Research to improve health care for neurological illness is a major mission of the Department of Neurology, which maintains a wide range of basic and clinical research programs. Below is a sampling of some of the research projects currently conducted in the department.
Recently, the faculty in our department have been extremely successful in securing federal grants for research. In the past year, we have nearly doubled our NIH support, going from five to nine grants, with a total increase in funding of $941,000 (over $2,000,000 in federally funded grants).
Research and Clinical Trials in Neurology
Below is a listing of the types of neurological diseases researchers in the Department of Neurology are studying. A description of the corresponding Clinical Programs for the neurological disorders can be found on our Adult Neurology page.
For information about clinical trials in neurology, please visit the Froedtert Hospital Neurosciences Clinical Trials page.
Areas of Interest
The autonomic disorders group conducts research focused on dysautonomias associated with pain such as functional abdominal pain, irritable bowel syndrome, interstitial cystitis, postural tachycardia syndrome, fibromyalgia, and cyclic vomiting syndrome. The aims of current studies are to ascertain the co-morbidities of these disorders, the familial occurrence patterns, and ultimately understand the genetic, epigenetic and environmental changes that influence their emergence across individuals. Another aim of the group is the study of structural disorders of the autonomic nervous system such as diabetic autonomic neuropathy and multiple system atrophy.
Current Autonomic Disorders Research
“Interstitial Cystitis Elucidation of Psychophysiologic and Autonomic Characteristics (ICEPAC)” - T Chelimsky, PI; R01-DK083538 NIH NIDDK. Co-Investigators: Buffington CAT, Janata, J, Chelimsky G, Hijaz A, Sanses T
The goal of this project is to determine the autonomic changes co-morbid with interstitial cystitis, compared to “generic” pelvic pain typified in the entity of myofascial pelvic pain. The underlying hypothesis is that interstitial cystitis is a member of the larger family of painful dysautonomias characterized by an aberrant stress response. The putative etiology of this aberrant response lies in epigenetic changes produced by an early life stress such as drug abuse during pregnancy or sexual abuse at a young age.
“Electroconvulsive therapy (ECT) in multiple system atrophy (MSA)” - T Chelimsky PI. CTSC grant from Case Western Reserve University
The hypothesis of this project is that patients with mid-course MSA will show reversal of their progression when treated with ECT. The putative mechanism of this improvement would be generation of glial-derived neurotrophic factor (GDNF), known to be absent in a mouse model of MSA and nearly undetectable in patients with MSA, and known to be the best correlate of depression response (rise in GDNF) to ECT.
Funding is being sought to study the role of estrogen in POTS (MCW medical student Rachel Sullivan), and to study fMRI aspects of painful autonomic disorders.
The Center's research programs include fMRI in Alzheimer's Disease and Mild Cognitive Impairment, and MR spectroscopy in Alzheimer's Disease and Frontal Lobe Dementia. The Center's physicians and nurses are participating in the Nun Study, a collaborative project with the University of Kentucky to determine early life risk factors for dementia. Several drug trials with memory enhancing agents are currently underway for the prevention as well as treatment of Alzheimer's Disease.
The Dementia Research Center provides educational opportunities for the community, and physicians through an on-site caregiver support group, local workshops and seminars as well as presentations at national and international conferences. Specialized training in Dementia is also provided for geriatricians, neurologists, psychiatry residents, and medical students.
Links of Interest
National Alzheimer's Association
Alzheimer's Association - Southeastern Wisconsin Chapter
Wisconsin Alzheimer's Institute
Dr. Michael McCrea’s research focuses primarily on the acute and chronic effects of traumatic brain injury (TBI). He is the principal investigator on several studies that use a multitude of modalities to research the natural course of clinical and physiological recovery after TBI. One of his main areas of interest is the effect of sport-related concussion on athletes competing in contact and collision sports at all competitive levels. More recently, he has been involved in studying the effects of concussion and traumatic brain injury in soldiers serving in the wars in Iraq and Afghanistan.
Current Traumatic Brain Injury Center Research
"An Independent, Head to Head Study of the Reliability and Validity of Neurocognitive Test Batteries for the Assessment of Mild TBI" - M. McCrea, PI; funded by the Walter Reed Army Institute for Research (WRAIR)/ Medical Research Material Command (MRMC); Brooke Lerner, PhD, Thomas Balkin, PhD, Co-Investigators
"Acute Effects and Recovery after Concussion in Athletes: A Quantitative Brain Electrical Activity Study Using BrainScope" - M. McCrea, PI; funded by DonJoy Orthopedics, Inc.; Alison Brooks, MD, Co-PI
"National Sports Concussion Outcome Study (NSCOS)" - M. McCrea, PI; funded by the National Collegiate Athletic Association (NCAA); Steven P. Broglio, PhD; James T. Eckner, MD; Christopher Giza MD; Kevin M. Guskiewicz, PhD; and Jeffrey S. Kutcher, MD, Co-Investigators
Research and Clinical Trials in Pediatric Neurology
From testing new treatments for brain tumors and epilepsy to improving surgical techniques, the Neurosciences team at Children's Research Institute works to enhance care for children with neurological disorders.
The Neurosciences team is dedicated to translational research, taking clinical problems from patients' bedsides to study in the laboratory. Laboratory discoveries are then converted into new treatments, preventions and therapies for patients.
Neurosurgical research is conducted in collaboration with the Neuroscience Research Center at The Medical College of Wisconsin. The 25,000-square-foot lab includes eight doctorate-level researchers and 20 support staff who regularly collaborate with children's hospitals across the country.
For information about clinical trials in neurology, please visit the Children's Wisconsin Neurosciences Clinical Trials page.
Functional Magnetic Resonance Imaging (fMRI) is an advanced method for mapping brain functions using MRI scanners. MCW researchers helped pioneer the development of functional magnetic resonance imaging (fMRI) of the brain in 1992, and MCW has continued to be a world leader in this field. Dr. Jeffrey Binder is chief investigator on an NIH grant to study language processing using fMRI, and also on an NIH grant to develop applications of fMRI in epilepsy surgery. The latter grant involves extensive collaborations with Dr. Wade Mueller of the Epilepsy Program and Dr. Sara Swanson of the Neuropsychology section. Dr. Binder and colleagues published the first reports on fMRI studies of auditory cortex, semantic language processing, and use of fMRI to determine language dominance.
fMRI researchers in the Department of Neurology collaborate closely with scientists from the Medical College's Biophysics Research Institute, a large academic department that has been a world leader in MR coil and pulse sequence development for fMRI.
Other faculty involved in fMRI research include Dr. Einat Liebenthal who uses simultaneous ERP and fMRI techniques to map human auditory language processes, Dr. Rutvik Desai who studies language processing, and Dr. Merav Sabri who is interested in attentional control.
The Neurology Department fMRI efforts are one component of a larger fMRI neuroscience research group at MCW that includes investigators from the Departments of Cellular Biology and Anatomy, Psychiatry, Physiology, and Radiology.
The Functional Imaging Research Center develops and maintains a state-of-the-art fMRI research infrastructure including two 3-Tesla MRI scanners dedicated full-time to human fMRI research, and a 9.4-Tesla scanner used for animal research.
The Language Imaging Laboratory, directed by Jeffrey Binder, MD, conducts basic research on normal and impaired language functions using functional magnetic resonance imaging (fMRI), event-related potentials (ERP), magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), and structural MRI. Clinical research focuses on new methods for language mapping prior to brain surgery and on understanding recovery from aphasia after stroke. Lab members have had continuous funding from the NIH since 1994 and have produced pioneering studies on the neurobiological basis of language.
Language Imaging Laboratory Research
"The Neurophysiology of Speech Perception" (R01 DC006287, Einat Liebenthal, PI).
This project uses fMRI, ERP, and MEG to study large-scale neural systems supporting the linguistic perception of speech. The focus is on mapping and functional characterization of cortex in the human superior temporal lobe that supports high-level auditory perception and categorization of vowel and consonant sounds.
"Sensory-Motor Systems and Conceptual Processing in the Healthy and Impaired Brain" (R01 DC010783 Rutvik Desai, PI)
This project uses fMRI, MEG, and behavioral studies in patients with motor system impairments to investigate the contribution of motor networks in the brain to the comprehension of action concepts. A series of experiments test the hypothesis that action concepts are understood in part through an internal action simulation process that involves motor and somatosensory systems.
"Presurgical Applications of Functional MRI in Epilepsy" (R01 NS035929, Jeffrey Binder, PI)
This award supports a multi-center study called "FMRI in Anterior Temporal Epilepsy Surgery (FATES)". The principal goal of the study is to determine the role of fMRI in evaluating patients undergoing temporal lobe surgery for medication-resistant epilepsy. Approximately 200 patients will be enrolled at 8 academic epilepsy centers throughout the US. The study aims to resolve longstanding issues surrounding the proper use of fMRI in presurgical mapping, factors that determine successful seizure control, and factors that affect language and memory function after surgery.
"The Neurobiology of Auditory Language Perception" (R01 DC003681, Greg Hickok, PI)
This multi-center consortium award supports behavioral and MRI studies in patients with aphasia as a result of left hemisphere stroke. The aim of the work is to understand the relationships linking variations in the pattern of brain damage that occurs in stroke with the corresponding variation in linguistic deficits that characterizes aphasia. This knowledge should lead to more precise classification of aphasic syndromes as well as new biologically grounded methods of rehabilitation.
"Mapping the Effects of the KIAA0319 Dyslexia Susceptibility Gene on the Neural Substrates of Reading" (MCW CTSI Award, Lisa Conant, PI)
This project investigates the effects of a gene associated with dyslexia on reading ability in a healthy cohort without dyslexia. The study will examine the hypothesis that variations in the KIAA0319 genotype are associated with subclinical individual variations in performance during reading and speech perception tasks.
Magnetoencephalography is a technique that measures the magnetic fields produced by electrical activity in neurons from the human brain. The Froedtert and Medical College's MEG program started in the Fall of 2008 and is dedicated to both clinical and research studies initiated by physicians and all investigators willing to obtain functional images of the brain 'in action', with millisecond time resolution.
MEG is used to evaluate patients from our Department and others, to map the brain and its functions prior to surgery and to develop innovative brain imaging methods for basic cognitive neuroscience and neuropsychology. Manoj Raghavan, MD, PhD, is the Medical Director and Jeffrey Stout, PhD is the technical manager of the MEG program.
Harry T. Whelan, MD, believes in a translational patient care philosophy, bringing research from bench to bedside.
Harry T. Whelan, MD
Bleser Family Endowed Chair in Neurology
Professor of Pediatric Neurology
Director of the Undersea & Hyperbaric Medicine Unit
Medical College of Wisconsin and Children’s Wisconsin
Overview of Whelan Lab: Clinical and Laboratory Research Programs
The long term goal of this research program is the translational application of infra-red light technology to medicine. We are addressing cell culture, basic biochemistry, animal models and human subjects with active studies at all three translational levels of research. Current programs include:
Photodynamic Therapy (PDT) for brain tumors and Neurofibromatosis
Dr. Whelan has been involved in the area of photodynamic therapy for malignant brain tumors, from canine models of gliomas, preclinical binding and photosensitizer localization studies, to clinical trials in both adult and pediatric subjects. He and his research team have studied various photosensitizers and light sources as well as explored PDT near functional brain tissue. Currently, they are conducting clinical trials in pediatric (Phase I) and adult populations (Phase II). This technique has the potential to significantly improve outcomes for a patient population with generally poor prospects, particularly those with recurrent tumors or tumors that are unable to be removed. For Neurofibromatosis we have launched a Phase II study designed to determine the long term efficacy of a single treatment of Topical PDT with Levulan® Kerastick® for patients diagnosed with neurofibromatosis type 1. Dr. Whelan and his research team were able to convincingly demonstrate that the drug was specifically converted to the active agent PPIX in the tumor region. TUNEL assay showed significant increase in number of apoptotic cells as compared to control, further showing cell death in treated tumor tissue. Publications he has written for include:
- Whelan HT, Schmidt MH, Segura AD, McAuliffe TL, Bajic DM, Murray KJ, Moulder JE, Strother DR, Thomas JP, Meyer, GA: The role of photodynamic therapy in posterior fossa brain tumors: A pre-clinical study in a canine glioma model. Journal of Neurosurgery. 1993; 79:562–568. PMID: 8410226.
- Schmidt MH, Bajic DM, Reichert KW, Martin TS, Meyer GA, Whelan HT: Light-emitting diodes as a light source for intra-operative photodynamic therapy. Neurosurgery. 1996; 38:552–557. PMID: 8837808.
- Schmidt MH, Meyer GA, Reichert KW, Cheng J, Krouwer HG, Ozker K, Whelan HT: Evaluation of photodynamic therapy near functional brain tissue in patients with recurrent brain tumors. Journal of NeuroOncology. 2004; 67:201–204. PMID: 15072468.
- Quirk BJ, Brandal G, Donlon S1, Vera JC, Mang TS, Foy AB, Lew SM, Girotti AW, Jogal S, LaViolette PS, Connelly JM, Whelan HT. Photodynamic therapy (PDT) for malignant brain tumors - where do we stand? Photodiagnosis Photodyn Ther. 2015 May 7. 2015 Sep;12(3):530-44 pii: S1572-1000(15)00044-7. doi: 10.1016/j.pdpdt.2015.04.009. [Epub ahead of print]
Photobiomodulation & Photobiology
Dr. Whelan has been inducted into the NASA Space Technology Hall of Fame for his research in the use of near-infrared (NIR) LEDs for wound healing and the treatment of brain tumors and neurofibromatosis. In a multiyear investigation approved by the Food and Drug Administration, Dr. Whelan has studied the use of LEDs to promote healing of mucositis from chemotherapy and radiation used to treat cancer in children. Dr. Whelan found that diabetic skin ulcers and other wounds in mice healed much faster when exposed to the special LEDs in the lab. NIR light stimulates improved energy metabolism in the mitochondria, leading to treatment for mitochondrial diseases which affect the brain, eye, heart and muscle. Dr. Whelan has been funded by the National Institutes of Health in a study of neurodegenerative disease, traumatic brain injury and other childhood traumas. He has also conducted a pilot study, supported in part by the Clinical Translational Science Institute, of NIR light therapy for diabetic macular edema, a form of diabetic eye disease. Publications he has written for include:
- Quirk,B., Torbey, M., Buchmann, E., Verma,S., Whelan, H.T. Near-Infrared Photobiomodulation in an Animal Model of Traumatic Brain Injury: Improvements at the Behavioral and Biochemical Levels. Photomedicine and Laser Surgery 30(9) 2012.
- Wong-Riley MMT, Eells JT, Whelan HT: Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: Role of cytochrome c oxidase. Journal of Biological Chemistry. 2005; 280:4761–4771. PMID: 15557336.
- Hodgson,B., Margolis,D.M.,Salzman,D.E, Eastwood,D., Tarima, S., Williams,L.D., Sande,J., Vaughn,W.P., Whelan,H.T. Amelioration of Oral Mucositis Pain by NASA Near Infra Red Light Emitting Diodes in Bone Marrow Transplant Patients, Supportive Care Cancer, Jul 3, 2011.
- Quirk, B.J., Sonowal, P., Jazayeri, M.A., Baker, J.E., Whelan, H.T. Cardioprotection from Ischemia-Reperfusion Injury by Near-Infrared Light in Rats. Photomed Laser Surg. (Epub ahead of print) 2014
- Priya Monrad, Kumar Sannagowdara, Xiuhua Bozarth, Sugandha Bhosrekar, Kurt Hecox, Michelle Nwosu, Michael Schwabe, Michael Meyer, Aniko Szabo, Jenna Prigge, Russ Lemke, Briana Horn, and Harry T. Whelan, Haemodynamic response associated with both ictal and interictal epileptiform activity using simultaneous video electroencephalography/near infrared spectroscopy in a within subject study. J Near Infrared Spectrosc. Nov 2015, 23: 209–218. Doi:10.1255/jnirs.1170.
- Quirk BJ, Whelan HT: Effect of Red to Near-Infrared Light on the Reaction of Isolated Cytochrome c Oxidase with Cytochrome c. Photomed Laser Surg 2016 Apr. 25 [Epub ahead of print]
Hyperbaric Oxygen & Diving
Dr. Whelan’s research involves the use of hyperbaric oxygen for neurological indications, wound care and undersea and diving medicine. He currently holds the rank of Captain in the United States Navy. Publications he has written for include:
- Helms, A, Evans, AW, Chu, J, Sahgal, A, Ostrowski, R, Sosiak,T, Wolf, G, Gillett, J, Whelan, H.T. Hyperbaric oxygen for neurologic indications: Action plan for multicenter trials in: stroke, traumatic brain injury, radiation encephalopathy & status migrainosus. Undersea Hyperb Med.38;(5):309– 319, Sep-Oct, 2011.
- Willoughby, R., Verma, S., Landisch, R., Schmainda, K., Prah, M., Quirk, B. Whelan, H.T. Presumed hydrogen sulfide-mediated neurotoxicity following Streptococcus anginosus group meningitis. Pediatric Infectious Disease Journal, Feb 2013.
- Seidel, R., Carroll, C., Thompson, D., Diem, R., Yeboah, K., Hayes, A.J., Hall, B., Whelan, H.T. Risk factors for oxygen toxicity seizures in hyperbaric oxygen therapy: Case reports from multiple institutions. UHM 2014;40(6) : 515-519.
- Valadao JM, Vigilante JA, DiGeorge NW, O'Connor SE, Bear A, Kenyon J, Annis H, Dituri J, Dituri AE, Whelan HT. Ketogenic diet for high partial pressure oxygen diving. Undersea Hyperb Med. 2014 Jul-Aug; 41(4):331-5. PMID: 25109086
- Dituri J, Sadler R, Sidiqi F, Sadler C, Javeed N, Annis H, Whelan H Echocardiographic evaluation of intracardiac venous gas emboli following in-water recompression, Undersea & Hyperbaric Medical Society Inc., UHMS Mar-Apr 2016 Vol 43, No.2