Third AnnualNEURAL ENGINEERING SYMPOSIUM April 4, 2019 Lois Pope LIFE Center, 7th Floor Apex Center

April 5, 2019 School of Nursing and Health Science, 3rd Floor Auditorium

http://www.coe.miami.edu/NERS/

April 4 and 5, 2019

Dear Colleagues, Welcome to the Third Annual Neural Engineering Symposium hosted by the Institute for Neural Engineering at the University of Miami.

We are an interdisciplinary research institute with a mission to catalyze translational neuroscience research at the University of Miami and transform our understanding of brain, its functions and pathology to improve human health. The Institute engages faculty, students and research staff across colleges and schools, with complimentary expertise and facilitates building interdisciplinary programs in translational neuroscience and neural engineering. Our teams of internationally and nationally recognized engineers, scientists, physicians and trainees are carrying out cutting-edge discovery, translational, and clinical investigations targeting all levels of nervous system function, and pathology. These discoveries, made possible by interdisciplinary collaborations and team science, provide the building blocks that form the foundation for improvements in human health, through development of novel technologies, approaches and interfaces for improved and early diagnosis and new therapies for disease.

To highlight translational neuroscience and neurotechnology development, to develop new initiatives, collaborations and engage with leading neuroscientists, engineers and industry from across the State of Florida, the Institute hosts an annual Neural Engineering Symposium. This is our third year hosting this event and we have a truly exciting program agenda. The program features lectures, panel discussions and poster presentations by scientists, neurosurgeons and experts in the field from the University of Miami, University of South Florida, Florida International University, University of Florida and Florida Atlantic University over the next two days. We are particularly excited to highlight research efforts our trainees, whether undergraduate students, doctoral students and post-doctoral associates or staff scientists. They will be the future leaders of our field, and lead to breakthrough neural engineering efforts.

The Third Annual Neural Engineering Symposium is supported by The University of Miami’s Next Level Award aimed to propel the Institute to excellence. We are grateful for the support from Provost Dr. Jeffrey Duerk and Vice Provost for Research Dr. John L. Bixby.

We also thank our partners, MagicLeap, Istovisio, the University of Miami Clinical and Translational Science Institute, College of Engineering, College of Arts and Science and the Miller School of Medicine for financial and administrative support.

We hope that you will enjoy the Symposium and learn about the breadth of the cutting-edge research and training not only at our University, but also within the State of Florida. Please don’t hesitate to contact us for additional information about how to get involved in our mission.

W. Dalton Dietrich, Ph.D. Scientific Director, The Miami Project to Cure Paralysis Associate Dean for Discovery Science Senior Associate Dean for Discovery Science Co-Director, Institute for Neural Engineering Professor of Neurological Surgery, Neurology, Biomedical Engineering and Cell Biology

Suhrud Rajguru, Ph.D.Associate Professor, Biomedical Engineering & OtolaryngologyCo-Director, Institute for Neural EngineeringAssistant Director, University of Miami Clinical and Translational Science Institute

MEETING AGENDA

Thursday, April 4, 2019

8:00 – 9:00 am Registration and Continental Breakfast

Session 1: Translational Neuroscience

9:00 am Welcoming and Opening Remarks by Vice Provost for Research, John L. Bixby, Ph.D.

9:00 – 9:20 am Clinical Network Neuroscience, Lucina Uddin, Ph.D. (University of Miami)

9:20 – 9:40 am Pigs as an Ideal Model for Translational Behavioral Neuroscience, Timothy A. Allen, Ph.D. (Florida International University)

9:40 – 10:00 am Complex Systems and the Brain, Steven Bressler, Ph.D. (Florida Atlantic University)

10:00–10:20 am Modeling Axonal Degeneration with Human Pluripotent Stem Cell Derived Motor Neurons, Mario Saporta M.D., Ph.D., M.B.A., F.A.A.N. (University of Miami)

10:20 – 10:40 am Assessing Altered Sensory Function and Gastrointestinal Distress in a Zebrafish Model of Autism, Julia Dallman, Ph.D. (University of Miami)

10:40 – 11:00 am Panel Discussion

11:15 – 1:45 pm Poster session, Dynamic Presentations and Lunch

Session 2: Neurotechnology and Development

2:00 – 2:20 pm A Brain Machine Interface for Functional Restoration of Grasp in Cervical Quadriplegia, Jonathan R. Jagid, M.D. (University of Miami)

2:20 – 2:40 pm Silicon Carbide Biotechnology, Stephen E. Saddow, Ph.D. (University of South Florida)

2:40 – 3:00 pm Nanoscale Mapping of Neural Circuits that Encode Temporal Features of Sound, George A. Spirou, Ph.D. (University of South Florida)

3:00 – 3:20 pm The Mismatch Negativity Operates on Conscious Stimulus Representations: Evidence from Magnetoencephalography and Informational Masking, Andrew Dykstra, Ph.D. (University of Miami)

3:20 – 3:40 pm Neurophysiology and Engineering Interactions: The Future of Rehabilitation Approaches, Monica A. Perez, P.T., Ph.D. & Jorge E. Bohorquez, Ph.D. (University of Miami)

3:40 – 4:00 pm Panel Discussion

MEETING AGENDA

Friday, April 5, 2019

8:30 – 9:00 am Registration and Continental Breakfast

Session 3: Science and Health Applications using Augmented Reality

9:00 – 10:00 am Spatial Computing and Healthcare, William Tapia (Magic Leap)

10:00–10:20 am A Neuroengineering Approach to Neurosensory Dysfunction: From Southwest Asia to Cuba and Beyond, Michael Hoffer, M.D. (University of Miami)

10:20 – 11:00 am Virtual, Augmented and Mixed Reality in Neurosurgery Michael Ivan, M.D. and Timur Urakov, M.D. (University of Miami)

11:00 – 11:20 am Leveraging Visual Cortex with VR/AR for Insight into 3D Data: Big Data and the Potential to Discover New Biological Principles, George Spirou, Ph.D. (University of South Florida)

11:20 – 12:00 pm Panel Discussion

12:00 – 2:00 pm Industry booths, demonstrations and lunch

DIRECTIONS April 4th: Directions to Lois Pope LIFE Center at the Miller School of Medicine, University of Miami

The Lois Pope LIFE Center, home of The Miami Project to Cure Paralysis, is located at: 1095 NW 14 Terrace Miami, FL 33136

The closest metrorail parking station is the Civic Center and is a short walk from the site of the Symposium.

For those driving, a parking garage is located next to the site at: 1500 NW 11th Street, Miami, 33136 or “Green Garage.”

The Symposium will take place on the 7th floor auditorium of the Lois Pope LIFE Center. Poster session will be held in the breezeway of the building.

April 5th: Directions to School of Nursing and Health Studies, University of Miami

The School of Nursing and Health Studies is located on the Coral Gables campus of the University of Miami at: 5030 Brunson Drive Coral Gables, FL 33146

The closest metrorail parking station is “University Station” and is a short walk from the site of the Symposium.

For those driving, it is recommended to park at the Pavia Parking Garage at the University of Miami, 5615 Pavia St, Coral Gables, FL 33146. It is a short walk from the School of Nursing and Health Studies.

FEATURED SPEAKERS APRIL 4, 2019

TRANSLATIONAL NEUROSCIENCELucina Uddin, Ph.D. Associate Professor, Department of Psychology, University of Miami Clinical network neuroscience The newly emerging fields of “network neuroscience” and “human connectomics” are based on the realization that theories from network science and complex systems can provide unique insights into brain and cognitive processes. Our current projects aim to translate

network neuroscience findings into the clinical realm. Contemporary theories in this domain posit that brain signal variability and dynamics across large-scale networks underlie flexible brain function. Findings from children with neurodevelopmental conditions including attention-deficit/hyperactivity disorder and autism spectrum disorder suggest that atypical development is characterized by marked alterations in brain signal variability that are related to symptomatology in these disorders. Our work contributes to an emerging consensus that quantification of brain dynamics and brain signal variability can provide novel insights into the neural mechanisms underlying individual differences in cognitive and behavioral flexibility.

Timothy A. Allen, Ph.D. Assistant Professor, Department of Psychology, Florida International University Pigs as an Ideal Model for Translational Behavioral Neuroscience In order to understand complex cognition, it will be critical to record and manipulate large networks of neurons across the brain. Whole-brain fMRI in humans has revealed network activation states thought to subserve cognitive function, and there is associated evidence

for homologous networks in other mammals. However, MRI experiments cannot evaluate the activity of individual neurons which requires invasive approaches most common in rodents and primates, each of which presents significant obstacles for large-scale neuronal recording and network manipulations during cognitive tasks. We suggest a new model using the domestic pig. Similar to humans, pigs have a large gyrencephalic neocortex with a total brain mass only 1/10th of the human. By contrast, the rat is lissencephalic and 1/500th the mass. In developing the pig as a model for behavioral neuroscience, we established two memory tasks. The first is a non-spatial conditional associative learning paradigm identical to one used in human fMRI studies. For the pig, the task was adapted with a touchscreen and run with custom PsychoPy scripts. Behavioral performance mirrored that observed in humans. Next, we aimed to copy spatial memory tasks used in rodents. We built a large automated T-maze (5m x 4m) with guillotine doors, return arms, and real-time tracking, all controlled via custom MATLAB functions. In the T-maze, pigs perform a spatial alternation task commonly used in electrophysiological studies of the hippocampus. Lastly, we developed a method for untethered chronic large-scale electrophysiological recordings in pigs. We designed a 3D printable stereotaxic enclosure system which supports at least eight separate chronic electrode probe assemblies for multisite implants. The electrophysiological recording system itself (SpikeGadgets) is also small enough to fit within our enclosure and onboards data to an SD card (up to 256 channels). This wireless implant setup allows subjects free mobility within and between behavioral rigs. Although early in our development of the pig model, it has become clear that there is unique opportunity here, not only for the addition of a large animal translational step in the research pipeline, but also toward addressing previously intractable questions regarding the function of large-scale networks of neurons during complex cognition.

Steven Bressler, Ph.D. Associate Professor, Department of Psychology, Florida Atlantic University Complex Systems and the Brain This talk is about Deep Learning, which is what Artificial Neural Networks (ANNs) are trained to do. Much recent interest in neural engineering has focused on ANNs as complex adaptive learning systems that are self-organized, pattern-forming networks operating by nonlinear

dynamics to adaptively learn. I will explain Deep Learning as a function of ANNs, acting as complex adaptive learning systems and modelled on how biological neural networks in the brain operate.

Mario Saporta, M.D., Ph.D., M.B.A., F.A.A.N. Assistant Professor, Department of Neurology, University of Miami Modeling Axonal Degeneration with Human Pluripotent Stem Cell Derived Motor Neurons Axonal degeneration is a main driver of disability in several neurodegenerative disorders, ranging from Alzheimer and Parkinson disease, multiple sclerosis, motor neuron disease and

peripheral neuropathies. Genetic neuropathies, collectively known as Charcot-Marie-Tooth disease (CMT), are a heterogeneous group of over 100 different disorders associated with mutations in genes involved in peripheral nervous system biology and offer a unique naturally occurring system to study mechanisms of axonal degeneration. CMT causes progressive muscle weakness and sensory loss affecting the distal regions of the body (length-dependent process) and significantly impairs patients’ gait and balance and hand dexterity. In this presentation, we will review basic concepts regarding the genetic neuropathies and discuss how we are using cellular reprogramming and differentiation to create human, disease relevant model systems to study disease mechanisms in CMT and to identify potential therapies for this group of very disabling neurodegenerative disorders. Our laboratory has developed innovative ways to culture and analyze induced pluripotent stem cell (iPSC)-derived motor neurons from patients with CMT to identify disease-relevant phenotypes for use in drug discovery. These techniques include three-dimensional iPSC-derived motor neuron cultures (spinal spheroids), isolation of axonal mass for transcriptomic and proteomic studies, and identification of in vitro biomarkers of axonal degeneration. Using this approach, we have identified a strong axonal phenotype in spinal spheroids from patients with CMT2E, a specific type of CMT associated with neurofilament light chain (NEFL) gene mutations and use it to identify compounds with potential therapeutic effect. We have also been able to map the axonal transcriptome of human motor neurons, providing clues to pathways required for distal axonal maintenance. In summary, cellular reprogramming and differentiation offer unprecedented opportunities to better understand mechanisms of axonal degeneration associated with human neurological disorders and to identify targets for therapy development in authentic models of these diseases.

Julia Dallman, Ph.D. Associate Professor, Associate Chair of the Department of Biology, University of Miami

Assessing Altered Sensory Function and Gastrointestinal Distress in a Zebrafish Model of Autism Autism Spectrum Disorder (ASD) is currently estimated to affect more than 1% of the world population. While ASD is diagnosed by communication deficits and repetitive behaviors, co-

occurring symptoms such as developmental delay, altered sensory processing, and gastrointestinal (GI) distress are also common. It is not clear whether or not these diverse symptoms are causally related. Here we assess multiple systems in a zebrafish to model Phelan McDermid Syndrome that is caused by mutations in SHANK3 gene.

NEUROTECHNOLOGY AND DEVELOPMENT

Jonathan R. Jagid, M.D. Associate Professor of Clinical Neurological Surgery and Neurology, University of Miami

A Brain Machine Interface for Functional Restoration of Grasp in Cervical Quadriplegia Neural interface research has been strongly motivated by the need to restore communication and control to the estimated 1.7% of the U.S. population, or some 5.3 million people, which

currently suffer from some form of paralysis - largely due to stroke (33.7%), spinal cord injury (SCI) (27.3%), and multiple sclerosis (18.6%). We recently recruited a patient with a chronic cervical spinal cord injury (C5 ASIA A) as a result of a motor vehicle accident to undergo placement of a brain machine interface aimed at restoring unilateral upper distal extremity function. During this talk we will describe the pre-clinical work leading up to the study, details of surgical implantation, and initial experiences with the implant. Early testing demonstrates the ability to decode movement intent information with an accuracy of approximately 90%, giving further hope that these technologies can be employed for the restoration of motor function in patients living with paralysis.

Stephen E. Saddow, Ph.D. Professor, Departments of Electrical Engineering and Medical Engineering University of South Florida Silicon Carbide Biotechnology Silicon carbide (SiC) is a semiconductor that displays ceramic-like properties. Long known for its hardness and resistance to chemical attack, research into developing SiC electronics

has been an active topic since the 1950’s. Numerous reports of SiC as a potential material for interfacing with the human body have been around for decades, but only recently has a comprehensive look into SiC for biomedical devices been undertaken. Starting in 2005 the USF SiC Group started to study the biocompatibility of various SiC single-crystalline forms, known as polytypes, and our research was aimed at both understanding the potential of SiC for biomedical applications and to understand why discrepancies in the literature existed: some reports stating that SiC was cytotoxic and other biocompatible. We have since this time studied various forms of SiC, mainly 3C-, 4H-, 6H- and amorphous SiC to various biological systems as skin and connective tissue, blood platelets, neurons, etc. We have also compared the in-vivo response of tissue (wild type mice) to 3C-SiC and Si and have found a very promising null response for 3C-SiC, at least for 30 days in-vivo. Additional work has shown similar results for a-SiC coated probes thus motivating the development of implantable biomedical devices using SiC as the requisite materials. At the University of South Florida a team of electrical engineers and neuroscientists have been developing silicon carbide (SiC) semiconductor devices for use as implantable neural interfaces (INIs). This lecture will discuss both the state of the art of SiC biotechnology as well as review other research in Prof. Saddow’s laboratory in the area of biomedical technology.

George A. Spirou, Ph.D. Professor, Department of Medical Engineering, University of South Florida

Nanoscale Mapping of Neural Circuits that Encode Temporal Features of Sound Bushy cells of the cochlear nucleus are the best characterized of all auditory CNS neurons. They receive convergent input from auditory nerve fibers via large terminals, and are thought to sharpen temporal coding via a coincidence detection mechanism. However, the structural

and functional basis for this hypothesis has not been appropriately tested. We reconstructed the neural circuit using volume electron microscopy, and ported cellular structures into a computational framework (NEURON) to test functional contributions of subcellular circuit elements to neural activity patterns. I will discuss the pipeline, required technical developments, and big data challenges to build nanoscale neural wiring diagrams, called connectomes, and the value and limitations of this approach in evaluating existing and discovering new biological principles.

Andrew Dykstra, Ph.D. Assistant Professor, Department of Biomedical Engineering, University of Miami The mismatch negativity operates on conscious stimulus representations: Evidence from magnetoencephalography and informational masking The mismatch negativity, or MMN, is a change-related brain response elicited by discriminable violations of acoustic regularity. One of the most oft-studied brain responses

in neuroscience, the MMN is thought to reflect automatic, pre-attentive, and even pre-conscious change detection. We examined the pre-conscious notion of the MMN using magnetoencephalography and a behavioral task called informational masking. Spectrally isolated and otherwise supra-threshold auditory oddball sequences were occasionally rendered inaudible by embedding them in random multi-tone masker “clouds”. Despite identical stimulation and task contexts as well as a clear representation of all stimuli in auditory cortex, the MMN was only observed when the preceding regularity was consciously perceived. The results call into question the pre-conscious interpretation of MMN and suggest instead that it operates on conscious stimulus representations. The results also raise the possibility that the MMN might index partial awareness in the absence of overt behavior.

Neurophysiology and Engineering Interactions: The Future of Rehabilitation Approaches Involuntary muscle activity (spasms) is the most debilitating aspect of spasticity after spinal cord injury because the contractions interfere with everyday tasks, and limit rehabilitation. We are developing a closed-loop control of tendon vibration to dampen muscle spasms as they occur. We aim to personalize this non-pharmacological treatment for maximal clinical and user benefit, and reduce use of anti-spasm medication. The combination of non-invasive physiological recordings with functional, clinical and participant-reported outcomes of spasticiy will reveal the mechanisms underlying the action of vibration on spasms, and importantly, the rationale to improve this novel approach to spasm management after spinal cord injury and other neurological disorders.

FEATURED SPEAKERS APRIL 5, 2019

SCIENCE AND HEALTH APPLICATIONS USING AUGMENTED REALITYWilliam Tapia MagicLeap

Spatial Computing and Healthcare The keynote presentation by MagicLeap will discuss the regulatory landscape for augmented reality, novel patient-worn applications using the platform developed, and healthcare professional-worn appli-cations using this platform.

Michael Hoffer, M.D. Professor, Departments of Otolaryngology and Neurological Surgery, University of Miami

A Neuroengineering Approach to Neurosensory Dysfunction: From Southwest Asia to Cuba and Beyond Mild traumatic brain injury is an increasingly common disability in modern society and has a

significant impact on the lives of those affected as well as society as a whole. While a great deal of effort and research funding has been dedicated to this disorder there are still many questions related to mTBI that remain to be answered. In order to answer these questions and better treat those who suffer from this disorder, an accurate diagnosis must be obtained. This is particularly challenging undertaking for a disorder that is very heterogenous in both etiology and its impact on those affected and a disorder in which no gold standard diagnostic test exists to utilize in developing new testing modalities. In this presentation we discuss the use of a virtual reality technology that tests oculomotor function, vestibular function, and reaction time (OVRT)can be utilized in diagnosing this disorder and in distinguishing more unusual phenomenon seen around the world. The talk will focus on the technology, how this technology provides information on underlying neurologic pathology, and the critical next developmental steps necessary to move this technology forward and increase its utility.

Jorge E. Bohorquez, Ph.D. Associate Professor in Practice, Department Biomedical Engineering University of Miami

Monica A. Perez, P.T., Ph.D. Professor, Department of Neurological Surgery, University of Miami

Virtual, Augmented and Mixed Reality in Neurosurgery Virtual, Augmented and Mixed Reality is exciting and versatile and we have only just begun to understand its true impact in medicine. The use of Augmented Reality (AR) is penetrating every major field including the Neurosurgery. The presentation will focus on AR’s uses for medical and patient education, preoperative strategic planning, and enhancement of Cranial and Spine surgery. Current limitations and future directives will also be discussed.

George A. Spirou, Ph.D. Professor of Medical Engineering, University of South Florida

Leveraging Visual Cortex with VR/AR for Insight into 3D Data: Big Data and the Potential to Discover New Biological Principles We carefully collect 3D image volumes to understand structure and its relationship to function, so why not view them in 3D? Viewing scenes in 3D frees our mind to observe new spatial relationships and consider what we see. New tissue processing and imaging

technologies permit imaging larger tissue volumes, up to entire brains, at increased resolution, and generate extremely large data files, thereby raising the bar for accessing the information they contain. This challenge prompted us to develop a software tool (www.syGlass.io) to visualize, analyze and annotate imaged objects and features regardless of file size. I will present syGlass, and also explore the difficulty of and possible solutions to communicating key information in 3D to collaborators, the scientific community, and the interconnected world.

POSTERS APRIL 4, 2019

11:15 am - 1:45 pm Lois Pope LIFE Center Breezeway

PS1. Effect of Local Administration of Mesenchymal Stem Cell Therapy on Auditory System in a Rat Model. Stefanie A. Pena, Rahul Mittal, Mario M. Perdomo, Abdulrahman Aljohani, Timothy Yassa, Hannah Marwede, Jeenu Mittal, Adrien A. Eshraghi., University of Miami

PS2. Efficacy of amniotic membrane as a nerve wrap around sciatic nerve reverse autografts in a rat model. Sydney Mathis, Erin Wolfe, Christopher Salgado, Zubin Panthaki, Taylor Wiener, Daisy Gonzalez. University of Miami

PS3. Development/Establishment of In Vitro Model to Understand the Effect of Electrical Stimulation on Inner Ear. Mario M. Perdomo, Zaid Al-Zaghal, Jeenu Mittal, Elijah J. Horesh, Christopher O’toole, Jorge Bohorquez, Carolyn Garnham, Rahul Mittal, Adrien A. Eshraghi. University of Miami

PS4. Implementation of the African Spiny Mouse model to investigate glial and neuronal responses to implantable neural interfaces. Alexis Brake, Atkinson, C. Simmons, M. Maden, K. J. Otto. University of Florida

PS5. Body-Machine Interface Training in Cervical Spinal Cord Injury. Carolina Fernandez, Luisa M. De Sa Martins, *Jeffrey W. Serville, Hang Jin Jo, Audrey A. Wilson, Jorge Bohorquez, Monica Perez. University of Miami

PS6. Comparison of diffusion-weighted imaging density metrics: Examining neurite and axonal density in vivo. Dea Garic, Anthony Steven Dick. Florida International University

Michael E. Ivan, M.D. Assistant Professor, Department of Neurological Surgery, University of Miami

Timur Urakov, M.D. Chief Resident in Neurological Surgery, Department of Neurological Surgery, University of Miami

PS7. Non-invasive Localized Induction of Therapeutic Hypothermia Mitigates Noise-Induced Hearing Loss. Samantha Rincon, Rachele Sangaletti, Ilmar Tamames, Anne Feliciano, Michael Hoffer, Curtis King, Suhrud M. Rajguru. University of Miami.

PS8. Infrared Photo-sensitivity in the Vestibular Neuroepithelium is Modulated by TRPV4. Federica M. Raciti, Weitao Jiang, Suhrud M. Rajguru. University of Miami.

PS9. Epineurial Lidocaine Injection Has a Neuroprotective Effect with Improved Recovery in a Rat Sciatic Nerve Model. Erin M. Wolfe, Harvey Chim, Christopher J. Salgado, Nicole Miller, Steven Ovadia, Sudheendra Rao, MD, Damien D. Pearse, University of Miami.

PS10. Design of a mediator-free, non-enzymatic electrochemical biosensor for glutamate detection. Elnaz Zeynaloo, Yu-Ping Yang, Anita Manfredi, Maria Careri, Sylvia Daunert, Leonidas Bachas. University of Miami.

PS11. Focused Pulsed Infrared Neural Stimulation of Posterior Canal Evokes Sinusoidal Vestibulo-Sympathetic Reflex Responses. Darrian Rice, Giorgio P. Martinelli, Gay R. Holstein, and Suhrud M. Rajguru. University of Miami.

PS12. In Vivo Assessment of Dexamethasone (DXM) Infused and Coated Poly (lactic-co-glycolic acid) (PLGA) Microneedles as an Improved Drug Delivery System for Intracochlear Biodegradable Devices. Devon Pawley, Stefania Goncalves, Esperanza Bas, Neil Nayak, Emre Dikici, Sapna Deo, Sylvia Daunert, Fred Telischi. University of Miami.

PS13. Combinatorial approach to improve stem cell mediated repair for spinal cord injury. Andrew Ciciriello, Dom Smith, Sydney Boyd, Brandon Applewhite, Lonnie Shea, Courtney Dumont. University of Miami.

PS14. A Comparison of Receptive Field Structures of Hierarchical Models of V2. Joshua Bowren, Luis Sanchez Giraldo, Odelia Schwartz.

PS15. Reactivity of glial cells at the Utah microeletrode array-tissue interface. Cassie Bennett, Anabel Alvarez-Ciara, Abhishek Prasad. University of Miami.

PS16. Preoperative MRI-based predictive modeling of brain tumor laser ablation. Anil Mahavadi, Walter J. Jermakowicz, Iahn Cajigas, Lia Dan, Santiago Guerra, Ghulam Farooq, Ashish Shah, Michael E. Ivan, Jonathan R. Jagid and Ricardo J. Komotar. Univeristy of Miami.

PS17. Chronic in vivo performance characterization of Pt/Ir floating microelectrode arrays using complex impedance spectroscopy. Ramanamurthy Mylavarapu, Qing-Shan Xue, Justin C Sanchez, Wolfgang J Streit, Abhishek Prasad. University of Miami.

PS18. A Noninvasive Microfluidic Platform: Understanding How Hand Actions and Nerve Regeneration Play Hand-to-hand. Genevieve Liddle, Moaed Abd, Erik Engeberg, Sarah Du, Emmanuelle Tognoli, Jianning Wei. Florida Atlantic University

PS19. Semi-automated method for estimating histopathological consequences of traumatic brain injury in rat brain sections. Anil Mahavadi, Shyam Gajavelli, Marcia Boulina, Esther Monexe, MaryLourdes Andrieu, Maria M Lujan, Liz Quesada, Rashida Ramakrawala, Markus Spurlock, Ross M Bullock. University of Miami.

PS20. Predictors of 30-day readmission in patients undergoing glioma surgery. Anil Mahavadi, Iahn Cajigas, MD PhD, Ashish H. Shah, MD, Veronica Borowy, BS, Nathalie Abitbol, MD, Michael E. Ivan, MD, MBS, Ricardo J. Komotar, MD, Richard H. Epstein, MD. University of Miami.

PS21. Inhibition of Fatty Acid Oxidation results in reduced stemness of Glioma Stem Cells. Shrita Sarkar, Shanta Dhar. University of Miami.

PS22. Unraveling ChR2-driven stochastic Ca2+ dynamics in astrocytes – A call for new interventional paradigms. Lakshmini Balachandar, Arash Moshkforoush, Carolina Moncion, Josue Santana, Jorge Riera Diaz. Florida International University

PS23. Fully-Passive Wireless Recording of Neural Activation in Wistar Rats. Carolina Moncion, Jordana Borges, Lakshmini Balachandar, Satheesh Bojja-Venkatakrishnan, John L. Volakis, Jorge Riera Diaz. Florida International University

PS24. Intraspinal microstimulation in the ventral horn modulates neural transmission in pain pathways of the deep dorsal horn. Maria F. Bandres, Valentina Melero, Jacob G. McPherson. Florida International University

PS25. High frequency nerve block of the Sciatic ameliorates mechanical sensitivity from peripheral ligation. L.Savannah Dewberry. Alexander Dru, MD, Kevin Otto, Kyle Allen University of Florida

PS26. Neuroprosthetic Engineering of an Organic Polymer-Based Microelectrode Array Platform for Inflammatory Drug Release. Chuan Liu, Michelle Nyugen, Kaixuan Liu, Abhishek Prasad, Jean-Hubert Olivier. University of Miami.

PS27. Conditional knockout of brd4 in cerebellar granule cells inhibits proliferation and impairs behavior. Marie E. Maloof, J. Mier, V. Stathias, J. K. Lee, D. J. Liebl, N. G. Ayad. University of Miami

PS28. A stochastic 2-compartment model of neocortical pyramidal cells. Beatriz Herrera, Arash Moshkforoush, Jorge Riera. Florida International University

PS29. Analysis of Individual Characteristics of Patients Treated with Deep Brain Stimulation Therapy for Disorders of Consciousness. G. Damian Brusko, Anshit Goyal, Iahn Cajigas, Jonathan R. Jagid. University of Miami.

PS30. A domestic pig model for large-scale electrophysiology recordings during conditional associative memory tasks. Adam Draper, H. V. Vinerean, A. T. Mattfeld, T. A. Allen. Florida International University

PS31. A Neural Network-Based Model to Predict Mortality and Hospital Length of Stay Following Motor Vehicle Collision. John Paul G. Kolcun, Brian R. Covello, Iahn Cajigas, Joanna E. Gernsback, Jonathan R. Jagid. University of Miami.

PS32. Real-time Estimation of Information Transmission Rate of QSS-VEP Brain Computer Interface Communication System. Ibrahim Kaya, Ozcan Ozdamar, Jorge Bohorquez. University of Miami.

PS33. Evaluation of Physiological Biomarkers for Use in Non-Invasive Diagnostic Techniques. Jeramy Baum, Chitvan Killawala, Umer Bakali, Emre Dikici, Kevin Miller, Kelly Withum, Sapna Deo, Leonidas Bachas, Carl Schulman, Sylvia Daunert. University of Miami.

PS34. Defensive behavior elicited via deep brain stimulation of the midbrain in freely moving micropigs. Ioan Opris, Stephano Chang, Francisco D. Benavides, Francisco J. Sanchez., Luz M. Villami, Andrea J. Santamaria, Yohjans Nunez, Juan P. Solano, James D. Guest, Brian R. Noga. University of Miami.

PS35. In vitro recapitulation of the dysfunctional neuromuscular junction in Charcot-Marie-Tooth disease. Ashutosh Agarwal, Rachel Besser, Renata Maciel, Isabella Claure, Ahmad Alassaf, Daniel Carbonero, Mario Saporta. University of Miami.

PS36. Magnetoelectric Nanotransducers to Enable Wireless Brain Interface. Sakhrat Khizroev, Brayan Navarrete, Krystine Pimentel, Adam Manoussakis, Marta Pardo, Daniel Bilbao, Tyler Nguyen, Xiaoming Jin, Ping Liang. University of Miami.

PS37. Electrophysiological Measures of Retinal Function Decline in Cognitive Impaired Patients. Edmund Arthur, Gabor Mark Somfai, Maja Kostic, Susel Oropesa, Carlos Mendoza-Santiesteban, Delia Cabrera DeBuc. University of Miami.

PS38. Blood Brain Barrier penetrating nanoparticle for the delivery of Coenzyme Q10 and Aspirin for neuroprotection in drug abuse. Mohammad Zahid Kamran, Anuj Shah, Bapurao Surnar, Madhavan Nair, Nagesh Kolishetti and Shanta Dhar University of Miami.

PS39. Representation of Complex Natural Scenes in Primary Visual Cortex. Sally P. Duarte. James Schummers. Florida International University.

PS40. High-frequency electrical stimulation of the schaffer collaterals in the anesthetized rat reinstates the slow oscillation in ca1 hippocampus following hyperthermia exacerbated traumatic brain injury. Joseph Wasserman, Laura Stone McGuire, Thomas Sick, Helen M. Bramlett, W. Dalton Dietrich. University of Miami.

PS41. Mechanisms of negative BOLD responses. Jorge Riera, Pedro Valdes-Hernandez, Arash Moshkforoush, Jorge Riera. Florida International University

PS42. The effects of a pro-angiogenic, RGD-functionalized, nanofiber composite hydrogel on mesenchymal stem cell-mediated repair of the injured spinal cord. Agnes Haggerty, X. Li, Y. Nitobe, I. Maldonado-Lasuncion, K. Yamane, M. Marlow, H-Q. Mao, M. Oudega. University of Miami.

PS43. Macrophage-Mesenchymal Stem Cell Interaction for Spinal Cord Repair: in vitro Observations and in vivo Relevance. Ines Maldonado-Lasuncio, Joost Verhaagen, Martin Oudega. University of Miami.

PS44. Anatomical Correlates and Surgical Considerations for Localized Therapeutic Hypothermia Application in Cochlear Implantation Surgery. Enrique Perez, Andrea Viziano, Zaid Al-Zaghal, Fred F. Telischi, Rachele Sangaletti, Weitao Jiang, Curtis King, Michael Hoffer, Suhrud M. Rajguru. University of Miami.

PS45. A Fully Implantable Brain Machine Interface for Restoration of Functional Hand Grasp in Cervical Quadriplegia. Iahn Cajigas, Noeline W. Prins, Sebastian Gallo, Jasim Ahmad Naeem, Santiago Guerra, Brandon Parks, Annie Palermo, Audrey Wilson, Lauren Zimmerman2, Katie Gant, Letitia Fisher, Monica A. Perez, Mark S. Nash, Steven Vanni, Michael Ivan, Jonathan Jagid, Abhishek Prasad. University of Miami.

PS46. Therapeutic Hypothermia: A Potential Therapy to Protect and Preserve Residual Hearing. Rachele Sangaletti, Samantha Rincon, Jayanti Singh, Elizabeth Dugan, Nina Latorre, John N. Barrett, Fred F. Telischi, W. Dalton Dietrich, Curtis King, Abhishek Prasad, Michael E. Hoffer, Suhrud M. Rajguru. University of Miami.

PS47. Mild Therapeutic Hypothermia Reduces Cortical Inflammation associated with Utah Microelectrode Array Implantation in the Rat. Elizabeth Dugan, C. Bennett; A. Prasad; S. Rajguru. University of Miami.

PS48. Characterization of the Cutaneous Reflex in People with Spinal Cord Injury. Bradley Deforest, Jorge Bohorquez and Monica Perez. University of Miami.

PS49. Corticospinal-Motoneuronal Plasticity Further Promotes Exercise-Mediated Recovery in Humans with Spinal Cord Injury. Robert Henry Powell, Hang Jin Jo, Audrey Wilson, and Monica A. Perez. University of Miami.

PS50. Novel Exercise Training Involving Fine and Gross Hand Function in Humans with Chronic Cervical Spinal Cord Injury. Hounsh K. Munshi, Tyler R. Sweetman, Audrey A. Wilson, Monica A. Perez University of Miami.

PS51. Labeling proteins within live animals. Michael DeFreitas, Tzyy-Chyn Deng, Chia-Jung Hsieh, Maria Boulina, Nima Sharifai,Hasitha Samarajeewa,Tatsumi Yanaba, James Baker, Michael D. Kim, Susan Zussman, Kenneth H. Wan, Charles Yu, Susan E. Celniker and Akira Chiba University of Miami.

PS52. Recurrent hypoglycemia exposure changes the level of activation of endoplasmic reticulum stress in hippocampus of treated diabetic rats. Ashish K. Rehn, Kunjan R. Dave University of Miami.

UNIVERSITY OF MIAMI NEURAL ENGINEERING SYMPOSIUM Abstracts

(Sorted by poster number)

PS1. Effect of Local Administration of Mesenchymal Stem Cell Therapy on Auditory System in a Rat Model. Stefanie A. Pena, Rahul Mittal, Mario M. Perdomo, Abdulrahman Aljohani, Timothy Yassa, Hannah Marwede, Jeenu Mittal, Adrien A. Eshraghi., University of Miami

Mesenchymal stem cells (MSCs) possess anti-inflammatory, anti-apoptotic and neuroprotective properties, making them an attractive target for the treatment of inner ear disorders. However, the first step is to determine the safety of MSCs in the cochlea. The aim of the present study was to determine the effect of non-surgical administration of rodent bone marrow derived MSCs (BM-MSCs) through transtympanic delivery on the cochlear function and to assess any adverse effects on the auditory system employing a rat model without immunosuppression. MSCs were generated from rat bone marrow and characterized using flow cytometry. MSCs were administered into rat ear through intratympanic injection. Animals injected with PBS or untreated served as control group. Cochlea were harvested at different days of post-treatment and stained with FITC phalloidin to visualize hair cells. Hearing thresholds were determined by auditory brainstem response (ABRs) and distortion product otoacoustic emissions (DPOAEs). Cochleae were subjected to TUNEL immunostaining to determine cell death. The levels of proinflammatory cytokines and oxidative stress in cochlear homogenates were determined by ELISA. We observed that MSCs have no adverse effect on the auditory hair cells. There was no statistical difference in number of hair cells between MSC treated and control group. The transtympanic administration of BM-MSCs have no significant effect on auditory hair cells and hearing thresholds as determined by ABRs and DPOAEs. The administration of MSCs did not lead to generation of any oxidative stress, no significant production of proinflammatory cytokines and do not induce cell death. Histopathological examination revealed no recruitment of inflammatory leukocytes and edema in the cochlea of BM-MSCs administrated rats. The results of this study suggest that MSC therapy is well-tolerated in the auditory system. Experiments are in progress in the laboratory where we are exploring the potential of MSC therapy in providing otoprotection against cochlear insults. MSCs possess a tremendous potential for the treatment of inner ear disorders that needs to be harnessed in the future investigations.

PS2. Efficacy of amniotic membrane as a nerve wrap around sciatic nerve reverse autografts in a rat model. Sydney Mathis, Erin Wolfe, Christopher Salgado, Zubin Panthaki, Taylor Wiener, Daisy Gonzalez. University of Miami

Clinically, repair of peripheral nerve injuries remains problematic due to the slow rate of axon regeneration, irreversible muscle fibrosis, and axonal misrouting. Nerve wraps provide a non-constricting protective encasement around peripheral nerves following neurorrhaphy, which facilitates axonal regeneration and improves functional recovery. Nerve wraps have been shown to mitigate epineurial scarring and adhesions, and to improve functional recovery of injured peripheral nerves. Human amniotic membrane is an easily obtainable biomaterial with no donor site morbidity and minimal inflammatory response. Amniotic membrane nerve wraps provide a neurotrophic effect, containing mesenchymal stem cells (MSCs) which possess, secrete, and attract neurotrophic factors, which may activate endogenous repair mechanisms. MSCs possess the ability to differentiate into neural phenotypes and enhance Schwann cell proliferation. We hypothesize that the use of human amniotic membrane nerve wraps will result in superior nerve regeneration and functional recovery following peripheral nerve injury and repair when compared to the absence of a nerve wrap. This pilot study demonstrates that application of amniotic membrane nerve wraps in a rodent sciatic nerve reverse autograft model results in a greater positive effect on functional outcome compared to the control groups at 12 weeks, as well as a lower average nerve adhesion grade, in support of our hypothesis. Comparative analysis of the nerve wrap will be beneficial for improvements in clinical outcomes of peripheral nerve repair. This study will also be useful in providing support for MSCs as a clinically translatable option for peripheral nerve injury.

The John M. and Jocelyn H.K. Watkins Distinguished Chair in Cell Therapies (Damien D. Pearse, Ph.D.) and Vivex Biomedical, Inc. are acknowledged for research support.

PS3. Development/Establishment of In Vitro Model to Understand the Effect of Electrical Stimulation on Inner Ear. Mario M. Perdomo, Zaid Al-Zaghal, Jeenu Mittal, Elijah J. Horesh, Christopher O’toole, Jorge Bohorquez, Carolyn Garnham, Rahul Mittal, Adrien A. Eshraghi. University of Miami

While there is a trend to implant patients with residual hearing, cochlear implantation (CI) may cause some loss of this residual hearing. The direct effect of implantation of the electrode in affecting macroscopic structures of the inner ear is well described. Recently, a hybrid approach has been developed, where both residual hearing and electrical stimulation are used. However, the effect of the electrical field generated by the implant has not been investigated to date. There is a need to develop in vitro models of electrical stimulation of CI, which closely mimic human clinical conditions that will help in understanding the precise contribution of electrical stimulation in cochlear damage. A custom stimulator circuit that allows to study several parameters, including stimulation amplitude, pulse width, and total stimulation duration was designed. The organ of Corti explant cultures from postnatal day three (P3) rats were used and placed in microchannel slide (Ibidi GmbH) in the incubator and exposed to stimulation or left unstimulated. We also determined the efficacy of an otoprotective compound in providing protection against adverse effects of electrical stimulation. Parameters (amplitude, pulsewidth and duration) were changed one at a time. The organ of Corti explants were subjected to FITC phalloidin staining to visualize hair cells using confocal microscopy. The number of surviving hair cells were counted. The organ of Corti was also subjected to CellROX and cleaved caspase 3 staining to determine the levels of oxidative stress and apoptosis, respectively. In vitro testing suggests that the electrical stimulation may cause some damage to hair cells, mainly with higher stimulation levels and longer times of stimulation. The identified otoprotective compound provides significant protection against loss of hair cells in response to electrical stimulation. The molecule mechanisms behind otoprotection involves abrogation of activation of oxidative stress and apoptosis pathways.

PS4. Implementation of the African Spiny Mouse model to investigate glial and neuronal responses to implantable neural interfaces. Alexis Brake, Atkinson, C. Simmons, M. Maden, K. J. Otto. University of Florida

Mammalian tissue injury typically results in the formation of a fibrotic tissue-based scar at the site of injury. In the field of neural interfaces, chronically implanted neural interfaces in the CNS lead to an encapsulating glial scar. Glial encapsulation serves as an ionic barrier, thus reducing the signal to noise ratio of nearby action potentials and overall functionality of the device. While other non-mammalian species have shown remarkable ability to fully regenerate tissue, such as the axolotl, the African Spiny Mouse (ASM) is the only known mammal able to fully regenerate injured tissues with minimal scarring. The unique regenerative abilities of this species make it a prime candidate for investigating the foreign body response (FBR) to implanted devices, which has traditionally been a highly variable and complex system to understand. Without a clear understanding of the FBR’s biological mechanism, research focused on FBR minimization has typically focused on altering the properties of the device. While this can be effective in FBR mitigation, it can negatively impact the functionality of the device. If the biological mechanism of the FBR could be identified and targeted, the FBR could be reduced or eliminated completely, allowing next generation device design to be optimized while achieving a favorable tissue response. This study presents a baseline examination of the cellular morphology of the ASM brain in the context of implantable neural interfaces and is intended as the first step in investigating how the regenerative abilities of the ASM could impact current understanding of the FBR and neuroregeneration.

Funding: This work was sponsored by UF Pre-eminence Start-up Funds and grants from the W.M.Keck Foundation (MM) and NSF (CS & MM).

PS5. Body-Machine Interface Training in Cervical Spinal Cord Injury. Carolina Fernandez, Luisa M. De Sa Martins, *Jeffrey W. Serville, Hang Jin Jo, Audrey A. Wilson, Jorge Bohorquez, Monica Perez. University of Miami

Body-machine interfaces (BMIs) have widely been used to help people with severe paralysis due to high-level cervical spinal cord injury (SCI) to control assistive technologies. Notably, many BMIs, such as tongue-controlled prosthetic limbs, controlled-based computer monitors and powered wheelchairs, typically use joints with few degrees of freedom and therefore require several days to weeks of training. Here, we examined the ability of individuals with cervical SCI and healthy subjects to control a customized-BMI using movement signals from the shoulder and elbow joints during a single 20-minute training session. The BMI consisted of two inertial sensors placed on the arm and the forearm. Subjects needed to learn to control a sensorimotor transformation between coordinated arm and cursor movements while performing a reaching task while recording electromyographic (EMG) signals from the triceps and biceps brachii. We found that all control and SCI subjects were able to learn a set of coordinated arm movements as shown by reduced movement time and cursor-to-target path length. However, SCI subjects learned to a lesser extent than controls. Although, both groups used similar muscle co-activation strategy between biceps and triceps through training individuals with SCI activated both muscles to a larger extent than controls. Our results indicate that individuals with cervical SCI can learn to control a customized-BMI using movement signals from shoulder and elbow joints in a single 20-minute training session and suggest that multi-joint signals might contribute to accelerate BMI control after the injury.

PS6. Comparison of diffusion-weighted imaging density metrics: Examining neurite and axonal density in vivo. Dea Garic, Anthony Steven Dick. Florida International University

Restricted diffusion imaging (RDI) is a novel diffusion-weighted neuroimaging metric that is proposed to measure cellular and axonal density (Yeh et al, 2016). This metric has been shown to be sensitive to tumors and inflammation in rats, but it has never been tested in humans. Neurite orientation dispersion and density imaging (NODDI) is another recent diffusion weighted imaging metric that aims to measure neurite density and has been shown effective in mapping density patterns in the monkey corpus callosum (Jesperson et al, 2012). Our study aimed to use these in vivo imaging methods to replicate anterior-to-posterior distribution of axonal density in the corpus callosum that are well-established in post-mortem tissue (Aboitiz et al, 1992). We hypothesized that the novel RDI metric would be the only diffusion metric currently capable of replicating the classic corpus callosum density pattern in both adult and developing samples. Our participants were 840 adults from the human connectome project (HCP) (undisclosed ages, age range= 20-40 years) and 129 children (M= 8.67 years) from the C-Mind database. In both samples, we were able to match the histological density patterns seen in post-mortem tissue. Specifically, contrast analyses showed a high degree of fit between the density patterns from the Aboitiz model and RDI in our adult sample, t(839)= 167.99 p< .001, and developing sample, t(126)= 227.4, p< .001. Furthermore, we found an inverse relationship between the Aboitiz model and the intracellular volume function of NODDI, t(839)= -24.56, p< .001. The anterior-posterior distribution of other metrics, which included generalized fractional anisotropy, quantitative anisotropy, fractional anisotropy, radial diffusivity, axial diffusivity, and mean diffusivity, did not match the pattern revealed in post-mortem tissue. These findings provide preliminary evidence in support of RDI and NODDI’s sensitivity to axonal and neurite density and could potentially have large implications for future clinical neuro-assessments.

PS7. Non-invasive Localized Induction of Therapeutic Hypothermia Mitigates Noise-Induced Hearing Loss. Samantha Rincon, Rachele Sangaletti, Ilmar Tamames, Anne Feliciano, Michael Hoffer, Curtis King, Suhrud M. Rajguru. University of Miami.

Noise-induced hearing loss (NIHL) remains one of the world’s leading sensorineural conditions, with an estimated 1.1 billion people at risk of NIHL due to occupational and recreational exposure to hazardous sounds (>85 dB SPL). In the present study, we assessed the therapeutic benefit and mechanisms of localized therapeutic hypothermia in the mitigation of cochlear injury from NIHL in a rat model. Juvenile Brown Norway rats were randomly separated into three groups: normothermic NIHL, hypothermia-treated NIHL, and non-NIHL control. Auditory brainstem responses were performed to

quantify changes in hearing threshold in anesthetized rats prior to NIHL and up to 28 days following trauma. Animals with normal hearing and aged 15-20 weeks were subjected, under isoflurane anesthesia, to two hours of continuous 4-8 kHz noise at intensities of 105 or 120 dB SPL. Mild hypothermia (31-33 C) was induced in cochleae of hypothermia-treated NIHL rats at 15 minutes post-exposure for a two-hour period. At 28 days post-exposure in female rats, cochleae were harvested for immunolabeling and counting of inner and outer hair cells. In a separate set of animals, cochleae were harvested up to 3 days post-exposure for labeling and counting of hair cells and ribbon synapses. To study the mechanisms of NIHL and therapeutic hypothermia, changes in apoptotic-related genes were measured using RT-PCR at 1 or 7 days post-exposure in male rats. Hypothermia-treated rats receiving 105 dB noise had significantly lower temporary threshold shifts at 1-7 days post-exposure. After exposure to 120dB noise, significant loss of outer hair cells was observed, resulting in permanent threshold shifts for both NIHL groups. However, ABR threshold shifts were lower for hypothermia-treated animals. Results of RT-PCR show that at 1 day post-exposure, hypothermia prevents additional damages by inhibiting the activation of caspase 3 and 8, thus interrupting the extrinsic apoptotic pathway. Delivery of non-invasive, controlled and localized mild therapeutic hypothermia to the inner ear is feasible and safe. Mild therapeutic hypothermia post-NIHL is efficacious and significantly lowers hearing threshold shifts and preserves residual hearing. Therapeutic hypothermia provides significant protection from neuropathy and synaptopathy likely via downregulation of apoptotic pathways and inflammation.

Supported by R21DC014324, R01DC013798 and Wallace H Coulter Center for Translational Research

PS8. Infrared Photo-sensitivity in the Vestibular Neuroepithelium is Modulated by TRPV4. Federica M. Raciti, Weitao Jiang, Suhrud M. Rajguru. University of Miami.

Pulsed infrared radiation (IR) is being investigated as a non-invasive technique for altering activity of excitable cells such as nerve and muscle. However, the mechanisms of action of IR are poorly understood. Previous studies suggest that IR induced intracellular [Ca2+] changes as a result of activation of temperature-dependent Transient Receptor Potential (TRP) channels. In the present work, we investigated the mechanisms underlying IR responses in the vestibular neuroepithelium focusing on the role of the thermosensitive TRP channels. We hypothesized that IR-activation of TRPV4 channels modulates [Ca2+]i leading to glutamate release from vestibular hair cells and the observed excitatory and inhibitory post-synaptic responses. The University of Miami Institutional Animal Care and Use Committee approved all procedures. Bilateral eye movements were recorded and characterized during pulsed IR stimulation of vertical semicircular canals in vivo in a rat model to assess the activity of the vestibular system (ISCAN Inc, Woburn, MA). Results were analyzed using custom MATLAB program. IR at 1860nm (200µs, 200Hz, various radiant exposures) was directed at the vestibular neuroepithelium via a 200µm dia. optical fiber. IR evoked eye movements were measured before and after the neurotransmission was impaired upstream by an acute treatment with Neomycin (100 mM), causing hair cells loss, or downstream by perfusion of CNQX (100 µM), a competitive AMPA/kainate receptor antagonist. Furthermore, the IR response was also recorded prior to and after reducing the temperature below the activation threshold of the TRPV4 (<26°C) with perfusion of temperature-controlled artificial perilymph. TRPV4 channels were targeted pharmacologically with specific blockers (GSK2193874 and HC067047) perfused at different concentrations. The IR evoked amplitude of eye movement reduced significantly following treatment with both CNQX and Neomycin. The amplitude of IR-evoked eye movement, also, reduced significantly with temperatures lower than TRPV4 activation threshold as well as after the perfusion of TRPV4 channel blockers. The eye movement recovered at the physiological temperatures and after washout of the compounds suggesting that TRPV4 channels play an important role in IR activation of the vestibulo-ocular motor pathway. These results suggest that IR stimulation primarily affects vestibular hair cells and that TRPV4 channels within the vestibular neuroepithelium drive the photothermal responses.

Funding NIH NIDCD 1R01DC008846 and 1R01DC013798.

PS9. Epineurial Lidocaine Injection Has a Neuroprotective Effect with Improved Recovery in a Rat Sciatic Nerve Model. Erin M. Wolfe, Harvey Chim, Christopher J. Salgado, Nicole Miller, Steven Ovadia, Sudheendra Rao, MD, Damien D. Pearse, University of Miami.

Nerve transfers for peripheral nerve injuries can result in variable outcomes. We investigated the neuroprotective effect of epineurial lidocaine injection in the donor nerve prior to transection, with the hypothesis that proximal axon loss would be decreased with consequent increased neuroregeneration and functional recovery. A rat sciatic nerve model was used with 4 intervention groups: 1) lidocaine; 2) lidocaine/calcium gluconate; 3) calcium gluconate (CG), or 4) saline (control). Behavioral testing and qualitative and quantitative histological evaluation was performed at 8 and 12 week endpoints. Histological assays included transmission electron microscopy, toluidine blue staining, retrograde Fluorogold labeling, whole mount immunostaining and tissue clearing of the nerve coaptation site and L4-L6 dorsal root ganglia. Functional assessments through the sciatic functional index and Basso, Beattie and Bresnahan scale showed a statistically significant increase in recovery at 8 and 12 weeks with lidocaine treatment. Significantly higher numbers of axons were obtained in the lidocaine treated groups. Retrograde Fluorogold labeling showed a statistically significant increase in the number of L4-L6 dorsal root ganglion neurons in lidocaine treated groups. Whole mount immunostaining identified extension of the axonal growth cone past the nerve coaptation site in lidocaine treated groups, but not in CG and saline groups. Analysis of neural ultrastructure in TEM images revealed significantly higher G-ratios (ratio of inner axonal perimeter to total outer perimeter of myelinated fibers) in CG and saline groups compared to lidocaine treated groups. Our results suggest that epineurial lidocaine injection prior to nerve transection has a neuroprotective effect, resulting in increased numbers of regenerating axons and improved functional recovery. These findings have direct clinical application as epineurial lidocaine can be used in surgery as a simple and inexpensive prophylactic pharmacological intervention for promoting improved clinical outcomes following procedures such as nerve transfers, which involve planned nerve transection.

PS10. Design of a mediator-free, non-enzymatic electrochemical biosensor for glutamate detection. Elnaz Zeynaloo, Yu-Ping Yang, Anita Manfredi, Maria Careri, Sylvia Daunert, Leonidas Bachas. University of Miami.

Glutamate is the major excitatory neurotransmitter in the brain, and an excess of glutamate can cause excitotoxicity, which is a common pathological process in many neurologic disorder such as stroke, brain trauma, and brain tumor. Therefore, monitoring glutamate in real time is of critical importance. Among various detection methods, electrochemical technique has shown great potential in point-of-care applications due to its high performance, easy miniaturization, low cost, and tiny sample volumes. Additionally, recently electrochemical sensors offer considerable promise as wearable sensing platforms in healthcare and biomedical applications. Enzyme-based electrochemical sensors are commonly used in electrochemical detection of analytes including glutamate. However, enzymatic electrochemical biosensors still suffer from limitations, such as indirect quantification of analytes, requirement of redox mediators, and strong matrix interference (ascorbic acid). Here, we present a novel mediator-free, non-enzymatic electrochemical biosensor for direct glutamate monitoring, based on immobilization of genetically engineered periplasmic glutamate binding protein (GluBP) onto gold nanoparticle (AuNP)-modified carbon printed electrodes. The comparison of SEM photos of AuNP deposited electrodes with GluBP-AuNP deposited electrodes confirmed the successful protein deposition on the surface of the electrodes. Cyclic voltammetry was performed to determine the glutamate concentration in phosphate buffer solution (pH=7.4). The results showed an excellent sensitivity with 0.1µM detection limit and the linearity was investigated in the 0.1µM-1µM range of glutamate concentration. The sensor specificity was tested with series of interfering substances, including amino acids (aspartate, glutamine, serine, and lysine), neurotransmitters (DOPA, GABA), and a common matrix interference (ascorbic acid). We showed that our biosensor exhibited high selectivity toward glutamate over those substances. Thus, we envision that our technique will have great potential in point-of-care applications as a diagnostic and prognostic tool for glutamate monitoring.

NSF, NIH, and University of Miami Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute BioNIUM.

PS11. Focused Pulsed Infrared Neural Stimulation of Posterior Canal Evokes Sinusoidal Vestibulo-Sympathetic Reflex Responses. Darrian Rice, Giorgio P. Martinelli, Gay R. Holstein, and Suhrud M. Rajguru. University of Miami.

Applications of sinusoidal galvanic vestibular stimulation and head tilts are known to evoke significant changes in the blood pressure and heart rate via the activation of vestibulo-sympathetic reflex. To investigate the contribution of individual endorgans to the VSR, we have developed the application of pulsed infrared radiation to activate the posterior semicircular canal in anesthetized adult male Long-Evans rats. A head post cemented to the skull of each rat and attached to a custom-designed stereotaxic frame restricted head movement during stimulation. Frequency modulated IR pulses (1863nm, 200us, 250pps, 0.05Hz) were delivered to the posterior canal crista via a 200 or 400 m optical fiber. Mean BP and HR were measured via a small animal single pressure implantable device inserted into the femoral artery prior to stimulation. Eye movements were simultaneously recorded using a custom-modified video-oculography system and post-mortem micro computed-tomography confirmed the site of stimulation. In three rats, the vestibular system was activated with electrical stimulation (200Hz pulse, 0.05Hz modulation) to mimic IR stimulation parameters and results were compared to changes evoked by focused IR stimulation. Sinusoidal IR (0.05 Hz) delivered to PC induced an initial drop in both BP (4.44  2.96 mmHg) and HR (17.45 13.07 bpm) followed by sinusoidal modulation. The responses ceased following IR stimulation. Corresponding eye movements and post-mortem microCT confirmed the PC ampullary region to be the primary target of stimulation. Results of electrical activation of peripheral vestibular system matched those from IR stimulation. In at least half of the animals, the high to low frequency ratio of heart rate variability increased during IR stimulation over baseline resting condition. PC receptor activation evoked robust changes in BP and HR and the responses were confirmed with electrical stimulation. HRV analysis indicates sympathetic activation during PC stimulation. Results are further suggestive of selective activation of the vestibular system by focused IR, which can be used to detail the VSR pathways and contributions of individual end organs.

Funding NIH NIDCD 1R01DC008846 (GRH) and 1R01DC013798 (SMR)

PS12. In Vivo Assessment of Dexamethasone (DXM) Infused and Coated Poly (lactic-co-glycolic acid) (PLGA) Microneedles as an Improved Drug Delivery System for Intracochlear Biodegradable Devices. Devon Pawley, Stefania Goncalves, Esperanza Bas, Neil Nayak, Emre Dikici, Sapna Deo, Sylvia Daunert, Fred Telischi. University of Miami.

Inner ear drug delivery techniques are challenging to develop due to the inherent complexity of the cochlear anatomy, which limits molecular transportation. A promising solution is the use of biodegradable polymers because the continuous release of bioactive molecules without introducing foreign compounds is highly desirable. Using a microneedle approach lends the drug infused polymeric microneedle the capability to pierce the tissue and be placed inside of the cochlea, allowing the appropriate amount of drug to be released overtime to the desired area. Biopolymer microneedles were prepared by mixing PLGA copolymer and DXM in an appropriate solvent. The solution was cast into a custom made mold engineered via photolithography and shaped as the desired microneedles. The needles were allowed to dry, removed from the mold, and coated with DXM. A fluorescent compound, Rhodamine B, was used instead of DXM to study the drug release profile. High performance liquid chromatography was also performed. Ototoxicity assessment was performed using whole organ of Corti (OC) explants dissected from 3-day-old rat cochleae, and the OC explants were exposed to the dexamethasone microneedles in culture. Fluorescent microscopy for viable hair cell (HC) counts (FITC-phalloidin) was also performed. ANOVA and Bonferroni post hoc testing were used for statistical analysis. Additionally, the biopolymer microneedles were blended with FM1-43, a dye that behaves as a permanent blocker of the mechanotransducer channel. The needles were introduced in the scala tympani in adult mice for in vivo assessment of the intracochlear drug release. Subsequently, animals were euthanized, cochlea were harvested and analyzed under confocal microscopy to assess the distance travelled in the cochlea. Drug infused polymeric microneedles provide a novel method to deliver dexamethasone to the inner ear over a controlled period of time without introducing foreign agents to the cochlea, and thus protect the hair cells from ototoxicity.

University of Miami Ear Institute, Dr. JT Macdonald Foundation Biomedical Nanotechnology Institute of the University of Miami and University of Miami Clinical and Translational Science Institute.

PS13. Combinatorial approach to improve stem cell mediated repair for spinal cord injury. Andrew Ciciriello, Dom Smith, Sydney Boyd, Brandon Applewhite, Lonnie Shea, Courtney Dumont. University of Miami.

Regenerating tissue following a traumatic spinal cord injury (SCI) is a multifaceted problem that will require an integration of various strategies to solve. Individually, it has been shown that neural stem cells (NSCs), hydrogels, and protein delivery all have demonstrated increased tissue repair post-injury, but each of these treatment models fall short of true regeneration and complete restoration of function. Specifically, NSCs exhibit poor survival in the complex injury environment, hydrogel systems lack any signaling factors to encourage regrowth, and protein delivery fails to provide any directionality for new tissue. In this study, we investigate a combinatorial approach including mouse embryonic day 14 (E14) spinal progenitor cells, poly(ethylene-glycol)-maleimide (PEG-Mal) hydrogel tubes, and interleukin 10 (IL-10) to act as a system that will robustly regenerate axons with appropriate cytoarchitecture and patterning. To study the effects, a C5 lateral hemisection was performed on mice aged 6-8 weeks, and animals receiving blank or IL-10 tubes were implanted acutely. At 2 weeks, all animals were injected with progenitor cells or saline controls directly into the integrated tubes. We hypothesize that implanting anti-inflammatory loaded tubes will provide both structural support and a reduction in inflammation resulting in a more hospitable microenvironment for NSC survival and thus enhance neural regeneration. Stem cell survival was assessed by labeling NSCs with enhanced green fluorescent protein (EGFP), and animals receiving tubes with IL-10 expressed a 13.6 fold higher EGFP+ rate compared to the gelfoam control and a 1.67 fold higher rate compared to blank tubes 2 weeks after transplantation (4 weeks post-injury). Additionally, ladder beam testing was used to assess restoration of function of the left forepaw. Mice receiving all three treatments recovered more rapidly compared to all other conditions suggesting there is merit in a combinatorial approach to improve NSC survival, in an effort to restore mobility.

Dr. JT Macdonald Foundation Biomedical Nanotechnology Institute of the University of Miami

PS14. A Comparison of Receptive Field Structures of Hierarchical Models of V2. Joshua Bowren, Luis Sanchez Giraldo, Odelia Schwartz.

Neurophysiology experiments and computational models provide considerable understanding of the first area of visual cortical processing, namely Primary Visual Cortex (V1). However, a comprehensive explanation of the receptive field structure of neurons in the Secondary Visual Cortex (V2), and what stimuli they are selective for, still remains incomplete. Recent hierarchical models of V2 provide an avenue for progress. By fixing computations corresponding to lower better-understood visual areas, as demonstrated by Hosoya and Hyvärinen (2015), the receptive field structures of V2 models can be derived from an ensemble of images and studied independently. In this work, we compared the receptive field representations obtained from two V2 models. First, we modified the model of Hosoya and Hyvärinen (2015) (model M1), where first layer model neuron responses are filtered for redundant information, then expanded with sparse coding to produce model V2 cell responses. Second, we modified this procedure (model M2) by incorporating a normalization computation that is ubiquitous in models of Primary Visual Cortex. We normalized the first layer model neuron responses based on the content of the image observed by the model, then followed with the rest of the computations described in model M1 (Coen-Cagli and Schwartz, 2013). Both models were trained on 4 million randomly sampled 48x48 image patches from the ImageNet database distributed for ILSVRC12 (Russakovsky et al., 2015). The learned receptive field structures of M1 included some of the patterns found in Hosoya and Hyvärinen (2015) along with circular structure. The incorporation of normalization further resulted in corner and curvature selective units. We quantified the similarity of the representations by finding for each given unit in one model the highest correlated unit in the other (34.6% of M1 units had matching M2 units with correlation above 0.3). We also compared the responses with two-dimensional approximations of both.

This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. 1451511. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. NSF Award Number: 1715475

PS15. Reactivity of glial cells at the Utah microeletrode array-tissue interface. Cassie Bennett, Anabel Alvarez-Ciara, Abhishek Prasad. University of Miami.

Relaying valuable information from the central nervous system is made possible with the use of intracortical microelectrode arrays. However, the presence of an intracortical electrode within the tissue creates a reactive local microenvironment, which leads to a cascade of proinflammatory and prooxidant factors, affecting the transcriptional rates of glial cells. Quantitative real time polymerase chain reaction (qRT-PCR) was used to quantify gene expression at acute to chronic time-points of 48-hr, 1-wk, 2-wk, and 4-wk. Genes that mitigate the reactivity of glial cells (astrocytes, microglia, and oligodendrocytes), which act as the main supporting cells of neurons, were monitored in rats implanted with a non-functional 4x4 Utah microelectrode array in the somatosensory cortex. Electrode implantation alters transcriptional rates of astrocytes, microglia, and oligodendrocytes as compared to unoperated controls, leading to the complexity of the injury on all cell types. Moreover, astrocytes remained transcriptionally active in chronic implants which could prolong implant-induced trauma and become deteriorative to neuronal health, potentially affecting chronic neuronal recordings.

This research was supported by Wallace H Coulter Center for Translational Research‚ Neural Engineering SEED Grant and NIH 1DP2EB022357. Special thanks to Dr. Florian Solzbacher and Rohit Sharma at the University of Utah for providing the non-functional Utah microelectrode arrays tested in this study.

PS16. Preoperative MRI-based predictive modeling of brain tumor laser ablation. Anil Mahavadi, Walter J. Jermakowicz, Iahn Cajigas, Lia Dan, Santiago Guerra, Ghulam Farooq, Ashish Shah, Michael E. Ivan, Jonathan R. Jagid and Ricardo J. Komotar. Univeristy of Miami.

Laser interstitial thermal therapy (LITT) yields precise thermal lesions under the guidance of MRI thermometry and is revolutionizing the management of brain tumors. However, one limitation is the inability to preoperatively predict how tumors will respond to thermal energy. The goal of this study was to determine whether preoperative variables correlated with intraoperative LITT ablation dynamics. Pixels representative of irreversible damage were quantified as a function of time after laser activation for the first 101 brain tumor patients treated with LITT at our institution. Ablation dynamics were measured using raw pixel counts and pixel counts fit with first order dynamics and related to independent variables derived from preoperative MRI, demographics, laser settings, and tumor pathology using stepwise regression. The resulting predictive models were then evaluated by comparing predicted vs. actual pixel counts using leave-one-out analysis. Total number of pixels ablated is larger for LITT performed at high laser power and long duration and for lesions with low T1 GAD signal. Rate of pixel increase is elevated with high laser power and for lesions with low T2 signal and prior radiotherapy. Pixel counts are well modeled with first order dynamics. Scale factor (C) is positively related to perfusion, laser power, and T2 signal and negatively related to T1 signal. Time constant (τ) is positively related to T2 signal and perfusion. Tshift is negatively related to T2 signal and laser power. Pathology did not impact ablation dynamics, although presence of radiation necrosis resulted in faster and larger ablations. A predictive model based on the independent variables accounts for 77% of the variance in ablation pixel counts. Features of the preoperative MRI correlate with brain tumor LITT ablation dynamics. Predictive models based on the preoperative MRI may one day be used to guide the planning and delivery of LITT.

PS17. Chronic in vivo performance characterization of Pt/Ir floating microelectrode arrays using complex impedance spectroscopy. Ramanamurthy Mylavarapu, Qing-Shan Xue, Justin C Sanchez, Wolfgang J Streit, Abhishek Prasad. University of Miami.

Long term functionality of microelectrode arrays is necessary for neuroprosthetic technologies. Understanding the electrode-tissue interface is imperative for providing the avenue to stable access of high-fidelity signals over a chronic period. Platinum/Iridium (Pt/Ir) electrode arrays have been incorporated into a large degree of neuroprosthetics studies, but a comprehensive understanding of electrode impedance and its relationships to other measures of functional performance is lacking for long-term in vivo applications in these floating microelectrode arrays (FMAs). In this study, we aim to characterize the functional performance of Pt/Ir FMAs in a large cohort of animals (n = 12) over multiple time courses (1-week, 3-week, 3-month, 6 month). We couple complex impedance spectroscopy with electrophysiological recordings and histology. FMAs were implanted into the rat somatosensory cortex and consisted of 16 microwires (1.5 mm length, 75 µm diameter). Electrode impedance spectroscopy and electrophysiological recordings were performed multiple times per week up to a period of 6 months. Electrophysiological recordings were quantified through array yield, or the percentage of electrodes in an array capable of isolating single neurons. Further, complex impedance spectra and changes in impedance magnitudes across frequencies were used to characterize electrode functionality over chronic time courses. Finally, electrodes exhibiting good yield, defined as isolating single units in over 50% of recordings, were compared to those with poor yield. Results illustrate shifts in impedance corresponding to other array types. Further, periods of high degrees of change in impedance spectra usually corresponded to poor electrode performance. We looked at trends in 1kHz and complex impedance spectra as well as their correspondence to trends in overall histology and electrode yield. These correlations illustrate the dynamic nature of the electrode-tissue interface and the utility of impedance spectra in providing insight on electrode functionality over the lifetime of chronic implants.

Work sponsored by the Defense Advanced Research Projects Agency (DARPA) through the Space and Naval Warfare Systems Center, Pacific Grant No. N66001-11-1-4009

PS18. A Noninvasive Microfluidic Platform: Understanding How Hand Actions and Nerve Regeneration Play Hand-to-hand. Genevieve Liddle, Moaed Abd, Erik Engeberg, Sarah Du, Emmanuelle Tognoli, Jianning Wei. Florida Atlantic University

Robotics has rapidly advanced in attaining dexterous, fine movement capabilities of multiple independently controllable body-segments. However, such technological advance has not found its way in prosthetics, mainly because prosthetic hand users have limited access to integrated artificial hand control and tactile feedback perception, both of which are crucial for the complex actions of daily living. To better understand the functional restoration of sensory perception, we develop a noninvasive neuroprosthetic platform. In our work, a replica of the neural implant is contained in an environmentally controlled microfluidic chamber with integrated microelectrodes. This neural implant replica is embedded in a closed-looped microfluidic structure where cultured mouse Dorsal Root Ganglion (DRG) neurons receive tactile information from a human prosthetic hand user. Therefore, the prosthetic hand user can benefit from the DRG axonal regeneration in vitro via a haptic actuator. The quality of the haptic actuator‚ feedback signal from the microfluidic chamber is dependent on the density of the DRG axonal regeneration, quantified by live-cell imaging analysis and immunohistochemistry. Our design process includes developing the microfluidic chamber with integrated microelectrodes, isolating and culturing DRG neurons from young adult mice, axotomizing DRGs for regeneration studies, and building the controller that maps robotic tactile sensations with realistic trains of action potential in the peripheral nerve replica. The long term goal and outcome of this work is to develop a biotechnological interface that will primarily serve prosthetic hands users, but can also be helpful for neural injuries and users of embedded neurotechnologies.

PS19. Semi-automated method for estimating histopathological consequences of traumatic brain injury in rat brain sections. Anil Mahavadi, Shyam Gajavelli, Marcia Boulina, Esther Monexe, MaryLourdes Andrieu, Maria M Lujan, Liz Quesada, Rashida Ramakrawala, Markus Spurlock, Ross M Bullock. University of Miami.

Penetrating traumatic brain injury (PTBI) induced disability due to progressive tissue loss, remains an unmet need. Current treatments are inadequate as they cannot further tissue loss nor boost endogenous reparative neurogenesis. Mitigating cell loss (neuroprotection) or promoting cell replacement (regeneration),

via stem cell transplantation, could potentially alter TBI outcomes. Quantitation of therapeutic effectiveness, safety of such intervention needs accurate measurements of lesion size, cell distribution. Commonly used data collection techniques in PTBI preclinical research are qualitative, constrained by equipment access. The objective of our study was to develop a proof-of-concept semi-automated program, combine slide scanning and image analysis, to accelerate preclinical research process by, alleviating time and equipment constraints on data collection, aid quantitative analysis and data visualization. In collaboration with Cleveland Clinic researchers, we developed a high precision, semi-automated computational MATLAB-based program with an intuitive graphical user interface to quantify histopathology in brain sections from rats with penetrating traumatic brain injury and human stem cell transplants. We developed functionality to determine (i) lesion volume, (ii) cell transplant volume and distribution and (iii) axonal damage in silver stained brain sections. Two groups of independent researchers used either our program or a standard labor-intensive manual method to quantify these parameters. Compared to the labor-intensive manual methods, our method afforded better time management and identical conclusions from data with reduced effort. Better 3-D visualization of lesion, transplant volume, and axonal damage in silver stained sections was feasible due to the use of a larger number of samples. Slide-scanning and image analysis using our program reduced manual labor, facilitated offline analysis, and was capable of rapidly processing large numbers of images. Incorporation of computer vision and machine learning based methods may help automate data analysis further.

Study was funded by U.S. Department of Defense W81XWH-16-2-0008, BA150111 CDMRP JPC-6. The authors acknowledge Dr. Thomas G Hazel, and Dr. Karl K Johe, Neuralstem, Inc. for the human neural stem cells (GFP labeled NSI-566 RSC).

PS20. Predictors of 30-day readmission in patients undergoing glioma surgery. Anil Mahavadi, Iahn Cajigas, MD PhD, Ashish H. Shah, MD, Veronica Borowy, BS, Nathalie Abitbol, MD, Michael E. Ivan, MD, MBS, Ricardo J. Komotar, MD, Richard H. Epstein, MD. University of Miami.

Reducing the time from operation to the reception of adjuvant chemoradiation is paramount for patients undergoing glioma surgery. Identifying and mitigating risk factors that can cause unnecessary readmissions, is therefore a critical step in glioma management. There is a lack of literature on the effects of intraoperative risk factors on 30-day readmission rates for the non-emergent cranial neurosurgical patient. The authors assessed the impact of intraoperative risk factors on 30-day readmission rates for the non-emergent glioma patient through a predictive model-driven approach. In a retrospective fashion, the intraoperative records of 294 patients who underwent glioma surgery at a single institution by a single surgeon were assessed. Data on operative variables including anesthesia specific factors were analyzed via univariate and stepwise regression analysis for impact on 30-day readmission rates. A predictive model was built to assess the capability of these results to predict a readmission and validated using leave-one out cross-validation. In multivariate analysis, end case hypothermia (OR = .27, 95% CI [.08 .90]), hypotensive time >10 minutes (OR = 3.1, 95% CI [1.19 8.1]) and hypertensive time >15 minutes (OR = 3.32, 95% CI [1.36 8.07]) were identified as intraoperative factors that were significantly associated with 30-day readmission rates (chi-squared statistic vs. constant model 23.7, p<0.001). Cross validation of the model for 30-day readmissions resulted in an overall model accuracy of 88.5%, a specificity of 99.1%, and area under the receiver operator curve (AUC) of 0.756. Intraoperative risk factors can accurately predict the likelihood of a cranial patient experiencing a readmission within 30 days. Close attention should be paid to duration of hypo and hypertension as well as end-case final temperature. Our model can be used to risk-stratify patients with a high degree of accuracy and improve postoperative patient follow-up and resource allocation. Prospective validation of our predictive model is needed to assess its potential role in guiding postoperative follow-up in patients at a higher risk of being readmitted.

PS21. Inhibition of Fatty Acid Oxidation results in reduced stemness of Glioma Stem Cells. Shrita Sarkar, Shanta Dhar. University of Miami.

Glioblastoma Multiforme (GBM) is one of the most lethal malignant primary brain tumors owing to their heterogeneity and self-renewal capacity (1). The Glioma stem cell (GSC) population is resistant to all the available conventional therapies. This demands an urgent need to develop alternative therapeutic strategies against these cells. Specific targeting of Cancer Stem Cells (CSCs) with chemotherapeutics still

remains a major challenge in the different categories of brain tumor. Cisplatin, the most widely used chemotherapeutic, is rarely used against brain tumors due to the development of resistance, and toxicity associated with this drug (2). We recently discovered in patient derived GSCs of varied background that they utilize fatty acid oxidation (FAO) as a major pathway for their growth and survival. Preliminary studies show that inhibition of this metabolic pathway leads to downregulation of the stemness characteristics of the GSCs. Thus, we embark on a journey to find a nano-therapeutic strategy which can inhibit FAO in GSCs and make this population vulnerable and less stem-cell like. Through a serendipitous discovery, we found that a cisplatin prodrug, has the ability to alter FAO in a series of cancer cells including GSCs. We also recently reported brain penetrating properties of a biocompatible polymeric nanoparticle which has the ability to load these cisplatin prodrugs (3-6). In this presentation, we will present the primary findings using this platform to set a stage for potential translation of a targeted nanoparticle delivered cisplatin prodrug to attack GSCs as an alternative treatment approach for GBM.

PS22. Unraveling ChR2-driven stochastic Ca2+ dynamics in astrocytes – A call for new interventional paradigms. Lakshmini Balachandar, Arash Moshkforoush, Carolina Moncion, Josue Santana, Jorge Riera Diaz. Florida International University

Control of astrocytes via modulation of Ca2+ oscillations using techniques like optogenetics can prove to be crucial in therapeutic intervention of a variety of neurological disorders. However, a systematic study quantifying the effect of optogenetic stimulation in astrocytes is yet to be performed. Here, we propose a novel stochastic Ca2+dynamics model that incorporates the light sensitive component – Channelrhodopsin 2 (ChR2). Utilizing this model, we studied the effect of various pulsed light stimulation paradigms on astrocytes for select variants of ChR2 (wild type, ChETA and ChRET/TC) in both an individual and a network of cells. Our results exhibited a consistent pattern of Ca2+ activity among individual cells in response to optogenetic stimulation, i.e., showing steady state regimes with increased Ca2+ basal level and Ca2+ spiking probability. Furthermore, we performed a global sensitivity analysis to assess the effect of stochasticity and variation of model parameters on astrocytic Ca2+ dynamics in the presence and absence of light stimulation, respectively. Results indicated that directing variants towards the first open state of the photo-cycle of ChR2 (O1) enhances spiking activity in astrocytes during optical stimulation. Evaluation of the effect of astrocytic ChR2 expression (heterogeneity) on Ca2+ signaling revealed that the optimal stimulation paradigm of a network does not necessarily coincide with that of an individual cell. Simulation for ChETA-incorporated astrocytes suggest that maximal activity of a single cell reduced the spiking probability of the network of astrocytes at higher degrees of transduction efficiency due to elevation of basal Ca2+ beyond physiological levels. Collectively, the framework presented in our study provides valuable information in the selection of paradigms that elicit optimal astrocytic activity using existing ChR2 constructs, as well as aid in the engineering of future optogenetic constructs.

This study was supported by the National Institutes of Health (1R56NS094784-01A), Wallace Coulter Foundation ‚ BME SEED grant ‚ Florida International University (FIU), and Dissertation Year Fellowship (DYF) from the University Graduate School at FIU (Arash Moshkforoush).

PS23. Fully-Passive Wireless Recording of Neural Activation in Wistar Rats. Carolina Moncion, Jordana Borges, Lakshmini Balachandar, Satheesh Bojja-Venkatakrishnan, John L. Volakis, Jorge Riera Diaz. Florida International University

High-resolution systems for monitoring neural activation are crucial for studying different neural disorders. This is especially true when treating epilepsy, as it has been reported that about 80% of surgeons use these systems to identify seizure origin site for surgical removal. These systems are highly-invasive as they require protruding wires from the scalp. This is detrimental to the quality of life and often limits recordings to a clinical setting thereby hindering the physician’s analysis. Many implantable devices have been designed, however, most require the use of a power source, which can generate tissue-damaging heat. We proposed a novel fully-passive and fully-implantable neurosensing system. This device consists of an implant and interrogator antenna, neural probes along with a demodulation circuit. Experiments proved an RF sensitivity of ~-135 dBm along with an ability to detect emulated neural signals with amplitude in the microvolt scale, implying the system is capable of sensing the signals generated by the brain. In vivo validation of this device entailed a series of electrophysiological recordings of cardiac activity, evoked neural activity and most recently epileptiform activity induced by temporal lobe epilepsy. Each in vivo

experiment was performed using the neurosensing system and with a wired commercially-available system for reference. Results indicate the neurosensing system can record both cardiac and neural activation in a manner comparable with wired systems. A major contributor to achieving these recordings was the low-impedance neural probes designed especially for the neurosensing system. This process involved several design considerations that directly affect probe impedance, including material selection and probe geometry. Most neural probes are closely impedance-matched to available systems (in the order of MΩ). Probes used to record with our system are in the order of kΩ. The neurosensing system will greatly impact future neurological research, as it offers a novel unobtrusive option.

This work was supported by the U.S. National Science Foundation (NSF) under Award Number 1763350.

PS24. Intraspinal microstimulation in the ventral horn modulates neural transmission in pain pathways of the deep dorsal horn. Maria F. Bandres, Valentina Melero, Jacob G. McPherson. Florida International University

Spinal cord injury (SCI) results in dramatic changes in neural excitability below the lesion, leading to debilitating motor impairments, dysregulation of reflexes, and neuropathic pain. Therapies seeking to restore sensorimotor function after SCI face the challenge of increasing spinal motor output while decreasing the spinal responses to sensory feedback that contribute to hyperreflexia and pain. Here, we characterized the use of electrical intraspinal microstimulation (ISMS) of the ventral horn, which can increase spinal motor output, to simultaneously decrease transmission in spinal pain pathways. All experiments were approved by the FIU IACUC and conducted in adult Sprague-Dawley rats under urethane anesthesia. After T13-L2 laminectomy, electrode arrays were implanted at the L5 dorsal root entry zone. Electrodes locations for ventral ISMS targeted Laminae 8-9 and electrode locations for quantifying transmission in pain pathways targeted Laminae 3-6 of the dorsal horn. We then identified convergent interneurons in the deep dorsal horn based on their responses to painful and non-painful mechanical stimulation of the receptive field. We delivered open-loop ventral ISMS while recording extracellularly from convergent interneurons. Prior to and after ISMS, we mechanically stimulated the receptive field by applying controlled forces (ranging from non-painful to painful). We found that even short periods of ventral ISMS could modulate transmission in convergent interneurons of the deep dorsal horn, often reducing neural transmission associated with painful peripheral stimuli. The mechanisms by which ventral ISMS reduces transmission in deep dorsal horn pain pathways are unknown. Nevertheless, they could be related to trans-synaptic activation of low-threshold, non-pain-related inputs to convergent interneurons. Our results demonstrate that neuroprosthetic therapies using ventral ISMS to increase motor output have the potential to concomitantly reduce transmission in spinal pain pathways. Future work is required to optimize these effects and to establish limits for avoiding unintended increases in pain-related neural activity.

This work was supported by NIH/NIHCD grant K12HD073945 and the Wallace H. Coulter Foundation.

PS25. High frequency nerve block of the Sciatic ameliorates mechanical sensitivity from peripheral ligation. L.Savannah Dewberry. Alexander Dru, MD, Kevin Otto, Kyle Allen University of Florida

Approximately 2% of the world population has been estimated to be affected by chronic treatment-resistant sciatica over the course of a lifetime. Pain management for these individuals often results in long-term opioid use, with a therapeutic risk-profile resulting in dependence and continuous dosage increases with diminished benefit. In this study, 5 lewis rats had a 0.023” inner diameter PE-60 cuff placed around their right sciatic nerve as a compression injury to model sciatica. Distally, a bipolar circumferential neurostimulator cuff was implanted with wires tunneled to a head stage port. Prior to surgery, the rats received baseline von-Frey testing, with an objective positive response recorded as a paw-lick. At 1 and 2 weeks postoperatively, the animals underwent Von Frey testing of the left and right hindpaws pre-block, during block (50kHz/3V), and post-block. Paw-lick responses were tabulated as a 50% withdrawal probability with ANOVA analysis between phases. The results showed a significant decrease in the 50% withdrawal score, indicating an increase in

mechanical sensitivity, at timepoints with no blocking stimulation applied relative to baseline scores. In addition, thresholds obtained during kilohertz nerve block stimulation are significantly higher than unblocked trials on the same day. Sciatic neuromodulation at kilohertz-level frequency produces preferential nerve block in a murine model of peripheral neuropathy with an implanted nerve stimulator cuff. The affected limb normalizes its tactile allodynic response to von Frey testing in a rapidly reversible fashion. Additionally, preliminary visual gait analysis demonstrates improvement in stride length and pace suggesting fiber-level selectivity. This pre-human model opens the door for the development of an implantable human modulation system to potentially cure painful chronic peripheral neuropathy.

PS26. Neuroprosthetic Engineering of an Organic Polymer-Based Microelectrode Array Platform for Inflammatory Drug Release. Chuan Liu, Michelle Nyugen, Kaixuan Liu, Abhishek Prasad, Jean-Hubert Olivier. University of Miami.

Microelectrode arrays (MEAs) have become the cornerstone of neuroprosthetic devices that rely on recordings from large populations of neurons to restore movement and control after injury. While high-density MEAs have been developed to access large neuronal ensembles, the inability of current systems to reliably record signals for long periods of time and the foreign body response throughout MEA implantation are still common challenges. While the use of passive drug release at the site of injury has been exploited to minimize neuroinflammation, this strategy has all but failed as a bolus of anti-inflammatory drugs is released at predetermined times that are often inconsistent with the ongoing innate inflammatory process. Common strategies do not focus on proper anchorage of soft hydrogel scaffolds on electrode surfaces, which often results in delamination of the porous network from electrodes. In this study, we seek to sense and characterize physiological events occurring at the electrode-tissue interface under the influence of drugs by engineering a multi-functional MEA platform that: (1) features robust yet flexible bio-friendly hydrogel coatings, (2) enables on-demand release of anti-inflammatory drugs, and (3) can still efficiently sense and report neural activities around electrode sites. We will release drugs via dismantlement of hydrophilic three-dimensional networks along with prototypical biodegradable polymers or using actuation properties of semiconducting polymers under the influence of electrical stimuli. The surface chemistry developed by our team is able to functionalize polyimide-coated electrodes with covalently anchored porous hydrogel networks bearing large numbers of highly biodegradable ester groups. Exponential long-lasting drug release is achieved using such hydrogels. The pore size of such hydrogel networks can be controlled by use of different chemical structures so that the release profile can be properly modulated. This type of novel electrodes with hydrogel-based smart coating will open up new avenues for engineering of anti-inflammatory neuroprosthetics.

UM Start-up, College of Arts and Sciences, BioNIUM

PS27. Conditional knockout of brd4 in cerebellar granule cells inhibits proliferation and impairs behavior. Marie E. Maloof, J. Mier, V. Stathias, J. K. Lee, D. J. Liebl, N. G. Ayad. University of Miami

Bromodomain and extraterminal domain (BET) inhibitors have entered clinical trials for various indications including several types of cancers. However, this has occurred in the absence of a complete understanding of the biology of BET proteins. We are investigating the role of BET proteins in cerebellar development and medulloblastoma, the most common pediatric brain tumor. Dysregulation of cerebellar granule cell progenitors (GCP) leads to medulloblastoma. Our laboratory has shown that the BET protein, Brd4, is highly expressed in GCPs prior to differentiation into mature granule cells. We hypothesize that Brd4 plays a fundamental role in GCP proliferation and may contribute to cell cycle dysregulation in medulloblastoma. To examine the role of Brd4 in GCP proliferation, we generated a conditional Brd4 knockout mouse line using the Tg (Atoh1-Cre) driver, to limit Brd4 deletion to GCPs. We verified Brd4 deletion in Tg (Atoh1-Cre+);Brd4fl/fl versus Tg (Atoh1-Cre-);Brd4fl/fl mice control littermates by isolating GCPs from postnatal day (P) 8 mice and performing Western blot analysis and quantitative PCR. We examined the morphology of the brain using histological staining on P8 mice. We evaluated the behavior of these mice using rotarod testing and blinded ataxia composite rank scoring. Conditional deletion of Brd4 in the cerebellum leads to proliferation dysregulation in GCPs as well as gross morphological deficits in the cerebellum. While the overall brain morphology is intact, the cerebellum of Tg (Atoh1-Cre+); Brd4fl/

fl is smaller and underdeveloped compared to Tg (Atoh1-Cre-); Brd4fl/fl mice control littermates. As a result, Tg (Atoh1-Cre+); Brd4fl/fl exhibit ataxia symptoms, including deficits in motor function and balance versus Tg (Atoh1-Cre-); Brd4fl/fl mice control littermates. Brd4 appears to play an essential role in proper granule cell progenitor proliferation and overall cerebellar development.

PS28. A stochastic 2-compartment model of neocortical pyramidal cells. Beatriz Herrera, Arash Moshkforoush, Jorge Riera. Florida International University

Cortical Pyramidal cells (PCs) have apical dendrites which extend up to layer I. Tuft dendrites are heavily innervated by fibers crossing through LI, which provide inputs from distant cortical areas and thalamus. Normally, distal dendritic inputs to the apical tuft are strongly attenuated as they spread towards the soma. However, if a single back-propagating action potential (AP) at the axon coincides with a distal dendritic input over a time window of several milliseconds, the generation of calcium spikes in the apical dendrites is facilitated and the gain of the neuron can be significantly increased (Larkum et al. 2004). The back-propagating AP activated calcium spike firing (BAC firing) is modulated through the action of the hyperpolarization-activated cation current (Berger et al. 2003). This current is activated by inhibitory inputs of cortical LV/VI Martinotti cells (Silberberg and Markram, 2007), as well as intra-laminar GABAergic interneurons into the PC apical dendrites. A better understanding of this autonomic regulation of PC activity, which underlies important features of cortical processing, can provide important insights into cognitive processing. In this study, we propose a stochastic two-compartmental neuronal model, i.e. somatic and dendritic compartments, to explain dynamic changes in the dendritic gain of LV PCs and their impact on AP genesis. The somatic compartment contains an after-hyperpolarization current, as well as voltage-dependent potassium and sodium currents. The dendritic compartment is comprised of voltage-dependent calcium L-type, persistent sodium, slow inactivating potassium currents, and a hyperpolarization-activated cation current. Using the model, we successfully replicated the main features of the BAC firing observed experimentally. We also provided the dependency of the dendritic gain as a function of inputs to both apical dendrites and soma. The model presented in this study can provide a theoretical platform where inter-neuronal communications and PC activity modulation from different cortical layers can be studied.

PS29. Analysis of Individual Characteristics of Patients Treated with Deep Brain Stimulation Therapy for Disorders of Consciousness. G. Damian Brusko, Anshit Goyal, Iahn Cajigas, Jonathan R. Jagid. University of Miami.

Currently, no standard treatment exists for patients with disorders of consciousness (DoC). However, DBS has emerged as a potentially promising therapeutic strategy. We performed a systematic review of the literature and subsequent bivariate analysis of human studies involving application of DBS for DoC. A literature search of electronic databases from inception to July 2018 was performed in accordance with PRISMA guidelines for studies that reported outcomes of patients with DoC undergoing DBS therapy. Only studies that reported individual level patient data on baseline characteristics and complete data on final outcomes (improved vs unimproved) were included. Ten human DBS trials for DoC were included with a total of 32 patients. Mean age (SD) of the cohort was 34(15) years and 31% were females. The most common etiology for DoC was TBI(50%, n=16), while most patients(n=12, 37.5%) were in a vegetative state at baseline. Among studies reporting the specific DBS target, central thalamic stimulation was the most common(n=26) in addition to midbrain(n=1, 0.03%) and other targets(claustrum and anterior insula,n=1). We found that 50%(n=16) of patients demonstrated some improvement in neurologic status, demonstrated either clinically by a neurologic exam or improvement or a standardized arousal scoring rubric. On bivariate comparison between improved and unimproved patients, age(mean:32.5 vs 36,p=0.22), sex(p=0.37), etiology of DoC(p=0.22), time to DBS implantation(mean:51 vs 23.3 years,p=0.25) and DBS target(p=1.0) were not found to be not significantly associated with recovery. Despite variability in outcomes for DoC patients treated with DBS, it may be a promising treatment modality with potential for recovery in select patients. Due to limited availability of individual patient data and limited exposure, few conclusions can be drawn about factors that may predict response. Thus, there is a need for standardization of outcome reporting in this patient population.

PS30. A domestic pig model for large-scale electrophysiology recordings during conditional associative memory tasks. Adam Draper, H. V. Vinerean, A. T. Mattfeld, T. A. Allen. Florida International University

To understand complex cognition neurophysiological studies of large-scale networks of neurons are necessary. While human studies using BOLD fMRI have shown evidence for task-related networks across the brain these studies lack the ability to evaluate mechanisms at the cellular level. Similar brain networks are assumed to support cognition across mammals (Lu et al., 2012), but the most common rodent and primate models present challenges in achieving high-volume multisite single-unit recordings in behaving animals. Rats are too small for large scale multisite recordings, and primate research involves many practical and ethical issues. Here we present the domestic pig as a solution to some of these issues. Pigs have large brains and thick skulls allowing for large implants targeting multiple brain regions. We first trained pigs (Sus scrofa domesticus) to perform a conditional associative learning paradigm identical to a task used in humans (Hamm & Mattfeld, 2019). For the pig, the task was adapted to use a touchscreen interface. We also trained and tested pigs on delayed non-match to sample spatial alternation in a T-maze similar to ones used in rodent experiments, but larger. Pigs performed well on both tasks. With the touchscreen conditional task behavioral performance mirrored that observed in humans using the same task and greater than chance performance on spatial alternation with up to 4-minute delays. Next, we developed a method for untethered chronic large-scale electrophysiological recordings in pigs. A 3D printable protective enclosure was designed to support eight separate chronic electrode probe assemblies each implanted in a different brain region. This approach proved stable enough to withstand the shock of collisions due to head hits and flopping over during sleep.

PS31. A Neural Network-Based Model to Predict Mortality and Hospital Length of Stay Following Motor Vehicle Collision. John Paul G. Kolcun, Brian R. Covello, Iahn Cajigas, Joanna E. Gernsback, Jonathan R. Jagid. University of Miami.

Motor vehicle collisions (MVC) account for 30-40,000 deaths and 29% of emergency department visits annually in the United States. In an attempt to accurately predict MVC outcomes, we queried a prospectively-maintained database at our institution’s level-one trauma center to identify all MVCs over a 20-year period. From a final dataset of 17,088 cases, patients were categorized by acute mortality (in the trauma bay), delayed mortality (during hospital admission), and length of stay (LOS) if admitted. We trained several classifiers to predict these outcomes, demonstrating that a convolutional neural network out-performed all other classes. All models included: age (years), Glasgow Coma Scale (GCS), and Injury Severity Score (ISS). The delayed mortality and hospital LOS models further included time to admission. In isolated testing phases, our models returned reliable, highly accurate predictions: the acute mortality model performed with 97% sensitivity, 93% specificity, and 0.98 AUROC; the delayed mortality model performed with 92% sensitivity, 90% specificity, and 0.98 AUROC; the LOS model performed with ±2.23 days mean absolute error after optimization. We have provided our current model for clinicians in a user-friendly web-based application, available at m5.med.miami.edu. This tool demonstrates a clear and effective application of neural network modeling to a significant clinical question, using technology to impact the management of patients in real-time.

PS32. Real-time Estimation of Information Transmission Rate of QSS-VEP Brain Computer Interface Communication System. Ibrahim Kaya, Ozcan Ozdamar, Jorge Bohorquez. University of Miami.

Visual Evoked Potential (VEP) based brain computer interfaces (BCIs) offer high communication speed and ease of use. At low stimulation rates (<3 reversal per second (rps)) synchronous averaging generate transient-VEP (TR-VEP) with characteristic peaks which do not overlap with each other. Rapid isochronic reversals, however, result in steady-state VEP (SS-VEP) periodic waveforms. Temporally jittered reversals generated with special sequences produce quasi-steady-state VEP (QSS-VEP) offer the extraction of TR-VEPs using deconvolution methods. In our previous study, off-line analysis of a two target (R and L) BCI using orthogonal sequence QSS-VEPs were shown to be capable of producing high (up to 70 bits per minute (bpm)) information transfer rates (ITR). This study, however, used Receiver operating characteristics (ROC) curves obtained using single target detection and did not provide estimates for real-time performance. To overcome this problem in this study an alternative simulation method is investigated for online ITR measurement using a single display presenting 1-bit (R and L) information in sequential form.

Sequential binary information (32 bits) at 10, 32, 50 and 70rps producing QSS-VEPs at different data durations (0.5s, 1s, 1.5s 2s) were recorded from subjects in real-time. Accuracy and ITR performances were computed using these 32 bits for each condition. Best performances (around 40 bpm) were obtained at 50 and 70rps rates using 1s recordings. This performance shows the superiority of code modulated VEP as implemented with QSS methodology in this study.

PS33. Evaluation of Physiological Biomarkers for Use in Non-Invasive Diagnostic Techniques. Jeramy Baum, Chitvan Killawala, Umer Bakali, Emre Dikici, Kevin Miller, Kelly Withum, Sapna Deo, Leonidas Bachas, Carl Schulman, Sylvia Daunert. University of Miami.

Sleep deprivation, fatigue and drowsiness are prominent issues in public health and safety. Previous studies show that one-sixth of lethal automobile accidents involve drowsiness. Additionally, studies from OSHA have found that fatigued workers are 2.9 times more likely to have a workplace accident. There is a need for a convenient and reliable means of diagnosing worker and driver fatigue and drowsiness. Previous work has shown that specific Volatile Organic Compounds (VOCs) are detectable in the breath of drowsy subjects. We have employed various techniques to detect biomarkers indicating fatigue and drowsiness in subjects’ breath. Biomarker detection outcomes are compared to subject responses on psychologically and neurologically relevant tests, including the Psychomotor Vigilance Task (PVT), Karolinska Sleepiness Scale (KSS), Percentage of Eye Closure Test (PERCLOS) and the Visual Analog Scale (VAS). These tests are employed to determine a correlation between biomarker presence and conventional measures of sleepiness. Monitoring drowsiness through non-invasive breath analysis using solid state sensor arrays presents a novel approach for diagnosis of fatigue and drowsiness. Moreover, a fully-realized diagnostic system for fatigue using breath analysis would allow for quick and non-invasive determinations of a subject’s level of drowsiness. This system would mark a significant advance in public health and safety to reduce the risk of accidents and injury.

PS34. Defensive behavior elicited via deep brain stimulation of the midbrain in freely moving micropigs. Ioan Opris, Stephano Chang, Francisco D. Benavides, Francisco J. Sanchez., Luz M. Villami, Andrea J. Santamaria, Yohjans Nunez, Juan P. Solano, James D. Guest, Brian R. Noga. University of Miami.

Animal and human survival depends on appropriate defensive behavior. Defensive behavior is controlled in part by midbrain circuits, including the mesencephalic locomotor region (MLR) and the periaqueductal grey (PAG). Deep brain stimulation (DBS) of the midbrain of the Yucatan micropig is a promising model for assessing neuromodulation of defensive behavior. However, a quantitative assessment of the MLR/PAG evoked responses via local field potentials (LFPs) and electromyographic (EMG) activity during defensive behavior is lacking. DBS of the MLR [cuneiform (CnF) and pedunculopontine (PPN) nuclei] and PAG was applied bilaterally using electrode arrays. LFP and EMG activity were evaluated quantitatively. Patterns of muscle activation in agonist/antagonist muscles of all four limbs were recorded using intramuscular EMG electrodes. EMG signals were rectified and band-pass filtered. Stance and swing phases of each limb during locomotion were characterized with and without stimulation. Circular statistics were used to determine coordination of flexor and extensor activity from EMG recordings. DBS of midbrain region of micropigs (n=6) increased the level of alertness. Stimulation of the PAG in open field produced fight or flight responses including freezing, cowering, turning and escape behavior, vocalizations and aggressive movements. CnF stimulation initiated and facilitated ongoing locomotion, increasing the speed as current/frequency increased. Postural effects including loss of extensor tone resulting in the animal sitting or lying down were observed with stimulation of the PPN. LFP power increased with initiation of movement and with increased speed of locomotion. These experiments demonstrate that the CnF nucleus-initiated locomotion in open field, PPN stimulation caused postural effects and the activation of PAG elicited defensive fight-or-flight behavior. The micropig model and the DBS approach may be very useful to dissect the neuronal circuitry of defensive behaviors including locomotion. This knowledge is critical to the feasibility, safety and tolerability of MLR stimulation for SCI and gait disorders.

DOD Award # SCI140238 and NINDS Grant 1R01 NS089972

PS35. In vitro recapitulation of the dysfunctional neuromuscular junction in Charcot-Marie-Tooth disease. Ashutosh Agarwal, Rachel Besser, Renata Maciel, Isabella Claure, Ahmad Alassaf, Daniel Carbonero, Mario Saporta. University of Miami.

Neuromuscular junction (NMJ) dysfunction has been identified in several forms of Charcot-Marie-Tooth disease (CMT). We seek to design a multi compartment cell culture system comprised of CMT neurospheres, aligned axons, and engineered anisotropic skeletal muscle tissue to model NMJ dysfunction in CMT using a human in vitro platform. Upon validation, this platform will enable mechanistic studies of CMT, as well as discovery of novel therapeutics. Mouse skeletal muscle cells (C2C12) and human neurospheres were co-cultured on a 2-phased hydrogel in maturation media. The hydrogel was fabricated by crosslinking gelatin (20% w/v) with microbial transglutaminase (mTg) (4%) and micromolded. A solution of laminin (10 μg/mL) and mTg (4%) was then incubated on top of the hydrogels for 1 hour. During hydrogel fabrication one of two patterns were stamped onto the gel: (1) 20 um x 10 um grooves for standard co-culture or (2) a compartmentalized design. Our 2-phase biomaterial allowed enhanced myotube growth and alignment. The C2C12 cells were immunostained for α-sarcomeric actinin, which revealed mature myotube formation with highly organized sarcomeres. Additionally, neurospheres adhered and extended axons after seeding on the gelatin-laminin hydrogel. The addition of neurosphere media to skeletal muscle cultures enhanced the percentage of myoblasts that differentiate into myotubes from 30% to 85%. Both co-cultures and compartmentalized systems were imaged using immunofluorescence. Co-localization of the terminal end of an axon and acetylcholine clusters indicates the presence of a neuromuscular junction. To confirm the existence of neuromuscular junctions, further functional studies are underway. Gelatin-laminin micromolded hydrogels, which utilize biomimetic extracellular matrix components, are an optimal substrate to co-culture iPSC-derived neurospheres and C2C12 cells. These engineered hydrogels promote myotube formation and axonal growth. Additionally, micromolded gelatin-laminin hydrogels can be utilized to engineer a multi compartment culture system.

PS36. Magnetoelectric Nanotransducers to Enable Wireless Brain Interface. Sakhrat Khizroev, Brayan Navarrete, Krystine Pimentel, Adam Manoussakis, Marta Pardo, Daniel Bilbao, Tyler Nguyen, Xiaoming Jin, Ping Liang. University of Miami.

The main goal of this project is to exploit the unique multi-functional properties of magnetoelectric nanoparticles (MENPs) to enable capabilities to (1) wirelessly stimulate (write) selective regions deep in the brain as well as (2) record (read back) local neural activity at the sub-neuronal level. Like any magnetic nanoparticles, MENPs can be moved in and out the brain by magnetic field gradients as well as used for image guiding owing to their non-zero magnetic moment. In addition, unlike any other nanoparticles known to date, due to the presence of the magnetoelectric (ME) effect, MENPs can also (1) induce local electric fields via application of magnetic fields as well as reciprocally (2) convert an electric field change due local neural activity into a change of the magnetic moment of the local nanoparticles, which in turn could be detected through a magnetic detection technique. We have demonstrated the feasibility of this technology through in vitro and in vivo studies. Particularly, we have proven that indeed these nanoparticles can be transferred across the blood-brain barrier (BBB) via application of magnetic field gradients on the order of 10,000 Oe/cm and then used for wirelessly controlled local stimulation of selected neurons. In addition to wirelessly controlled writing information in the brain, we have demonstrated that owing to their multifunctional properties, these nanoparticles can optionally be used for high-specificity wireless targeted drug delivery and release to any specific neuron(s) deep in the brain. We have also described the physics of MENP-based high-contrast imaging of neural activity deep in the brain – the approach underlying the reading mechanism with these nanotrasducers. Last but not least, we have designed several types of MENPs and, along with other researchers, have proven their safety to the human body.

PS37. Electrophysiological Measures of Retinal Function Decline in Cognitive Impaired Patients. Edmund Arthur, Gabor Mark Somfai, Maja Kostic, Susel Oropesa, Carlos Mendoza-Santiesteban, Delia Cabrera DeBuc. University of Miami.

The neurodegeneration that occurs in the cerebral cortex of cognitive impaired (CI) patients is associated with retinal ganglion cell loss. Hence, electrophysiological measures of retinal function in patients with

CI may reveal subtle decline in retinal function in these patients compared to an age-matched normative cohort. Prospective age-matched subjects (n=39) with and with no CI and without the presence of any ophthalmic history were recruited (age>55+ years). The Montreal Cognitive Assessment was used to measure CI and full-field electroretinogram (ERG) was performed to assess the retinal function or evaluate the bioelectrical activity of the retina according to the International Society for Clinical Electrophysiology of Vision (ISCEV) protocol. A disposable, self-adhering skin contact electrode array was placed on the cheek inferior to the lateral half of the lower eyelid and a lead was connected to this strip to initiate the ERG recordings. The protocol used the ISCEV 6 step, measuring the light-adapted condition first. Assessments consisted of light and dark adapted ERG including rod, maximal dark-adapted and cone responses. ERG implicit time (IT) and amplitude values were recorded for each eye of the participants. Fractal dimension assessed retinal vascular parameters. Independent t tests compared ERG IT and amplitude between CI patients vs. cognitive healthy patients. Pearson correlation coefficient assessed the association between retinal vascular parameters and IT. A p-value < 0.05 was considered statistically significant. For all full-field ERG measurements, smaller amplitudes (median [90% CI]) (12.6 µV [10.9 ‚ 14.4]) and larger peak times (IT) (31.2 ms [29.6,32.8]) were observed in participants with cognitive impairment vs. cognitive healthy participants ‚ amplitude (37.4 µV [36.6 ‚ 38.2]), IT (29.6 [29.4 ‚29.8]), p <0.001. The increase in IT associated with the manifestation of pathologic changes of the retina was highly consistent in all patients with cognitive deterioration, and showed practically no overlap between control data and pathologic values: the range of variation seen for control data is between 29.4 and 29.8 ms, while for patients with cognitive impairment it is between 29.6 and 32.8 ms. IT was significantly associated with fractal dimension measures of vascular complexity in the cognitive impaired participants, p < 0.05. Our results show decline in retinal bioelectrical activity in patients with CI possibly related to the neurodegeneration occurring in the retina of these patients which has been shown to be associated with that occurring in the brain. The decline in retinal function in CI patients is associated with the retinal vascular complexity. Assessment of retinal function using ERG may hence serve as a biomarker for the early detection of CI.

PS38. Blood Brain Barrier penetrating nanoparticle for the delivery of Coenzyme Q10 and Aspirin for neuroprotection in drug abuse. Mohammad Zahid Kamran, Anuj Shah, Bapurao Surnar, Madhavan Nair, Nagesh Kolishetti and Shanta Dhar University of Miami.

Oxidative stress is a probable neurotoxic mechanism for the patients infected with HIV-1 and drugs abuser. Further, activation of microglia and macrophages for neuro-inflammation, mitochondrial dysfunctions, and formation of reactive oxygen species in astrocytes impair the ability of astrocytes towards neuroprotection. Most of the therapeutic options cannot be used to treat neurocognitive diseases due to the inability of majority of neuroprotectants to cross the blood brain barrier (BBB). Our laboratory has developed biodegradable nanoparticle platforms which penetrates BBB and targets mitochondria of cells (1, 2, and 3). In the current study, we are using FDA approved poly(lactic co-glycolic) acid (PLGA), and polyethylene glycol (PEG) functionalized with a terminal triphenylphosphonium (TPP) cation and coenzyme Q10 to create a mitochondria targeted biodegradable CoQ10 loaded nanoparticle (NP) to decrease oxidative stress in astrocytes in the drug abuse population. We observed that CoQ10 loaded NP crossed BBB and protects astrocytes against oxidative stress. We will be exploring the therapeutic efficacy of CoQ10 in combination with aspirin loaded NP in an HIV infection and drug abuse model. This finding will open up the true therapeutic window for HIV infected patients who are at high risk due to drug abuse. References: 1. Marrache, S. and Dhar, S. Proc. Natl. Acad. Sci. USA, 2012, 109, 16288-16293 2. Marrache, S.; Pathak, R. K.; and Dhar, S. Proc. Natl. Acad. Sci. USA, 2014, 111, 10444-10449 3. Feldhaeusser, B.; Platt, S. R.; Marrache, S.; Kolishetti, N.; Pathak, R. K.; Montgomery, D. J.; Reno, L. R. Howerth, E.; and Dhar, S. Nanoscale, 2015, 7, 13822-13830.

This work was supported by the Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida and H & N Wertheim Research Pilot Project, Florida International University, Florida, USA

PS39. Representation of Complex Natural Scenes in Primary Visual Cortex. Sally P. Duarte. James Schummers. Florida International University.

Neurons in primary visual cortex (V1) respond selectively to multiple features of a visual stimulus, including the orientation, spatial frequency, retinotopic location and the eye to which they are presented. Neurons are clustered such that nearby neurons respond best to the same value of each of these parameters, resulting in feature maps across cortical space. The coordinated mapping of multiple stimulus features implies that neighboring neurons should have similar tuning for all stimulus features, and thus encode highly redundant information about the visual scene. However, numerous experimental studies have shown remarkably low correlation in the responses of nearby neurons. Additionally, when more complex stimuli are presented, such as natural scenes, responses between nearby neurons are heterogeneous and the population activity is highly sparse. This suggests that there is much less redundancy between neurons than the feature maps imply. Here we use a combination of wide-field and two photon fluorescent imaging of the genetically-encoded calcium indicator GCaMP6s in ferret visual cortex to characterize the multi-dimensional receptive fields of thousands of neurons and their relationship to the large scale organization of multiple feature maps. We show that despite the feature maps, the overlap of the multi-dimensional receptive fields of adjacent neurons is remarkably low and has only modest spatial dependence. We dissected the contribution of each stimulus feature to the low and poorly organized receptive field overlap, and found that orientation tuning contributes most to the spatial organization of overlap, and that retinotopy introduces significant local scatter, which is the predominant factor driving low redundancy. We then extrapolate these results to examine whether the multidimensional receptive field and a simple functional neuronal model can accurately predict neuron responses to complex natural scenes. Our goal is to provide a more refined understanding of how real-world visual stimuli are represented across a population of neurons in primary visual cortex.

PS40. High-frequency electrical stimulation of the schaffer collaterals in the anesthetized rat reinstates the slow oscillation in ca1 hippocampus following hyperthermia exacerbated traumatic brain injury. Joseph Wasserman, Laura Stone McGuire, Thomas Sick, Helen M. Bramlett, W. Dalton Dietrich. University of Miami.

Disorders of cognitive function following Traumatic Brain Injury (TBI) correlate with disruptions of oscillatory electrical activity recorded from cortical and subcortical structures. As cognitive function may decline in humans following TBI, so is the case between experimental rodent models of TBI. The present study, demonstrates that when hyperthermia occurs within the brain before, during, and after Marmarou’s closed head model of TBI, power decreases during the slow oscillation and increases during theta and gamma frequency oscillations recorded from stratum radiatum CA1 Hippocampus in the urethane anesthetized animal thirty days after injury. In addition to the presence of aberrant baseline oscillatory activity, when somatosensory input was administered in the form of a tail-pinch, power decreased and frequency increased within the slow oscillation in sham operated controls. This phenomenon was absent in animals that had undergone TBI or TBI + Hyperthermia, possibly due to disrupted extrahippocampal axon fibers impinging onto the hippocampus. By delivering high-frequency stimulation at 100 Hz to the Schaffer Collaterals, the most prominent excitatory input to CA1, the aforementioned electrophysiological deficits disappeared: Power and peak frequency values for the slow oscillation in TBI + Hyperthermia animals resembled that of sham operated control animals. Additionally, 100 Hz stimulation of the Schaffer Collaterals rendered the hippocampus responsive to tail-pinch induced increases in the speed of theta oscillations in animals who had undergone TBI+Hyperthermia. In the freely moving animal, high frequency oscillations (100 -300 Hz) or ripples, are observed in the local field potential of CA1 during moments of memory consolidation. This high frequency oscillation represents inhibitory neurons hyperpolarizing CA1 pyramidal cells. These inhibitory neurons are driven by Schaffer Collaterals. This phenomena taken together with these results suggest that electrical stimulation of the Schaffer Collaterals may be a strategy to control the behavior of rhythmic oscillations in the hippocampus during disease states.

Funding: Department of Defense.

PS41. Mechanisms of negative BOLD responses. Jorge Riera, Pedro Valdes-Hernandez, Arash Moshkforoush, Jorge Riera. Florida International University

Alongside Positive BOLD Responses (PBR), Negative ones (NBR) appear in interictal epileptiform discharges (IEDs). Contrary to PBR, there is no consensus about the NBR mechanisms. We identify five of these and propose biophysical models to describe them: 1) arterial blood stealing (ABS)(Harel, et al., 2002), 2) vein blood backpressure (VBB)(Bandettini, et al., 2012), 3) lateral/callosal inhibition (LCI)(Shmuel, et al., 2006), 4) neuronal disruption of activity (NDA), with a slow recovery, of resting state networks(Laufs, et al., 2007) or 5) altered neurometabolic couplings (ANC)(Song et al., 2016). We show that, under realistic hysiological/ observation noise and model parameter variability, the HRFs estimated from BOLD data of these different mechanisms are distinguishable. Balloon models describe the PBR, LCI and NDA mechanisms, with the incorporation of a baseline neuronal activity that is decreased by inhibitory inputs (and delayed in NDA) driven by PBR exhibiting areas. We model ABS and VBB as two windkessels sharing the same feeding artery and the same output vein, respectively, accounting for blood resistance and viscosity. We model ANC using the Oxygen to Transport model (Zheng, et al., 2002), but increasing the neurometabolic coupling gains. To obtain estimates of the HRF of each of the abovementioned mechanisms we simulated 100 realizations of 40-min BOLD signals after IEDs. Each model in a state-space form comprises a set of SDE equations and the BOLD observation equation. The systems were integrated using the Local-Linearization method. These BOLD signals were fitted to an ARX model to obtain the HRF temporal profiles that were classified using Discriminant Analysis of the first 3 PCAs. Results: BOLD responses predicted by the models and their sensitivity to a set of the relevant parameters were obtained. The 3D representation and their classification of the ARX-based PCA components were also obtained. Conclusions: We propose 5 NBR mechanisms. We demonstrate they can be distinguished using BOLD signals. The clinically relevant mechanisms in epilepsy related to changes in neuro-vascular and neuro-metabolic couplings (PBR and ANC) can be identified from the other mechanisms.

This work was supported by the National Institutes of Health (R56NS094784-01A1). We appreciate the members of the Neuronal Dynamic Mass Laboratory and Prof. Pedro A. Valdes-Sosa for their comments and suggestions.

PS42. The effects of a pro-angiogenic, RGD-functionalized, nanofiber composite hydrogel on mesenchymal stem cell-mediated repair of the injured spinal cord. Agnes Haggerty, X. Li, Y. Nitobe, I. Maldonado-Lasuncion, K. Yamane, M. Marlow, H-Q. Mao, M. Oudega. University of Miami.

Spinal cord injury (SCI) results in nervous tissue loss and so far untreatable functional impairments. Preclinical studies have demonstrated that a transplant of bone marrow-derived mesenchymal stem cells (MSCs) elicits paracrine effects resulting in anatomical repair and partial functional recovery. The effects of transplanted MSCs on spinal cord repair depend on their survival. MSCs are anchorage-dependent cells that are susceptible to anoikis, i.e., programmed cell death due to lack of adherence to a substrate. Thus, MSC transplant-mediated repair may be affected by lack of a binding substrate. It is known that MSCs adhere via integrin receptors to the tripeptide, arginine-glycine-aspartic acid (RGD). We investigated the effects of an RGD-functionalized nanofiber hydrogel composite biomaterial (NHC) on MSC transplant survival and the effects on anatomical repair and functional recovery in a clinically relevant adult rat model of spinal cord contusion. NHC consists of pro-angiogenic hyaluronic acid and axon growth-promoting nanofibers which form an injectable composite gel that closely resembles the physical properties (i.e. stiffness/porosity) of the spinal cord nervous tissue. NHC could target a multitude of factors that influencing MSC transplant survival and tissue remodeling after SCI. Pilot data suggests NHC improves MSC transplant survival and anatomical repair of the damaged spinal cord.

This work is supported by the Miami Project, State of Florida, Maryland Stem Cell Research Fund (2018-MSCRFCO-4088), and Department of Veteran Affairs (I01BX007080).

PS43. Macrophage-Mesenchymal Stem Cell Interaction for Spinal Cord Repair: in vitro Observations and in vivo Relevance. Ines Maldonado-Lasuncio, Joost Verhaagen, Martin Oudega. University of Miami.

Mesenchymal stem cells (MSCs) transplanted in the injured spinal cord exert paracrine actions resulting

in angiogenesis, neuronal survival, and axonal growth and myelination, which are often accompanied by functional improvements. An intraspinal MSC transplant encounters active immune cells that are mainly inflammatory macrophages. MSCs and macrophages are known to reciprocally interact thereby influencing the overall repair process. We studied the effect of MSC-macrophage interactions in vitro and explored the effects of inflammatory preconditioning of MSCs for repair of the injured spinal cord. We exposed MSCs to differently polarized macrophages or their conditioned medium and investigated the effects on MSC secretome and transcriptome. Exposure of MSCs to inflammatory macrophages increases their secretion of vascular endothelial growth factor (VEGF), which is important for the initiation of angiogenesis, and of anti-inflammatory cytokines, including IL4 and IL10, which are responsible for the polarization of anti inflammatory and regulatory macrophages. Exposure to anti-inflammatory macrophages increases the secretion of platelet-derived growth factor (PDGF), which is important for a number of repair-related events including blood vessel stabilization. In addition, we exposed macrophages to synthetic or MSC-derived anti-inflammatory media and analyzed their phenotype. Co-culture of macrophages with activated MSCs induces a significantly higher increase in expression of anti-inflammatory markers compared with co-culture with naive MSC. Our in vitro data provided the basis for exploring the effects of macrophage-mediated preconditioning of MSCs on their reparative potential for the injured spinal cord. Our results highlight the significance of macrophage-MSC interactions for MSC-mediated spinal cord repair.

NIH Grant NS101298; Craig H Neilsen Foundation 460461; State of Florida; Department of Veterans Affairs

PS44. Anatomical Correlates and Surgical Considerations for Localized Therapeutic Hypothermia Application in Cochlear Implantation Surgery. Enrique Perez, Andrea Viziano, Zaid Al-Zaghal, Fred F. Telischi, Rachele Sangaletti, Weitao Jiang, Curtis King, Michael Hoffer, Suhrud M. Rajguru. University of Miami.

Electrode insertion during cochlear implantation (CI) surgery can result in hair cell damage and may result in a loss of residual low-frequency hearing. Amongst hearing preservation strategies, local application of therapeutic hypothermia has shown promising results. Using a custom-designed probe and system, our group has demonstrated the feasibility of delivering controlled hypothermia to the inner ear without requiring modifications in the surgical approach. However, anatomical variations and suitability of different surgical approaches, including the standard facial recess (FR) approach versus a transtympanic approach need to be further investigated. The aim of the present study is to utilize anatomical and radiologic measurements and experimental outcomes from cadaveric human temporal bones to investigate the feasibility of delivering local hypothermia. Ten human adult cadaveric temporal bones were scanned with micro-CT. By means of software analysis, distances between the chorda tympani and the facial nerve and FR height were measured and total FR area was derived. Further measurements predicting RW visibility were recorded. Each bone was drilled and a standard FR approach was developed. The St. Thomas classification (STC) was then used to record degree of RW visibility. This grading was repeated following further drilling for optimizing visualization of the RW or independent cochleostomy and placement of the cooling probe through the FR or myringotomy. Following previously published protocols, hypothermia was delivered through both approaches and temperatures recorded by thermistors placed inside the RW (Apex), at RW niche, over the lateral semicircular canal (LC) and the supero-lateral mastoid edge (M). The average FR area was 13. 87 mm2(SD 5. 52) ranging from 8. 44 to 24. 28 mm2. Regarding STC grading, the introduction of the cooling probe through either approach did not impede full visualization of the RW or cochleostomy. The average maximum temperature decrease, using the FR approach, was 4. 57 °C (SD ± 1. 68) for RW and 3. 42 °C (SD ± 1. 12) for Apex, while a transtympanic approach produced a mean decrease of 4. 11 °C (SD ± 0,98) for RW and 3. 22 °C (SD ± 0. 95) for Apex. No significant differences were found between the two probe approaches. Results show that local hypothermia delivery during CI surgery, using a customized probe, can be efficiently achieved both through a FR and transtympanic approach regardless of anatomical constraints and without limiting optimal surgical visualization.

Supported by Cochlear Research Grant

PS45. A Fully Implantable Brain Machine Interface for Restoration of Functional Hand Grasp in Cervical Quadriplegia. Iahn Cajigas, Noeline W. Prins, Sebastian Gallo, Jasim Ahmad Naeem, Santiago Guerra, Brandon Parks, Annie Palermo, Audrey Wilson, Lauren Zimmerman2, Katie Gant, Letitia Fisher, Monica A. Perez, Mark S. Nash, Steven Vanni, Michael Ivan, Jonathan Jagid, Abhishek Prasad. University of Miami.

Neural interface research has been strongly motivated by the need to restore communication and control to the estimated 1.7% of the U.S. population, or some 5.3 million people, which currently suffer from some form of paralysis - largely due to stroke (33.7%), spinal cord injury (SCI) (27.3%), and multiple sclerosis (18.6%). We recently enrolled a patient with a chronic cervical spinal cord injury (C5 ASIA A) as a result of a motor vehicle accident to undergo placement of a brain machine interface aimed at restoring unilateral upper distal extremity function (ClinicalTrials.gov NCT02564419). To evaluate the safety and efficacy of a fully implanted brain machine interface consisting of the Medtronic PC+S and the Bioness H200 hand rehabilitation orthosis for the functional restoration of hand grasp in a patient with cervical quadriplegia. Pre-operative evaluation with functional magnetic resonance was used to map the site of cortical activation during imagined dominant (right) hand movements and diffusion tensor imaging used to identify the location of the corticospinal tract fibers the previously controlled dominant hand movement in the subject. The pre-operative imaging was used to plan a small craniotomy over the left motor cortex and electrodes were placed with the assistance of frameless stereotaxy. Intraoperative electrical stimulation and electromyograms (EMG) were used to identify motor cortex by evoking EMG activity in muscles proximal to the level of spinal cord injury. After post-surgical recovery, a computer task was developed to engage the subject in thinking of either hand movement or rest while electrocorticographic (ECoG) activity was recorded. These “open-loop” trials were used to train various classifiers in predicting “move” or “rest” states based on observations of the ECoG activity. In “closed-loop” experiments, the decoded desired hand state was used to drive functional electrical stimulation of the dominant hand utilizing the Bioness H200 orthosis. Functional performance was measured by a modified Jebson Taylor test and range of motion. Surgical implantation occurred with no complications and the patient was discharged home on post-operative day 2. Early testing demonstrates the ability to decode movement intent information with an online accuracy of 89.8% ± 6.8% with a tree bagging classifier over 12 sessions (in 7 weeks). Several other classifiers such as linear discriminant analysis, k-nearest neighbor, and support vector machine were tested offline. Functional improvement was observed in reduction of the average time to perform Jebson Taylor test: page turning from ~160 seconds to ~7 seconds, lifting small objects from ~90 seconds to ~6 seconds, feeding from ~370 seconds to ~14 seconds and stacking checkers from ~150 seconds to ~12 seconds. Subject was not able to write at the beginning, but by the end of 7 weeks, was able to write 4-6 letters. Pinch force increased from 1lb to 3lb within 7 weeks. Our results demonstrate that a fully implanted brain machine interface can be safely implanted and used to reliably decode movement intent from motor cortex allowing for volitional control of hand grasp in a laboratory setting. Improvement was further quantified with time to complete functional tasks. Further work will aim to allow use of the device in a home setting, a critical step for the widespread use of these approaches to restore motor function in patients living with paralysis.

Miami Project to Cure Paralysis

PS46. Therapeutic Hypothermia: A Potential Therapy to Protect and Preserve Residual Hearing. Rachele Sangaletti, Samantha Rincon, Jayanti Singh, Elizabeth Dugan, Nina Latorre, John N. Barrett, Fred F. Telischi, W. Dalton Dietrich, Curtis King, Abhishek Prasad, Michael E. Hoffer, Suhrud M. Rajguru. University of Miami.

Localized mild to moderate therapeutic hypothermia has been widely studied for neuro-protection against secondary injuries due to brain trauma, strokes, and spinal cord injuries. Multiple studies have considered the effects of temperature of the cochlea and its influences on auditory responses and a protective role of hypothermia in the inner ear has been suggested. In a preclinical model, we have recently shown that acute and localized application of mild hypothermia reduced the trauma associated with cochlear implantation and preserved residual hearing. Here, we review the evidence highlighting therapeutic efficacy and translational potential of hypothermia and investigate the mechanisms underlying its protective effects in the inner ear. The University of Miami Institutional Animal Care and Use Committee approved all procedures. Two different models of traumatic injury were used in the preclinical in vivo rodent model: surgical cochlear implantation

and noise-induced trauma. Residual function was measured using auditory brainstem responses and distortion product otoacoustic emissions. An in vitro model was also developed to test the efficacy of hypothermia against oxidative stress and hydrogen peroxide mediated cellular impairment and apoptosis. RNA-seq, Western Blot and rt- qPCR were performed at multiple time points to quantify gene and protein level expression of selected factors in control, euthermic and hypothermia-treated conditions. Additionally, a quantification of immune cells with the use of flow cytometry technique was performed. Finally, cadaveric temporal bone and mathematical stimulations were developed to study translational potential of such approach. Functional measurements suggested that mild hypothermia provided during cochlear implantation surgery or following noise application significantly reduced threshold shifts post trauma. Mild therapeutic hypothermia reduced inflammation and oxidative stress and increased activity of anti-apoptotic pathways, while increasing cell viability and reducing cell death. Moreover, flow cytometric analysis shows that hypothermia treatment significantly reduces the number of activated microglia, macrophages and lymphocytes/leukocytes recruited at the site of the injury (between 5 to 10-fold reduction) when compared with euthermic conditions. Multiple cellular processes including inflammatory reactions, oxidative stress mechanisms, apoptosis and necroptosis mediate the death or survival of hair cells and neurons. Understanding the mechanisms underlying protective effects of hypothermia will guide its translational potential and lead to identification of potential targets for combinatorial therapeutic modalities.

Supported by NIH 1UL1TR000460, 1R21DC014324, 1R01DC013798, Wallace H Coulter Center for Translational Research and Cochlear grants.

PS47. Mild Therapeutic Hypothermia Reduces Cortical Inflammation associated with Utah Microelectrode Array Implantation in the Rat. Elizabeth Dugan, C. Bennett; A. Prasad; S. Rajguru. University of Miami.

Neuroprosthetics hold tremendous promise to advance our understanding of the nervous system through basic research, and to restore lost sensory inputs and motor outputs through brain-computer interfaced (BCI) devices. Maintaining high quality neuronal signals for long periods of time are key challenges that must be thoroughly addressed to develop clinical applications for neuroprosthetics. Previous studies have shown that acute and chronic inflammation, oxidative stress, and BBB disruption are likely factors that contribute towards inconsistent chronic electrode performance. Methods to reduce the host response is essential to the development of clinically effective BCI devices and may be achieved with mild therapeutic hypothermia. The therapeutic benefits of mild hypothermia for some neurological conditions include a reduction in inflammatory processes and restoration of the blood brain barrier (BBB). Initiating cooling immediately after or prior to an injury is known to yield improved survival and most favorable neurological outcomes in both the short and long-terms and when localized and administered at the time of trauma, beneficial effects are enhanced. To examine the benefits of mild therapeutic hypothermia during implantation, our laboratory has designed a custom device and a protocol to deliver controlled hypothermia to the implant site without requiring any modifications to the current surgical approach. Male Sprague-Dawley rats (250-300g; n=12) were implanted with custom-made, non-functional Utah Microelectrodes Array (UMEA) consisting of 4 x 4 grid of 1.5mm long parylene-coated silicon shanks. Mild therapeutic hypothermia was applied to the implant site (n=6) following completion of the craniotomy and prior to surgical implantation of the UMEA. The temperature of the implant site was slowly lowered by 3-4 degrees by decreasing the cooling probe temperature 5 degrees every 2 minutes. When the target temperature was reached, the UMEA was inserted, and cooling continued for 120 minutes followed by a slow rewarming phase identical to the initial cooling phase. We compared mRNA expression levels for genes associated with apoptosis, inflammation and the blood brain barrier (BBB) at 48 hours, 72 hours, 7 days and 14 days post implantation between normothermic and hypothermic groups. We show significant beneficial molecular responses to therapeutic hypothermia and demonstrates the efficacy of hypothermia in reducing inflammation and altering molecular activity that may benefit restoration of the functional properties of the BBB following UMEA implantation.

Wallace H Coulter Center for Translational Research and Neural Engineering SEED grants

PS48. Characterization of the Cutaneous Reflex in People with Spinal Cord Injury. Bradley Deforest, Jorge Bohorquez and Monica Perez. University of Miami.

Involuntary muscle contractions (spasms) affect many people with spinal cord injury (SCI). The cutaneous reflex is commonly used to study the underlying mechanisms of spasms including prolonged excitatory post synaptic potentials and persistent inward currents. The cutaneous reflex is highly variable between individuals with SCI and it has not been thoroughly characterized in the tibialis anterior and soleus muscles. Therefore, we aimed to characterize the cutaneous reflex in these two muscles in people with SCI and examined relationships between clinical measures of spasticity and spasms. The reflex was evoked by electrical stimulation of the mid arch of the foot and EMG was recorded in tibialis anterior (TA) and soleus (SOL) in 28 individuals with SCI. Spasticity was evaluated with the Modified Ashworth Scale and spasm frequency with the Penn Spasm Frequency Scale. Injury characteristics were determined by the International Standards for Neurological Classification of Spinal Cord Injury. Stimulation evoked EMG in TA in all participants, but SOL EMG was evoked in only 14 out of the 28 participants tested (50%; 9 motor complete, 5 motor incomplete). Participants with spared sensory function in their feet had shorter onset latency in TA (70.9 ± 16.7 ms) compared with those without sensory function (85.9 ± 22.9 ms; p<0.05). Reflex variables were not correlated with age, injury duration, spasticity, spasm frequency nor use of anti-spasmodic medication. Larger and longer reflex EMG in TA was associated with larger responses in SOL. These results improve our understanding of the cutaneous reflex in humans with SCI and support the view that spasms are distinctly different from spasticity. We argue that additional evaluations are critical to properly characterize spasms in clinical settings.

Thank you to Sina Sangari for assessment of the Modified Ashworth Scale. Funding: NIH- NINDS 1R01NS100810-01A1

PS49. Corticospinal-Motoneuronal Plasticity Further Promotes Exercise-Mediated Recovery in Humans with Spinal Cord Injury. Robert Henry Powell, Hang Jin Jo, Audrey Wilson, and Monica A. Perez. University of Miami.

Rehabilitative exercise aims to engage residual spared neural networks on humans with spinal cord injury (SCI) to improve functional recovery. We hypothesized that exercise combined with noninvasive stimulation targeting spinal synapses further promotes functional recovery. Twenty-five individuals with chronic incomplete cervical, thoracic, and lumbar SCI were randomly assigned to 10 sessions of exercise combined with paired corticospinal-motoneuronal stimulation (PCMS) or sham-PCMS. During PCMS, 180 pairs of stimuli were timed to have corticospinal volleys evoked by transcranial magnetic stimulation (TMS) over the primary motor cortex arrived at corticospinal-motoneuronal synapses of upper- or lower-limb muscles (depending on the injury level) 1-2 ms before antidromic potentials were elicited in motoneurons by electrical stimulation of a peripheral nerve. Participants exercised for 45 min after both protocols. We found that the size of corticospinal responses elicited by TMS and maximal voluntary contraction in targeted muscles increased when exercise was combined with PCMS but not sham-PCMS. Clinical functional outcomes improved after both protocols. Notably, physiological and behavioral effects were preserved for 6-months only in the group receiving exercise with PCMS. Our findings indicate that targeted noninvasive stimulation of spinal synapses is an effective strategy to enhance exercise-mediated recovery in humans with different levels of SCI.

The University of Miami, Department of Neurological Surgery, the Miami Project to CureParalysis, Bruce W. Carter Department of Veterans Affairs Medical Center

PS50. Novel Exercise Training Involving Fine and Gross Hand Function in Humans with Chronic Cervical Spinal Cord Injury. Hounsh K. Munshi, Tyler R. Sweetman, Audrey A. Wilson, Monica A. Perez University of Miami.

Hand motor function is severely impaired in a large number of humans with chronic cervical spinal cord injury (SCI). Evidence has shown that exercise training improves hand motor function in the chronic phase of SCI, however, performance gains remained limited. Here, we examined the effect of a novel customized exercise training targeting fine and gross hand functions in humans with chronic cervical SCI. This specialized hand training behaviors have shown to involve corticospinal (Tazoe and Perez, 2018) and reticulospinal (Baker and Perez, 2018) pathways. Subjects were assessed using a modified version of the Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) before and after 10 to 20 training sessions

lasting ~45 min each. We found that humans with chronic incomplete SCI can improve fine and gross hand function after repeated training sessions. Importantly, our results indicate that humans with chronic cervical SCI showed more pronounced improvements in hand function with larger number of repetitions, particularly in gross motor function. We propose that novel customized fine and gross hand function training programs can engage successfully engage residual neural connections to hand muscles in the chronic phase of SCI and can represent an effective strategy to maximize the after-effects of rehabilitation programs.

University of Miami, Miller School of Medicine, The Miami Project to Cure Paralysis and Department of Veteran’s Affairs.

PS51. Labeling proteins within live animals. Michael DeFreitas, Tzyy-Chyn Deng, Chia-Jung Hsieh, Maria Boulina, Nima Sharifai,Hasitha Samarajeewa,Tatsumi Yanaba, James Baker, Michael D. Kim, Susan Zussman, Kenneth H. Wan, Charles Yu, Susan E. Celniker and Akira Chiba.

We describe a scalable protein lableling method for charting protein interaction network within animals. Genetically encoded fluorescent proteins, GAL4- responsive expression control and position-specific genome integration enable labeling proteins A, B and C each with a choice of eGFP, mCherry and NirFP in specified cells of imaging-friendly animals such as Drosophila embryos/larvae. The short non-structural polypeptide linking lables to proteins randomizes dipole orientation k2 and simplifies the computation of protein interactions. While followig multiple proteins through development and behavior of animals, the labels offer separable pairs of Förster resonance energy transfer betweenproteins A and B and proteins B and C.

PS52. Recurrent hypoglycemia exposure changes the level of activation of endoplasmic reticulum stress in hippocampus of treated diabetic rats. Ashish K. Rehni, Kunjan R. Dave. University of Miami.

Stroke or cardiac arrest in diabetics causes increased ischemic brain injury. Therapy for diabetes induces unavoidable recurrent hypoglycemia (RH) and we showed that prior RH exposure enhances ischemic brain damage in insulin-treated diabetic (ITD) rats. However, the mechanism causing this injury is not well understood. We showed that cerebral ischemia increases protein kinase RNA-like endoplasmic reticulum kinase (PERK) phosphorylation and C/EBP homologous protein (CHOP) levels in ITD rats exposed to RH (ITD+RH) rats. However, the effect of RH on ER stress in ITD rats is unknown. Therefore, we tested the hypothesis that prior RH exposure modulates ER stress in ITD rats by determining the levels of total and phospho-PERK, and CHOP in naïve, ITD, and ITD+RH groups. After 2-3 weeks, streptozotocin diabetic male Wistar rats were treated with insulin pellets to correct hyperglycemia. After 2-3 weeks, more insulin was given to elicit hypoglycemia for 3 hours/day for 5 days. Hippocampi were harvested overnight after last episode of hypoglycemia. Phosphorylated PERK to total PERK ratio in ITD+RH group was higher by 35-74% as compared with control groups. Total PERK levels in RH-exposed ITD rats was lower by 45-54% as compared with control groups. RH did not alter CHOP levels in hippocampus. Therefore, we conclude that prior RH exposure decreases PERK levels in ITD rats and may mediate increased ischemic damage in RH-exposed ITD rats. Understanding the role of ER stress in RH-induced aggravation of ischemic brain damage may help in developing new therapies for diabetics experiencing stroke or cardiac arrest.

Support: NIH grant NS073779 and AHA grant 18POST34070061.

In Partnership with