The goal of this proposal is to localize human epileptic networks by characterizing their electrophysiological activity over a wide range of spatiotemporal scales. Decades of clinical intracranial EEG (IEEG) using restricted spatial (centimeter scale) and temporal (~0.5-100 Hz) bandwidth, based more on tradition than modern neuroscience, have frustrated epileptologists looking for discrete, resectable """"""""electrographic lesions"""""""" during evaluation for epilepsy surgery. Similarly, recent efforts to apply direct brain stimulation to abort seizures after they are sufficiently established to be detected on standard clinical macroelectrodes have, so far, met with only partial success. We hypothesize that enhancing the spatial and temporal resolution of clinical intracranial EEG can improve the efficacy of epilepsy surgery and responsive brain stimulation to control seizures. Human epileptic networks produce pathological activity that ranges from seizures and spikes, generated by cubic centimeters of brain tissue, to high frequency oscillations that occur on sub-millimeter dimensions. Recent evidence suggests that important components of these signals are found at frequencies not detected by standard clinical IEEG. Using simultaneous IEEG recordings from microwire arrays and clinical macroelectrodes, our group has begun to characterize two potential signatures of epileptogenic brain, high frequency oscillations and """"""""micro-seizures,"""""""" that are outside the resolution of conventional clinical IEEG. In this application, we propose analysis of continuous, high-resolution, wide- bandwidth IEEG recorded simultaneously from microwire arrays and clinical macroelectrodes in order to localize human epileptic networks. We will correlate our findings with surgical outcome, prospectively, in a cohort of patients undergoing evaluation for epilepsy surgery. This work builds upon our established effort in Translational Neuroengineering melding state of the art epilepsy care with cutting-edge research.

Public Health Relevance

The neuronal networks of human epileptic brain are multiscale;extending from cellular assemblies organized on the scale of cortical columns (~300 - 600

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS063039-03
Application #
8053265
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Fureman, Brandy E
Project Start
2009-04-15
Project End
2014-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
3
Fiscal Year
2011
Total Cost
$300,310
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Cimbalnik, Jan; Kucewicz, Michal T; Worrell, Greg (2016) Interictal high-frequency oscillations in focal human epilepsy. Curr Opin Neurol 29:175-81
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Khambhati, Ankit N; Davis, Kathryn A; Lucas, Timothy H et al. (2016) Virtual Cortical Resection Reveals Push-Pull Network Control Preceding Seizure Evolution. Neuron 91:1170-1182

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