Funded Awards

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.

Gait impairment and freezing of gait (FOG) lead to falls, loss of independent living, and injury (even death) in patients with Parkinson’s disease (PD). These symptoms have limited treatment options that are not well addressed by current deep brain stimulation (DBS) methods. Dr. Bronte-Stewart and colleagues will test the feasibility of subthalamic nucleus (STN) neural and kinematic adaptive DBS (NaDBS and KaDBS, respectively) in PD patients, as well as the safety and tolerability of the use of dopaminergic medication in coordination with adaptive stimulation. This innovative approach using neuro-biomechanical features may enable the first clinical studies of bilateral STN aDBS for FOG, laying the groundwork for improved gait therapy in PD and other neurological disorders.

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.

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.

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.

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.

Essential Tremor (ET) is a progressive disease that leads to significant disability and markedly diminished quality of life. Deep brain stimulation (DBS) in the ventralis intermedius (VIM) thalamus has been an effective treatment for ET, but is associated with problematic side effects (e.g., slurred/slow speech, muscle imbalance) and may lose efficacy over time in people with severe ET. Drs. Oweiss, Foote, and colleagues will utilize the Medtronic Summit RC+S DBS system to investigate how limb movement and tremor relate to neural activity in the VIM and ventralis oralis thalamus, then use this information to develop a dual-lead, closed-loop stimulation approach for people with severe ET who are refractory to open loop VIM DBS.

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. 

Loss of control of eating can lead to obesity, and even circumvent anti-obesity treatments like bariatric surgery. Evidence from mouse models suggests that stimulating a region of the brain called the nucleus accumbens can attenuate binge-eating behavior. Via a public-private partnership, Drs. Halpern, Malenka, Lock, and Skarpaas propose to adapt a device already used for deep brain stimulation, the RNS® System from NeuroPace, Inc., to detect specific low frequency oscillations in the brain that indicate a loss of control event. When the appropriate signal is detected, delivery of deep brain stimulation to the nucleus accumbens could potentially prevent binge eating. This study will focus on identifying the brain signals that indicate a loss of control of eating episode and the appropriate stimulation response for early feasibility studies in human patients.

People with post-traumatic stress disorder (PTSD) are afflicted with intense suffering, lack of productivity, and a higher risk of suicide with few treatment options. Dr. Langevin and collaborators will use the NeuroPace responsive neurostimulation system (RNS) to perform chronic recordings and stimulation in the basolateral amygdala (BLA) and ventral hippocampus (vHPC) of people with intractable PTSD. The team will investigate the relationship between neural activity and PTSD episodes to identify biomarkers of hypervigilance and re-experiencing. They will then use responsive stimulation to modulate the BLA-vHPC neural network to, hopefully, reduce the symptoms of PTSD in patients.

Chronic pain is a major healthcare problem and many pain syndromes are notoriously refractory to almost all treatment. Deep brain stimulation (DBS) for pain has shown promise, but current approaches provide ‘open-loop’ continuous stimulation and are prone to loss of effect over time. Drs. Chang, Starr, and colleagues will use the Medtronic Activa PC+S System to identify electrophysiological signals in the orbitofrontal cortex and anterior cingulate cortex associated with pain, then develop a closed-loop DBS paradigm to enable the targeted delivery of stimulation only when pain signals in the brain are elevated. The team will then test whether this personalized stimulation approach leads to reliable symptom relief for chronic pain patients over extended periods of time.

Although the primary goal of epilepsy care is to prevent and stop seizures from occurring, restoring conscious awareness in patients whose seizures cannot be stopped (by means of medication, surgery, or deep brain stimulation) could improve patients’ quality of life. Dr. Blumenfeld and colleagues plan to restore consciousness during seizures in people with temporal lobe epilepsy by bilaterally stimulating thalamic central lateral nuclei. The group will utilize the Medtronic Summit RC+S system, an investigational device that the team will integrate into the Epilepsy Personal Assistant Device (EPAD), which is a cloud-based application developed for data processing and storage, real-time analysis, and up-to-date closed loop stimulation.