Funded Awards

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Title Investigator Institute Fiscal Year FOA Number Status Project Number Priority Area Summary
A Biomimetic Approach Towards a Dexterous Neuroprosthesis BONINGER, MICHAEL UNIVERSITY OF PITTSBURGH AT PITTSBURGH 2018 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity

Brain-computer interfaces and neuroprosthetics have provided a significant benefit to patients with cervical spinal cord injuries. However, current technology is limited in its abilities to allow the user to control how much force is exerted by the prosthesis and to provide sensory feedback from the prosthetic hand. In a public-private collaboration with Blackrock Microsystems, Dr. Boninger and colleagues are looking to improve the dexterity of neuroprostheses by incorporating microstimulation of the somatosensory cortex. This stimulation could provide tactile feedback to the user and hopefully allow the user to better control the force applied. Ultimately, this approach will improve the dexterity and control of prosthetic limbs used by patients with spinal cord injuries.

Adaptive DBS in Non-Motor Neuropsychiatric Disorders: Regulating Limbic Circuit Imbalance Goodman, Wayne K Baylor College Of Medicine 2016 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Deep brain stimulation (DBS) is currently a treatment option for patients with obsessive-compulsive disorder (OCD), but there is room for improvement both in terms of increasing treatment effectiveness and reducing unwanted side effects. In this project, Goodman and his team aim to utilize next-generation DBS systems that can record, stimulate, and make real-time adjustments to stimulation parameters based on the patient’s brain activity. Specifically, they propose to develop a stimulation paradigm that will allow the DBS system to automatically adjust stimulation to better control OCD-related distress while minimizing unwanted DBS-induced hypomania, which they will test in an early feasibility study with a small number of OCD patients. This work may help refine DBS therapy for neuropsychiatric and neurological diseases and disorders more broadly.
Asynchronous distributed multielectrode neuromodulation for epilepsy Devergnas, Annaelle Gross, Robert E (contact) Gutekunst, Claire-anne N Mahmoudi, Babak Emory University 2016 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Dominant hemisphere mesial temporal lobe epilepsy (MTLE) is a form of epilepsy for which it is particularly difficult to control seizures. In this project, Gross and colleagues will test a next-generation deep brain stimulation (DBS) device and a novel stimulation paradigm in a non-human primate model of MTLE. If they are successful in controlling seizures in this model, the team will advance to an early clinical feasibility study in a small number of MTLE patients, measuring seizure reduction and memory testing for safety. Success in this small clinical study could lay the foundation for a clinical trial utilizing this novel DBS method in patients with MTLE, and possibly other forms of epilepsy.
Central thalamic stimulation for traumatic brain injury Butson, Christopher R Giacino, Joseph Thomas Henderson, Jaimie M Machado, Andre Guelman Schiff, Nicholas D (contact) Weill Medical Coll Of Cornell Univ 2015 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Traumatic brain injury (TBI) afflicts hundreds of thousands of Americans each year, producing chronic cognitive disabilities that lack effective treatment. Preliminary studies with TBI patients and non-human primates suggest that these cognitive disabilities may be due to disrupted circuit function in the brain, specifically involving impaired connections between the thalamus and the frontal cortex. Working with a group of TBI patients who can function independently but remain limited by chronic cognitive impairment, Schiff and colleagues aim to build on these studies, using the latest device technology to deliver deep brain stimulation to the thalamus. The researchers hope to obtain a variety of behavioral and electrophysiological data to inform development of a next-generation device therapy for cognitive impairment associated with TBI.
Clinical Testing of an Intracortical Visual Prosthesis System Troyk, Philip R Illinois Institute Of Technology 2016 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Blindness can have a negative impact on quality of life, and is associated with relatively high rates of depression and social isolation, and relatively low levels of employment. The IntraCortical Visual Prosthesis (ICVP) team led by Dr. Troyk has worked to develop an ICVP that can compensate for blindness by stimulating the visual centers of the brain. This project aims to provide proof of principle with a small number of human volunteers, to demonstrate that the ICVP successfully produces visual sensory perception and to assess the utility of the induced visual percepts.
Closed loop deep brain stimulation for Parkinson's disease Starr, Philip Andrew University Of California, San Francisco 2016 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Deep brain stimulation (DBS) has an important clinical role in the management of movement disorders, including Parkinson’s disease (PD). However, current DBS therapy for PD relies on continuous stimulation, regardless of changes in brain circuit function related to changes in disease expression (i.e. oscillation between too little and too much movement). In this project, Starr and his team will use next-generation DBS devices to develop and test a method of automatically adjusting stimulation parameters based on brain signals that reflect the patient's clinical state, to optimize DBS for PD. In a small number of patients, they will measure local brain activity in each patient and use that information to develop individualized stimulation paradigms; these algorithms will then be programmed into the DBS devices, to demonstrate proof of principle for this novel, closed-loop DBS system.
Closing the Loop on Tremor: A Responsive Deep Brain Stimulator for the Treatment of Essential Tremor Foote, Kelly D Gunduz, Aysegul (contact) University Of Florida 2016 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity

Essential tremor (ET) is an incurable, degenerative brain disorder that results in increasingly debilitating tremor. Deep Brain Stimulation (DBS) is used as an effective treatment for ET, but the continuous brain stimulation provided by current DBS methods is likely unnecessary given the intermittent nature of ET symptoms, and may underlie DBS-induced side effects such as slurred speech and difficulty walking. It also may unnecessarily hasten the need for surgery to replace depleted DBS batteries. In this project, Gunduz and Foote propose to use modern DBS devices capable of recording and stimulating simultaneously, to continuously monitor brain activity and deliver stimulation only when necessary to control tremor. This work may provide proof-of-concept for the first chronic closed-loop DBS system for the treatment of a debilitating movement disorder in humans.

Combined Cortical and Subcortical Recording and Stimulation as a Circuit-Oriented Treatment for Obsessive-Compulsive Disorder Dougherty, Darin D (contact) Eskandar, Emad N Massachusetts General Hospital 2016 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
4-7 million Americans suffer from obsessive-compulsive disorder (OCD), and at least half of these patients do not receive adequate relief from medication or talk therapy. Deep brain stimulation (DBS) is used as a treatment for patients with intractable OCD, but only works for about half of these patients. In an effort to improve DBS for OCD, Dougherty and Eskandar have proposed to develop and test in a small early feasibility study a next-generation, brain circuit-oriented DBS treatment for drug-refractory OCD. In their project, they will measure brain activity to test a hypothesis about the specific circuit dysfunction that underlies OCD, and they will test whether DBS stimulation can disrupt this circuit dysfunction in order to relieve OCD symptoms.
CranialProgrammer: Image-Guided Directional Deep Brain Stimulation Programming Using Local-Field Potentials Duke, Austin NEXEON MEDSYSTEMS PUERTO RICO OPERATING COMPANY, INC 2018 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity

While Deep Brain Stimulation (DBS) devices can alleviate symptomology of patients with chronic conditions like Parkinson’s disease, appropriate placement is paramount and challenging, particularly for directional stimulating leads. Dr. Austin plans to develop and test CranialProgrammer, image-guided software that uses local field potentials to help clinicians map patient brain regions for optimal placement of DBS leads. In partnership with NeuroTargeting, LLC, the software will integrate with the implanted DBS system of Parkinson’s patients to allow visualization of patient data coupled with imaging technologies. This software could dramatically improve the ability of neurologists to program directional DBS leads, providing therapeutic benefit to myriad DBS patients.

 

Deep brain stimulation for depression using directional current steering an individualized network targeting Goodman, Wayne K Pouratian, Nader Sheth, Sameer Anil (contact) Columbia University Health Sciences 2017 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Deep brain stimulation (DBS) for treatment-resistant depression (TRD) has shown promise, but has delivered inconsistent results. Sheth’s team hypothesizes that patient-specific, network-guided neuromodulation is critical, and that lack of clinical success is partly due to off-target stimulation (i.e., a failure to modulate appropriate brain networks). Using next-generation, precision DBS with directional steering capability in patients with TRD, the team will delineate patient-specific, depression-relevant networks and demonstrate behavioral changes with network-targeted stimulation. They will target the subgenual cingulate and ventral capsule/ventral striatum, along with other TRD-implicated regions, then identify and engage symptomatic networks. In addition to managing TRD, this study may have implications for understanding neurocircuit dysfunction in other neuropsychiatric conditions.
Deep cerebellar electrical stimulation for post-stroke motor recovery Baker, Kenneth B Machado, Andre Guelman (contact) Cleveland Clinic Lerner Com-cwru 2016 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Despite current efforts at rehabilitation, one third of stroke patients have long-term motor deficits severe enough to require assistance with the activities of daily life. Machado and colleagues are working to develop therapies that promote recovery of motor function and improve quality of life for such individuals. Specifically, the goal of this project is to demonstrate proof of principle of a next-generation, multi-electrode, closed-loop system for deep brain stimulation in the cerebellum’s dentate nucleus. It is hoped that such stimulation can facilitate motor recovery for patients with persistent, moderate-to-severe, upper extremity hemiparesis due to stroke.
Development and Translation of an Intracranial Auditory Nerve Implant LIM, HUBERT HYUNGIL et al. UNIVERSITY OF MINNESOTA 2018 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity

Despite providing significant restoration of the ability to hear speech, cochlear implants have been limited in their ability to restore full hearing, particularly in loud environments or situations when multiple sounds are present at once. Drs. Lim, Oxenham, Franklin, Rieth, Solzbacher, and Lenarz are exploring a new, auditory nerve implant device and surgical techniques with the potential to improve upon current cochlear implants in humans. This new device will directly target the auditory nerve, which connects the cochlea to the brainstem. The researchers, who will also be developing a new surgical technique for implantation and validate efficacy and safety, hope that this will allow for improved hearing, including speech and music.

Early Feasibility Clinical Trial of a Visual Cortical Prosthesis Dorn, Jessy D (contact) Greenberg, Robert Jay Pouratian, Nader Second Sight Medical Products, Inc. 2018 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity

Currently, a recently developed retinal prosthesis, the Argus® II, restores vision to over 200 patients with retinitis pigmentosa. Argus II electrically stimulates the retina, inducing visual perception. However, retinal implants can only help a small subset of the millions of people suffering from profound blindness. In this early feasibility clinical trial, Greenberg’s team will implant (and test) a prosthesis on the medial surface of the visual cortex. Building on the platform of the Argus II, the proposed prosthesis will electrically stimulate the visual cortex, to restore visual perception. This project could help restore useful vision to many people with blindness from disorders like diabetic retinopathy or glaucoma, or damage to the eyes, optic nerve, or thalamus. 

Electrophysiological Biomarkers to Optimize DBS for Depression Mayberg, Helen S Emory University 2017 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Deep brain stimulation of subcallosal cingulate (DBS-SCC) white matter is an emerging new therapy for treatment resistant depression (TRD). An important next step is to develop biomarkers for guiding lead placement and titrating stimulation parameters during ongoing care. Mayberg’s team will develop and test electrophysiological biomarkers for device configuration in individuals receiving DBS-SCC for TRD. They aim to optimize and standardize treatment based on functional anatomy and electrophysiological variables, replacing current methods that rely on? depression severity scores and psychiatric assessments. If successful, this work will impact future clinical trial design and provide a new approach to long-term management of symptoms in patients receiving this treatment.
High-Bandwidth Wireless Interfaces for Continuous Human Intracortical Recording Hochberg, Leigh R (contact) Nurmikko, Arto Massachusetts General Hospital 2015 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
More than 100,000 people in the United States suffer from quadriplegia, with the most extreme cases resulting in loss of all voluntary movement, including speech. Dr. Hochberg has led development of BrainGate, a brain implant system designed to allow users to control an external device, such as a prosthetic arm, by thought alone. In this project, Dr. Hochberg and his team aim to push the envelope with BrainGate to make a fully implanted medical treatment system, freeing patients from externally tethered components, and giving them greater control over their home environments and daily lives. Ultimately, the goal is to transition from a device that is used occasionally under medical supervision to one that patients can use independently on an ongoing basis.
Neurophysiologically Based Brain State Tracking & Modulation in Focal Epilepsy Worrell, Gregory A Mayo Clinic Rochester 2015 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Epilepsy is a common neurological disease, and over one-third of epilepsy patients have seizures that are not controlled by conventional therapy. Surgery can be curative, but only for a subset of patients. Advances in neural engineering have produced devices that are poised to transform management of drug-resistant epilepsy; they will ultimately take the form of wireless devices that integrate the ability to measure brain activity, predict seizure onset, and deliver therapeutic stimulation to limit seizure activity. Worrell and colleagues aim first to undertake a preclinical study in dogs with naturally occurring epilepsy, to test one such device, and if this is successful then conduct a pilot clinical trial in human epilepsy patients
Noninvasive Biomarkers to Advance Emerging DBS Electrode Technologies in Parkinson's Disease Walker, Harrison Carroll University Of Alabama At Birmingham 2016 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Deep brain stimulation (DBS) is an important clinical option for patients with Parkinson’s disease (PD), but the optimum stimulation parameters differ from patient to patient. As a result, patient outcomes vary between individuals and across clinical trials. In this project, Walker et al. will utilize non-invasive electroencephalography (EEG) measurements of how the brain responds to DBS, to guide the activation and adjustment of next-generation DBS devices and electrodes. The researchers will test whether this personally optimized DBS is superior to conventional DBS, in terms of effectiveness and reduced side effects for patients.
Scalar Closed-Loop STN/GPi DBS Based on Evoked and Spontaneous Potentials Turner, Dennis Alan Duke University 2017 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
The current standard of care for advanced Parkinson’s disease (PD) with motor complications is to implant a single deep brain stimulation (DBS) lead to stimulate either the subthalamic nucleus (STN) or globus pallidus interna (GPi). However, single-site stimulation can be ineffective against balance symptoms and freezing of gait, and some patients develop additional motor complications despite DBS due to disease progression. Turner’s team will implant bilateral STN + GPi/GPe electrodes in PD patients, and assess the efficacy of either STN or GPi/GPe stimulation versus dual STN + GPi stimulation. The group will also use advanced medical device technology to compare closed-loop paradigms to conventional open-loop stimulation. This project could help people with severe PD receive improved treatment options.
Spinal root stimulation for restoration of function in lower-limb amputees Fisher, Lee E (contact) Weber, Douglas J University Of Pittsburgh At Pittsburgh 2017 Active
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Despite recent advancements in prosthetics, prosthetic devices still lack a means of providing direct sensory feedback, which would improve balance control, reduce falling risk, and could significantly diminish severe phantom limb pain. In individuals with trans-tibial amputation, Fisher’s team will use spinal cord stimulator leads to electrically stimulate the dorsal root ganglia and dorsal rootlets. They intend to generate sensations of pressure and movement in the amputated limb, and reduce phantom limb pain, which correlates with greater prosthesis use. The group will use electromyography to analyze the relationship between stimulation and evoked reflexive responses, and thus optimize stimulation programming. To improve gait function, the group will study how signals from pressure/angle sensors within the prosthetics can be used to modulate sensory feedback via stimulation. These experiments could assist development of a neuroprosthesis that would improve quality of life for individuals with trans-tibial amputation.