MGH
HMS
Neurology
Thier Research Bldg.
Room 415.
50 Blossom Street
Boston, MA 02114
Tel: (617) 726-3888
Welcome to the Fried Lab

Introduction

The remarkable successes of cochlear implants and deep brain stimulation (DBS) for the treatment of Parkinson’s disease raise the possibility that a wide range of neurological, psychiatric, and sensory disorders can be similarly treated with electric stimulation from a neural prosthetic. As such, devices for treatment of epilepsy, cluster headaches, chronic depression, balance disorders, and several types of blindness are under development. Unfortunately, the effectiveness of new treatments has been somewhat limited. In addition, even in successful applications, unwanted side effects have been reported. Our lab seeks to improve the effectiveness of these applications by understanding how and why neurons respond to electric stimulation and then using that knowledge to develop improved methods of stimulation.

General Overview

Understanding the response of CNS neurons to electric stimulation

The response to stimulation in axons has been well studied and theoretical models of the interaction are well supported by experimental data (the one-dimensional and uniform structure of axons facilitated the theoretical understanding). The response to stimulation in neurons of the CNS is considerably more complex however. Here, stimulating electrodes are in close proximity to multiple compartments of targeted cells (soma, dendrites, axons). Many of the compartments are three-dimensional and the underlying biophysical properties across compartments are highly non-uniform (e.g. the sodium channel density in different compartments can vary considerably). We are interested in how and why different compartments respond to electric stimulation and more importantly, whether we can use different stimulating configurations (electrode and/or stimulus waveforms) to modulate which compartments or even which classes of neurons get activated.

Retinal prosthetic

Retinal degenerative diseases such as age related macular degeneration (ARMD) and retinitis pigmentosa (RP) are the leading cause of blindness in the US and other industrialized countries. These diseases lead to a loss of photoreceptors, the neurons primarily responsible for transducing light into an electrochemical signal. Importantly however, retinal neurons downstream of photoreceptors do not degenerate, raising the possibility that artificial stimulation can be used to restore some form of vision.

The viability of this approach has been confirmed by multiple clinical trials, each reporting that light percepts, called phosphenes, are reliably elicited in response to electric stimulation from implanted electrodes. Unfortunately, the usefulness of vision elicited in this manner remains somewhat limited. For example, individual phosphenes do not reliably ‘assemble’ into predictable spatial patterns, limiting the spatial information that can be conveyed to the patient. Even the description of individual phosphenes varies considerably with differences in size, color, shape and intensity all reported.

While many factors are likely to contribute to the limited quality of elicited vision, the use of sub-optimal methods of stimulation are thought to play a significant role. For example, electrode arrays are often positioned in close proximity to the nerve fiber layer – the layer in which ganglion cell axons course towards the optic disk. These axons are themselves highly sensitive to stimulus pulses, and therefore, distant ganglion cells whose axons pass closely to the stimulating electrode are likely to be activated. This distorts retinotopy (the correspondence between the spatial pattern of the stimulus and the spatial pattern of elicited neural activity) which is likely to contribute to the poor quality of percepts reported during clinical trials. Methods to avoid axonal stimulation have not yet been developed.

Current Projects

Understanding the response of retinal neurons to electric stimulation. Nearly 15 years ago, Humayun et al showed that electric stimulation of the retina in blind subjects could elicit light percepts (phosphenes). Despite much effort however, the quality of elicited vision remains somewhat limited. To improve this, we are studying how and why retinal neurons respond to different forms of electric stimulation. By understanding the basic principles by which these neurons response to stimulation, we hope to be able to develop powerful new stimulation techniques that create specific patterns of neural activity – ideally, patterns that replicate one or more elements of the patterns used physiologically by the healthy retina.

Testing to support development of retinal prosthetics. The Boston Retinal Implant Project is a collaboration of physicians, physiologists, biologists, engineers and rehabilitative specialists with the specific goal of developing an implantable microelectronic prosthesis to restore vision to patients with certain forms of retinal blindness. Our lab is part of the collaboration and we work with other group members to test the effectiveness of new electrode configurations and new stimulation schemes. In addition, new stimulation schemes developed in this laboratory will be used in the new device. The lab collaborates with other, similar development efforts from around the world.

The response of neurons in the sub-thalamic nucleus to stimulation. Many of the electric stimulation challenges in the retina are identical to those faced by other neural prosthetics. For example, activation of passing axons in the basal ganglia is thought to underlie many unwanted side affects that arise from DBS treatment of Parkinson’s disease. We have developed a new method in the retina that does not activate passing axons and are evaluating the ability of this method to perform similarly for stimulation of the basal ganglia. We are also working on methods that selectively target specific classes of neurons within the STN.