Epilepsy is a disease affecting 1-2% of the population. Currently, the only known cure for epilepsy is surgery, which is much more effective at eliminating seizures arising from the medial temporal lobe compared with the neocortex. The problem with neocortical epilepsy is that the population of neurons underlying each epileptiform discharge varies over time. In addition, the spatial relationship between interictal events and the ictal onset zones, which are critical in defining the region of epileptogenesis, is not well understood and essential to the surgical treatment of epilepsy. Electrophysiological recording methods, although currently the """"""""gold standard"""""""" in mapping epilepsy, are inadequate to address these questions based on restrictions due to volume conduction or sampling limitations. Optical recording techniques can overcome many of these limitations by sampling large areas of cortex simultaneously to provide information about blood flow, metabolism and extracellular fluid shifts that are intimately related to excitatory and inhibitory neuronal activity. In fact, optical recordings may actually be more sensitive to certain aspects of epileptic activity than electrophysiologic recordings. The first goal of this study is to examine the shifting spatio-temporal dynamics of the epileptogenic aggregate in both acute and chronic experimental models of in vivo rodent neocortical epilepsy using optical recording of intrinsic signals. Simultaneous electrophysiological and optical measurements will be obtained at varying wavelengths to explore several fundamental questions in neocortical epileptogenesis. The second goal will be to translate these findings into the operating room and map human neocortical epilepsy with the same optical techniques. Outcome following surgical resections to treat neocortical epilepsy will be correlated with the optical maps to determine the utility of intrinsic signal imaging in guiding brain surgery. These experiments will set the groundwork for implementing optical recordings in general clinical practice as a novel technique for mapping and predicting human seizures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS049482-04
Application #
7261285
Study Section
Clinical Neuroscience and Disease Study Section (CND)
Program Officer
Fureman, Brandy E
Project Start
2004-09-01
Project End
2010-06-30
Budget Start
2007-07-01
Budget End
2010-06-30
Support Year
4
Fiscal Year
2007
Total Cost
$368,369
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Neurology
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Zhao, Mingrui; Alleva, Rose; Ma, Hongtao et al. (2015) Optogenetic tools for modulating and probing the epileptic network. Epilepsy Res 116:15-26
Ma, Hongtao; Harris, Samuel; Rahmani, Redi et al. (2014) Wide-field in vivo neocortical calcium dye imaging using a convection-enhanced loading technique combined with simultaneous multiwavelength imaging of voltage-sensitive dyes and hemodynamic signals. Neurophotonics 1:015003
Patel, Kunal S; Zhao, Mingrui; Ma, Hongtao et al. (2013) Imaging preictal hemodynamic changes in neocortical epilepsy. Neurosurg Focus 34:E10
Ma, Hongtao; Zhao, Mingrui; Schwartz, Theodore H (2013) Dynamic neurovascular coupling and uncoupling during ictal onset, propagation, and termination revealed by simultaneous in vivo optical imaging of neural activity and local blood volume. Cereb Cortex 23:885-99
Geneslaw, Andrew S; Zhao, Mingrui; Ma, Hongtao et al. (2011) Tissue hypoxia correlates with intensity of interictal spikes. J Cereb Blood Flow Metab 31:1394-402
De la Cruz, Estanislao; Zhao, Mingrui; Guo, Lihua et al. (2011) Interneuron progenitors attenuate the power of acute focal ictal discharges. Neurotherapeutics 8:763-73
Zhao, Mingrui; Nguyen, John; Ma, Hongtao et al. (2011) Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus. J Neurosci 31:13292-300
Cox, Marshall P; Ma, Hongtao; Bahlke, Matthias E et al. (2010) LED-Based Optical Device for Chronic In Vivo Cerebral Blood Volume Measurement. IEEE Trans Electron Devices 57:174-177
Zhao, Mingrui; Ma, Hongtao; Suh, Minah et al. (2009) Spatiotemporal dynamics of perfusion and oximetry during ictal discharges in the rat neocortex. J Neurosci 29:2814-23
Ma, Hongtao; Zhao, Mingrui; Suh, Minah et al. (2009) Hemodynamic surrogates for excitatory membrane potential change during interictal epileptiform events in rat neocortex. J Neurophysiol 101:2550-62

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