Eishi Asano - US grants

[unreadable] DESCRIPTION (provided by applicant): The long-range objectives of this research include establishment of more universal criteria for neocortical epilepsy surgery in children, with the assistance of quantitative analysis of intracranial EEG and neuroimaging data, as well as understanding of the mechanisms of ictal epileptic discharges seen on EEG in pediatric neocortical epilepsy using in vivo quantitative multimodality analyses. The training aspects of this proposal focus on progression to independence as a researcher. The educational plan include supervised research in quantitative analyses of intracranial EEG and neuroimaging as well as formal training and experience in applied biostatistics, data management, and the ethical conduct of research. One-fifth of epilepsy in children is medically intractable. A subset of children with intractable neocortical epilepsy have benefited from respective surgery of the presumed epileptogenic zone. Yet, the chance of long-term seizure-free outcome by respective brain surgery is reported as low as 50% in children with extra temporal lobe epilepsy. Objective delineation of abnormalities on positron emission tomography (PET) imaging has recently yielded better surgical outcomes (-80% seizure-free) in our institute, but even this is not optimum. The applicant hypothesizes that an epileptic brain has a spatial gradient of epileptogenicity and that some of the failed surgery may have been due to the incomplete resection of epileptogenic cortex, which is missed by imaging studies and optimal EEG analysis. The concept of a gradient of epileptogenicity is supported by observations that 1) some patients experience seizure recurrence several years after resection of the presumed epileptogenic zone, including neuroimaging abnormalities and 2) discontinuation of antiepileptic drugs after apparently successful epilepsy surgery induce seizure recurrence in one-third of patients. Since EEG parameters retain continuous values among intracranial electrodes, we will determine whether surgical outcome is correlated with the degree of neurophysiological abnormalities in the cortex not respected by surgery, and establish the cutoff threshold resulting in the best surgical outcome in children with neocortical epilepsy (including epileptic spasms). Epileptic seizures are represented as sustained rhythmic ictal discharges on EEG, of which underlying mechanisms are unknown. Since ictal discharges typically show synchronization and propagation to other brain regions, in vitro analysis of isolated human brain tissues may not be representative of the entire epileptic circuitry. In contrast, in vivo quantitative analyses of ictal electrographic changes in children with neocortical partial seizures, using intracranial EEG and functional neuroimaging data will provide a different perspective regarding the mechanism and clinical significance of ictal discharges on the EEG. Ultimately, such knowledge may lead to better surgical and pharmaco-therapies for seizure disorders. If funded, the applicant will achieve the necessary training in an excellent environment to develop into an independent investigator. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The objectives of this research are: (i) validation of "in-vivo animation of event-related gamma-oscillations on electrocorticography (ECoG)" as a language mapping method for children who undergo brain surgeries, and (ii) better understanding of the human language system. About 1% of the general population has epilepsy;one-fifth of epilepsy in children is medically intractable;subsets of children with intractable focal epilepsy benefit from surgical resection of the epileptogenic zone. Brain tumor is often associated with focal epilepsy in children, and surgical resection of tumor together with the epileptogenic focus is indicated in such children. The goals of both epilepsy and brain tumor surgeries include identification and preservation of the eloquent cortices such as the language cortex. However, conventional brain mapping using electrical stimulation lacks sufficient sensitivity to identify the language areas in children under age 10 years, often takes several hours to complete, and has a risk of stimulation-induced seizures. Thus, alternative language mapping techniques would be highly desirable in these children. We have recently developed a novel language mapping method which we refer to as "in-vivo animation of event-related gamma-oscillations". This new and innovative method appears promising for language mapping in children. As the next step, we will validate this mapping method using electrical stimulation and postoperative neuropsychological testing in this project. Specifically, we will determine whether brief auditory-language tasks will successively delineate gamma augmentation in the cortical sites responsible for receptive language function, expressive language function and overt speech. We will also determine whether a visual-language task will successively delineate gamma augmentation in the cortical sites responsible for receptive language function and expressive language function. Innovation in our project includes: (i) the study focusing on young subjects across a wide range of age (5 - 20 years), in about 40% of whom identification of the language cortex is difficult using electrical stimulation, (ii) in-vivo animation of cortical activation on an individual three-dimensional MRI with a good temporal resolution [10 msec] and a good spatial resolution [1 cm], and (iii) assessment of ECoG signals least affected by artifacts derived from overt speech tasks. This project is clinically significant since the results will be directly translatable into patient management and our event-related ECoG analysis has the potential to become a mainstream language mapping method which is less-invasive, more time-efficient, and more patient-friendly compared to the currently used electrical stimulation method. PUBLIC HEALTH RELEVANCE: The goals of this research are (i) validation of the new mapping technique: "in-vivo animation of language- induced gamma oscillations on electrocorticography" as a new diagnostic tool for children who undergo brain surgeries and (ii) better understanding of the human language system. We will apply brief language tasks to children who undergo brain surgeries and identify the language-related brain areas, which are otherwise difficult to localize using the conventional electrical stimulation method. The results will introduce a novel, more time-efficient and patient-friendly language mapping method and are expected to improve the language outcome after brain surgeries in children.