinal cord to influence a wide range of motor, autonomic, and sensory functions. The complexity and wide distribution of supraspinal neurons present significant technical challenges, leading most spinal cord injury research to focus on a handful of major pathways such as the corticospinal, rubrospinal, and raphespinal. Much less is known about many additional populations that carry information to modulate or compensate for these main pathways, or which carry pre-autonomic and other information of high value to individuals with spinal injury. A confluence of …

An Analysis Of Taste Neuron Morphological Variability: Influences Of Neuron Type And Plasticity., Lisa Christina Ohman

Electronic Theses and Dissertations

Taste neurons are functionally and molecularly diverse, but their morphological diversity was, until recently, completely unexplored. Taste neurons were considered relay cells, communicating information from taste-transducing cells to the brain without variation in morphology. Instead, individual taste neurons are tremendously morphologically variable. To determine how differences in branching relate to the number and types of taste-transducing cells providing neuronal input, I combined sparse cell genetic labeling with a whole-mount immunohistochemistry and analysis workflow. I found that the maximum number of taste-transducing cells capable of providing convergent input onto individual gustatory neurons varied with a range of 1-22 taste-transducing cells. Consistently, …

Axon Initial Segment Morphology Across Typical Cortical Development And In Mouse Models Of Neurodevelopmental Disorders With A High Incidence Of Epilepsy, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) are commonly associated with a high incidence of epileptic seizures which result from excessive firing of neurons. The axon initial segment (AIS) is a neuronal compartment essential for the control of activity patterns of neurons. The AIS undergoes important modifications during development, but the molecular mechanisms that affect the development, morphology, and protein composition of the AIS are still not well understood. We examined AIS morphology of medial prefrontal cortex (mPFC) pyramidal neurons in wildtype mice across development and in two mouse models of NDDs. Results indicate restructurings at the AIS during typical development, some of which …

Ampk Modulation Ameliorates Dominant Disease Phenotypes Of Ctrp5 Variant In Retinal Degeneration, Kiyoharu J. Miyagishima, Ruchi Sharma, Malika Nimmagadda, Katharina Clore-Gronenborn, Zoya Qureshy, Davide Ortolan, Devika Bose, Mitra Farnoodian, Congxiao Zhang, Andrew Fausey, Yuri V. Sergeev, Mones Abu-Asab, Bokkyoo Jun, Khanh V. Do, Marie Audrey Kautzman Guerin, Jorgelina Calandria, Aman George, Bin Guan, Qin Wan, Rachel C. Sharp

School of Graduate Studies Faculty Publications

Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder caused by a missense substitution in CTRP5. Distinctive clinical features include sub-retinal pigment epithelium (RPE) deposits, choroidal neovascularization, and RPE atrophy. In induced pluripotent stem cells-derived RPE from L-ORD patients (L-ORD-iRPE), we show that the dominant pathogenic CTRP5 variant leads to reduced CTRP5 secretion. In silico modeling suggests lower binding of mutant CTRP5 to adiponectin receptor 1 (ADIPOR1). Downstream of ADIPOR1 sustained activation of AMPK renders it insensitive to changes in AMP/ATP ratio resulting in defective lipid metabolism, reduced Neuroprotectin D1(NPD1) secretion, lower mitochondrial respiration, and reduced ATP production. These metabolic …

Using Imputation To Provide Harmonized Longitudinal Measures Of Cognition Across Aibl And Adni, Rosita Shishegar, Timothy Cox, David Rolls, Pierrick Bourgeat, Vincent Doré, Fiona Lamb, Joanne Robertson, Simon M. Laws, Tenielle Porter, Jurgen Fripp, Duygu Tosun, Paul Maruff, Greg Savage, Christopher C. Rowe, Colin L. Masters, Michael W. Weiner, Victor L. Villemagne, Samantha C. Burnham

Research outputs 2014 to 2021

To improve understanding of Alzheimer’s disease, large observational studies are needed to increase power for more nuanced analyses. Combining data across existing observational studies represents one solution. However, the disparity of such datasets makes this a non-trivial task. Here, a machine learning approach was applied to impute longitudinal neuropsychological test scores across two observational studies, namely the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) providing an overall harmonised dataset. MissForest, a machine learning algorithm, capitalises on the underlying structure and relationships of data to impute test scores not measured in one study aligning …

The Effects Of Molecular Crowding And Cpg Hypermethylation On Dna G-Quadruplexes Formed By The C9orf72 Nucleotide Repeat Expansion., Kadir A. Ozcan, Layla T. Ghaffari, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

A nucleotide repeat expansion (NRE), (G₄C₂)_n, located in a classically noncoding region of C9orf72 (C9), is the most common genetic mutation associated with ALS/FTD. There is increasing evidence that nucleic acid structures formed by the C9-NRE may both contribute to ALS/FTD, and serve as therapeutic targets, but there is limited characterization of these nucleic acid structures under physiologically and disease relevant conditions. Here we show in vitro that the C9-NRE DNA can form both parallel and antiparallel DNA G-quadruplex (GQ) topological structures and that the structural preference of these DNA GQs can be dependent …

Designs And Outcomes Of Transcranial Magnetic Stimulation (Tms) And Repetitive Transcranial Magnetic Stimulation (Rtms) Circuits, Daniel Senda

UNLV Theses, Dissertations, Professional Papers, and Capstones

This thesis reports the design and outcomes of several circuits intended for transcranial magnetic stimulation (TMS) and repetitive transcranial magnetic stimulation (rTMS) research. In simple terms, TMS circuits are composed of four main blocks: high voltage power source, energy storage bank, control switch, and coil. Each one of these blocks has characteristics that influence how well the circuit will perform for TMS procedures. A successful TMS research circuit must have the ability to emit controlled electromagnetic pulses through a coil connected to it. For the first block, voltages ranging from 50 V to 2 kV were used. In the second …

Multiple Approaches To Auditory Rhythm: Development Of Sustained Musical Beat And The Relation To Language, Development Of Rhythmic Categories Via Iterated Production, And A Meta-Analytic Study Of Neural Entrainment To Beat, Karli Marie Nave

UNLV Theses, Dissertations, Professional Papers, and Capstones

Rhythm is ubiquitous to human communication, coordination, and experience of music. In this dissertation, I address three empirical questions through three different methodologies, all of which contribute to the growing body of literature on human auditory rhythm processing. In Chapter 2, I present a registered report detailing the results of independent conceptual replications of Nozaradan, Peretz, Missal, & Mouraux (2011), all using the same vetted protocol. Listeners performed the same tasks as in Nozaradan et al. (2011), with the addition of behavioral measures of perception. In neuroscience, neural correlates to musical beat perception have been identified, yet little to no …

Multi-Vendor And Multisite Evaluation Of Cerebrovascular Reactivity Mapping Using Hypercapnia Challenge, Peiying Liu, Dengrong Jiang, Marilyn Albert, Christopher E. Bauer, Arvind Caprihan, Brian T. Gold, Steven M. Greenberg, Karl G. Helmer, Kay Jann, Gregory A. Jicha, Pavel Rodriguez, Claudia L Satizabal, Sudha Seshadri, Herpreet Singh, Jeffrey F. Thompson, Danny J. J. Wang, Hanzhang Lu

Neuroscience Faculty Publications

Cerebrovascular reactivity (CVR), which measures the ability of cerebral blood vessels to dilate or constrict in response to vasoactive stimuli such as CO2 inhalation, is an important index of the brain's vascular health. Quantification of CVR using BOLD MRI with hypercapnia challenge has shown great promises in research and clinical studies. However, in order for it to be used as a potential imaging biomarker in large-scale and multi-site studies, the reliability of CO2-CVR quantification across different MRI acquisition platforms and researchers/raters must be examined. The goal of this report from the MarkVCID small vessel disease biomarkers consortium is to evaluate …

Higher Coffee Consumption Is Associated With Slower Cognitive Decline And Less Cerebral Aβ-Amyloid Accumulation Over 126 Months: Data From The Australian Imaging, Biomarkers, And Lifestyle Study, Samantha L. Gardener, Stephanie R. Rainey-Smith, Victor L. Villemagne, Jurgen Fripp, Vincent Doré, Pierrick Bourgeat, Kevin Taddei, Christopher Fowler, Colin L. Masters, Paul Maruff, Christopher C. Rowe, David Ames, Ralph N. Martins, Aibl Investigators

Research outputs 2014 to 2021

Background:

Worldwide, coffee is one of the most popular beverages consumed. Several studies have suggested a protective role of coffee, including reduced risk of Alzheimer’s disease (AD). However, there is limited longitudinal data from cohorts of older adults reporting associations of coffee intake with cognitive decline, in distinct domains, and investigating the neuropathological mechanisms underpinning any such associations.

Methods: The aim of the current study was to investigate the relationship between self-reported habitual coffee intake, and cognitive decline assessed using a comprehensive neuropsychological battery in 227 cognitively normal older adults from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study, over …