Working closely with Dr. Luis Lujan, Ph.D., M.S., the Applied Computational Neurophysiology and Neuromodulation Laboratory combines pre-clinical and clinical neurophysiological (electrophysiological, neurochemical, and optical) data collection and analysis with computational modeling strategies to advance neuromodulation interventions for the treatment of neurologic and psychiatric conditions.

As a dedicated physician-scientist, Kai Miller, MD, PhD., is interested in developing therapeutic cybernetics, neurosurgical, stereotaxy, and large-scale brain dynamics with a focus on enhancing the effectiveness of brain-computer interface for patients with Amyotrophic Lateral Sclerosis (ALS), sensory-motor cortex research for patients with Parkinson’s disease, and deep brain stimulation for movement disorders such as epilepsy.

The goal of his research in the Cybernetics and Motor Physiology Laboratory is to translate his expertise in electrophysiological neuroscience to therapeutic technologies that can improve patients’ clinical care as well as meaningfully improve quality of life for patients suffering from neurologic diseases.

The lab team is committed to improving existing methods and developing innovative techniques to measure the electrophysiology of the brain. They want to create more precise closed-loop stereotactic procedures that take advantage of new emerging hardware. The team hopes to develop new devices that can induce brain plasticity after injury, control cybernetic prostheses, and intervene with distributed circuits in neuropsychiatric disease and movement disorders. 

Research in Mayo Clinic's Device Development and Experimental Therapeutics Lab focuses on the advancement of neurosurgery in techniques and technology to assist surgery. Most work concentrates on expanding indications for the treatment of disease for neurosurgery and using brain stimulation for the treatment of epilepsy.

The lab works on mechanical aspects of devices to improve current operative procedures and innovates new ways to treat diseases relevant to neurosurgery. Most treatments are focused on diseases relevant to our clinical practice of benign skull base tumors and epilepsy.

In addition, the lab employs outcome analysis, advanced imaging, and techniques for benign skull base tumors, such as pituitary adenomas, vestibular schwannomas, and meningiomas, as well as malignant skull base tumors, such as esthesioneuroblastoma and chordoma.

This laboratory team focuses on developing synthetic polymeric scaffolds and controlled delivery of bioactive molecules for peripheral nerve and spinal cord repair and regeneration. This National Institutes of Health (NIH)-funded research endeavor combines strong collaborative efforts of neurosurgeons, neuroscientists, orthopedists, tissue engineers, and cellular neurobiologists and polymer chemists. The goal of this project is to introduce and commercialize biodegradable conduits for clinical use.

High-frequency deep brain stimulation (DBS) is an effective treatment for Parkinson's disease, tremor, epilepsy, dystonia, and depression. However, the precise mechanisms of action for the therapeutic effects of DBS are unknown. Since both DBS and lesionectomy target similar brain regions, it has been thought that electrical stimulation works through neuronal inhibition. However, the lab has found that DBS results in excitation of neuronal and glial elements, suggesting that electrically excited neurotransmitter release may be the mechanism of action of DBS.

Accordingly, the Neural Engineering Laboratory is studying how DBS affects changes in neuronal action potential firing and modifies neural network activities. To study the mechanism of action of DBS, the lab performs fluorescent microscopy along with intracellular and extracellular electrophysiological recordings. The lab also utilizes electrochemical techniques of constant potential amperometry to measure neurotransmitter levels both in the in vivo and in vitro setting.

Through this research, the members of the lab hope to combine sophisticated electrophysiological recordings with miniaturized analytical elements (microprocessors) to augment and repair disrupted brain functions. Thus, the lab members are actively involved with biomedical engineers to develop the next generation of DBS devices.

The Neuro-Informatics Laboratory is dedicated to advancing patient care and safety, with a specific focus in the following areas:

• Surgical outcomes. Working closely with the Mayo Clinic Robert D. and Patricia E. Kern Center for Science of Health Care Delivery and other departments, the Neuro-Informatics Laboratory mines national databases and utilizes machine learning to track and model the impact and safety of surgical and nonsurgical interventions.
• Spinal biomechanics and novel spinal devices. The Neuro-Informatics Laboratory works with the Mayo Clinic Division of Engineering and the Orthopedic Biomechanics Laboratory to study the impact of spinal surgeries on the biomechanics of the spine and develop devices that can make spinal surgery safer and provide alternatives to fusion.
• Spinal cord injury and spinal disk degeneration. The Neuro-Informatics Laboratory's multidisciplinary team investigates the molecular underpinnings of spinal disease intending to establish new treatments. These treatments utilize stem cell interventions for patients with low back pain and spinal cord injury as well as genomic treatments for degenerative disk disease.

The Neurosurgical Oncology Laboratory focuses on the cellular and immunological characteristics of malignant brain tumors. Particular areas of interest include immunotherapy, brain tumor stem cells, and mouse models of malignant gliomas. The laboratory has demonstrated an interrelated cellular network mediates immunosuppression in patients with malignant gliomas. This includes glioma cells (differentiated and stem cell phenotypes), tumor-infiltrating monocytes-microglia, circulating myeloid-derived suppressor cells, and regulatory T cells.

Multiple molecular mechanisms contribute to these cells' effects, but evidence from the lab has implicated a central role for the immunosuppressive T cell costimulatory molecule homologue B7-H1. Much of the lab’s work is aimed at disrupting this network to facilitate immunotherapies and develop appropriate murine models of glioma-mediated immunosuppression to allow pre-clinical testing.

A significant aim of the lab’s work is to translate discoveries to the clinic through glioma vaccine clinical trials. This effort is facilitated by the presence of a Good Manufacturing Practices (GMP) laboratory for generating clinical-grade cellular therapy reagents at Mayo Clinic. Additionally, members of the Mayo Clinic Brain Cancer SPORE work closely with this laboratory. Specialized Program of Research Excellence (SPORE) grants are highly competitive group grants awarded by the National Cancer Institute for translational cancer research programs. Only three Brain SPOREs have been awarded nationwide, underscoring Mayo Clinic's exceptional capacity to perform translational research in neuro-oncology.

The Neurosurgery Regenerative Laboratory engages in advanced research in regenerative neuroscience from the molecular to cell biological and integrative levels. Specific topics under investigation include molecular analysis of receptors and signal transduction mechanisms; axon guidance, target recognition, and regeneration; formation and plasticity of synapses; control of neural cell fate; development of neural networks; regulation of glioma cell motility; and mechanisms controlling vascular development and regeneration.

The lab offers an integrated approach to training in modern neurobiology, utilizing molecular, biochemical, and cell biological techniques as well as advanced optical imaging. Members of the lab have the opportunity to work closely with the spinal cord injury research team at Mayo.

In the past decades, brain cancer has replaced leukemia as the most common cancer-causing death among children and adolescents. The Experimental Drug and Therapeutics for Pediatric Brain Tumor Lab of David J. Daniels, M.D., Ph.D., aims to improve the prognosis of children with malignant brain tumors through early diagnosis, novel strategies, and targeted therapies based on the unique molecular underpinnings of individual brain tumors.

Malignant brain tumors, including glioblastomas, diffuse intrinsic pontine gliomas (DIPGs), medulloblastomas, and ependymomas, are among the most lethal cancers and inflict a disproportionate impact on younger populations. Effective new therapies are needed to alleviate the suffering and improve the prognosis of children facing these central nervous system tumors. Dr. Daniels' focus is on the diagnosis and treatment of these tumors.

Dr. Daniels and his colleagues seek to develop and rigorously test methods that facilitate aggressive surgical resection for pediatric brain tumors while maintaining or improving safety. The techniques include integrating functional imaging, including functional MRI and diffusion tensor imaging tractography, into image-guidance systems, and intraoperative MRI. They are also pursuing novel strategies such as fluorescence-guided resection and ultra-early diagnosis of tumor types.