Neurosciences Commons^™

Best Practices For Long-Term Monitoring And Follow-Up Of Alemtuzumab-Treated Ms Patients In Real-World Clinical Settings., Krista Barclay, Robert Carruthers, Anthony Traboulsee, Ann D Bass, Christopher Laganke, Antonio Bertolotto, Aaron Boster, Elisabeth G Celius, Jérôme De Seze, Dionisio Dela Cruz, Mario Habek, Jong-Mi Lee, Volker Limmroth, Sven G Meuth, Celia Oreja-Guevara, Patricia Pagnotta, Cindy Vos, Tjalf Ziemssen, Darren P Baker, Bart Van Wijmeersch

Neuroscience Articles

Multiple sclerosis (MS) is a chronic autoimmune neurological disease that typically affects young adults, causing irreversible physical disability and cognitive impairment. Alemtuzumab, administered intravenously as 2 initial courses of 12 mg/day (5 consecutive days at baseline, and 3 consecutive days 12 months later), resulted in significantly greater improvements in clinical and MRI outcomes vs. subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting MS (RRMS) who were either treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response to prior therapy (CARE-MS II; NCT00548405). Efficacy with alemtuzumab was maintained over 7 years in subsequent extension studies (NCT00930553; NCT02255656), in …

An Investigation Of Stimulants: Reviewing Their Effects On The Brain, Including Memory And Microglia, Michael Douchey

UNO Student Research and Creative Activity Fair

Stimulants are a class of drugs that have a variety of effects on the brain, including changes in receptor activity in the brain areas responsible for- memory, attention, emotion, motor control, and the reward pathway. Stimulants may be generally classified by their availability. For example, prescription stimulants, which include drugs such as methylphenidate (Concerta™, Ritalin™) and mixed amphetamine salts (Adderall™), must be prescribed by medical professionals. Another regulated stimulant, albeit one available without a prescription, is nicotine; a highly addictive chemical that is age-restricted by the U.S. federal government. Nicotine is found in tobacco products, and in tobacco-free alternatives including …

The Material-Weight Illusion Disappears Or Inverts In Objects Made Of Two Materials, Vivian C. Paulun, Gavin Buckingham, Melvyn A. Goodale, Roland W. Fleming

Brain and Mind Institute Researchers' Publications

© the American Physiological Society. The material-weight illusion disappears or inverts in objects made of two materials. J Neurophysiol 121: 996 –1010, 2019. First published January 23, 2019; doi:10.1152/jn.00199.2018.—The material-weight illusion (MWI) occurs when an object that looks heavy (e.g., stone) and one that looks light (e.g., Styrofoam) have the same mass. When such stimuli are lifted, the heavier-looking object feels lighter than the lighter-looking object, presumably because well-learned priors about the density of different materials are violated. We examined whether a similar illusion occurs when a certain weight distribution is expected (such as the metal end of a hammer …

The Gradient Of The Reinforcement Landscape Influences Sensorimotor Learning, Joshua G.A. Cashaback, Christopher K. Lao, Dimitrios J. Palidis, Susan K. Coltman, Heather R. Mcgregor, Paul L. Gribble

Brain and Mind Institute Researchers' Publications

© 2019 Cashaback et al. Consideration of previous successes and failures is essential to mastering a motor skill. Much of what we know about how humans and animals learn from such reinforcement feedback comes from experiments that involve sampling from a small number of discrete actions. Yet, it is less understood how we learn through reinforcement feedback when sampling from a continuous set of possible actions. Navigating a continuous set of possible actions likely requires using gradient information to maximize success. Here we addressed how humans adapt the aim of their hand when experiencing reinforcement feedback that was associated with …

Design And Actuation Of A Fabric-Based Worm-Like Robot, Akhil Kandhari, Anna Mehringer, Hillel J. Chiel, Roger D. Quinn, Kathryn A. Daltorio

Faculty Scholarship

Soft-bodied animals, such as earthworms, are capable of contorting their body to squeeze through narrow spaces, create or enlarge burrows, and move on uneven ground. In many applications such as search and rescue, inspection of pipes and medical procedures, it may be useful to have a hollow-bodied robot with skin separating inside and outside. Textiles can be key to such skins. Inspired by earthworms, we developed two new robots: FabricWorm and MiniFabricWorm. We explored the application of fabric in soft robotics and how textile can be integrated along with other structural elements, such as three-dimensional (3D) printed parts, linear springs, …

Ephrin-B3 Controls Excitatory Synapse Density Through Cell-Cell Competition For Ephbs., Nathan T. Henderson, Sylvain J. Le Marchand, Martin Hruska, Simon Hippenmeyer, Liqun Luo, Matthew B. Dalva

Department of Neuroscience Faculty Papers

Cortical networks are characterized by sparse connectivity, with synapses found at only a subset of axo-dendritic contacts. Yet within these networks, neurons can exhibit high connection probabilities, suggesting that cell-intrinsic factors, not proximity, determine connectivity. Here, we identify ephrin-B3 (eB3) as a factor that determines synapse density by mediating a cell-cell competition that requires ephrin-B-EphB signaling. In a microisland culture system designed to isolate cell-cell competition, we find that eB3 determines winning and losing neurons in a contest for synapses. In a Mosaic Analysis with Double Markers (MADM) genetic mouse model system in vivo the relative levels of eB3 control …

Understanding Perirhinal Contributions To Perception And Memory: Evidence Through The Lens Of Selective Perirhinal Damage, Marika C. Inhoff, Andrew C. Heusser, Arielle Tambini, Chris B. Martin, Edward B. O'Neil, Stefan Köhler, Michael R. Meager, Karen Blackmon, Blanca Vazquez, Orrin Devinsky, Lila Davachi

Brain and Mind Institute Researchers' Publications

© 2019 Elsevier Ltd Although a memory systems view of the medial temporal lobe (MTL) has been widely influential in understanding how memory processes are implemented, a large body of work across humans and animals has converged on the idea that the MTL can support various other decisions, beyond those involving memory. Specifically, recent work suggests that perception of and memory for visual representations may interact in order to support ongoing cognition. However, given considerations involving lesion profiles in neuropsychological investigations and the correlational nature of fMRI, the precise nature of representations supported by the MTL are not well understood …

Treatment Combinations For Alzheimer’S Disease: Current And Future Pharmacotherapy Options, Jeffrey L. Cummings, Gary Tong, Clive Ballard

Integrated Health Sciences Faculty Research

Although Alzheimer’s disease (AD) is the world’s leading cause of dementia and the population of patients with AD continues to grow, no new therapies have been approved in more than a decade. Many clinical trials of single-agent therapies have failed to affect disease progression or symptoms compared with placebo. The complex pathophysiology of AD may necessitate combination treatments rather than monotherapy. The goal of this narrative literature review is to describe types of combination therapy, review the current clinical evidence for combination therapy regimens (both symptomatic and disease-modifying) in the treatment of AD, describe innovative clinical trial study designs that …

Intrinsic Functional Boundaries Of Lateral Frontal Cortex In The Common Marmoset Monkey, David J. Schaeffer, Kyle M. Gilbert, Joseph S. Gati, Ravi S. Menon, Stefan Everling

Brain and Mind Institute Researchers' Publications

© 2019 the authors. The common marmoset (Callithrix jacchus) is a small New World primate species that has been recently targeted as a potentially powerful preclinical model of human prefrontal cortex dysfunction. Although the structural boundaries of frontal cortex were described in marmosets at the start of the 20th century (Brodmann, 1909) and refined more recently (Paxinos et al., 2012), the broad functional boundaries of marmoset frontal cortex have yet to be established. In this study, we sought to functionally derive boundaries of the marmoset lateral frontal cortex (LFC) using ultra-high field (9.4 T) resting-state functional magnetic resonance imaging (RS-fMRI). …

Human Consciousness Is Supported By Dynamic Complex Patterns Of Brain Signal Coordination, A. Demertzi, E. Tagliazucchi, S. Dehaene, G. Deco, P. Barttfeld, F. Raimondo, C. Martial, D. Fernández-Espejo, B. Rohaut, H. U. Voss, N. D. Schiff, A. M. Owen, S. Laureys, L. Naccache, J. D. Sitt

Brain and Mind Institute Researchers' Publications

Adopting the framework of brain dynamics as a cornerstone of human consciousness, we determined whether dynamic signal coordination provides specific and generalizable patterns pertaining to conscious and unconscious states after brain damage. A dynamic pattern of coordinated and anticoordinated functional magnetic resonance imaging signals characterized healthy individuals and minimally conscious patients. The brains of unresponsive patients showed primarily a pattern of low interareal phase coherence mainly mediated by structural connectivity, and had smaller chances to transition between patterns. The complex pattern was further corroborated in patients with covert cognition, who could perform neuroimaging mental imagery tasks, validating this pattern’s implication …

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 …

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 …

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, …

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 …