The purpose of this study is for a team of chemical engineers, materials engineers and neuroscientists at MIT to develop a combined micro-cannula and deep brain electrical stimulation device for the treatment of anxiety and mood disorders. Anxiety and mood disorders are common and debilitating disorders that afflict millions of Americans. The emerging thought is that these disorders are actually rooted in disruptions in activity across neural circuits, as opposed to defects in any one region. Current treatments comprising oral and i.v. administration of therapeutics are too coarse, both spatially and temporally, to appropriately attenuate the dynamic activity across neural circuits. Our goal is to develop an implantable micro-cannula device that is capable of simultaneous infusion of multiple therapeutics, as well as electrical stimulation and real time chemical sensing. This device will be micro-fabricated in such a way as to be minimally invasive, yet durable enough to be scaled to non-human primate use. The combination of precise anatomical targeting and diverse stimulatory (electrical & chemical) capabilities should improve our ability to modulate activity across specific neural circuits with the appropriate kinetics. This proposal, and the assembled research team, combines the varied fields of micro-fabrication, materials engineering, chemistry, biology and neuroscience. Our specific goals are summarized as follows: 1) Design for failsafe delivery of neuro-modulatory therapeutics.
This aim will ensure that the desired doses are delivered accurately and reproducibly. 2) Evaluate methods of improving the structural integrity and biocompatibility of the device via metal deposition and chemical functionalization. Neuro-stimulatory electrodes have been shown to lose function over prolonged periods of implantation due to gliosis. Our proposed studies will develop a method for prolonging device function by retarding gliosis. 3) Refine the peripheral components (reservoir, pump and tubing) to be a stand-alone unit suitable for chronic implantation. This will increase the utility of the proposed device, as well as represent an important step towards clinical usage. 4) Demonstrate behavior change in animal (non-human primate) models of anxiety and mood disorders by delivering stimulation (electrical & chemical) via the proposed device. 5) Demonstrate that the behavioral change is a result of modulating neural circuit activity by the proposed device.
Our aim i s to, demonstrate the failsafe function of the device in vivo and investigate its capability to ameliorate anxiety and mood disorder based behaviors via precise spatiotemporal control. In a final step we plan to develop feedback based activation of the device by real time sensing of pathological activity. This represents an important step towards clinical usage where anxiogenic stimuli are frequently unknown and un-predictable.

Public Health Relevance

Intractable psychiatric disorders are severely debilitating, and the emerging understanding of their origins has identified the need for an advanced chronic implant to deliver electrical and chemical stimulation to attenuate pathological activity in neural circuits. This work combines biomaterials, device microfabrication and neuroscience to develop a cannula based device that can simultaneously deliver electrical and chemical stimulation. The device will be fabricated to achieve failsafe function, prolonged biocompatibility and its function will be validated in non-human primate models of psychiatric disorders.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Biomaterials and Biointerfaces Study Section (BMBI)
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Wolfson, Michael
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Massachusetts Institute of Technology
Internal Medicine/Medicine
Schools of Arts and Sciences
United States
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