Our research group focuses on developing and translating neuromodulation technologies for the treatment of neurological disorders. We focus on understanding how the brain responds and adapts to stimulation-based therapies from a combination of experimental and computational perspectives. These studies provide us with a rationale to in turn develop, evaluate, and translate new approaches for improving patient care.
(1) Neurophysiology: Our group 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.
(2) Computational Modeling: Our group also develops multi-scale computational neuron models to further our understanding of the biophysical and physiological mechanisms of neuromodulation. In partnership with the Minnesota Supercomputing Institute, we run large-scale simulations that predict how deep brain stimulation affects neural pathways adjacent to and downstream of the stimulated electrodes. We have several projects that use these models retrospectively (e.g. relating clinical outcome to targeted pathway) and prospectively (e.g. predicting how stimulation through a new electrode design would impact activity in the brain).
(3) Translational Studies: The third arm of our research laboratory involves developing new types of neuromodulation strategies, for treating movement disorders, that are inspired by the underlying neuroscience of therapeutic deep brain stimulation. Our group evaluates these technologies experimentally with the goal of leveraging our industrial partnerships to then translate these therapies from the laboratory to the clinic.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Connolly AT, Vetter RJ, Hetke JF, Kipke DR, Pellinen DS, Anderson DJ, Baker KB, Vitek JL, and Johnson MD. (2016) "A novel lead design for modulation and sensing of deep brain structures." IEEE Transactions on Biomedical Engineering. 63(1): 148-157.
Xiao Y, Peña E, and Johnson MD. (2015, in press) "Theoretical optimization strategies for directionally segmented deep brain stimulation electrode arrays." IEEE Transactions on Biomedical Engineeering.
Neren D, Johnson MD, Legon W, Ling G, and Divani AA. (2015, in press) "Vagus nerve stimulation and other neuromodulation methods for treatment of traumatic brain injury." Neurocritical Care.
Connolly AT, Muralidharan A, Hendrix C, Gupta R, Stanslaski S, Denison T, Baker KB, Vitek JL, and Johnson MD. (2015) "Local field potential recordings in a non-human primate model of Parkinson's disease using the Activa® PC+S." Journal of Neural Engineering, 12:066012.
Xiao Y, Johnson MD. Spherical statistics for characterizing the spatial distribution of deep brain stimulation effects on neuronal activity. J Neurosci Methods. 2015 Aug 11;255:52-65.
Agnesi F, Muralidharan A, Baker KB, Vitek JL, Johnson MD. Fidelity of frequency and phase entrainment of circuit-level spike activity during DBS. J Neurophysiol. 2015 Aug;114(2):825-34.
Connolly AT, Jensen AL, Baker KB, Vitek JL, Johnson MD. Classification of pallidal oscillations with increasing parkinsonian severity. J Neurophysiol. 2015 Jul;114(1):209-18.
Zitella LM, Teplitzky BA, Yager P, Hudson HM, Brintz K, Duchin Y, Harel N, Vitek JL, Baker KB, Johnson MD. Subject-specific computational modeling of DBS in the PPTg area. Front Comput Neurosci. 2015 Jul 14;9:93.
Zitella LM, Xiao Y, Teplitzky BA, Kastl DJ, Duchin Y, Baker KB, Vitek JL, Adriany G, Yacoub E, Harel N, Johnson MD. In Vivo 7T MRI of the Non-Human Primate Brainstem. PLoS One. 2015 May 12;10(5):e0127049.
Connolly AT, Jensen AL, Bello EM, Netoff TI, Baker KB, Johnson MD, Vitek JL. Modulations in oscillatory frequency and coupling in globus pallidus with increasing parkinsonian severity. J Neurosci. 2015 Apr 15;35(15):6231-40
Teplitzky BA, Connolly AT, Bajwa JA, Johnson MD. Computational modeling of an endovascular approach to deep brain stimulation. J Neural Eng. 2014 Apr;11(2):026011.
Chu LL, Xu Y, Yang JR, Hu YA, Chang HH, Lai HY, Tseng CC, Wang HY, Johnson MD, Wang JK, Lin CY. Human cancer cells retain modest levels of enzymatically active matriptase only in extracellular milieu following induction of zymogen activation. PLoS One. 2014 Mar 24;9(3):e92244.
Agnesi F, Connolly AT, Baker KB, Vitek JL, Johnson MD. Deep brain stimulation imposes complex informational lesions. PLoS One. 2013 Aug 26;8(8):e74462.
Zitella LM, Mohsenian K, Pahwa M, Gloeckner C, Johnson MD. Computational modeling of pedunculopontine nucleus deep brain stimulation. J Neural Eng. 2013 Aug;10(4):045005.
Johnson MD, Lim HH, Netoff TI, Connolly AT, Johnson N, Roy A, Holt A, Lim KO, Carey JR, Vitek JL, He B. Neuromodulation for brain disorders: challenges and opportunities. IEEE Trans Biomed Eng. 2013 Mar;60(3):610-24.
Agnesi F, Johnson MD, Vitek JL. Deep brain stimulation: how does it work? Handb Clin Neurol. 2013;116:39-54.
Keane M, Deyo S, Abosch A, Bajwa JA, and Johnson MD. "Improved spatial targeting with directionally segmented deep brain stimulation leads for treating essential tremor." Journal of Neural Engineering, 2012 Aug;9(4):046005.
Johnson MD, Zhang J, Ghosh D, McIntyre CC, and Vitek JL. (2012) "Neural targets for relieving parkinsonian rigidity and bradykinesia with pallidal deep brain stimulation." Journal of Neurophysiology, 108:567-577.
Connolly AT, Bajwa JA, and Johnson MD. (in press) "Cortical magnetoencephalography of deep brain stimulation for the treatment of postural tremor." Brain Stimulation
Lempka S, Johnson MD, Moffitt M, Otto KJ, Kipke DR, and McIntyre CC. (2011) “Theoretical analysis of intracortical microelectrode recordings.” Journal of Neural Engineering, 8(4):045006
Martens HCF, Toader E, Decré MMJ, Anderson DJ, Vetter R, Kipke DR, Baker KB, Johnson MD, and Vitek JL. (2011) “Spatial steering of deep brain stimulation volumes using a novel lead design.” Clin. Neurophys., 122(3):558-566.
Lempka SF, Johnson MD, Miocinovic S, Vitek JL, and McIntyre CC. (2010) “Current-controlled deep brain stimulation reduces in vivo voltage fluctuations observed during voltage-controlled stimulation.” Clin. Neurophys., 121(12):2128-2133.
Lee J, Johnson MD, Kipke DR. (2010) “A tunable biquad switched-capacitor amplifier for neural recordings.” Trans Biomed Circ and Sys., 4(5):295-300.
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.
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.
Mera TO, Johnson MD, Rothe D, Zhang J, Xu W, Ghosh D, Vitek JL, and Alberts JL. (2009) "Objective quantification of arm rigidity in MPTP-treated primates." Journal Neuroscience Methods, 177:20-29.
Johnson MD and McIntyre CC. (2008) "Quantifying the neural elements activated and inhibited by globus pallidus deep brain stimulation." Journal of Neurophysiology, 100(5):2549-2563.
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. [article featured on the cover]
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.
Johnson MD, Kao OE, and Kipke DR. (2007) "Spatiotemporal pH dynamics following insertion of neural microelectrode arrays." Journal of Neuroscience Methods, 160(2): 276-287.
Otto KJ, Johnson MD, and Kipke DR. (2006) "Bias voltages change neural interface properties and improve unit recordings with chronically implanted microelectrodes." IEEE Transactions on Biomedical Engineering, 53(2): 333-340.
Johnson MD, Otto KJ., and Kipke DR. (2005) "Repeated voltage biasing improves unit recording by reducing resistive tissue impedances." IEEE Transactions on Neural Systems and Rehabilitation Engineering, 13(2): 160-165.
Current Graduate Students:
Alex Doyle (Neuroscience, University of Minnesota).