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2018

Friday September 14, 2018
NEC seminar

NOTE LOCATION: Nord 240, 9:00 AM
Speaker: Hillary Bedell
Advisor: Prof. Capadona
Title: A review of active anti-inflammatory approaches to reduce the biological response to intracortical microelectrodes

Abstract
One of the current tools used to probe the brain is the intracortical microelectrode which can record from single neurons or small populations of neurons. Despite the enthusiasm for brain interfacing technologies which utilize the intracortical microelectrode, it is widely understood that microelectrodes exhibit limited long-term viability where recordings typically fail 6 months to 1 year after implantation. This is due to multimodal failure mechanisms including the biological response. There are many strategies undertaken by research groups to reduce this biological response to intracortical microelectrodes. This talk will outline different active anti-inflammatory approaches being explored to reduce the inflammatory response to these devices. The talk will end detailing my current work—an exploratory study to find key molecular players in neuroinflammation in response to intracortical microelectrodes.

 

Friday August 10, 2018
NEC seminar

Nord 400, 9:00 AM
Speaker: Hendrik Dewald
Advisor: Prof. Kirsch
Title: Impact of Peripheral Nerve Block on Flexion Synergy Expression at the Wrist and Hand in Stroke

Abstract
Stroke is a leading cause of serious long-term disability, affecting about 3% of males and 2% of females nationwide. Following a hemiparetic stroke, the majority of individuals suffer a loss of independent joint control through the consistent expression of abnormal limb synergies. These synergies significantly impair paretic limb reach distance and hand use, with activation of shoulder abductor muscles becoming intrinsically coupled with flexion at the elbow, wrist, and hand. More severely impaired individuals may not be able to open the hand, even with the weight of the paretic arm supported.

Recent research has shown that these synergies originate in the central nervous system and that there is no change in muscle passive stiffness properties at the fingers. Rather, the ongoing and continuous activation of flexors due to the abnormal drive is at play. The studies proposed here intend to circumvent this abnormal command from the central nervous system through the application of a peripheral nerve block, potentially preventing the abnormal activation of wrist and finger flexors.

Firstly, we will characterize the impact of ulnar and ulnar/median nerve block by lidocaine on hand opening and synergy-induced unintentional grasp forces in stroke patients. Secondly, we will observe the lidocaine block's effect on prediction of intent by electromyographic signals and efficacy of surface-based functional electrical stimulation assistive devices. We hypothesize that blocking these nerves will reduce abnormal wrist and finger flexor hypertonicity significantly and improve control of, and intent-derivation for, assistive approaches.

Lastly, we will investigate the possible future application of more clinically relevant high-frequency alternating current nerve conduction block techniques through observation of a surface-based tibial nerve block in able-bodied individuals. We hypothesize that the onset response of these techniques will not cause significant discomfort to subjects.

Should this exploratory study reveal sufficient efficacy of nerve block in the relief of flexor hypertonicity in stroke and minimal discomfort from the onset response, new opportunities in stroke rehabilitation interventions become possible. This includes the use of implanted nerve cuff electrodes to implement partial or complete nerve block, thus making the use of FES to power hand function viable.

 

Friday July 27, 2018
NEC seminar

Nord 400, 9:00 AM
Speaker: Alistair McEwan
Ainsworth Chair of Technology and Innovation
The University of Sydney
Cerebral Palsy Alliance
Biomedical Devices and Instrumentation Coordinator, BMET
Institute Faculty of Engineering and Information Technologies
Title: Neural interfaces for cerebral palsy

Abstract
From an engineering point of view I will outline the latest understanding and needs in Cerebral Palsy, the most common childhood disability with no cure and delayed diagnosis. We will also describe opportunities for control of muscle groups, spasticity and sensory perception including pain. While people with spinal cord injury have been the target of motor prosthesis to date there are additional challenges to explore in cerebral palsy such as developmental differences and viable afferent pathways that may convey pain and other sensory signals. We see opportunities in both central and peripheral stimulation and monitoring. Our group has a background in impedance recordings which might be used as a novel monitoring tool or to optimise stimulation patterns. We also use electrical tissue properties to better identify pathological tissue and guide electrical stimulation, electroporation and heating in the management of electrical signalling pathways.

 

Friday July 20, 2018
NEC seminar

Nord 400, 9:00 AM
Speaker: Elizabeth Heald
Advisors: Prof. Peckham
Title: Utilizing Muscle Activity from Below the Spinal Cord Injury Level for Neuroprosthetic Control

Abstract
As neuroprosthetic technology improves, there is an increased need for command signals to control the additional functionality that can be provided to users. In a previous study, EMG recordings from the lower extremity of subjects with motor complete SCI indicated that the majority showed some degree of volitional activity in at least one muscle, even though no joint movement was observed. This is in agreement with a growing body of work indicating that even in motor complete SCI, most cases still demonstrate some axonal sparing across the lesion. If descending motor commands can be volitionally and reliably produced, the EMG generated may be used as a command signal, even if it is too small to produce discernable joint movement. Utilizing these signals as command inputs could offer an innovative solution to the problem of too few control signals in current neural prosthesis systems. In this talk, results will be presented from an experiment demonstrating feasibility of using below-injury myoelectric activity as a command signal for an upper extremity grasp neuroprosthesis. In addition, I will discuss a biofeedback training paradigm which is being implemented in an ongoing study with the goal of improving the quality of weak below-injury muscle signals to that which would be useful for neuroprosthetic control.

 

Friday July 14, 2018
NEC seminar

Nord 400, 9:00 AM
Speaker: Dr. Brooke Odle
Advisors: Drs. Ron Triolo and Musa Audu
Title: Estimating the Interaction Forces of the Upper Extremities and Support Devices

Abstract
Knowledge of upper extremity (UE) effort exerted on a support device under real world conditions is important for understanding the voluntary contributions to the postural shifts by persons with motor or sensory disorders to complete many activities of daily living while standing. This information is critical to further advance the development of neural stimulation control systems for enhancing balance during standing and walking after paralysis. In this talk, experimental pilot studies that resulted in the development and evaluation of linear models that accurately account for intact volitional control exerted by the UEs on a support device will be presented and discussed.

Congratulations Bolu Ajiboye, PhD and Robert Kirsch, PhD
First Place - 2018 International Annual BCI-Research Award

The Cleveland FES Center congratulates Bolu Ajiboye, PhD and Robert Kirsch, PhD on receiving first place for the 2018 International Annual Brain Computer Interface (BCI) Research Award, for their project entitled "Restoring Functional Reach-to-Grasp in a Person with Chronic Tetraplegia using Implanted Functional Electrical Stimulation and Intracortical Brain-Computer Interfaces."

The Brain Computer Interface Award is one of the highest achievements in BCI research. It is an annual award organized by the BCI Foundation recognizing outstanding and innovative research in the field of Brain-Computer Interfaces.

 

Friday June 29
NEC Seminar

9:00 AM, Nord 400
Speaker: Jessica De Abreu
Advisor: Prof. Kirsch
Title: Virtual reality models for studying object interaction effects in BCI-controlled reaching tasks

Abstract
Recent studies using brain computer interfaces (BCI) demonstrated unexpected changes in neural activity when participants attempted to interact with objects. In order to restore motor function to people with paralysis, it is important to characterize changes in neural activity that may occur during interaction with objects and to elucidate the underlying mechanisms driving these changes. In this talk we will introduce virtual reality (VR) models as tools for investigating how neural activity changes during tasks that require interaction with objects. We will provide a brief tutorial about how to implement realistic virtual reality simulations. The audience should expect to leave with a basic understanding of how VR models implement physics and how current VR software supports and limits VR model usage in neuroscience and neuroengineering.

Friday, June 22, 2108
NP Seminar
Noon, BRB 105
Speaker: Peter Kirkwood,PhD
Emeritus Reader
Sobell Department of Motor Neuroscience & Movement Disorders
Institute of Neurology
University College London
Title: Following Sherrington: Integration in Intercostal Motoneurons

Abstract
Since Sherrington, the spinal motoneuron is well known as the integrator of many different inputs. However, assessing what contribution each of these sources makes to bring any motoneuron to threshold in a natural movement is mostly unknown. Respiration, as a motor act that proceeds relatively normally under experimental conditions, is very valuable in this regard and among various muscles whose motoneurons receive a respiratory signal, particularly useful data may be obtained from the intercostals.

Friday, June 15, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Ryan Reyes
Advisor: Prof. Ron Triolo
Title: Development and Metabolic Testing of a Hybrid Neuroprosthesis for Walking After Paraplegia

Abstract
Traditional commercial exoskeletons enable persons paralyzed by spinal cord injury (SCI) to regain ambulatory function. We are developing a "Muscle First" Motor-Assisted Hybrid Neuroprosthesis (MAHNP), which uses implanted neural stimulation to activate the leg muscles in order to generate the majority of the forces required for walking. Conventional commercially available exoskeletons are unable to be driven by the muscles due to having non-backdrivable transmissions at the joint, and depend on external motors at the joints for all motive power. However, the MAHNP features motorized backdrivable joints with low passive resistance which allow the user's muscles to produce the majority of forces required for ambulation. It is possible to reduce the passive resistance to near zero with active motor compensation. To inform future decisions in our exoskeleton design, we tested the effect of motorized friction compensation on the metabolic cost of using the MAHNP with able-bodied subjects. We found that the decrease of passive friction from 6 Nm of torque to 0 Nm of torque was not statistically significant. The implications of these results will be discussed, as well as our current and future development goals.

Friday, June 8, 2018
NP Seminar

8:30 am, Linsalata Alumni Center, Foster Castele Great Hall
Case Western Reserve University

Speaker: Tim Denison, PhD
Vice President of Research and Core Technology, Medtronic
Title: Designing for Value: One Positive and One Disastrous Case Study

For more information, please contact Cheryl Dudek
(216) 231-3257 cdudek@FEScenter.org

Live stream video link for each lecture at www.FEScenter.org/Seminar

Friday, June 1, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Kelsey Bower
Advisor: Prof. McIntyre
Title: Modeling deep brain stimulation of afferent axon terminals: the role of axon morphology and head model complexity

Abstract
Numerous cell types exist in the region of the subthalamic nucleus (STN), including fibers of passage, local STN cells, and terminating STN afferents. Histological studies in the rat have identified "hyperdirect" axons which originate in motor cortex and project terminating collaterals to the STN. Recent optogenetic studies, capable of dissecting the neural circuitry and selectively stimulating these distinct neural elements, suggest that cortico-STN afferents may play an important role in the therapeutic effects of DBS. The goal of this study is to identify the behavior of terminating afferents in response to DBS using a computational modeling approach.

A computational model of a branched axon terminal was generated, with a structure that mimicked hyperdirect axons. Two models of the human head were also generated, representing a simple and a realistic head model. The axon models were placed within the internal capsule of the head model in order to best represent the location of the hyperdirect pathway. Activation thresholds of terminating fibers were compared to that of diameter-matched fibers of passage to identify the effects of termination. Small diameter terminating fibers exhibited lower thresholds than diameter-matched fibers of passage, however this trend was reversed in some large diameter fibers. Results suggest that numerous parameters affect the relative excitability of terminating axons, including morphology and electrical properties of the terminal nodes.

Friday, May 25, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Joseph Marmerstein, Ph.D. Candidate, Biomedical Engineering
Advisor: Prof. Durand
Title: Chronic Recording of Rat Vagal Tone with Carbon Nanotube Yarn Electrodes

Abstract
The study of small peripheral nerves such as those in the autonomic nervous system holds great promise for the detection and treatment of a variety of pathologies. In particular, the vagus nerve, which is a highway of autonomic activity, has been receiving increased attention due to it's interaction with nearly every internal organ in the body. Additionally, vagal tone is a clinical measure that is generally correlated with patient outcomes in many diseases, leading to interest in the vagus nerve as a therapeutic target for everything from epilepsy to autoimmune disorders. However, vagal tone has never been directly measured and is only correlated to clinical factors such as heart rate variability. Dr. Durand's group has developed a novel way for interfacing with the vagus, via carbon nanotube (CNT) yarn microelectrodes. A new technique for CNT yarn implantation may increase yield and allow this technology to be more easily used by other researchers. These CNT yarn electrodes have been implanted chronically in the vagus nerve of rats, and may allow for a true measurement of vagal tone for the first time.

Note: There will not be an NEC Seminar on Friday May 11.

Friday, May 4, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Brian Sanner, Ph.D Candidate
Advisor: Prof. Tyler
Title: Verification Testing of an Inline High Density Connector for Implanted Functional Electrical Stimulation

Abstract
An inline high density connector (I-HDC) with 34 independent channels was developed to minimize volume displacement of tissue while creating a robust, chronic, system for modularizing and managing the wire leads of implanted functional electrical systems (FES). The HDC was fabricated in two configurations, a loopback (LB-HDC), which is implanted subcutaneously and has groups of channels shorted together to test connectivity and crosstalk over chronic periods, and the inline configuration, which connects the percutaneous leads to the proximal side of the HDC and the distal side to a 16-channel c-FINE. These were implanted in the feline model (n=3 and n=2, respectively) for the first round of testing to verify functional requirements, with current findings in the ongoing study to be presented here.

Friday, April 27, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Prof. Mortimer
Topic: Authorship

Prof. Mortimer has provided the following two documents for reading prior to the meeting:
Authorship (doc)
Examples (doc)

Friday, April 13, 2018
APTC Distinguished Lecture Series

11am-12pm, Cleveland Clinic Lerner Research Institute, Room NE1-205

Speaker: Shelley Fried, PhD
Title: Restoring function with neural prostheses: work towards the development of more effective stimulation strategies

Dr. Shelley Fried is a Health Scientist at the Boston VA Medical Center and an Associate Professor in the Department of Neurosurgery at Harvard Medical School, both in Boston, MA. Dr. Fried has a PhD in Vision Science from UC Berkeley where he studied the mechanisms by which the normal retina transforms light into neural signals. He did postdoctoral training at both UC Berkeley and at the Massachusetts General Hospital in Boston studying electric stimulation of the retina. His research explores how and why neurons respond to artificial stimulation with the goal of developing improved methods and strategies. Active areas of research include electric stimulation of the retina, magnetic stimulation of primary visual cortex and the function of the early visual pathways. Prior to obtaining his PhD, Dr. Fried worked for 12 years in the medical device industry developing a wide range of anesthesia and respiratory therapy products.

For more information, please go to https://friedlab.mgh.harvard.edu/

 

Friday, April 13, 2018
NP Seminar

8:30am, BRB 105

Speaker: Sliman Bensmaia, PhD
Title: Biological and Bionic Hands: Natural Neural Coding and Artificial Perception

Abstract
Our ability to manipulate objects dexterously relies fundamentally on sensory signals originating from the hand. To restore motor function with upper-limb neuroprostheses requires that somatosensory feedback be provided to the tetraplegic patient or amputee. Given the complexity of state-of-the-art prosthetic limbs, and thus the huge state-space they can traverse, it is desirable to minimize the need of the patient to learn associations between events impinging upon the limb and arbitrary sensations. With this in mind, we seek to develop approaches to intuitively convey sensory information that is critical for object manipulation - information about contact location, pressure, and timing - through intracortical microstimulation (ICMS) of primary somatosensory cortex (S1). To this end, we test in psychophysical experiments with monkeys, the sensations evoked by ICMS of S1. Based on these results, we show how to build a biomimetic encoding algorithm for conveying tactile feedback through a cortical interface and show that artificial touch improves the dexterity of brain-controlled bionic hands.

Friday, April 6, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Grant McCallum, PhD
PI: Prof. Durand
Title: "Neural activity within solid breast tumors and the implications on metastasis"

Abstract
Breast cancer is a global problem. Worldwide, breast cancer accounts for nearly a quarter of all cancers in women and it is estimated that 1.7 million women are diagnosed with the disease annually. In the United States, in 2016, 249,260 women and 2,600 men were diagnosed with invasive breast cancer, and another 61,000 women were diagnosed with in situ breast cancer. The chance of a woman being diagnosed with breast cancer during her lifetime has increased from about 1-in-11 in 1975 to 1-in-8 today. An estimated 90% of deaths due to breast cancer are a consequence of metastatic disease, whether the cancer was metastatic at diagnosis or a metastatic recurrence that developed later.

An increasing amount of evidence supports the autonomic nervous system's role in the etiology and evolution of solid tumors, including prostate, pancreas and breast. Solid tumors were once believed to lack innervation. However, recent scientific articles indicate that nerve fibers infiltrate primary tumors through neurogenesis. Increasing nerve densities are associated with more aggressive tumor grades and poor patient survival. Signaling molecules (neurotrophins, neuropeptides, axon guidance molecules and neurotransmitters) traditionally associated with nervous system function have also been implicated in cancer and may play an important role in promoting cancer by mediating the reciprocal cross-talk between nerves and cancer cells, particularly in the context of the tumor microenvironment.

Numerous animal model studies have provided a starting point to understand the autonomic nervous system's influence on breast cancer progression. However, not one of these studies has reported direct recordings and/or quantified the neural activity within the solid breast tumor to ascertain whether these neural fibers are active and if so, what neural signaling patterns are occurring within the solid tumor during its development through metastasis.

Collaborating with Prof. Karathanasis' lab and using their 4T1 (triple-negative) breast cancer mouse model, we have implanted our microwire electrodes into the solid tumor and performed chronic recordings and bioluminescence imaging (BLI) to track the neural activity and tumor growth through metastasis. Preliminary recording, imaging and histology data will be presented along with the ultra, low-noise chronic recording system setup used. We hypothesize that recorded neural activity can be used to predict the occurrence of metastasis in this animal model. Furthermore, encouraging evidence has emerged that it may be possible to differentiate pre-metastatic vs. metastatic conditions based on overall signaling patterns and a subset of the active neural population.

 

Friday, March 29, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Ivana Cuberovic
Advisor: Prof. Dustin Tyler
Title: Cognitive Factors Driving Perception of Sensory Location

Abstract
There are approximately 2 million amputees in the United States. When a person suffers an amputation, they lose both the motor capabilities of the limb and all somatosensory feedback from it. Electrical stimulation is a means of restoring sensation to such persons. Previous work in our lab has demonstrated the ability to evoke focal, intensity-graded sensations of pressure across the surface of the phantom hand.

One of the fundamental dimensions of sensation we aim to accurately reproduce with sensory stimulation is the location of evoked percepts. Tactile stimuli have been shown to improve task performance in both tactile-only and in multi-modal sensory feedback conditions when the feedback is spatially congruent to the task. We hypothesize that the anatomic relationship between peripheral nerve somatotopy and the sensory homunculus in the sensory cortex defines the possible locations of evoked sensation, but that it does not account for changes in tactile location perception under various cognitive conditions, such as those found in haptic illusions.

Here we sought to probe cognitive influences on the perception of electrically-evoked sensory locations within anatomic bounds. First, we quantified the effects of changing limb posture on perceived location. We then investigated the influence of task-performance on perceived location. Finally, we show preliminary data investigating the relative contribution of visual capture to changes in perceived location during task performance. We hypothesize that perceptual processes such as visual capture and expectation influence the precise location of perceived sensation within broad anatomic bounds.

Friday, March 23, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Platon Lukyanenko
Advisor: Prof. Dustin Tyler
Title: A muscle synergy basis for a continuous, proportional, simultaneous prosthetic hand controller allows reduced training time without performance degradation.

Abstract
Of the nearly 100k upper limb amputees in the united states, 20-40%, varying by survey, abandon their prosthetic devices. Recent pushes by groups such as DARPA and the VA have allowed the creation of advanced prosthetic limbs including the Deka and Modular Prosthetic Limb, but not yet the means for their control. Modern experimental prosthetic hand controllers generally interpret user generated EMG to determine a user's intent and then drive a prosthetic hand's motors. Rarely do these controllers allow 'simultaneous' movement of multiple degrees of freedom, variable movement speed of these degrees in a manner 'proportional' to user intent, 'continuous' combinations of movements evoked, and low training times on the user's part. We develop a synergy-based prosthetic controller which provides continuous, proportional, simultaneous hand control using implanted EMG, with the potential for very short training times, and evaluate it using a VR based posture matching task and a novel 'simultaneity' metric. Successful use of the synergy approach serves to enhance its validity as a framework for interpreting neural drives.

Friday, March 16, 2018
NP Seminar

8:30 AM, Wolstein Research Building Room 1413

Title: Interfacing with Autonomic Nerves

Speaker: Dominique Durand, PhD
Elmer Lincoln Lindseth Professor in Biomedical Engineering
Director, Neural Engineering Center
Case Western Reserve University

For more information, contact Cheryl Dudek (216) 231-3257, cdudek@FEScenter.org

Friday, March 9, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Natalie Cole
Title: "Reducing the dimensionality of time-varying hand function with muscle synergies"
Advisor: Prof. Bolu Ajiboye

Abstract
Muscle synergies have been shown to reduce the muscle activation patterns of complicated, multi-dimensional sets of movements and postures to simplified, coordinated muscle recruitment. Regarding hand function specifically, it has been shown that the complexity of hand function is physiologically simplified at the kinematic and muscle activation level as evidenced by correlated and co-varying degrees of freedom. Additionally, muscle synergies extracted from a limited set of hand postures have been successfully used to reconstruct the muscle activation patterns required to reproduce a wide range of new hand postures However, it is unclear whether static synergy modules can be used to reproduce the time-varying muscle activation patterns observed during actual hand movement (i.e. during grasp formation and functional use). This work first examines whether a low-dimensional set of static synergies can be extracted from and recreate muscle activation patterns observed during time-varying (non-isometric) hand function as well as or better than static synergies derived from (isometric) hand postures. The results show that static muscle synergies can be extracted from functional task EMG and the performance for reconstructing muscle activations during functional tasks is comparable whether using static synergies derived from postural tasks or functional tasks.

Friday, March 2, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Breanne Christie
Title: "Evaluating the functional performance and cognitive burden of lower limb sensory neuroprostheses"
Advisors: Drs. Ronald Triolo and Dustin Tyler

Abstract
Somatosensory feedback from the sole of the foot and ankle joint plays an important role in maintaining balance and postural stability. In people with lower limb loss, the feedback from foot-floor contact pressure or ankle position is compromised. Compared to able-bodied individuals, they typically have lower balance confidence, higher fall risk, and asymmetrical weight distribution. In a preliminary study, we successfully restored natural sensation in two unilateral trans-tibial amputees using chronic neural interface technology. We implanted nerve cuff electrodes on the distal sciatic, tibial, and common peroneal nerves in the residual limb. By delivering electrical pulse trains to the nerve, we were able to elicit sensations referred to the missing limb. After finding charge thresholds and mapping percept location to electrodes, we developed an instrumented prosthesis equipped with pressure sensors embedded in shoe insoles. When pressure sensors were activated, appropriate electrical stimulation was delivered to the nerve to evoke sensation in the corresponding locations of the missing limb. We have begun to examine the effects of sensory feedback on gait, static balance, and cognitive burden. During gait experiments, participants walk on a treadmill with embedded force plates. A SMART Balance Master ® with embedded force plates is used to perform two balance tests. In a sensory organization test (SOT), a surface platform sways, visual surroundings sway, and/or subjects close their eyes. During translation tests, the surface platform is unexpectedly translated forward or backward by 6cm. Finally, to assess cognitive burden, a dual-task paradigm combines static standing with spelling 5-letter words backwards. During translation tests and conditions of the SOT missing visual input, preliminary results indicate that one participant adopts a more symmetrical weight distribution when sensory feedback is incorporated. He also has decreased anterior-posterior sway (p<0.05) when visual input is blocked while the platform rotates about the ankle joint. Overall, our findings suggest that restoring sensory feedback to individuals with lower limb loss could potentially minimize overuse of their intact limb and improve postural stability in response to perturbations.

 

Friday, February 23, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Nicholas Couturier
Advisor: Prof. Durand
Title: Low-frequency fiber tract stimulation for seizure suppression in cortical epilepsies

Abstract:
Frontal Lobe Epilepsy (FLE) is the second most common form of focal epileptic disorders. FLE is characterized by highly diverse seizure symptoms often delaying accurate diagnosis. Unlike the more common temporal lobe epilepsy, FLE tends to be more refractory to anti-epileptic drug treatment accounting for up to half of all intractable epilepsies. Furthermore, the success rate of surgical resections for neocortical seizures is only 50-60% compared to 75% for temporal lobectomy. A novel treatment for refractory epilepsy of neocortical origin is investigated based on the success of previous studies in deep brain stimulation for mesial temporal lobe epilepsy. We previously reported seizure suppression of 90% in animal models as well as in patients. Seizure suppression is achieved through direct stimulation of the fiber tracts connecting structures in both hemispheres of the brain. We stimulate at low frequencies between 1-30 Hz to elicit a long-lasting hyperpolarization in the post-synaptic neurons. For epileptic foci in the frontal cortex, we stimulate the corpus callosum acutely for 1 hour to suppress seizures both during stimulation as well as after stimulation. Initial experiments demonstrate significant seizure suppression in an acute cortical model of epilepsy. Additional acute experiments, as well as chronic experiments, are being planned to validate the effectiveness of fiber tract stimulation for seizure suppression.

 

Friday, February 16, 2018
NP Seminar

8:30 AM, Wolstein Research Building Room 1413

Speaker: Julius DeWald, PhD
Chair and Professor
Department of Physical Therapy and Human Movement Sciences
McCormick School of Engineering and Physical Medicine & Rehabilitation
Northwestern University

download flyer

Friday, February 2, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Cale Crowder
Advisor: Robert Kirsch, PhD

Title: Applications of deep learning in brain-computer interfaces

Abstract:
Cervical-level spinal cord injuries can result in paralysis from the neck down -- a condition know as tetraplegia. In order to return motor function to study participants with spinal cord injuries, our research group has created an intramuscular functional electrical stimulation (FES) system controlled by an intracortical brain-computer interface (BCI). The FES-BCI system relies on many components including: a module to denoise the BCI signals, a module to extract features from the denoised signals, a decoder to translate extracted features into kinematic commands, and a controller to map kinematic commands to FES patterns. In this presentation, we will propose deep learning as a method to optimize the components of our FES-BCI system. Furthermore, we will suggest that deep learning can be used to elucidate the structure and function of the human motor cortical system.

Friday, January 26, 2018
NEC Seminar

9:00 AM, Nord 400

Speaker: Rajat Shivacharan
Advisor: Prof. Durand

Title: Spontaneous neural activity can propagate non-synaptically

Abstract:
It is well documented that synapses play a significant role in the transmission of information between neurons. However, in the absence of synaptic transmission, neural activity has been observed to continue to propagate. This raises the question as to what is mediating this propagation. Experiments conducted in our lab have shown that propagation of epileptiform behavior in rodent hippocampi propagates at a speed of ~0.1 m/s. This observed propagation can take place in the absence of synaptic transmission and gap junctions and is outside the range of ionic diffusion and axonal conduction. Recent studies suggest ephaptic coupling, or endogenous electric fields, can activate neighboring neurons, thereby generating a self-propagating wave. However, there is no experimental data suggesting ephaptic coupling is sufficient for spontaneous, self-regenerating propagation of neural activity. Recent in vitro and in vivo data from the rodent hippocampus will be presented that shows neural activity can propagate through a physical cut in the tissue, thereby completely eliminating synaptic transmission and other close cell-to-cell communication mechanisms, and showing electric fields alone are sufficient to mediate non-synaptic propagation.

Friday, January 19, 2018
NP Seminar

8:30 AM, Wolstein Research Building Room 1413

Speaker: Aaron Batista, PhD
Associate Professor, Bioengineering
Principal Investigator, Sensory Motor Integration Laboratory and Engineering
University of Pittsburgh

Title: How does the brain change when we learn?

Abstract:
How does the brain change when we learn? Those changes must lead to the emergence of new patterns of activity in the population of neurons that control the newly-learned behavior. By using a Brain-Computer Interface (BCI) paradigm, we can observe changes in neural population activity that lead directly to new behavioral capacities. We find that a simple network principle governs whether novel BCI mappings will be learned quickly or more slowly. We can then examine the neural activity patterns that are expressed following learning. We find that different principles of nework reorganization underlie fast and slow BCI learning.

2017

Friday, December 15, 2017
NEC Seminar

9:00 AM, Nord 400

Speaker: Kristen Gelenitis
Advisor: Prof. Triolo

Title: Exploiting C-FINE Selectivity to Prolong Moment Output with Neural Stimulation

Abstract:
Implanted nerve cuffs in the lower extremities of individuals with spinal cord injury (SCI) have been successful in allowing recipients to achieve standing with electrical stimulation. Current systems use constant, simultaneous stimulation of the knee extensor muscles through multiple contacts on the femoral nerve to achieve the necessary knee moment output. However, constant stimulation can induce rapid fatigue of the targeted muscles which can limit standing durations. In order to offset the effect of fatigue, increase maximal standing times, and improve the consistency of clinical outcomes, more advanced stimulation paradigms that reduce the duty cycle of each muscle by alternating the stimulation delivered through each contact have been investigated. Previous work in our lab has demonstrated the ability of these paradigms to effectively prolong moment output in humans. The study presented in this talk focuses on an analogous animal model that will be used to understand how to better control these stimulation paradigms in clinical applications.

NOTE: This is the final NEC seminar for 2017.

Friday, Decenber 8, 2017
NP Seminar

8:30 AM, Wolstein Research Building Room 1413

Speaker: Parag G. Patil, MD, PhD
Associate Professor
University of Michigan

Title: Vive La Difference: Managing Structural and Functional Diversity in DBS for Movement Disorders  See flyer

Abstract:
Our brains are like faces - we each have one but no two are quite the same. The same holds true for individuals with Parkinson disease and tremor, as well as for candidates for other neuromodulation and neuroprosthetic therapies. Commonalities and generalizations guide therapeutic development and scientific inquiry. At the same time, our success in managing diversity determines the quality of care that we deliver to our patients. At the Universityof Michigan, we have taken a multidisciplinary approach to patient selection and an atlas-independent image-analytical and electrophysiological modeling approsch to outcome evaluation. We believe that this collaborative, neurogengineering approach to DBS will allow us to individually optimize therapy benefits and deepen understanding of the neural mechanisms underlying successful DBS.

Friday, December 1, 2017
NEC Seminar

9:00 AM, NORD 400
Speaker: Hillary Bedell
Advisor: Prof. Capadona
Title: The effects of dual targeting of an innate immune receptor pathway and mechanical mismatch of the tissue-electrode interface on the neuroinflammatory response to intracortical microelectrodes

Abstract: Intracortical microelectrodes afford researchers an effective tool to precisely monitor neural spiking activity for both applications in neuroscience research and the restoration of function through a brain computer interface (BCI). Unfortunately, the neural signals detected by these electrodes decline over time. Previous work from our lab has indicated that a specific innate immune receptor pathway is a viable target to improve intracortical microelectrode recordings. Our lab has also demonstrated that use of a softening material, whose modulus more closely matches that of the brain, for an electrode decreases the inflammatory response at both acute and chronic time points. In the study presented in this talk, we evaluate the combinatorial targeting of both the innate immune receptor pathway and the mechanical mismatch using a different softening electrode made from a thiolene-acrylate shape memory polymer (SMP). Using immunohistochemistry at 2 and 16 week end time points we demonstrate that the SMP microelectrode in fact resulted in a significant increased inflammatory response over a control silicon electrode despite more desirable mechanical properties. Hypotheses to explain this surprising result will be explored.

Friday, November 17, 2017 CANCELED due to a scheduling conflict
NEC Seminar

9:00 AM, NORD 400

Speaker: Platon Lukyanenko
Advisor: Prof. Tyler

Title: Towards an Independent 4-Degree-Of-Freedom Prosthetic Hand Controller

Abstract:
Past results (presented by H Dewald on 11/10/17) indicate that a stable 3 degree-of-freedom prosthetic hand controller can be designed for transradial amputees through a VR based data-collection and then online posture-matching-evaluation task using implanted EMG electrodes through a KNN approach. Such an approach provides a controller comparable to intact-hand performance in the context of time-to-target, and which remains stable for many months.

There is, however, a large difference between a 3 and 4 DoF controller in the context of assumptions which can be made, data which can be collected, and subsequently the requirements imposed on a prospective control method. This talk will examine several hypothetical cases which must be addressed by such a controller, difficulties with present methods, and several prospective approaches for overcoming current controller limitations including context-dependent thresholding and class-specific PCA.

Friday, November 10, 2017
NEC Seminar

9:00 AM, NORD 400

Speaker: Hedrik Dewald
Advisor: Prof. Kirsch

Title: Simultaneous and Independent Control of a Virtual Three-Degree of Freedom Prosthetic Hand using Implanted Intramuscular Electrodes

Abstract:
Eight bi-polar electromyographic electrodes were surgically placed within residual muscles of a transradial amputee. End of range-of-motion posture tasks were used to collect training data for various controllers of simultaneous velocity for three degrees of freedom of a virtual reality hand - hand aperture, wrist flexion/extension, and wrist rotation. Machine learning approaches were used to convert magnitude and frequency-related features of the EMG signals into continuous joint velocities. A virtual reality posture matching task was used to test online system performance, with performance of the subject's intact hand measured by electrogoniometer and used as a position controller considered the standard for comparison. Results show comparable performance in time-to-target between machine learning algorithms and the intact hand, but reduced path efficiency. Long-term controller performance was also found to be stable, with no need for retraining.

Friday, November 3, 2017
NP Seminar

8:30 AM, BRB 105

Speaker: Sherif M Elbasiouny, PhD, PE, PEng
Assistant Professor
Wright State University

Title: Neuroengineering Approaches in Neuroprosthetics and Neurodegeneration  Download flyer

Abstract:
This talk will present how neuroengineering approaches are making advances in the fields of neuroprosthetics and neurodegeneration. In neuroprosthetics, state-of-the art prostheses use the EMG signal to decode the amputee's motor intent; however, the EMG signal does not provide accurate information on the finer characteristics of the desired movement, making them inadequate to control the sophisticated movements of modern prostheses. This talk will present our effort in developing a new technology based on the motor neuron (motoneuron) firing signals. Using computational approaches, we have constructed a multi-scale, highly realistic computational model of the spinal sensorimotor circuit under different neuromodulatory states. This model was used as a research platform to develop novel, robust motor decoder algorithms based on the motoneuron firing behavior for closed-loop control of prosthetic movement.

In neurodegeneration, this talk will present a novel cross-disciplinary neuroengineering approach that we developed to examine the cellular abnormalities underlying motoneuron degeneration in the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). In addition to understanding how the motoneuron regulates its excitability under disease conditions, this approach has uncovered cellular abnormalities masked from experimental investigation and identified novel drug targets, leading to a novel ALS treatment.

Friday, October 27, 2017
NEC Seminar

9:00 AM, NORD 400

Speaker: Elizabeth Heald
Advisor: Prof. Peckham

Title: Myoelectric Signals as Neuroprosthetic Control Sources: A Potential Application for Below-Injury EMG activity in SCI

Abstract:
Motor neuroprostheses expand the functional abilities of individuals with chronic SCI to a level that cannot currently be achieved with any other intervention. Current clinical implementations of these systems utilize myoelectric activity from non-paralyzed muscles as command signals to control the functional output of the device. As neuroprosthetic technology improves, there is an increased need for command signals to control the additional functionality that can be provided to users. Our previous work has demonstrated the presence of volitional EMG activity in the lower extremity in a majority of subjects with chronic, motor complete cervical SCI. This activity may be suitable to serve as a command signal in a neuroprosthetic system. In this presentation, I will review how recorded EMG signals are translated into functional movements in clinical upper extremity neuroprostheses. I will then present our plans to implement biofeedback training paradigms with the goal of improving myoelectric signal quality from below-injury muscles, and our interface for evaluating the suitability of these signals for neuroprosthetic control.

Friday, October 20, 2017
NP Seminar

8:30 AM, BRB 105

Speaker: James Patton, PhD
Professor, Bioengineering
University of Illinois Chicago

Title: Models of Motor Control and Learning in Therapeutic Rehabilitation

Abstract:
It has been shown to be powerful to leverage what we know (i.e., existing models) about neural adaptation in neurorehabilitation. These models stem from how people learn through mistakes, and several techniques on using such models might dictate better training conditions helped by robotic technology. However, the clinical trials model has not proven to be effective test because of few samples and restrictive inclusion criteria. This talk will show how such "small data" problems lend themselves well to scrutiny and interrogation from modern predictive modeling and validation techniques, suggesting a more "organic" model for gathering data.

Friday, October 6, 2017
NEC Seminar

9:00 AM, Nord 400

Speakers: Breanne Christie "Latency Of The Perceived Sensation Evoked By Peripheral Nerve Stimulation In People With Lower Limb Amputations" and Dan Young "Restoring Thought-Controlled Movements After Paralysis: Artifact Reduction Techniques for iBCI Control of FES Actuated Movements"

Friday, September 29, 2017
NEC Seminar

9:00 AM, Nord 400

Speaker: Jesssica de Abreau
Advisor: Prof. Robert Kirsch
Title: Characterization of object interaction effects for improving the functional performance of FES-iBCI systems

Abstract:
Spinal cord injuries (SCI) affect more than 276,000 patients in the United States, severely impairing activities of daily living. Lesions in the upper spinal cord may lead to tetraplegia, causing paralysis of the four limbs. Previous surveys of patients with tetraplegia report that regaining arm and hand function is ranked as the highest priority for improving quality of life. In BrainGate, we combine functional electrical stimulation (FES) with intracortical brain computer interfaces (iBCI) to bridge spinal cord injuries and restore motor function to patients with paralyzed upper limbs. Our system relies on two intracortical electrode arrays implanted in the primary motor cortex, used to decode motor intent. A percutaneous FES system is used to provide arm and hand muscle stimulation, reproducing the intended movement. Recently, our study has provided the first proof-of-concept of a combined FES-iBCI neuroprosthesis in restoring upper limb function to patients with tetraplegia. Our system allowed our participant to move his own arm to execute functional tasks such as feeding and drinking.

In this talk, we will discuss the effects of object interaction and how they might affect the performance of FES-iBCI systems. Object interaction effects have been briefly mentioned in literature in the context of iBCIs. The effect of object interaction has been described as a repulsive force field surrounding an object with which the participant intends to interact, particularly in tasks in the physical world and with many of degrees of freedom. Here, we discuss experiments to investigate and characterize the effects of object interaction in FES-BCI neuroprostheses. This investigation will allow further insight into strategies for neural control of kinematics during functional tasks.

Friday, September 22, 2017
NEC Seminar

9:00 AM, Nord 400

Speaker: Sydney Song
Advisor: Prof. Capadona
Title: A Combined Approach to Reducing Neuroinflammation in Response to Intracortical Microelectrodes

Abstract
To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuroinflammatory response. This increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and non-biologic components of the overall neural interface circuit. To combat neuroinflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. The Capadona Lab utilizes basic science techniques to provide a more complete mechanistic understanding of the molecular and biological-mediated failure modes for intracortical microelectrodes. The current study investigates a combination of mechanism associated with neuroinflammatory-mediated microelectrode failure.

Specifically, one mechanism for microelectrode failure we investigate is neuroinflammation and subsequent neurodegeneration. We approach this mechanism by impeding the signaling pathway leading to activation of immune cells. Another mechanism for failure we investigate is the micro-motion of the stiff device in soft brain. We approach this mechanism by using a compliant material to reduce injury. Previous studies have shown promise in both of these approaches. We hypothesize that two approaches to reducing tissue damage, one from biological, and one from material science, when combined, will further reduce the brain injury due to intracortical recording devices.

Friday, September 15, 2017
NP Seminar

8:30 AM, Nord 400

Speaker: Robert Turner, PhD
Professor, Dept. of Neurobiology and Center for the Neural Basis of Cognition, University of Pittsburgh, School of Medicine
Title: How Does DBS Work? Insights From Neurophysiology

Abstract
Deep brain stimulation (DBS) is a surgical therapy proven to be highly effective for a variety of neurologic disorders including essential tremor, Parkinson's disease, and dystonia. It is surprising then that considerable mystery remains about the mechanism of action of DBS (i.e., understanding how DBS "works" to ameliorate symptoms). This seminar will review recent studies of the effects of DBS on neuronal activity, including some performed in the lab, with the goal of showing how DBS may work by attenuating the transmission of abnormal "pathologic" neuronal activity across the affected brain circuits.

 

Friday, September 8, 2017
9:00 AM, Nord 400

Speaker: Ryan Reyes
Advisor: Prof. Ronald Triolo
Title: Development of a "Muscle First" Motor-Assisted Hybrid Exoskeleton for Walking After Paraplegia

Abstract: Traditional commercial exoskeletons enable persons paralyzed by spinal cord injury (SCI) to regain some ambulatory function. However, the majority of commercially available exoskeletons are fully motorized, and thus perform all the movement required for ambulation. Thus, their users do not experience all the physiological health benefits of exercising the large lower extremity muscles. We are developing a "Muscle First" Motor-Assisted Hybrid Exoskeleton, which uses implanted neural stimulation to activate the leg muscles in order to generate the majority of the forces required for ambulation. The exoskeleton provides the bracing necessary for stability and to shape limb trajectories, while providing rest periods for the stimulated muscles. The Motor-Assisted Hybrid Exoskeleton provides just enough additional joint moment to produce repeatable stepping motions as muscles fatigue. This enables a smaller, lighter exoskeleton, coordinated ambulation, as well as the physiological benefits discussed above. The research presented here details the current technology development and the initial forays into determining the best methods for coordinated muscular and motorized control.

Friday, September 1, 2017
9:00 AM, Nord 400

Speaker: Christopher Delianides
Advisor: Prof. Ronald Triolo
Title: Electrical Stimulation of the Upper Sciatic for Strong Hip Extension and Balanced Ankle Moments in SCI Patients

Abstract: In the United States alone, there are nearly 300,000 people living with spinal cord injury (SCI), with around 17,000 new cases every year. Electrical stimulation of peripheral nerves can be an effective method of generating contractions of the otherwise paralyzed muscles, leading to increased independence and improvement in markers of overall health. Previous work on the femoral and distal sciatic nerves using composite flat interface nerve electrodes (C-FINEs) has demonstrated a high degree of selectivity for activation of quadriceps and ankle musculature, as well as the superiority of these cuff electrodes over more commonly used intramuscular electrodes with respect to long-term stability and surgical complexity. Activation of knee extensors and ankle dorsiflexors and plantar flexors in this manner provided recipients with new options for achieving standing and stepping motions. Continuation of this work seeks to increase the capabilities of these patients with the addition of strong hip extension generated by the hamstrings, requiring cuff placement more proximal on the sciatic nerve than has been previously attempted. Proximal placement along the nerve also provides the challenge of selective activation of ankle musculature for balancing plantar/dorsiflexion and ankle inversion/eversion. The research presented here details the exploratory phase of this proposal, including histology and cadaver work, intraoperative testing, and fascicular modeling of responses to electrical impulse, as well as development of a novel transducer for intraoperative ankle moment measurement.

Friday, August 25, 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Kiley Armstrong
Advisor: Prof. Ronald Triolo
Title: Automatic Detection of Destabilizing Wheelchair Conditions.

Abstract: Nearly 42% of injurious events after SCI are caused by wheelchair tips and falls. Constant neural stimulation of the otherwise paralyzed core, hip, and trunk muscles can stabilize seated posture, as well as return users to erect sitting positions in response to applied disturbances. The goal of this study is to automatically detect potentially destabilizing conditions encountered by manual wheelchair users and activate the appropriate muscles to prevent falls and stabilize the seated operator. Wireless inertial measurement units containing tri-axial acceleration and gyroscopic sensors were mounted on the wheelchair frame with 4 individuals with low cervical and thoracic level injuries. An algorithm utilizing the accelerometer and gyroscopic data was constructed to detect and classify the turn and collision events, and trigger appropriate stimulus patterns. The research in this presentation investigated the detection accuracy of the algorithm, as well as the feasibility for modulated stimulation to hip and trunk extensor muscles to restore erect sitting posture after a destabilizing event.

Wednesday, August 23, 2017
NP Seminar - 3:00PM Wolstein Research Bldg Room 1413
Speaker: Marmar Vaseghi, MD, PhD
Title: Parasympathetic dysfunction in cardiac disease and the role of vagal nerve stimulation in treatment of ventricular arrhythmias. PDF

Abstract: Myocardial infarction causes sympathetic activation and parasympathetic dysfunction, which act in concert to increase the risk of sudden death due to ventricular arrhythmias. Although blockade of the sympathetic nervous system has been invaluable in the treatment of patients with heart failure and ventricular arrhythmias, little is know about the mechanisms underlying parasympathetic dysfunction.
New data is delineating consequences of myocardial infarction on parasympathetic myocardial neurotransmitter levels and on the function of parasympathetic cardiac and extra-cardiac ganglia, pointing to a decrease central parasympathetic drive as the reason behind the parasympathetic abnormalities observed in heart failure. Increasing parasympathetic drive with vagal nerve stimulation and elucidating its electrophysiological effects in the ventricle in the setting of chronic myocardial infarction could present an important avenue for treatment of patients heart failure and ventricular arrhythmias. However, the degree and frequency of vagal nerve stimulation has yet to be elucidated, particularly given the controversial results of this therapy in clinical trials of heart failure patients. Any effects of vagal nerve stimulation, however, on treatment of ventricular tachycardia after myocardial infarction could serve as important option for patients with cardiomyopathy, who present with VT storm and recurrent defibrillator shocks, despite standard medical therapy and ablation procedures.

Friday, August 11, 2017
NEC Seminar
9:00 AM, Nord 400

The NEC seminar will consist of four short presentations by undergraduates who are completing their summer internships.

Keith Dona (PI: Capadona)
Keying Chen (PI: Evon Ereifej)
Josh Rosenberg (PI: Matt Schiefer)
Miranda Anderson-Kenney (PI: Dustin Tyler)

Friday, August 4, 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Chia-Chu Chiang, Ph.D.
Title: Identifying two traveling waves in the epileptic brain by voltage imaging

Abstract: Fast and slow neural waves have been observed to propagate in the human brain during seizures. Yet the nature of these waves is difficult to study in a surgical setting. Here we report an observation of two different traveling waves propagating in the in-vitro epileptic hippocampus at speeds similar to those in the human brain. A fast and a slow traveling wave were recorded simultaneously with a genetically encoded voltage sensitive fluorescent protein (VSFP Butterfly 1.2) and a high speed camera. The results of this study indicate that the fast wave is NMDA-sensitive but the slow wave is not. Image analysis and model simulation demonstrate that the slow wave is moving slowly, generating the fast wave and is therefore a moving source of the epileptiform activity. This slow moving source is associated with a propagating neural calcium wave detected with calcium dye (OGB-1) but is independent of NMDA receptors, not related to ATP release, and much faster than those previously recorded potassium waves. Our model simulation suggests that the slow traveling neural source can propagate by the ephaptic effect like epileptiform activity. These findings provide an alternative explanation for slow propagation seizure wavefronts associated with fast propagating interictal spikes.

Friday, July 28, 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Joseph Marmerstein
Advisor: Prof. Durand
Title: Chronic Recording of Rat Vagal Nerve Activity with Carbon Nanotube Yarn Electrodes

Abstract: The study of small peripheral nerves such as those in the autonomic nervous system holds great promise for the detection and treatment of a variety of pathologies. In particular, the vagus nerve, which is a highway of autonomic activity, has been receiving increased attention due to it's interaction with nearly every internal organ in the body. Dr. Durand's group has developed a novel way for interfacing with these nerves, via carbon nanotube (CNT) yarn microelectrodes. CNT yarn electrodes were implanted in the left cervical vagus nerve of rats over a 3+month period, and vagal activity was recorded chronically during a variety of physiological challenges applied to the anesthetized rat. Recently, a new recording set-up has allowed for extended recordings of vagal activity in awake, behaving animals, which will allow for new experiments and studies to be performed.

Friday, July 21, 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Kelsey Bower
Advisor: Prof. McIntyre
Title: Modeling Deep Brain Stimulation of Branched Axon Terminals

Abstract: Optogenetic studies of neural pathways have been instrumental in dissecting the neural circuitry involved in DBS for Parkinson's Disease (PD). Recent optogenetic studies of the hyperdirect pathway have suggested that stimulation of this pathway may be sufficient for improving the motor symptoms of PD. Computational models consisting of relevant anatomy and the DBS electrode can be a useful tool for optimizing DBS for specific pathways.

State-of-the-art DBS models utilize multi-compartment double-cable models to predict the neural response to extracellular stimulation. These models have been shown to effectively reproduce results from in vivo electrophysiological studies and are generally accepted as the gold-standard for predicting neural activation. The accuracy of these predictions, however, is dependent on the structural accuracy of the axon model, as small changes in the axon structure can result in large changes in the predicted neural response. This is especially relevant in STN DBS; axons projecting to the subthalamic region exhibit a branched terminating structure, yet most neural models neglect to consider this termination. The goal of this project is to evaluate how the axon terminal affects action potential generation in response to extracellular stimulation, and identify the errors in neural activation prediction associated with ignoring this structural characteristic.

Friday, July 14, 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Griffin Rial
Advisor: Dr. Jeffrey Capadona
Title: I-Corps@Ohio: Assessing the Commercial Viability of University Technologies with Panel Discussion to Follow

Abstract: Research in the Capadona lab focuses on understanding and mitigating deleterious aspects of the neuroinflammatory response to implanted devices in the brain. Recently, we have developed and tested an anti-inflammatory coating and its efficacy on intracortical microelectrodes with the goal of translating the technology to patients.

Over the past 10 weeks, we participated in the I-Corps@Ohio program. This program is modeled after an NSF program, and funded through the Ohio Department of Education. The goal of this program is to assess the commercial viability of a technology developed in an academic research setting. Using a lean startup process, we conducted 100 customer discovery interviews to test if a commercial market exists for our technology. In the process, we became aware of additional clinical needs for our technology, and modified our commercialization pathway. In this seminar, Griffin will present an overview of the I-Corps@Ohio program, and tell you about our team's lessons learned and final conclusions.

Following an overview of the I-Corps program, Griffin will moderate a panel composed of other Case students who participated in the I-Corps program this summer. The panel will include Zhehao Zhang (Gratzl Lab), Jacob Antunes (Viswanath Lab), and Youjoung Kim (Portillo Lab). They will discuss their I-Corps experience, and answer any questions the audience may have.

Monday, July 10, 2017
10:30 AM, Wolstein Research Building
Room 6136

Speaker: Sohail (Muhammad) Moor, University of Calgary
Title: Studying cortical effects of deep brain stimulation using optical imaging.

Friday, July 7, 2017
NEC Seminar
9:00 AM, Nord 400
Speaker: Brian Sanner
Title: High density in-line connector for serviceable high-channel count implantable systems

Functional electrical stimulation (FES) and electrode recording systems are being used for an increasingly broad array of clinical treatments. As these systems become more complex they approach the physical limitation of implantable real-estate within the body to contain the many electrically isolated leads. Furthermore, with the continual advancement of technology it is likely that there will be many evolutions of technology during a patient's lifetime. Further, if there is a component failure, replacement of an entire system could induce unnecessary surgical risk, as well as require the removal and replacement of successful components. This might not be possible or might result in less performance in the replacement system. A high density 34-channel pad and pin in-line connector that is of comparable size to the 8-channel in-line Medtronic connector currently approved for clinical use was developed by our collaborator, Dr. Shire at Cornell University. It has undergone saline soak testing, and just completed its first in vivo test in the feline model where it was implanted for over six months. The next step is in vivo animal model testing of the connector in-line with a peripheral nerve cuff electrode to evaluate its performance in use for FES.

Friday, June 16, 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Dennis Bourbeau, PhD
Title: Electrical stimulation to improve bowel function

Background: Neurogenic bowel dysfunction is a common concern for persons with spinal cord injury(SCI), which may result in slowed colonic motility, chronic constipation, and fecal incontinence. It adversely affects quality of life and typically requires rigorous bowel care routines, which often involves significant time expenditure for the individual and/or caregivers. We aim to develop an alternative approach using functional electrical stimulation to restore bowel function for persons with neurogenic bowel dysfunction. The objectives of this study were to determine if reflex colonic activity can be elicited by electrical stimulation of the colon and to identify the effect of stimulation variables, such as stimulation pattern and electrode location.

Methods: Acute experiments were conducted in nine neurally intact cats under chloralose anesthesia. Proximal colon, distal colon, and rectum were electrically stimulated with continuous and burst patterns. Proximal colon, distal colon, and rectal pressures were recorded via balloon catheters. Pressure amplitude was the primary outcome measure, and rate of pressure change and onset delay were secondary measures.

Results: Electrical stimulation of the colon evoked localized colon contractions in the colon segment directly below the electrodes in all cats. Constant frequency stimulation produced ischemia and a tetanic colon contraction, but burst pattern stimulation at similar amplitudes did not alter tissue appearance, and colonic pressures increased more slowly. Colon pressures increased with increasing stimulus amplitude, frequency, pulse width, and burst number. Rectal stimulation did not evoke significant colon responses without affecting limb responses simultaneously. Proximal colon stimulation resulted in only proximal colon pressure increases. Distal colon stimulation generated both distal and proximal colon pressure increases. Isoflurane anesthesia eliminated proximal pressure responses and reduced distal pressure responses, suggesting that reflex pathways were activated via distal colon stimulation.

Conclusion: Colonic pressures can be produced via both direct and reflex pathways using electrical colon stimulation. A neural stimulation approach has the potential to improve colonic motility. Further preclinical work is needed, including study of SCI animal models, prior to translation to human clinical research.

Friday, June 9, 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Anisha Rastogi
Mentor: Dr. Ajiboye
Title: Evaluation of intracortical neural activity during attempted force production across multiple hand grasp configurations

Background: Intracortical brain computer interfaces (iBCIs) have the potential to restore hand grasping in individuals with tetraplegia. While most human-operated iBCIs have utilized only kinematic information from motor cortex, natural grasping and object interaction also requires the use of force-related information. We have previously demonstrated that neural modulation to attempted hand grasping forces is preserved in one individual with tetraplegia. However, this study only evaluated neural modulation during attempted power grasping. Previous literature has shown that the motor cortex encodes activity that are tuned over a variety of movement parameters, which include both grasping force and hand grasp configuration. Here, we evaluate the extent to which hand grasp configuration affects force-related neural activity, as well as the ability to discriminate between different levels of force. Methods: Participants of the BrainGate2 Clinical Trial were asked to attempt to produce four discrete force levels (light, medium, hard, no force) with the dominant upper limb, using a power grasp and one of three pincer grasps. During the task, we obtained full broadband neural recordings from two, 96-channel microelectrode arrays (Blackrock Microsystems, Salt Lake City, UT) in the dominant motor cortex. From each channel, we extracted and characterized single unit activity and two time-varying neural features (spike firing rates and high frequency spike power). Features were used as inputs to a linear discriminant analysis (LDA) classifier to offline-discriminate force levels produced during each hand grasping configuration. Results and Conclusions: We found that most neural features exhibit force modulation that is dependent upon hand grasp configuration. On a population level, classification performance (our ability to predict the users' attempted force level from neural activity) exceeded chance levels for all hand grasping configurations. However, we found that individual force levels were best discriminated during attempted power grasping. These results could affect how we decode forces in a closed-loop iBCI system.

Friday, June 2. 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Ivana Cuberovic
Mentor: Prof. Dustin Tyler
Title: Experience with high density composite flat interface nerve electrodes on a sensory restoration application.

Abstract: While prostheses have undergone many mechanical advancements in recent years, they still do not provide natural and intuitive feedback to users. To restore sensation, four subjects have been implanted with nerve cuff electrodes over the past five years. In two subjects, the implanted components included eight-channel Flat Interface Nerve Electrodes (FINEs), four-channel spiral cuff electrodes, and spring and pin connectors. The other two subjects have systems consisting of fifteen-channel High Density Composite Flat Interface Nerve Electrodes (HD C-FINEs) and eight-in-line connectors. An initial comparison of the systems with respect to sensory stability is presented here.
Both systems evoke focal tactile sensations across the phantom hand. Many of the evoked sensations are in functionally useful locations, including the fingertips, ulnar border, and palm. As expected, the fifteen channel system provides fuller coverage of the hand. Unexpectedly, the C-FINE systems exhibit increased variance in reported locations for a given contact, both as a function of time and as a function of elbow angle.

Friday, May 26. 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Emily Graczyk
Mentor: Prof. Dustin Tyler
Title: Impact of sensory feedback on user experience, prosthesis use, and activity performance: Results from the first home study of a sensory enabled prosthesis

Abstract: While neural prostheses to restore sensory feedback to upper limb amputees have the potential to improve task performance and quality of life, studies of sensory restoration systems (SRSs) have only been conducted in controlled laboratory environments. In this study, for the first time, two subjects used a SRS autonomously in a home setting. Because the experience of using an SRS for an extended period of time and in new settings is likely to have multifaceted impacts on the participants, a battery of functional tests, surveys, and user experience interviews were conducted. The SRS consisted of an Ottobock VariPlus Speed prosthetic hand customized with an embedded aperture sensor and fingertip pressure sensors on the thumb, index, and middle fingers, an external nerve stimulator with a custom sensory stimulation program, and cabling to connect the stimulator to percutaneous leads connected to FINEs around the participants' median nerves. The stimulator mapped pressure signals from the finger sensors into stimulation pulse trains and delivered the stimulation to individual electrode contacts in the FINE. The two trials of the take home SRS were successfully completed and demonstrate initial feasibility. Subjects were able to independently don and doff the SRS, change stimulation settings, and calibrate the prosthetic sensors. Stimulation parameters and sensation locations remained stable throughout the duration of the study. The subjects wore the SRS longer and reported using their prosthesis to do more activities when sensation was enabled. Interviews and usage logs indicated that subjects preferred using the prosthesis with sensory feedback. Robustness, reliability, and ease of use are critical design features for an SRS.

 

Friday, May 19, 2017
Seminar
11 AM Cleveland Clinic Lerner Research Institute, room NE1-205

Speaker: Dr. Luis Alvarez
Title: Neural Culture Screening Platform to Accelerate Regenerative Electrode Design

Dr. Luis Alvarez will be presenting "Neural Culture Screening Platform to Accelerate Regenerative Electrode Design" in the APT Center Distinguished Lecture Series. Dr. Alvarez is the founding Principal Investigator of the Regenerative Biology Research Group (www.regenbiogroup.org) at the National Cancer Institute where he leads a team of investigators to develop translational regenerative medical approaches to address loss of function resulting from combat trauma and cancer. Dr. Alvarez will discuss his group's development of a neural culture platform that can be used to screen biologically-active surface coatings and mechanical properties and applications of the platform in material selection for neural electrodes, in drug screening, or as selective neural guide where precise spatial control over axon placement is required either pre- or post-extension.

Map & Directions | Dr. Alvarez biography and Abstract

Friday, May 19, 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Nick Couturier
Mentor: Prof. Dominique Durand
Title: Low-frequency fiber tract stimulation for seizure suppression in cortical epilepsies

Abstract: Frontal Lobe Epilepsy (FLE) is the second most common form of focal epileptic disorders. FLE is characterized by highly diverse seizure symptoms often delaying accurate diagnosis. Unlike the more common temporal lobe epilepsy, FLE tends to be more refractory to anti-epileptic drug treatment accounting for up to half of all intractable epilepsies. Furthermore, the success rate of surgical resections for neocortical seizures is only 50-60% compared to 75% for temporal lobectomy. A novel treatment for refractory epilepsy of neocortical origin is investigated based on the success of previous studies in deep brain stimulation for mesial temporal lobe epilepsy. We previously reported seizure suppression of 90% in animal models as well as in patients. Seizure suppression is achieved through direct stimulation of the fiber tracts connecting structures in both hemispheres of the brain. We stimulate at low frequencies between 1-10 Hz to elicit a long-lasting hyperpolarization in the post-synaptic neurons. For epileptic foci in the frontal cortex, we stimulate the corpus callosum acutely for 30 minutes to suppress seizures both during stimulation as well as after stimulation. Initial experiments demonstrate significant seizure suppression in an acute cortical model of epilepsy. Additional acute experiments, as well as chronic experiments, are being planned to validate the effectiveness of fiber tract stimulation for seizure suppression.

Friday, May 12, 2017
NP Seminar - Industry Round Table & Reception
8:30 AM, Wolstein Research Building, Room 1413

Speakers: Maria Bennett, MS, President and CEO, SPR Therapeutics. Steve Fening, PhD, Director, Case-Coulter Translational Research Partnership

Download flyer [pdf]

Friday, April 28, 2017
NEC Seminar
9:00 AM, Nord 400
Speaker: Brian Sanner
Advisor: Dr. Dustin Tyler
Title: TBA

Friday, April 21, 2017
NEC Seminar

9:00 AM, Nord 400
Speaker: Breanne Christie
PI
: Dr. Dustin Tyler and Dr. Ron Triolo

Title: "Long-Term Stability of Stimulating Spiral Nerve Cuff Electrodes on Human Peripheral Nerves"

Abstract: Electrical stimulation of the peripheral nerves has been shown to be effective in restoring sensory and motor functions in the lower and upper extremities. This neural stimulation can be applied via non-penetrating spiral nerve cuff electrodes, though minimal information has been published regarding their long-term performance for multiple years after implantation. Since 2005, fourteen human volunteers with cervical or thoracic spinal cord injuries, or upper limb amputation, were chronically implanted with a total of 50 spiral nerve cuff electrodes on nine different nerves (mean time post-implant 6.7+3.1 years). The spiral nerve cuffs examined remain functional in motor and sensory neuroprostheses for 5-11 years after implantation. They exhibit stable charge thresholds, clinically relevant recruitment properties, and good muscle selectivity. Non-penetrating spiral nerve cuff electrodes appear to be a suitable option for long-term clinical use on human peripheral nerves in implanted neuroprostheses.

Friday, March 31, 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: Max Freeberg
Mentor: Prof. Triolo
Title: TBA
Abstract: TBA

Friday, March 24, 2017
NEC Seminar
9:00 AM, Nord 400

Speaker: David Cunningham, Ph.D.
Human Performance and Engineering Laboratory
Kessler Foundation Research Center
Title: Tailoring brain stimulation to the nature of rehabilitative therapies and their unique mechanisms of neuroplasticity

Abstract:
Over the past decade there has been growing interest in combining non-invasive brain stimulation with rehabilitation in order to accelerate rehabilitative outcomes in patients with chronic stroke. The primary application of non-invasive brain stimulation has involved augmenting mechanisms of neuroplasticity which are unique to intensively training the paretic limb and restraining or otherwise discouraging movement of the non-paretic limb. However, several groups have discussed the importance of bilateral therapies, involving the paretic and non-paretic limb simultaneously, as they may provide a more feasible alternative, especially for patients with a greater disability. Still, because there is limited understanding of what neurophysiologic mechanisms underlie bilateral therapies there has been a lack of discussion on how to pair non-invasive brain stimulation in order to complement bilateral task practice. Further, the pairing of non-invasive brain stimulation with therapy has also failed to consider mechanisms of neuromuscular fatigue which occurs over the duration of a therapeutic session. This talk presents two experiments which investigates the mechanisms of bilateral therapy and neuromuscular fatigue and discusses tailoring non-invasive brain stimulation based on their unique mechanisms of neuroplasticity.

Friday, March 17, 2017
Note Time and Location Changes
12:00PM, Wickenden 321

Speaker: Frank Willett
Mentor: A. Bolu Ajiboye, Ph.D.

Title: (Dissertation Defense) "Intracortical Brain-Computer Interfaces: Modeling the Feedback Control Loop, Improving Decoder Performance, and Restoring Upper Limb Function with Muscle Stimulation"

Abstract:
Intracortical brain-computer interfaces (iBCIs) can help to restore movement and communication to people with chronic tetraplegia by recording neural activity from the motor cortex and translating it into the motion of an external device (typically a computer cursor or robotic arm). In this work, we focus on three avenues for advancement: (1) better understanding the feedback control loop created by the interaction between the user and the iBCI, (2) leveraging that understanding to improve the performance of decoding algorithms that translate neural activity into movement, and (3) restoring control over a person's own arm and hand by using a combined iBCI and muscle stimulation system.

In Chapters 2-3, we develop a deeper understanding of how linear decoders operate in closed-loop. Using data from the BrainGate2 pilot clinical trial, we develop a feedback control model that describes how users modulate their neural activity to move towards their target, stop accurately, and correct for movement errors. We use the model to characterize the errors made by linear decoders and find that they are signal-independent (i.e. they do not scale with the size of the user's motor command). As a consequence, we show that linear decoders only work well within a narrow range of movement scales and perform poorly when both precise and gross movements are required, in contrast to able-bodied movements that achieve success over a wide range of scales.

In Chapters 4-6, we explore three avenues for improving decoder performance based on the above results. First, we improve the linear decoder's ability to enable movements of different scales by adding a separate decoding pathway that can extract non-linear movement scale information from the neural activity. We show that this new pathway improves the user's ability to stop precisely on the target without sacrificing movement speed. Second, we show that our feedback control model can be used to optimize decoder performance by predicting, via simulation, which parameters will lead to the best closed-loop performance. Third, we test whether the feedback control model can improve decoder calibration by more accurately estimating the user's intended movements. Contrary to expectation, we found that all intention estimation methods we tested performed equivalently, despite differing significantly in their ability to accurately describe user intent.

In Chapters 7-8, we make progress towards a combined iBCI and functional electrical stimulation (FES) system that can restore motion to a person's own arm and hand. In a non-human primate model, we develop and test a new decoding method that enables direct cortical control over muscle stimulation and that can be calibrated automatically (without the need for expert design of muscle stimulation patterns). Finally, we demonstrate, for the first time, a person in the BrainGate2 pilot clinical trial using a combined FES + iBCI system to make continuously controlled, multi-joint reaching and grasping movements to match target postures and to complete functional tasks (eating mashed potatoes and drinking from a cup of coffee).

Friday, March 10, 2017
8:30 AM, Wolstein Research Building, Room 1413
NP Seminar

Speaker: Benjamin D. Greenberg, MD PhD
Center for Neurorestoration and Neurotechnology
Providence VA Medical Center
Title: Brain Circuit-Based Treatments for Obsessive-Compulsive Disorder: A model for Neuropsychiatry

Friday, February 24, 2017
Nord 400, 9:00 AM
NEC Seminar

Speaker: Cale Crowder
Advisor: Dr. Robert Kirsch
Title: System Identification of the Human Motor Cortex

Abstract: Cervical spinal cord injury (SCI) can result in paralysis of all four limbs - a condition known as tetraplegia. Recently, our research group demonstrated an intramuscular functional electrical stimulation (FES) system controlled by an intracortical brain computer interface (BCI) implanted in the human motor cortex. The combined FES-BCI system was able to restore limited movement to a study participant's paralyzed arm. While the participant was able to perform simple tasks, such as self-feeding, self-drinking, and self-bathing, the FES-BCI system was inconsistent in its behavior. The purpose of the present study is to simplify the FES-BCI system controller in order to achieve better performance. Our objective is to extract additional information from the motor cortex in order to decrease the mental energy exerted by our participant in controlling the FES-BCI system. To extract additional information from the motor cortex, we are utilizing so-called "system identification," which uses established methods to build a model of a physiological system. During this seminar, we will describe the challenges of using a FES-BCI system, provide an introduction to system identification, and demonstrate, via modeling, how system identification can be used to extract information from the human motor cortex.

Friday, February 24, 2017
Seminar
11am, Cleveland Clinic Lerner Research Institute, in room NE1-205

Dr. Peter Adamczyk will be presenting "Semi-Active Foot Prostheses for Low-Power Gait Restoration" in the APT Center Distinguished Lecture Series. Dr. Adamczyk directs the UW Biomechatronics, Assistive Devices, Gait Engineering and Rehabilitation Laboratory (UW BADGER Lab), at the University of Wisconsin-Madison, which aims to enhance physical and functional recovery from orthopedic and neurological injury through advanced robotic devices. Dr. Adamczyk will discuss his group's work on the mechanisms by which these injuries impair normal motion and coordination, and target interventions to encourage recovery and/or provide biomechanical assistance.

Dr. Adamczyk's presentation information is attached, as well as a map and parking directions.

Lab Website: http://uwbadgerlab.engr.wisc.edu/

Call for individual meetings

If you would like to meet with Dr. Adamczyk, please email Andrew Shoffstall (andrew.shoffstall@case.edu) by Friday, February 17th, with your availability for the following times and locations:

Cleveland Clinic: Friday, February 24th, from 8am - 11am
Case Western Reserve University: Friday, February 24th, from 2pm - 5pm

Map and Parking directions | Adamczyk Talk Info

 

Friday, February 17, 2017
Nord 400, 9:00 AM
NEC Seminar

Speaker: Daniel Young
Advisor: Dr. Bolu Ajiboye
Title: Artifact Reduction Techniques Enable Neural Control of FES Actuated Movements

Abstract
Hundreds of thousands of people live with loss of motor function due to spinal cord injury (SCI) and have indicated strong interest in neuroprosthetics that restore arm movements. Functional Electrical Stimulation has restored independence to people with spinal cord injuries, enabling activities such as eating, writing, and grooming. Intracortical brain computer interfaces (iBCI's) have been explored as potential command interfaces for neuroprosthetics because they can record neural activity related to complex reaching kinematics (10+ degrees of freedom) in humans with paralysis. In order to restore thought-controlled arm and hand movements after paralysis, our group implanted one participant with two recording intracortical microelectrodes in the left primary motor cortex and 24 stimulating intramuscular electrodes in the right limb.
However, iBCI's utilize precise recordings of microvolt sized signals while FES generates relatively larger electric fields in the paralyzed limbs. Electrical artifacts during stimulation can interfere with extracting accurate movement intentions and may limit the usefulness of iBCIs for control of FES prostheses. This work characterizes the stimulation artifacts we recorded on the intracortical microelectrodes and demonstrates their effect on our system performance. We implemented three cleaning methods for reducing the artifacts and present results comparing their effectiveness. The best cleaning method reduced artifact sizes by 2+ orders of magnitude and fully recovered neural information during stimulation periods. This method can be easily implemented in real time, enabling closed-loop brain control of both intramuscular and surface FES prosthetics.

Friday, February 10, 2017
8:30 AM, Wolstein 1413
NP Seminar

Speaker: Andre Machado, M.D.
Title: TBA

Friday, February 3, 2017
No Seminar

Friday, January 27, 2017
NEC Seminar

Nord 400, 9:00 AM
Speaker: Kubinar Gunalan
Advisor: Prof. Cameron McIntyre
Title: Methods to predict axonal activation in patient-specific models of deep brain stimulation

Abstract: Deep brain stimulation (DBS) of the subthalamic region is an established clinical therapy for the treatment of Parkinson's disease. Most computational models of DBS predict the generation of action potentials in axons surrounding the stimulating electrode and clinical software tools employing axon stimulation models are now commonly used to estimate the volume of tissue activated. However, the simplifying assumptions used in various DBS models can have a substantial impact on the stimulation predictions. I will review a range of different computational models for predicting axonal activation, including McNeal-type, Warman-type, and Butson-type models, and evaluate their accuracy in the context of clinical subthalamic DBS. In general, the results demonstrate that simplified models perform poorly when compared to detailed McNeal-type models.

Friday, January 20, 2017
Neural Prosthesis Seminar

Wolstein Auditorium, 8:30 AM
Speaker: Stephen B. McMahon
Div. Neuroscience, Kings College London
Title: Chronic pain mechanisms and how they may be affected by spinal cord stimulation

Friday, January 13, 2017
NEC Seminar

Nord 400, 9:00 AM
Speaker: Rajat Shivacharan
Advisor: Prof. Dominique Durand

Title: Can neural activity propagate via electric fields?

Abstract: Although electric fields are frequently overlooked due to more prominent neuron to neuron communication such as synaptic transmission, current studies on epileptiform behavior strongly suggest electric field transmission can play an important role in neural propagation. Experiments conducted in our lab have shown that propagation of epileptiform behavior in rodent hippocampi propagates at a unique speed of 0.1 m/s and can take place in the absence of synaptic transmission, leaving electric field as the logical mode of transmission. However, none of these studies show that the spontaneous bursting activity is solely generated from electric fields. Using in vitro experiments, we test the hypothesis that spontaneous epileptiform activity in the hippocampus can propagate via electric fields.