Functional Magnetic Resonance Imaging (fMRI)
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.
Language Imaging Laboratory
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.
Neuromodulation Research Lab
Neuromodulation is the therapeutic alteration of activity in the nervous system by means of electromagnetic devices. Examples of this type of therapy include deep brain stimulation (DBS) for movement disorders, cortical and vagal nerve stimulation for epilepsy, and transcranial magnetic stimulation (TMS) for depression. The theory of operation behind this type of therapy is that electrical currents are induced in the brain either via implanted electrodes or magnetic induction. The induced current impinges on nearby anatomical areas and leads to a functional response. In the best case this results in good therapeutic improvement for the patient, with minimal side effects. In well-selected patients who are treated by an experienced clinical team, the improvement from this type of therapy can be dramatic.
For example, debilitating Parkinsonian tremor can be completely arrested by DBS in a matter of seconds. However, for patients who do not respond well to this type of therapy there are few tools available to understand how to better treat them.
In contrast to medications that have a well-defined dose-response relationship, the concept of a dose does not yet exist in neuromodulation therapy. Most of the guidance that is available on how to prescribe this therapy is based on empirical evidence derived from trial and error. Unfortunately, collecting data in this way does not lend itself to developing evidence-based guidelines on how to apply therapies that are known to be acutely sensitive to changes in stimulation location and parameters such as frequency, pulse width, and amplitude. To address these problems, the Butson lab uses a combination of patient studies and patient-specific computational models to predict and visualize the effects of neuromodulation therapy. This approach can provide insights that would be difficult to obtain using either method alone. Studies that are currently underway are:
DBS for Parkinson’s disease
Cortical stimulation for depression
TMS for depression
Intraoperative microstimulation during DBS surgery
DBS for traumatic brain injury
Sleep Research Laboratory
Carol A. Everson, PhD , established the Sleep Research Laboratory in the Department of Neurology and conducts research into the effects of sleep and sleep loss on metabolic, immune, and endocrine functions. The overarching goals are to understand the ways in which sleep loss impairs health, and to discover the physical properties that account for why sleep seems restorative. The research initiatives are supported largely by awards from the National Institute of Health and help to fulfill the goals of the NIH Sleep Disorders Research Plan, which is to advance understanding of sleep and circadian functions in both the brain and the body across the lifespan.
Current Sleep Research Laboratory Research
Oxidative stress responses to loss and recovery of sleep. The objectives of these studies are to identify targets of oxidative stress-associated damage resulting from sleep loss and to determine the extent to which antioxidant depletion and cell damage affect physiological and clinical signs.
Metabolic abnormalities and nutritional demands resulting from lack of sleep. The objectives of these studies are to determine changes to nutritional demands and how calories are disposed of differently when there is a lack of sleep compared to when there is sufficient sleep. The outcomes are expected to extend to discoveries of cellular functions linked to sleep.
Abnormal bone remodeling and increased blood cell production caused by insufficient sleep. Recent discoveries point to problems with remodeling of bone and altered plasticity of marrow as consequences of chronic sleep loss. Current and follow-up studies will establish the reasons for these pathologies and how they affect individuals based on age and gender.
Cell injury as a consequence of lack of sleep. The objective of these studies is to determine cause and effect relationships between cell injury and proinflammatory processes, both of which are consequences of sleep loss.
The findings are expected to facilitate discoveries leading to preventative measures and treatments to alleviate the health consequences of poor sleep.
Harry T. Whelan, MD, is the Bleser Family Endowed Chair in Neurology, Children’s Hospital of Wisconsin and director of the MCW Hyperbaric Medicine Unit. His research focuses on the use of near-infrared light-emitting diodes (LEDs) for wound healing and the treatment of brain tumors, stroke, neurofibromatosis, traumatic brain injury, diabetic macular edema, mitochondrial diseases, and other conditions. His work has been funded by NIH, NASA, and the Defense Advanced Research Projects Agency (DARPA). He has over 100 publications on topics in the fields of cancer, laser therapy, LED therapy, and diving/hyperbaric medicine. Dr. Whelan found that diabetic skin ulcers and other wounds in mice heal much faster when exposed to LEDs. Near-infrared light stimulates improved energy metabolism in the mitochondria, leading to potential treatments for mitochondrial diseases, which affect the brain, eye, heart and muscle, and acute management of stroke and epilepsy. Dr. Whelan presented this translational bench-to-bedside research to the United States Congress at the NASA Spin-off Day on Capitol Hill as an example of how space research is helping patients. Dr. Whelan is a Diving Medical Officer in the U.S. Navy, a consultant to the Navy Experimental Diving Unit and the Canadian Ministry of Defence, and serves as the Senior Undersea Medical Officer for the “Deep Submergence Unit”, with clinical and research experience in Hyperbaric Medicine, wound care and combat casualty care.
Current Whelan Laboratory Research
"Cerebral Oxygen Saturation in Children with Epilepsy: A Pilot Study"
This is a pilot study that aims to address the relationship of regional cerebral oximetry, measured using near-infrared spectroscopy, with seizure activity in the peri-ictal period in children with epilepsy. The following hypotheses will be tested: 1. Regional cerebral saturation of oxygen will increase prior to the onset of seizure activity; 2. Regional cerebral saturation of oxygen will have a carried response during seizure activity depending on the seizure type; 3. Regional cerebral saturation of oxygen will return to baseline following cessation of seizure activity.
"Amelioration Of Oral Mucositis Pain By NASA Near Infra Red Light Emitting Diodes In Bone Marrow Transplant Patients: a Randomized Multi-Center Controlled Clinical Trial"
The aim of this project is to investigate the use of extra-orally applied near infra-red (NIR) phototherapy for the reduction of oral pain secondary to chemo- and radiation-therapy-induced mucositis in adult and pediatric hematopoietic stem cell transplant (HSCT) patients.
"Near-infrared Light (NIR) Therapy for Diabetic Macular Edema: A Pilot Study"
NIR-LED treatment promotes retinal healing and improves visual function following high intensity laser retinal injury by augmenting cellular energy metabolism, enhances mitochondrial function, increases cytochrome C oxidase activity, stimulates antioxidant protective pathways, and promotes cell survival. LED therapy has been approved as a non-significant risk (NSR) device for treatment of eye disorders, has a low treatment cost, and may serve as an effective, non-invasive alternative or adjunctive treatment to laser photocoagulation, the current standard of care for diabetic macular edema. The aims of this projects are to determine the effects of short term (3 month) NIR-LED therapy on anatomic and functional abnormalities of diabetic macular edema as assessed by visual acuity, optical coherence tomography, and fundus biomicroscopy.
"Near-infrared light-emitting diode (NIR-LED) therapy for Leber’s Hereditary Optic Neuropathy (LHON)"
The overall objective of this project is to test the hypothesis that NIR-LED therapy will stimulate mitochondrial function, attenuate oxidative stress, and improve cell survival and vision in subjects with LHON.
"Photodynamic Therapy (PDT) for Brain Tumor Dispersal"
This project examines the hypothesis that patients with progressive/recurrent malignant brain tumors undergoing PDT with Photofrin will show a dose dependent improvement in free survival and overall survival outcomes. PDT will also be effective against infratentorial tumors and in pediatric patients. The protocol will establish the maximum tolerable dose of Photofrin in adults and in children using a dose-escalation scheme, then measure effectiveness trends at one-year and two-year post-PDT time points.