Neurosciences Commons^™

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 …

Identifying Key Elements To Assess Patient’S Acceptability Of Neurorehabilitation In Stroke Survivors–A Delphi Method, Manonita Ghosh, Kaoru Nosaka, Lisa Whitehead, Kazunori Nosaka

Research outputs 2014 to 2021

Purpose: Assessing patient acceptability of treatment is a clinical concern. No guidance exists to determine the best way to measure acceptability in stroke neurorehabilitation. This study identifies key elements to measure patient’s acceptance of stroke neurorehabilitation by establishing expert consensus.

>Materials and methods: A four-phase Delphi method with a three-round electronic-based survey was conducted. Experts were considered as stroke survivors or their caregivers and professionals in stroke neurorehabilitation. A twenty-five-item list was sourced from a literature review and discussion with a consumer panel (n = 22). In Round-1 (n = 118) and Round-2 (n = 80), experts …

Associations Of The Lipidome With Ageing, Cognitive Decline And Exercise Behaviours, Maria Kadyrov, Luke Whiley, Belinda Brown, Kirk I. Erickson, Elaine Holmes

Research outputs 2022 to 2026

One of the most recognisable features of ageing is a decline in brain health and cognitive dysfunction, which is associated with perturbations to regular lipid homeostasis. Although ageing is the largest risk factor for several neurodegenerative diseases such as dementia, a loss in cognitive function is commonly observed in adults over the age of 65. Despite the prevalence of normal age-related cognitive decline, there is a lack of effective methods to improve the health of the ageing brain. In light of this, exercise has shown promise for positively influencing neurocognitive health and associated lipid profiles. This review summarises age-related changes …

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 …

A Steroid Receptor Coactivator Small Molecule "Stimulator" Attenuates Post-Stroke Ischemic Brain Injury, Lisa K Mcclendon, Roberto L Garcia, Tyler Lazaro, Ariadna Robledo, Viren Vasandani, Zean Aaron Evan Luna, Abhijit S Rao, Aditya Srivatsan, David M Lonard, Clifford C Dacso, Peter Kan, Bert W O'Malley

Faculty, Staff and Students Publications

Introduction: Pathologic remodeling of the brain following ischemic stroke results in neuronal loss, increased inflammation, oxidative stress, astrogliosis, and a progressive decrease in brain function. We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia. Since steroid receptor coactivators are ubiquitously expressed in the brain, we reasoned that an MCB-613 derivative (MCB-10-1), could protect the brain following ischemic injury. To test this, we administered MCB-10-1 to rats following middle cerebral artery occlusion and reperfusion.

Methods: Neurologic impairment and tissue damage responses were evaluated on day …

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, …