University of Minnesota
Department of Biomedical Engineering
http://www1.umn.edu/bme
612-624-4507

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Matthew Johnson

Matthew D. Johnson

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Neuromodulation Mechanisms and Technology

My group is primarily interested in developing and refining neural interface technologies to improve the quality of life for people with movement disorders. Deep brain stimulation (DBS) is one such technology, which over the past twenty years has helped numerous patients with Parkinson’s disease, dystonia, and essential tremor reclaim control over their motor function. The therapy involves placing small electrodes in regions of the brain that exhibit pathological activity, which contributes to the movement disorder, and then stimulating those regions with continuous pulses of electricity. My lab focuses on understanding how the brain responds and adapts to such stimulation-based therapies from a combination of computational and experimental perspectives. The knowledge gained from these studies in turn provides us with a framework to develop, evaluate, and translate new approaches for improving patient outcome.

Computational Modeling

Computer models are useful for predicting how a neuron or population of neurons might respond to stimulation. Our lab couples 1) finite element models of electric fields generated in neural tissue with 2) neuron models built from sets of mathematical equations that replicate the biophysical properties of membrane and synapse dynamics. The neuron models range in scale from multi-compartment reconstructions of neurons labeled with histological methods to large-scale neural networks of the sensorimotor system. We use these tools both retrospectively (e.g. relating clinical outcome to targeted pathway) and prospectively (e.g. predicting how stimulation through a new electrode design might impact activity in the brain).

Neurophysiology and Behavior

Our lab also investigates the therapeutic mechanisms of neuromodulation experimentally through multi-channel electrophysiological and neurochemical techniques in animal models of movement disorders. We are particularly interested in how neurons encoding movement are modulated during deep brain stimulation, how stimulation at different therapeutic efficacies influences these neurons, and how the modulation of neuronal firing patterns changes during chronic stimulation.

Device Development

The design space for neuromodulation technology remains unbounded because we still lack a clear understanding of which neural elements to target for improving each motor symptom. Indeed, deep brain stimulation in humans and animal models of movement disorders have shown that one can stimulate in any one of several different brain regions and relieve motor symptoms; however, if the electrode(s) are not placed correctly within a given nuclei or fiber pathway, little improvement in motor symptoms will result with stimulation. In such cases, the clinical benefit is often masked by the appearance of unwanted side-effects. We are developing new types of implants and stimulation strategies that are inspired by the underlying neuroscience. Our group evaluates these technologies in our animal models of movement disorders with the goal of translating these therapies from the laboratory to the clinic.

Selected Publications

Johnson MD, Vitek JL, and McIntyre CC (2009). “Pallidal stimulation that improves parkinsonian motor symptoms also modulates neuronal firing patterns in primary motor cortex in the MPTP-treated monkey.” Experimental Neurology, 219(1): 359-362.

Johnson MD, McIntyre CC, and Vitek JL. (2009) “Deep brain stimulation: Mechanisms of action.” In Youmans Neurological Surgery, edited by Winn HR. Philadelphia: Saunders.

Bajwa J, Johnson MD, and Vitek JL. (2009) “Pathophysiology of dystonia.” In Textbook of Stereotactic and Functional Neurosurgery, edited by Lozano AM, Gildenberg PL, and Tasker RR. New York: McGraw-Hill, pp. 1779-1800.

Mera TO, Johnson MD, Roth D, Zhang J, Xu W, Ghosh D, Vitek JL, and Alberts JL (2009) “Objective quantification of arm rigidity in MPTP-treated primates.” Journal of Neuroscience Methods, 177(1): 20-29.

Lempka SF, Miocinovic S, Johnson MD, Vitek JL, and McIntyre CC (2009) “In vivo impedance spectroscopy of deep brain stimulation electrodes.” Journal of Neural Engineering 6(4): 1-11.

Johnson MD and McIntyre CC (2008) “Quantifying the neural elements activated and inhibited by globus pallidus deep brain stimulation.” Journal Neurophysiology 100:2549-2563, 2008.

Johnson MD, Miocinovic S, McIntyre CC, and Vitek JL (2008) “Mechanisms and targets of deep brain stimulation in movement disorders.” Neurotherapeutics 5(2): 294-308.

Johnson MD, Franklin RK, Gibson MD, Brown RB, and Kipke DR. (2008) “Implantable microelectrode arrays for simultaneous electrophysiological and neurochemical recordings.” Journal of Neuroscience Methods, 174(1): 62-70.