2008 — 2012 |
Kim, Jennifer [⬀] |
F30Activity Code Description: Individual fellowships for predoctoral training which leads to the combined M.D./Ph.D. degrees. |
Role of Inhibitory Interneurons in Generating Febrile Seizures
[unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] Seizures are sudden attacks or convulsions due to abnormal, hypersynchronous discharges from a population of neurons in the brain. Approximately 5-10% of people will experience one seizure in their lifetime. Febrile seizures are the most common cause of seizures in late infancy and early childhood. Though this type of seizure is prevalent throughout the world, very little is known about its mechanisms. A recent study suggested that fever induces hyperventilation and respiratory alkalosis, and that an increase in brain pH may be the proximate cause of febrile seizures. In my proposed project, I plan to test the hypothesis that temperature- and pH-induced changes of inhibitory circuits contribute to the generation of febrile seizures. First, I will examine how spontaneous and evoked extracellular field potentials in the CA1 field of the hippocampus change under conditions of high temperature and high pH. These results will allow me to determine whether high temperature, high pH or the combination of both increase hyperexcitability. Second, I will use whole-cell patch recording methods to evaluate whether temperature or pH changes alter the intrinsic membrane excitability and synaptic connections of two specific types of inhibitory interneurons or pyramidal neurons. I will use whole-cell recordings from pairs of identified interneurons or from interneuronpyramidal cell pairs. I will use small hyperpolarizing and depolarizing current steps to measure both subthreshold and active properties of each cell. I will measure changes in spontaneous synaptic activity and specific excitatory and inhibitory synaptic connections. I will correlate changes in synaptic and intrinsic properties of inhibitory interneurons with the onset of epileptiform activity in local networks. Third, I will investigate the potential role of temperature- and pH-sensitive transient receptor potential vallinoid receptor 1 (TRPV1 receptor) activation in increasing neuronal excitability during high temperature and/or pH conditions by comparing TRPV1 knockout to wild-type mice. Both in vivo and in vitro methods will be used to fully evaluate the potential effects of TRPV1 receptors. [unreadable] My results should contribute significantly to our understanding of the basic mechanisms of febrile [unreadable] seizures. With better insight into the causes of febrile seizures, we may be able to optimize prophylaxis and treatment. This work would contribute directly to the mission of NINDS to reduce the burden of neurological disease. [unreadable] [unreadable] [unreadable]
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0.915 |
2020 — 2021 |
Kim, Jennifer A [⬀] |
K23Activity Code Description: To provide support for the career development of investigators who have made a commitment of focus their research endeavors on patient-oriented research. This mechanism provides support for a 3 year minimum up to 5 year period of supervised study and research for clinically trained professionals who have the potential to develop into productive, clinical investigators. |
Eeg and Mri Biomarkers to Predict Post-Traumatic Epilepsy
Project Summary Dr. Jennifer A. Kim is a critical care neurologist and neuroscientist at Yale-New Haven Hospital. Her long-term career goal is to become an independently funded translational investigator with expertise in signal processing of neurophysiologic and neuroimaging data to identify early biomarkers of secondary brain injury in critically ill patients, particularly related to post-traumatic epilepsy. Post-traumatic epilepsy is a disabling complication of traumatic brain injury (TBI). There is an urgent need to find biomarkers of post-traumatic epilepsy to identify patients at high risk for developing this complication. It is a population in which early biomarker identification could improve patient monitoring and ultimately treatment development to circumvent epileptogenesis. Post- traumatic epilepsy contributes to worsening of the already high rates of TBI morbidity, disability and cost of care, thus emphasizing the importance of preventing this complication. We need to find biomarkers to best define those most likely to benefit from potential treatments and make such treatment discovery trials more feasible. During the proposed training period, the candidate will expand upon her knowledge of EEG signal processing and machine learning techniques and acquire new skills in neuroimaging analysis using Magnetic Resonance technologies and biostatistics. To accomplish this, Dr. Kim has brought together a strong mentorship team of Dr. Hal Blumenfeld (primary mentor) and co-mentors Drs. Todd Constable, Brandon Westover and Brian Edlow who have expertise in multi-modal approaches to studying epilepsy, functional MRI analysis, computational EEG analysis and structural TBI imaging, respectively. Under their mentorship, Dr. Kim proposes to: 1) quantify epileptiform abnormality (EA) frequency and identify EA waveform features that optimally predict PTE, 2) determine if direct hippocampal injury, assessed by cortical thickness and contusion volume, stratifies PTE risk 3) assess whether indirect hippocampal injury, based on structural and functional MRI connectivity analyses, portend PTE. The overall goal is to identify early biomarkers of patients at high risk for post-traumatic epilepsy to target development of anti-epileptogenesis treatments. Bringing together advanced neurophysiologic and neuroimaging analysis and this strong mentorship support, this project opens new avenues for optimizing follow-up care and advancing potential treatment development for all traumatic brain injury patients at risk for post-traumatic epilepsy. This well-defined patient-oriented research proposal, in concert with the mentorship and structured didactic curriculum, will provide Dr. Kim with the skills that are essential to develop an independent career in neurophysiological and neuroimaging research that translates to improving patient outcomes.
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0.97 |