About

Matthew D. Johnson is a Professor and Institute for Translational Neuroscience Scholar in the Department of Biomedical Engineering at the University of Minnesota. His research focuses on innovating neuromodulation technologies to improve the quality of life for individuals with neurological disorders. His active projects develop patient-specific computational models coupled with optimization algorithms to program neuromodulation systems in humans, aiming to personalize therapy for each individual. Johnson's educational background includes a BS in Engineering Sciences from Harvard University, an MS and PhD in Biomedical Engineering from the University of Michigan, and post-doctoral training at the Lerner Research Institute of the Cleveland Clinic. His work has contributed to understanding and differentiating responses in neurological conditions such as essential tremor and Parkinson’s disease, and he has published extensively on topics related to deep brain stimulation and neural pathways involved in movement disorders.

Research topics

• Computer Science
• Psychology
• Neuroscience
• Medicine
• Artificial Intelligence
• Internal medicine
• Biology
• Physics

Selected publications

• Feasibility and Safety of a Taekwondo Community-based Exercise Program for Older Adults and People with Parkinson’s Disease: A Pilot Study

  Parkinsonism & Related Disorders · 2025-04-17

  article
  PublisherDOI

• Impairment of neuronal activity in the dorsolateral prefrontal cortex occurs early in parkinsonism

  Frontiers in Neuroscience · 2025-01-17 · 5 citations

  articleOpen access

  Background: Parkinson's disease (PD) is often characterized by altered rates and patterns of neuronal activity in the sensorimotor regions of the basal ganglia thalamocortical network. Little is known, however, regarding how neuronal activity in the executive control network of the brain changes in the parkinsonian condition. Objective: Investigate the impact of parkinsonism on neuronal activity in the dorsolateral prefrontal cortex (DLPFC), a key region in executive control, during a go/nogo reaching task. Methods: = 1) before and after the induction of mild parkinsonism using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Results: Coincident with development of mild parkinsonian motor signs, there was a marked reduction in the percentage of DLPFC cells with significant task-related firing rate modulation during go and nogo conditions. Conclusion: These results suggest that DLPFC dysfunction may occur early in parkinsonism and contribute to cognitive impairments and disrupted executive function often observed in PD patients.

  PublisherOA PDFDOI

• Differential modulation of the pedunculopontine nucleus with targeted subthalamic nucleus deep brain stimulation

  Brain stimulation · 2025-01-01

  articleOpen accessSenior author

  The pedunculopontine nucleus (PPN) of the brainstem has triggered interest in the recent past in relation to Parkinson's disease as it is suggested that the nucleus is a major component of the regulation and control of movement.The nucleus is widely interconnected with the basal ganglia, degenerates in Parkinson's disease, and is associated with freezing of gait.Although deep brain stimulation (DBS), is used as a therapy to treat Parkinson's disease, little is known on how subthalamic nucleus stimulation affects the PPN.This study applied deep brain stimulation to the subthalamic nucleus (STN) in two non-human primates and recorded neuronal spiking activity in the PPN.We found that PPN cells had heterogeneous responses to stimulationeranging from firing rate inhibition and excitation to firing pattern changes with antidromic and orthodromic inhibition.Firing rate changes occurred with lower stimulation amplitude and firing pattern changes became apparent after higher amplitude stimulation.Additionally, higher amplitude stimulation resulted in a majority of trials showing entrainment of spiking activity to deep brain stimulation.These results suggest that PPN spiking activity is differentially affected by stimulation depending on stimulation location and recruitment of various fiber tracts in, and around, the subthalamic nucleus.These findings give us a greater understanding of subthalamic nucleus DBS effects on a key brainstem nuclei involved in Parkinson's disease.

  PublisherOA PDFDOI

• Differentiating Postural and Kinetic Tremor Responses to Deep Brain Stimulation in Essential Tremor

  Movement Disorders Clinical Practice · 2024-11-07 · 2 citations

  articleOpen accessSenior authorCorresponding

  BACKGROUND: While deep brain stimulation (DBS) targeting the ventral intermediate nucleus (VIM) of thalamus or posterior subthalamic area (PSA) can suppress forms of action tremor in people with Essential Tremor, previous studies have suggested postural tremor may respond more robustly than kinetic tremor to DBS. OBJECTIVES: In this study, we aimed to more precisely quantify the (1) onset/offset dynamics and (2) steady-state effects of VIM/PSA-DBS on postural and kinetic tremor. METHODS: Tremor data from wireless inertial measurement units were collected from 11 participants with ET (20 unilaterally assessed DBS leads). Three postural hold tasks and one kinetic task were performed with stimulation turned off, in 2-min intervals after enabling unilateral DBS at the clinician-optimized DBS setting (15 min), and in 2-min intervals following cessation of DBS (5 min). RESULTS: At baseline, kinetic tremor had significantly higher amplitudes, standard deviation, and frequency than postural tremor (P < 0.001). DBS had a more robust acute effect on postural tremors (54% decrease, P < 0.001), with near immediate tremor suppression in amplitude and standard deviation, but had non-significant improvement of kinetic tremor on the population-level across the wash-in period (34% decrease). Tremor response was not equivalent between wash-in and wash-out timepoints and involved substantial individual variability including task-specific rebound or long wash-out effects. CONCLUSIONS: Programming strategies for VIM/PSA-DBS should consider the individual temporal and effect size variability in postural versus kinetic tremor improvement. Improved targeting and programming strategies around VIM and PSA may be necessary to equivalently suppress both postural and kinetic tremors.

  PublisherOA PDFDOI

• Neural pathways associated with reduced rigidity during pallidal deep brain stimulation for Parkinson’s disease

  Journal of Neurophysiology · 2024-08-07 · 3 citations

  articleOpen accessCorresponding

  Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways.

  PublisherDOI

• Impairment of Neuronal Activity in the Dorsolateral Prefrontal Cortex Occurs Early in Parkinsonism

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-22

  preprintOpen access

  Background: Parkinson's disease (PD) is often characterized by altered rates and patterns of neuronal activity in the sensorimotor regions of the basal ganglia thalamocortical network. Little is known, however, regarding how neuronal activity in the executive control network of the brain changes in the parkinsonian condition. Objective: Investigate the impact of parkinsonism on neuronal activity in the dorsolateral prefrontal cortex (DLPFC), a key region in executive control, during a go/nogo reaching task. Methods: Using a within-subject design, single and multi-unit neuronal activity was recorded in the DLPFC of a nonhuman primate before and after the induction of mild parkinsonism using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Results: Coincident with development of mild parkinsonian motor signs, there was a marked reduction in the percentage of DLPFC cells with significant task-related firing rate modulation during go and nogo conditions. Conclusions: These results suggest that DLPFC dysfunction may occur early in parkinsonism and contribute to cognitive impairments and disrupted executive function often observed in PD patients.

  PublisherOA PDFDOI

• Mapping polarization sensitive optical coherence tomography and ultra-high-field diffusion MRI in the macaque brain

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-04-25

  preprintOpen access

  Abstract This paper provides comparisons between microstructure and two-dimensional fiber orientations measured optically using polarization sensitive optical coherence tomography (PS-OCT) and those estimated from ultra-high-field diffusion MRI (dMRI) at 10.5T in the macaque brain. The PS-OCT imaging is done at an in-plane resolution of ∼10 microns in and around the thalamus. Whole brain dMRI is acquired at an isotropic resolution of 0.75 mm. We provide comparisons between cross-polarization and optical orientation from PS-OCT with the fractional anisotropy and two-dimensional orientations extracted from dMRI using a diffusion tensor model. The orientations from PS-OCT are also extracted computationally using a structure tensor. Additionally, we demonstrate the utility of mesoscale, PS-OCT imaging in improving the MRI resolution by learning the mapping between these contrasts using a super-resolution Generative Adversarial Network.

  PublisherOA PDFDOI

• A Reproducible Pipeline for Parcellation of the Anterior Limb of the Internal Capsule

  Biological Psychiatry Cognitive Neuroscience and Neuroimaging · 2024-07-23 · 2 citations

  articleOpen access

  BACKGROUND: The anterior limb of the internal capsule (ALIC) is a white matter structure that connects the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation for obsessive-compulsive disorder. There is strong interest in improving deep brain stimulation targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions. METHODS: Following algorithm development and refinement, we analyzed 43 control participants, each with 2 sets of 3T magnetic resonance imaging data and a subset of 5 control participants with 7T data from the Human Connectome Project. We generated 22 segmented ALIC fiber bundles (11 per hemisphere) based on PFC regions of interest, and we analyzed the relationships among bundles. RESULTS: We successfully reproduced the topographies established by previous anatomical work using images acquired at both 3T and 7T. Quantitative assessment demonstrated significantly smaller intraparticipant variability than interparticipant variability for both test and retest groups across all but one PFC region. We examined the overlap between fibers from different PFC regions and a response tract for obsessive-compulsive disorder deep brain stimulation, and we reconstructed the PFC hyperdirect pathway using a modified version of our pipeline. CONCLUSIONS: Our diffusion magnetic resonance imaging algorithm reliably generates biologically validated ALIC white matter reconstructions, thereby allowing for more precise modeling of fibers for neuromodulation therapies.

  PublisherDOI

• Model-based closed-loop control of thalamic deep brain stimulation

  Frontiers in Network Physiology · 2024-04-08 · 4 citations

  articleOpen access

  Introduction: Closed-loop control of deep brain stimulation (DBS) is beneficial for effective and automatic treatment of various neurological disorders like Parkinson’s disease (PD) and essential tremor (ET). Manual (open-loop) DBS programming solely based on clinical observations relies on neurologists’ expertise and patients’ experience. Continuous stimulation in open-loop DBS may decrease battery life and cause side effects. On the contrary, a closed-loop DBS system uses a feedback biomarker/signal to track worsening (or improving) of patients’ symptoms and offers several advantages compared to the open-loop DBS system. Existing closed-loop DBS control systems do not incorporate physiological mechanisms underlying DBS or symptoms, e.g., how DBS modulates dynamics of synaptic plasticity. Methods: In this work, we propose a computational framework for development of a model-based DBS controller where a neural model can describe the relationship between DBS and neural activity and a polynomial-based approximation can estimate the relationship between neural and behavioral activities. A controller is used in our model in a quasi-real-time manner to find DBS patterns that significantly reduce the worsening of symptoms. By using the proposed computational framework, these DBS patterns can be tested clinically by predicting the effect of DBS before delivering it to the patient. We applied this framework to the problem of finding optimal DBS frequencies for essential tremor given electromyography (EMG) recordings solely. Building on our recent network model of ventral intermediate nuclei (Vim), the main surgical target of the tremor, in response to DBS, we developed neural model simulation in which physiological mechanisms underlying Vim–DBS are linked to symptomatic changes in EMG signals. By using a proportional–integral–derivative (PID) controller, we showed that a closed-loop system can track EMG signals and adjust the stimulation frequency of Vim–DBS so that the power of EMG reaches a desired control target. Results and discussion: We demonstrated that the model-based DBS frequency aligns well with that used in clinical studies. Our model-based closed-loop system is adaptable to different control targets and can potentially be used for different diseases and personalized systems.

  PublisherOA PDFDOI

• Classification of electrically-evoked potentials in the parkinsonian subthalamic nucleus region

  Scientific Reports · 2023-02-15 · 3 citations

  articleOpen accessSenior authorCorresponding

  Electrically evoked compound action potentials (ECAPs) generated in the subthalamic nucleus (STN) contain features that may be useful for titrating deep brain stimulation (DBS) therapy for Parkinson's disease. Delivering a strong therapeutic effect with DBS therapies, however, relies on selectively targeting neural pathways to avoid inducing side effects. In this study, we investigated the spatiotemporal features of ECAPs in and around the STN across parameter sweeps of stimulation current amplitude, pulse width, and electrode configuration, and used a linear classifier of ECAP responses to predict electrode location. Four non-human primates were implanted unilaterally with either a directional (n = 3) or non-directional (n = 1) DBS lead targeting the sensorimotor STN. ECAP responses were characterized by primary features (within 1.6 ms after a stimulus pulse) and secondary features (between 1.6 and 7.4 ms after a stimulus pulse). Using these features, a linear classifier was able to accurately differentiate electrodes within the STN versus dorsal to the STN in all four subjects. ECAP responses varied systematically with recording and stimulating electrode locations, which provides a subject-specific neuroanatomical basis for selecting electrode configurations in the treatment of Parkinson's disease with DBS therapy.

  PublisherOA PDFDOI

Recent grants

• Pathophysiology-based approaches to deep brain stimulation for Parkinson's disease

  NIH · $18.2M · 2021

• IGERT: Interacting with the Brain: Mechanisms, Optimization, and Innovation

  NSF · $3.0M · 2011–2018

• Algorithms for programming DBS systems for Essential Tremor

  NIH · $4.0M · 2012–2025

• NIH Grant F32NS061541

  NIH · $94k · 2011

• Spatiotemporal Optimization of Deep Brain Stimulation for Parkinson's Disease

  NIH · $5.1M · 2016–2027

Frequent coauthors

• Jerrold L. Vitek

  University of Minnesota System

  57 shared

• Noam Harel

  University of Minnesota

  26 shared

• Luke A. Johnson

  University of Minnesota System

  20 shared

• Kenneth B. Baker

  Cleveland Clinic Lerner College of Medicine

  19 shared

• Rémi Patriat

  University of Minnesota

  17 shared

• J. Sudijono

  Applied Materials (Germany)

  17 shared

• Allison T. Connolly

  Abbott (United States)

  16 shared

• Bradford G. Orr

  University of Michigan–Ann Arbor

  16 shared

Labs

• Tissue Mechanics LaboratoryPI

Education

• M.S., Ph.D, Biomedical Engineering

  University of Michigan

  2007

• S.B., Engineering and Applied Sciences

  Harvard University

  2002