Neurosciences Commons^™

Obtaining And Maintaining Cortical Hand Representation As Evidenced From Acquired And Congenital Handlessness, Daan B. Wesselink, Fiona Mz Van Den Heiligenberg, Naveed Ejaz, Harriet Dempsey-Jones, Lucilla Cardinali, Aurelie Tarall-Jozwiak, Jörn Diedrichsen, Tamar R. Makin

Brain and Mind Institute Researchers' Publications

© Lukinova et al. A key question in neuroscience is how cortical organisation relates to experience. Previously we showed that amputees experiencing highly vivid phantom sensations maintain cortical representation of their missing hand (Kikkert et al., 2016). Here, we examined the role of sensory hand experience on persistent hand representation by studying individuals with acquired and congenital hand loss. We used representational similarity analysis in primary somatosensory and motor cortex during missing and intact hand movements. We found that key aspects of acquired amputees’ missing hand representation persisted, despite varying vividness of phantom sensations. In contrast, missing hand representation of …

Unmet Need For Mental Health Services Among People Screened But Not Admitted To An Early Psychosis Intervention Program, Jordan Edwards, Ross Norman, Paul Kurdyak, Arlene G. Macdougall, Lena Palaniyappan, Cindy Lau, Kelly K. Anderson

Brain and Mind Institute Researchers' Publications

Information is lacking on people screened for early psychosis intervention (EPI) but not admitted to the program. Using health administrative data, we constructed a retrospective cohort of incident cases of psychosis in the catchment of an EPI program. Use of mental health services was compared between people screened and not admitted with an EPI-admitted group. The non-admitted group had higher rates of subsequent emergency department visits, psychiatric hospitalizations, and involuntary admissions. These patterns are indicative of unmet need, and people screened but not admitted to EPI may benefit from protocols to improve transitions of care with other service providers.

Initial Characterization Of The Indole-3-Carboxamide Bic-154 As A Fast Onset And Reversible Orai Channel Blocker, Tetyana Zhelay, Kalina Szteyn, Elisa Liardo, Jae Eun Cheong, Steffi Koerner, Anil Ekkati, Lijun Sun, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

Calcium ion elevations are required for human T-lymphocyte proliferation in response to antigen recognition by a T-cell receptor. Calcium influx through the plasma membrane is necessary for efficient T-cell proliferation and effector function. The calcium channels responsible for Ca2+ influx in lymphocytes have been identified and Orai interacting with ER Ca2+ sensor STIM were shown to be crucial for persistent calcium mobilization. Loss-of-function mutations in Orai1 or STIM1 result in severe combined immunodeficiency (SCID) with muscle hypotonia. Suppression of calcium influx through Orai/STIM channels gives rise to various lymphoproliferative defects. Thus, deletion of Orai or STIM in mice results in …

Selection Criteria For Posterior Circulation Stroke And Functional Outcome Following Mechanical Thrombectomy, Vivian Xu, Ahmad Sweid, Md, Stavropoula Tjoumakaris, Md, Kavya Shivashankar, Ba, Karim Hafazalla, Bs, Michael R. Gooch, Md, Nabeel Herial, Md, Robert H. Rosenwasswer Md, Pascal Jabbour, Md

Phase 1

Objective: 20% of all acute ischemic strokes (AIS) are caused by posterior circulation strokes, which carry an intensified mortality touching 95%. Early recanalization improves outcome as shown by several reports; however, safety, patient selection, and prognostic factors remain lacking. An investigation of the safety and prognostic factors for posterior circulation mechanical thrombectomy (MT) was performed.

Methods: A retrospective review of patients presenting with posterior circulation AIS, who underwent MT between 2010 and 2018.

Results: Of 443 patients who underwent MT for AIS, 83 patients had posterior circulation strokes. 95% of procedures were conducted under general anesthesia. The median NIHSS upon …

Predictors Of Ventriculostomy Infection In A Large Cohort, Christine Wamsley, Ba, Ahmad Sweid, Md, Stavropoula Tjoumakaris, Md, Erica J. Mann, Ba, Christopher Neely, Bs, Jeffrey Head, Ba, Michael R. Gooch, Md, Nabeel Herial, Md, Robert Rosenwasswer, Md, Pascal Jabbour, Md

Phase 1

Introduction: External ventricular drains (EVDs) are neurosurgical devices used to treat hydrocephalus and monitor intracranial pressure. Ventriculostomy-associated infections (VAIs) are a complication of EVD placement associated with increased morbidity and mortality, as well as cost. A previous study at Jefferson reported a decrease in VAI’s with the use of antibiotic-coated catheters.

Objective: The aim of this study was to assess the current rate of VAI’s and determine risk factors associated with infections.

Methods: Using Epic, the electronic medical records software, we conducted a retrospective review of patients who underwent EVD placement at Thomas Jefferson University Hospital and Jefferson Hospital for …

Roles For The Uptake2 Transporter Oct3 In Regulation Of Dopaminergic Neurotransmission And Behavior, Paul J. Gasser

Biomedical Sciences Faculty Research and Publications

Transporter-mediated uptake determines the peak concentration, duration, and physical spread of released monoamines. Most studies of monoamine clearance focus on the presynaptic uptake₁ transporters SERT, NET and DAT. However, recent studies have demonstrated the expression of the uptake₂ transporter OCT3 (organic cation transporter 3), throughout the rodent brain. In contrast to NET, DAT and SERT, OCT3 has higher capacity and lower affinity for substrates, is sodium-independent, and is multi-specific, with the capacity to transport norepinephrine, dopamine, serotonin and histamine. OCT3is insensitive to inhibition by cocaine and antidepressant drugs but is inhibited directly by the glucocorticoid hormone corticosterone. Thus, …

Lymphopenia And Dmts For Relapsing Forms Of Ms: Considerations For The Treating Neurologist., Edward J Fox, Guy J Buckle, Barry Singer, Vibhuti Singh, Aaron Boster

Neuroscience Articles

PURPOSE OF REVIEW: To provide neurologists with an update on the proposed mechanisms of action (MOAs) of disease-modifying therapies (DMTs) for the treatment of relapsing MS, and their effect on peripheral blood leukocytes, in order to inform treatment decisions.

RECENT FINDINGS: DMTs have vastly differing MOAs, including effects on peripheral blood leukocyte counts, particularly lymphocytes. The clinical implications of changes in lymphocyte counts need to be understood in the context of the underlying MOAs of each respective DMT, with treatment tailored to individual patient needs.

SUMMARY: DMTs can alter lymphocyte counts, subsets, activation, and distribution, and thus can influence immune …

The Tenets Of Teneurin: Conserved Mechanisms Regulate Diverse Developmental Processes In The Drosophila Nervous System, Alison T. Depew, Michael A. Aimino, Timothy J. Mosca

Department of Neuroscience Faculty Papers

To successfully integrate a neuron into a circuit, a myriad of developmental events must occur correctly and in the correct order. Neurons must be born and grow out toward a destination, responding to guidance cues to direct their path. Once arrived, each neuron must segregate to the correct sub-region before sorting through a milieu of incorrect partners to identify the correct partner with which they can connect. Finally, the neuron must make a synaptic connection with their correct partner; a connection that needs to be broadly maintained throughout the life of the animal while remaining responsive to modes of plasticity …

Transdisciplinarity At The Boundaries: Exploring A Sylvan Metaphor For Health, Peter J. Whitehouse

Faculty Scholarship

Transdisciplinarity is an action oriented intellectual and ethical endeavor to address complex ecological, economic, and political challenges that humans face. Language is viewed as a powerful tool for necessary cultural change. Blending art and science looking for the difficult to define but critically important hidden spaces between apparently rigid conceptual structures is a core of transdisciplinarity. Metaphor is a particular powerful tool for examining boundaries and developing creative blends of structures and processes. Forests are biologically and culturally critical to life on the planet. In this paper we explore, a performance character named Sylvanus, the Tree Doctor, named after the …

Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner

Sanders-Brown Center on Aging Faculty Publications

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining …

Dorsal Striatum Does Not Mediate Feedback-Based, Stimulus-Response Learning: An Event-Related Fmri Study In Patients With Parkinson's Disease Tested On And Off Dopaminergic Therapy, Nole M. Hiebert, Adrian M. Owen, Hooman Ganjavi, Daniel Mendonça, Mary E. Jenkins, Ken N. Seergobin, Penny A. Macdonald

Brain and Mind Institute Researchers' Publications

© 2018 Learning associations between stimuli and responses is essential to everyday life. Dorsal striatum (DS) has long been implicated in stimulus-response learning, though recent results challenge this contention. We have proposed that discrepant findings arise because stimulus-response learning methodology generally confounds learning and response selection processes. In 19 patients with Parkinson's disease (PD) and 18 age-matched controls, we found that dopaminergic therapy decreased the efficiency of stimulus-response learning, with corresponding attenuation of ventral striatum (VS) activation. In contrast, exogenous dopamine improved response selection accuracy related to enhanced DS BOLD signal. Contrasts between PD patients and controls fully support these …

Ca2+ Sensor Synaptotagmin-1 Mediates Exocytosis In Mammalian Photoreceptors, Justin J. Grassmeyer, Asia L. Cahill, Cassandra L. Hays, Cody Barta, Rolen M. Quadros, Channabasavaiah B. Gurumurthy, Wallace B. Thoreson

Journal Articles: Pharmacology & Experimental Neuroscience

To encode light-dependent changes in membrane potential, rod and cone photoreceptors utilize synaptic ribbons to sustain continuous exocytosis while making rapid, fine adjustments to release rate. Release kinetics are shaped by vesicle delivery down ribbons and by properties of exocytotic Ca²⁺ sensors. We tested the role for synaptotagmin-1 (Syt1) in photoreceptor exocytosis by using novel mouse lines in which Syt1 was conditionally removed from rods or cones. Photoreceptors lacking Syt1 exhibited marked reductions in exocytosis as measured by electroretinography and single-cell recordings. Syt1 mediated all evoked release in cones, whereas rods appeared capable of some slow Syt1-independent release. Spontaneous …

Utilization Of A Parental Approach To Informed Consent In Intravenous Tissue Plasminogen Activator Administration Decision-Making: Patient Preference And Ethical Considerations, Ann M. Murray, Ashley B. Petrone, Amelia K. Adcock

Faculty & Staff Scholarship

Objective. While administration of intravenous tissue plasminogen activator (IV-tPA) is the standard of care in acute ischemic stroke and has been shown to have statistically significant benefit, there can also be potentially life-threatening complications; however, there is no standard informed consent approach. (e purpose of this study was to present a parental, technical, and general model of informed consent for IV-TPA and to determine which approach was preferred. Methods. Survey respondents were asked to hypothetically decide whether or not to provide consent for their family member to receive IV-tPA. Respondents were presented with 3 informed consent models: one emphasizing parental …

Micrornas And The Genetic Nexus Of Brain Aging, Neuroinflammation, Neurodegeneration, And Brain Trauma, Saumyendra N. Sarkar, Ashley E. Russell, Russell Elizabeth B. Engler-Chiurazzi, Keyana N. Porter, James W. Simpkins

Faculty & Staff Scholarship

ABSTRACT: Aging is a complex and integrated gradual deterioration of cellular activities in specific organs of the body, which is associated with increased mortality. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, neurovascular disorders, and neurodegenerative diseases. There are nine tentative hallmarks of aging. In addition, several of these hallmarks are increasingly being associated with acute brain injury conditions. In this review, we consider the genes and their functional pathways involved in brain aging as a means of developing new strategies for therapies targeted to the neuropathological processes themselves, but also as …

Neurogenesis In Neurodegenerative Diseases: Role Of Mfg-E8, Cletus Cheyuo, Monowar Aziz, Ping Wang

Faculty & Staff Scholarship

Neurodegenerative diseases are devastating medical conditions with no effective treatments. Restoration of impaired neurogenesis represents a promising therapeutic strategy for neurodegenerative diseases. Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein that plays a wide range of cellular functions including phagocytosis of apoptotic cells, anti-inflammation, tissue regeneration, and homeostasis. The beneficial role of MFG-E8 has been shown in cerebral ischemia (stroke), neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, and traumatic brain injury. In stroke, MFG-E8 promotes neural stem cell proliferation and their migration toward the ischemic brain tissues. These novel functions of MFG-E8 are primarily mediated …

Characterizing The Development Of Episodic Memory And Assessing The Reliability Of Fmri Measures, Lingfei Tang

Wayne State University Dissertations

The ability to remember past events is critical for everyday life and showed robust improvement over development from childhood to adulthood. With advances in noninvasive neuroimaging methods such as functional MRI in recent years, research efforts have been focused on identifying neural correlates underpinning developmental gains in memory performance. In my dissertation work, using a widely-validated subsequent memory paradigm, I aim to characterize functional MRI correlates of memory development. Specifically, I focused my investigation on identifying age differences in the functional patterns of two brain regions critical for memory, the prefrontal cortex and the hippocampus. Focusing on the prefrontal cortex …

Investigating The Visual Number Form Area: A Replication Study, Rebecca Merkley, Benjamin Conrad, Gavin Price, Daniel Ansari

Brain and Mind Institute Researchers' Publications

© 2019 The Authors. Published by the Royal Society The influential triple-code model of number representation proposed that there are three distinct brain regions for three different numerical representations: verbal words, visual digits and abstract magnitudes. It was hypothesized that the region for visual digits, known as the number form area, would be in ventral occipitotemporal cortex (vOTC), near other visual category-specific regions, such as the visual word form area. However, neuroimaging investigations searching for a region that responds in a category-specific manner to the visual presentation of number symbols have yielded inconsistent results. Price & Ansari (Price, Ansari 2011 …

A Touchscreen Motivation Assessment Evaluated In Huntington's Disease Patients And R6/1 Model Mice, Christopher J. Heath, Claire O'Callaghan, Sarah L. Mason, Benjamin U. Phillips, Lisa M. Saksida, Trevor W. Robbins, Roger A. Barker, Timothy J. Bussey, Barbara J. Sahakian

Brain and Mind Institute Researchers' Publications

Copyright © 2019 Heath, O'Callaghan, Mason, Phillips, Saksida, Robbins, Barker, Bussey and Sahakian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Apathy is pervasive across many neuropsychiatric disorders but is poorly characterized mechanistically, so targeted therapeutic interventions remain elusive. A key …

Translational Tests Involving Non-Reward: Methodological Considerations, Benjamin U. Phillips, Laura Lopez-Cruz, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). This review is concerned with methods for assessing the processing of unrewarded responses in experimental animals and the mechanisms underlying performance of these tasks. A number of clinical populations, including Parkinson’s disease, depression, compulsive disorders, and schizophrenia demonstrate either abnormal processing or learning from non-rewarded responses in laboratory-based reinforcement learning tasks. These effects are hypothesized to result from disturbances in modulatory neurotransmitter systems, including dopamine and serotonin. Parallel work in experimental animals has revealed consistent behavioral patterns associated with non-reward and, consistent with the human literature, modulatory roles for specific neurotransmitters. Classical tests involving an important …

White Matter Injury Predicts Disrupted Functional Connectivity And Microstructure In Very Preterm Born Neonates, Emma G. Duerden, Sheliza Halani, Karin Ng, Ting Guo, Justin Foong, Torin J.A. Glass, Vann Chau, Helen M. Branson, John G. Sled, Hilary E. Whyte, Edmond N. Kelly, Steven P. Miller

Brain and Mind Institute Researchers' Publications

© 2018 The Authors Objective: To determine whether the spatial extent and location of early-identified punctate white matter injury (WMI) is associated with regionally-specific disruptions in thalamocortical-connectivity in very-preterm born neonates. Methods: 37 very-preterm born neonates (median gestational age: 28.1 weeks; interquartile range [IQR]: 27–30) underwent early MRI (median age 32.9 weeks; IQR: 32–35), and WMI was identified in 13 (35%) neonates. Structural T1-weighted, resting-state functional Magnetic Resonance Imaging (rs-fMRI, n = 34) and Diffusion Tensor Imaging (DTI, n = 31) sequences were acquired using 3 T-MRI. A probabilistic map of WMI was developed for the 13 neonates demonstrating brain …