R01NS116504

Optimized Intracranial EEG Targeting in Focal Epilepsy Based upon Neuroimaging Connectomics

Despite recent advances in neuroimaging, approximately 2/3 of intractable epilepsy patients that undergo surgical evaluation continue to require intracranial EEG (IEEG), arguably the most invasive diagnostic test in medicine. We currently lack methods to quantitatively map noninvasive imaging measures of structure and function to IEEG. Specifically, there is a critical need to validate whole-brain noninvasive neuroimaging network-based biomarkers to guide precise placement of electrodes and translate noninvasive network neuroimaging to change the paradigms of clinical care.

The long-term goal of this proposal is to predict IEEG functional dynamics and surgical outcomes using noninvasive MRI-based measures of structure and function. Our overall objective, which is the next step toward attaining our long-term goal, is to develop open-source noninvasive imaging tools that map epileptic networks by integrating MRI and IEEG data. Our central hypothesis is that noninvasive measures of structure and function relate to and can predict the intricate functional dynamics captured on IEEG.

The central hypothesis will be tested in patients undergoing IEEG targeting the temporal lobe network by pursuing three specific aims:

1) To map the patient-specific structural connectome to IEEG seizure onset and propagation.
2) To correlate seizure onset and propagation on IEEG with network measures derived from resting-state functional MRI (rsfMRI).
3) To integrate the structural (Aim 1) and functional (Aim 2) connectome with standard qualitative clinical data to predict IEEG network dynamics and surgical outcomes.

Under the first aim, patients will undergo diffusion tensor imaging (DTI) prior to stereotactic IEEG, an IEEG method that inherently samples long-range networks. The functional IEEG network will be mapped to DTI, thus defining how seizures are constrained by the underlying structural connectome as they propagate.

Under the second aim, patients with temporal lobe epilepsy will undergo rsfMRI on 7T MRI prior to stereotactic IEEG. Functional network measures from rsfMRI and IEEG will be coregistered, and rsfMRI will be used to predict functional EEG ictal and interictal networks.

In the third aim, two models predicting IEEG network dynamics and epilepsy surgical outcomes will be created, building off of methods developed in aims 1 and 2.

The proposed research is innovative because it represents a substantive departure from the status quo by directly connecting noninvasive multimodal imaging with measures of functional network dynamics in IEEG. The proposed research is significant because it is expected that successful completion of these aims will yield personalized strategies for IEEG targeting based on noninvasive neuroimaging.

Trustees Of The University Of Pennsylvania

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Philadelphia, Pennsylvania 191044229 United States

Single Zip Code

Bioengineering Research Grants (BRG) (R01 Clinical Trial Required) (PAR-19-159)

Amendment Since initial award the total obligations have increased 396% from $660,904 to $3,275,399.