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Epilepsy Research

Epilepsy research at MCW

The Froedtert-MCW Epilepsy Program has benefited from a strong tradition of translational neuroimaging research that is a particular strength at the Medical College of Wisconsin. Research pioneered at our institution has been central to the development of clinical fMRI for the presurgical evaluation of patients with epilepsy and brain tumors. Other resources available for basic and applied research include a state-of-the-art magnetoencephalography (MEG) laboratory, access to invasive EEG data, SISCOM, FDG-PET, diffusion tensor imaging (DTI) with tractography, high-field (7 Tesla) human MRI, near-infrared spectroscopy (NIRS), a transcranial magnetic stimulation (TMS) laboratory with real-time navigation capability and simultaneous EEG recording options, and a variety of tools for multimodal image registration.

Research Areas

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Presurgical Mapping with Functional MRI (fMRI)

The Language Imaging Laboratory, led by Jeffrey Binder, MD, pioneered fMRI as a less invasive alternative for determining language dominance prior to epilepsy surgery.

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The Epilepsy Connectome Project

Partial epilepsy is increasingly viewed as a network-level phenomenon involving progressive changes in brain morphology and inter-regional connectivity. Preliminary evidence suggests that these changes may be related to the duration and severity of epilepsy, severity of cognitive and psychiatric co-morbidities, and variation in medication responsiveness. The Epilepsy Connectome Project (ECP), funded by the National Institute of Neurological Disorders and Stroke (NINDS), aims to test these hypotheses by acquiring detailed neuroimaging and clinical data in a large (n = 150), prospective sample of patients with temporal lobe epilepsy who vary in epilepsy duration, seizure burden, and neurobehavioral status. The project is a collaboration between teams at MCW (J. Binder, PI) and UW-Madison (M.E. Meyerand, PI). MRI acquisitions closely follow Human Connectome Project guidelines and include high-resolution structural imaging, 40 minutes of “resting state” fMRI, 4 cognitive task activation protocols (emphasizing language, semantic memory, emotional face processing, and social cognition), and high-resolution diffusion tensor imaging. Magnetoencephalography (MEG) acquisitions include resting state and 3 task activation protocols. Neurobehavioral assessments cover a wide range of domains using instruments from the NIH Toolbox, standard clinical measures, and experimental measures.

Recruitment ran from January 2016 through March 2020, at which point enrollment was ended due to the Covid-19 pandemic. We enrolled 149 temporal lobe epilepsy patients. Of these, 131 completed the full MRI and behavioral baseline protocol, and 82 completed MEG. Healthy control data include 60 participants in the MRI protocol, 84 in the behavioral protocol, and 44 in the MEG protocol. Data analyses continue on this large and multi-faceted dataset. All data will be made publicly available in late 2021 for use by the scientific community.

Novel findings published to date include:

  • Identification of connectivity differences between patients and controls using machine learning methods applied to resting-state fMRI data (Hwang et al., 2019b)
  • Relationships between verbal memory function and effective connectivity between nodes of the ‘default mode’ network (Cook et al., 2019)
  • Structural and functional connectivity correlates of cognitive slowing in TLE patients (Hwang et al., 2019a)
  • Neuroanatomical changes underlying personality trait differences between patients and controls (Rivera-Bonet et al., 2019)
  • Neurobiological and sociodemographic features of cognitive phenotypes in TLE (Hermann et al., 2020)
Brain Electrophysiology Research

Electroencephalography (EEG), electrocorticography (ECoG), and Magnetoencephalography (MEG) represent important diagnostic tools in the evaluation of patients with epilepsy. Research efforts broadly focus on developing and validating novel methods for using brain signals to localize brain-regions that give rise to seizures and to map important functional areas that need to be preserved when surgical treatments are considered.

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Neuropsychological and Surgery Outcomes Research
Studies on the neuropsychology of epilepsy have advanced our knowledge of brain behavior relationships through examination of the effects of seizures, AEDs, and surgical intervention on higher cognitive functioning.

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Functional Mapping with Near-Infrared Spectroscopy (NIRS)

Near infrared spectroscopy (NIRS) is a well-established, noninvasive tool to continuously assess regional tissue oxygenation in the brain. It was first described by Jöbsis 40 years ago and has been used in various clinical settings, especially in the field of neuroscience. The brain has high energy demands, and activation of brain tissue is accompanied by an increase in cerebral blood flow and volume in activated regions. This “neurovascular coupling” is the basis for many functional neuroimaging techniques, including NIRS, fMRI, positron emission tomography (PET) and single-photon emission computerized tomography (SPECT). By measuring the relative changes of different hemoglobin species, changes in cerebral blood flow can be calculated with NIRS. The coupling of NIRS with noninvasive neuroimaging techniques has potential for widespread clinical applications in neuroscience, including language mapping and epileptogenic zone localization, and detection of postsurgical cerebral reorganization as well as in neurocritical care. Several traits of NIRS make it a unique tool in both clinical care and neuroscience research, including its ease of use, low cost, and portability. Although spatial resolution is much lower than with fMRI, the temporal resolution of NIRS is considerably higher. Because no large device is required, brain activity can be monitored with NIRS even as a participant moves about in the environment, making it a uniquely powerful tool for studying brain activity in awake infants, children, and even underwater divers.

Previous research in human participants suggests that increases in prefrontal cerebral flow during cognitive tasks can be detected by NIRS. Reliable lateralization of this activation signal during a word-generation task was demonstrated in one preliminary study, which also suggested agreement between NIRS and Wada language lateralization in a small patient sample (n = 6). A second small study using a verbal fluency task also suggested good correlation between NIRS, fMRI, and Wada testing in both adult and pediatric patients with epilepsy.

Researchers in the Whelan Lab, headed by Harry Whelan, MD, are using a functional NIRS (fNIRS) imaging system to map cortical functions in healthy volunteers. The fNIRS system uses an array of 102 sensors in a cap, which is fitted on the head in a manner similar to an electroencephalography (EEG) cap. The large number of sensors enables investigation of a very large extent of the cortical surface, which is necessary to accurately localize signals and detect interactions between various brain functional regions. We are currently testing volunteers with motor tasks, vision tasks, and a language task protocol previously validated extensively with fMRI. We are presently engaged in benchmarking the performance of fNIRS against fMRI. We hope that the fNIRS system will allow us to conduct, outside of an MRI magnet, the same sort of cortical function testing that has become well accepted with fMRI (Chen et al., 2020). It is also our belief that with an appropriately water-tight and pressure resistant fNIRS system, we will be able to measure activity in cognitive brain networks at a variety of depths and oxygen conditions. This will allow not only pre-dive and post-dive measurements of cognitive function, but measurement during a dive.

Meet Our Team

Faculty

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Christopher Todd Anderson, MD

Associate Professor

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Patrick Bauer, MD

Assistant Professor

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Scott Beardsley, PhD

Associate Professor, Biomedical Engineering

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Jeffrey R. Binder, MD

Vice Chair for Research, Professor of Neurology, Professor of Cell Biology, Neurobiology and Anatomy, Professor of Biophysics, Director of Stroke and Neurobehavior Programs, Department of Neurology, Director of Language Imaging Laboratory, Department of Neurology

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Chad Carlson, MD

Professor; Vice Chair, Education

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Lisa L. Conant, PhD

Associate Professor

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William Gross, MD, PhD

Assistant Professor

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Sean M. Lew, MD

Mardak Vanderburg Chair in Neurosurgery, Professor & Chief of Pediatric Neurosurgery; Co-Director, Epilepsy Surgery Program, Children’s Wisconsin; Director, Residency Program

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Julie K. Janecek, PhD, ABPP

Assistant Professor

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Manoj Raghavan, MD, PhD

Professor of Neurology

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Sara J. Swanson, PhD, ABPP

Chief, Professor

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Laura Glass Umfleet, PsyD

Associate Professor

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Vahab Youssof Zadeh, PhD

Assistant Professor; Technical Director, MEG Program

Staff

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Linda Allen

Coordinator

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Elizabeth Awe

Clinical Research Coordinator II

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Scott Baierle

Clinical Research Coordinator II

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Wei-Liang Chen

Research Technician

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Joe Heffernan, MS

Staff Scientist

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Yu-Wen Lee

Research Technician

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Marsha Malloy, RN

Research Nurse II

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Jed Mathis, BS

Staff Scientist

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Brendan Quirk

Research Scientist II

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Jeffrey Sugar

Engineer III

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Anthony Zinos

Research Assistant

Funding Support & References

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Funding Support

National Institute of Neurological Disorders and Stroke (NINDS)
U01 NS093650: “The Epilepsy Connectome Project”
J. Binder, M.E. Meyerand, Co-Principal Investigators

National Institute of Neurological Disorders and Stroke (NINDS)
R01 NS035929: “Presurgical Applications of Functional MRI in Epilepsy”
J. Binder, Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)
U01 NS108916: “Dynamics and Causal Functions of Large-Scale Cortical and Subcortical Networks”
J. Wolpaw (National Center for Adaptive Technologies, Albany), Principal Investigator

Office of Naval Research
ONR: N00014-19-1-2560: “Neurobiological and physiological measurements from free swimming marine mammals”
H.T. Whelan, Principal Investigator

Bleser Family Foundation
“Neurology Research Program in Brain Blood Flow”
H.T. Whelan, Principal Investigator

NIH Clinical Translational Science Institute of Southeast Wisconsin
KL2 Mentored Career Development Scholar Award: “Defining the Neural Dynamics of Concept Retrieval Using Electrocorticography”
W. Gross, Principal Investigator; J. Binder and W. Mueller, Mentors

Advancing a Healthier Wisconsin Endowment
Project #5520462: “Cognitive Neuroscience Research Program”
B.-F. Fitzsimmons, Principal Investigator

References

Alper K, Raghavan M, Isenhart R, Howard B, Doyle W, John R, et al. Localizing epileptogenic regions in partial epilepsy using three-dimensional statistical parametric maps of background EEG source spectra. Neuroimage 2008; 39(3): 1257-65.

Binder JR, Sabsevitz DS, Swanson SJ, Hammeke TA, Raghavan M, Mueller WM. Use of preoperative functional MRI to predict verbal memory decline after temporal lobe epilepsy surgery. Epilepsia 2008; 49: 1377-94.

Binder JR, Swanson SJ, Hammeke TA, Morris GL, Mueller WM, Fischer M, et al. Determination of language dominance using functional MRI: A comparison with the Wada test. Neurology 1996; 46: 978-84.

Binder JR, Tong J-Q, Pillay SB, Conant LL, Humphries CJ, Raghavan M, et al. Temporal lobe regions essential for preserved picture naming after left temporal epilepsy surgery. Epilepsia 2020; 61: 1939–48.

Chen W-L, Wagner J, Heugel N, Sugar J, Yu-Wen Lee, 2, , Conant L, et al. Functional near-infrared spectroscopy and its clinical application in the field of neuroscience: Advances and future directions. Frontiers in Neuroscience 2020; 14: 724.

Cook CJ, Hwang G, Mathis J, Nair VA, Allen L, Almane DN, et al. Effective connectivity within the default mode network in left temporal lobe epilepsy: Findings from the Epilepsy Connectome Project. Brain connectivity 2019; 9(2): 174-83.

Elverman KH, Resch ZJ, Quasney EE, Sabsevitz DS, Binder JR, Swanson SJ. Temporal lobe epilepsy is associated with distinct cognitive phenotypes. Epilepsy and Behavior 2019; 96: 61-8.

Hart JJ, Rao SM, Nuwer M. Clinical functional magnetic resonance imaging. Cognitive and Behavioral Neurology 2007; 20: 141-4.

Havlik E, Conant L, Murphy HE, Mau KA, Janecek JK, Raghavan M, et al. Memory outcome after left anterior temporal lobectomy in patients with and without hippocampal sclerosis. June 2020 Meeting of the American Academy of Clinical Neuropsychology. Washington DC; 2020.

Hermann B, Conant LL, Cook CJ, Hwang G, Garcia-Ramos C, Dabbs K, et al. Cognitive phenotypes of temporal lobe epilepsy: Findings from the Epilepsy Connectome Project. NeuroImage: Clinical 2020; in press.

Hermann B, Seidenberg M, Lee EJ, Chan F, Rutecki P. Cognitive phenotypes in temporal lobe epilepsy. J Int Neuropsychol Soc 2007; 13(1): 12-20.

Hwang G, Dabbs K, Conant LL, Nair VA, Mathis J, Nencka A, et al. Cognitive slowing and its underlying neurobiology in temporal lobe epilepsy. Cortex 2019a; 117: 41-52.

Hwang G, Nair VA, Mathis J, Cook CJ, Mohanty R, Zhao G, et al. Using low-frequency oscillations to detect temporal lobe epilepsy with machine learning. Brain connectivity 2019b; 9(2): 184-93.

Ibarra N, Murphy H, Janecek JK, Umfleet L, Binder JR, Raghavan M, et al. Predictors of quality of life after anterior temporal lobectomy. International Neuropsychological Society; 2021.

Janecek JK, Swanson SJ, Sabsevitz DS, Hammeke TA, Raghavan M, Binder JR. Naming outcome prediction in patients with discordant Wada and fMRI language lateralization. Epilepsy Behav 2013a; 27: 399-403.

Janecek JK, Swanson SJ, Sabsevitz DS, Hammeke TA, Raghavan M, Rozman ME, et al. Language lateralization by fMRI and Wada testing in 229 patients with epilepsy: Rates and predictors of discordance. Epilepsia 2013b; 54(2): 314-22.

Janecek JK, Winstanley FS, Sabsevitz DS, Raghavan M, Mueller W, Binder JR, et al. Naming outcome after left or right temporal lobectomy in patients with bilateral language representation by Wada testing. Epilepsy and Behavior 2013c; 28: 95-8.

Jones-Gotman M, Smith ML, Risse GL, Westerveld M, Swanson SJ, Baxendale S, et al. The contribution of neuropsychology to diagnostic assessment in epilepsy. Epilepsy and Behavior 2010; 18: 3-12.

Murphy H, Mau K, Janecek J, Raghavan M, Carlson C, Anderson C, et al. Changes in personality after anterior temporal lobectomy (ATL). 2020 International Neuropsychological Society. Denver, CO; 2020.

Quasney EE, Elverman KH, Sabsevitz D, Binder JR, Umfleet LG, Raghavan M, et al. Wada language lateralization index and Wada memory asymmetry scores as predictors of verbal memory decline after left temporal lobectomy. 46th Annual Meeting of the International Neuropsychological Society. Washington, D.C.; 2018.

Raghavan M, Li Z, Carlson C, Anderson CT, Stout J, Sabsevitz DS, et al. MEG language lateralization in partial epilepsy using dSPM of auditory event-related fields. Epilepsy and Behavior 2017; 73: 247-55.

Rivera-Bonet CN, Hermann B, Cook CJ, Hwang G, Dabbs K, Nair VA, et al. Neuroanatomical correlates of personality traits in temporal lobe epilepsy: Findings from the Epilepsy Connectome Project. Epilepsy and Behavior 2019; 98: 220-7.

Ruff IM, Swanson SJ, Hammeke TA, Sabsevitz DS, Mueller WM, Morris GL. Predictors of naming decline after dominant temporal lobectomy: Age at onset of epilepsy and age of word acquisition. Epilepsy and Behavior 2007; 10: 272-7.

Sabsevitz DS, Swanson SJ, Hammeke TA, Spanaki MV, Possing ET, Morris GL, et al. Use of preoperative functional neuroimaging to predict language deficits from epilepsy surgery. Neurology 2003; 60: 1788-92.

Sabsevitz DS, Swanson SJ, Morris GL, Mueller WM, Seidenberg M. Memory outcome after left anterior temporal lobectomy in patients with expected and reversed Wada memory asymmetry scores. Epilepsia 2001; 42: 1408-15.

Springer JA, Binder JR, Hammeke TA, Swanson SJ, Frost JA, Bellgowan PSF, et al. Language dominance in neurologically normal and epilepsy subjects: a functional MRI study. Brain 1999; 122: 2033-45.

Stewart CC, Swanson SJ, Sabsevitz DS, Rozman ME, Janecek JK, Binder JR. Predictors of language lateralization in temporal lobe epilepsy. Neuropsychologia 2014; 60: 93-102.

Swanson SJ, Conant LL, Humphries CJ, LeDoux M, Raghavan M, Mueller WM, et al. Changes in description naming for common and proper nouns after left anterior temporal lobectomy. Epilepsy and Behavior 2020; 106: in press.

Szaflarski JP, Gloss D, Binder JR, Gaillard WD, Golby AJ, Holland SK, et al. Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 2017; 88(4): 395-402.

Umfleet LG, Janecek JK, Quasney E, Sabsevitz DS, Ryan JJ, Binder JR, et al. Sensitivity and specificity of memory and naming tests for identifying left temporal-lobe epilepsy. Applied Neuropsychology: Adult 2015; 22: 189-96.

Youssofzadeh V, Stout J, Ustine C, Gross WL, Conant LL, Humphries CJ, et al. Mapping language from MEG beta power modulations during auditory and visual naming. Neuroimage 2020; 220: 117090.