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.)
- Sci Rep. 2023 Feb 15;13(1):2685. Classification of electrically-evoked potentials in the parkinsonian subthalamic nucleus region.
- Brain Stimul. 2023 Feb 4:S1935-861X(23)01684-4. Lateral cerebellothalamic tract activation underlies DBS therapy for Essential Tremor.
- Bello EM 2nd, Blumenfeld M, Dao J, Krieg JDS, Wilmerding LK, Johnson MD. Considerations using harmaline for a primate model of tremor. Tremor Other Hyperkinet Mov (N Y). 2021 Sep 13;11:35. doi: 10.5334/tohm.634.
- Johnson MD, Dweiri YM, Cornelius J, Strohl KP, Steffen A, Suurna M, Soose RJ, Coleman M, Rondoni J, Durand DM, Ni Q. Model-based analysis of implanted hypoglossal nerve stimulation for the treatment of obstructive sleep apnea. Sleep. 2021 Apr 27;44(44 Suppl 1):S11-S19.
- Brinda AK, Doyle AM, Blumenfeld M, Krieg J, Alisch JR, Spencer C, Lecy E, Wilmerding LK, DeNicola A, Johnson LA, Vitek JL, Johnson MD. Longitudinal analysis of local field potentials recorded from directional deep brain stimulation lead implants in the subthalamic nucleus. J Neural Eng. 2021 Apr 27. doi: 10.1088/1741-2552/abfc1c.
- Yu Y, Escobar Sanabria D, Wang J, Hendrix CM, Zhang J, Nebeck SD, Amundson AM, Busby ZB, Bauer DL, Johnson MD, Johnson LA, Vitek JL. Parkinsonism alters beta burst dynamics across the basal ganglia-motor cortical network. J Neurosci. 2021 Mar 10;41(10):2274-2286.
- Bello EM, Agnesi F, Xiao Y, Dao J, Johnson MD. Frequency-dependent spike-pattern changes in motor cortex during thalamic deep brain stimulation. J Neurophysiol. 2020;124(5):1518-1529.
- Johnson LA, Wang J, Nebeck SD, Zhang J, Johnson MD, Vitek JL. Direct activation of primary motor cortex during subthalamic but not pallidal deep brain stimulation. J Neurosci. 2020 Mar 4;40(10):2166-2177.
- Moore KM, Oelberg WL, Glass MR, Johnson MD, Been LE, Meisel RL. Glutamate afferents from the medial prefrontal cortex mediate nucleus accumbens activation by female sexual behavior. Front Behav Neurosci. 2019 Oct 4;13:227.
- Slopsema JP, Peña E, Patriat R, Lehto LJ, Gröhn O, Mangia S, Harel N, Michaeli S, Johnson MD. Clinical deep brain stimulation strategies for orientation-selective pathway activation. J Neural Eng. 2018;15(5):056029.
- Grado LL, Johnson MD, Netoff TI. Bayesian adaptive dual control of deep brain stimulation in a computational model of Parkinson's disease. PLoS Comput Biol. 2018 Dec 6;14(12):e1006606
- Peña E, Zhang S, Patriat R, Aman JE, Vitek JL, Harel N, Johnson MD. Multi-objective particle swarm optimization for postoperative deep brain stimulation targeting of subthalamic nucleus pathways. J Neural Eng. 2018 Dec;15(6):066020.
- Xiao Y, Agnesi F, Bello EM, Zhang S, Vitek JL, Johnson MD. Deep brain stimulation induces sparse distributions of locally modulated neuronal activity. Sci Rep. 2018 Feb 1;8(1):2062.
- Ramirez-Zamora A, Giordano JJ, Gunduz A, Brown P, Sanchez JC, Foote KD, Almeida L, Starr PA, Bronte-Stewart HM, Hu W, McIntyre C, Goodman W, Kumsa D, Grill WM, Walker HC, Johnson MD, Vitek JL, Greene D, Rizzuto DS, Song D, Berger TW, Hampson RE, Deadwyler SA, Hochberg LR, Schiff ND, Stypulkowski P, Worrell G, Tiruvadi V, Mayberg HS, Jimenez-Shahed J, Nanda P, Sheth SA, Gross RE, Lempka SF, Li L, Deeb W, Okun MS. Evolving spplications, technological challenges and future opportunities in neuromodulation: Proceedings of the fifth annual deep brain stimulation think tank. Front Neurosci. 2017;11:734.
- Escobar Sanabria D, Johnson LA, Nebeck SD, Zhang J, Johnson MD, Baker KB, Molnar GF, Vitek JL. Parkinsonism and vigilance: alteration in neural oscillatory activity and phase-amplitude coupling in the basal ganglia and motor cortex. J Neurophysiol. 2017;118:2654-2669.
- Moore KM, Himmler BT, Teplitzky BA, Johnson MD, Meisel RL. Measuring in vivo changes in extracellular neurotransmitters during naturally rewarding behaviors in female Syrian hamsters. J Vis Exp. 2017 Sep 12;(127). doi: 10.3791/56135.
- Wang J, Johnson LA, Jensen AL, Baker KB, Molnar GF, Johnson MD, Vitek JL. Network-wide oscillations in the parkinsonian state: alterations in neuronal activities occur in the premotor cortex in parkinsonian nonhuman primates. J Neurophysiol. 2017;117:2242-2249.
- Peña E, Zhang S, Deyo S, Xiao Y, Johnson MD. Particle swarm optimization for programming deep brain stimulation arrays. J Neural Eng. 2017;14(1):016014.
- Connolly AT, Vetter RJ, Hetke JF, Kipke DR, Pellinen DS, Anderson DJ, Baker KB, Vitek JL, Johnson MD. A novel lead design for modulation and sensing of deep brain structures." IEEE Trans Biomed Eng. 2016;63:148-157.
- Neren D, Johnson MD, Legon W, Ling G, Divani AA. Vagus nerve stimulation and other neuromodulation methods for treatment of traumatic brain injury. Neurocrit Care. 2016;24:308-19.
- Connolly AT, Muralidharan A, Hendrix C, Gupta R, Stanslaski S, Denison T, Baker KB, Vitek JL, Johnson MD. Local field potential recordings in a non-human primate model of Parkinson's disease using the Activa® PC+S. J Neural Eng. 2015 Dec;12(6):066012.
- Xiao Y, Johnson MD. Spherical statistics for characterizing the spatial distribution of deep brain stimulation effects on neuronal activity. J Neurosci Methods. 2015;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;114(2):825-834.
- Connolly AT, Jensen AL, Baker KB, Vitek JL, Johnson MD. Classification of pallidal oscillations with increasing parkinsonian severity. J Neurophysiol. 2015;114:209-218.
- 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;35:6231-6240
- 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.
Current Graduate Students:
Alex Doyle (Neuroscience, University of Minnesota).
Emily Lecy (Neuroscience, University of Minnesota).