Medical College of Wisconsin Neurology Research

Research at the WE Energies Center for Aphasia Research and Recovery (WE-CARE) at MCW is headed by neurologist Jeffrey Binder, MD, in collaboration with neuropsychologist Sara Pillay, PhD, neuroscientist Priyanka Shah-Basak, PhD, and other scientists at MCW and UW-Milwaukee. This work is conducted in close collaboration with the Language Imaging Laboratory, also directed by Dr. Binder, which has for decades been at the forefront of neuroimaging research on basic mechanisms of language processing in the human brain. Aphasia studies build on the insights resulting from this foundational research, which has informed new methods of aphasia diagnosis and spurred novel theories of language learning and dynamic recovery processes. Through WE-CARE, research also focuses on development of a comprehensive language assessment battery, neuromodulation clinical trials, and a research-driven Intensive Program for Aphasia Therapy (IPAT).

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Scientists in the Cognitive Neuroscience Research Program use neuroimaging and brain stimulation methods to investigate the neural basis of mental functions such as perception, memory, attention, and language processing. They also conduct studies in individuals with neurological disorders to better understand relationships between brain damage and cognitive impairments. These studies will lead to more accurate diagnostic methods and more effective treatments for aphasia, memory loss, dyslexia, and other neurological conditions that affect cognition.

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Investigators in the Comprehensive Epilepsy Center conduct research focused on early detection and prevention of epilepsy, fMRI studies of brain mapping for surgical management of epilepsy, clinical trials of anticonvulsant medications, and basic research on epilepsy mechanisms using computational models and cortical slice preparations.

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Movement disorders specialists participate in a variety of therapeutic trials of pharmacological agents and deep brain stimulation techniques for the treatment of Parkinson's Disease, Huntington’s Disease, Essential Tremor, Dystonia and other movement disorders.

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Researchers in Neurology, led by Staley Brod, MD, and Ahmed Obeidat, MD, PhD, investigate a variety of neuroimmunologic disorders, including multiple sclerosis, neuromyelitis optica, and autoimmune encephalitis. Their goals are to understand the etiology and pathophysiology of these disorders, improve diagnosis through advanced imaging and quantitative neurological testing, and develop and evaluate new treatments.

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The Dementia Program at MCW initiated comprehensive diagnostic, follow-up, and research services through its Memory Disorders Clinic, the Brain Autopsy Program, and a variety of research study protocols. The Neurodegenerative Translational Research Program (NTRP) aims to be a leader in cutting-edge research on Alzheimer’s Disease and other dementias with the Memory Disorders Clinics serving approximately 1000 new and/or established patients annually. Research focuses on neuromodulation, pharmaceutical trials, and imaging to help those with Alzheimer’s Disease, Mild Cognitive Impairment and other Memory Disorders.

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The Neuromuscular and Autonomic disorders group focuses on dysautonomias associated with pain such as functional abdominal pain, irritable bowel syndrome, interstitial cystitis, postural tachycardia syndrome, fibromyalgia, and cyclic vomiting syndrome, as well as clinical trials of pharmacological agents for slowing the progression of Amyotrophic Lateral Sclerosis (ALS) and other neuromuscular diseases.

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The Neuro-Oncology program carries out clinical trials of chemotherapeutic and other experimental treatments for brain cancer, near infrared spectroscopy (NIRS) as well as fMRI studies of tumor angiogenesis aimed at improving early detection and treatment outcomes. Clinical trials are conducted by Jennifer Connelly, MD and Harry Whelan, MD.

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Neurocritical care services provided by neurointensivist Dr. Ann Helms, and advanced interventional neurology served by Dr Brian-Fred Fitzsimmons, and Dr. John Lynch in the Stroke and Neurovascular Center conduct clinical trials of treatments for acute stroke and stroke prevention, as well as basic research on mechanisms of brain ischemia.

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

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.

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Magnetoencephalography is a technique that measures the magnetic fields produced by electrical activity in neurons from the human brain. The Froedtert & the Medical College of Wisconsin 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.

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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:

1. 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.
2. 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.
3. 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.
4. 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:

1. 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.
2. 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.
3. 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.
4. 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
5. 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.
6. 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:

1. 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.
2. 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.
3. 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.
4. 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
5. 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