Absence seizures occur most commonly in children as staring spells lasting 5-10 seconds, associated with a rhythmic """"""""spike-wave"""""""" discharge (SWD) on electroencephalography (EEG). Although considered a form of generalized epilepsy, both human and animal EEG recordings suggest that SWD involve selective cortical and subcortical networks, while sparing other regions. Our central hypothesis is that increased neuronal firing in specific networks leads to regional heterogeneity in SWD. Since this may have important therapeutic significance, our main goal is to determine which specific anatomical networks are selectively involved, and whether neuronal activity during SWD increases or decreases in these brain regions. Previous studies have failed to adequately address this problem. While functional MRI (fMRI) has become a common tool in neuroscience research, here we will combine fMRI with other neuroimaging and local physiology methods to enhance data interpretation. Using an established rodent epilepsy model, we will first relate neuronal activity to neuroimaging signals through simultaneous, co-localized electrophysiology and fiber optic cerebral blood flow (CBF) and pO2 recordings during SWD. We recently calibrated blood oxygen level dependent (BOLD) fMRt; separately measuring fMRI, CBF and cerebral blood volume (CBV) to obtain quantitative maps of the cerebral metabolic rate of oxygen (CMRO2), a more direct measure of neuronal activity. Therefore, we will next obtain high spatial resolution CMRO2 maps during SWD through calibrated BOLD. Finally, we will study dynamic changes through high temporal resolution EEG-triggered fMRI during SWD. Knowledge of the specific regional networks involved in spike-wave seizures, and whether increases or decreases in neuronal activity occur, may lead ultimately to targeted treatment in these regions including gene therapy, selective )harmacological agents, or deep brain stimulation. The approach used in this well-characterized model may also enhance the ability to interpret noninvasive epilepsy neuroimaging studies in humans. ? ?
| Youngblood, Mark W; Chen, William C; Mishra, Asht M et al. (2015) Rhythmic 3-4Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures. Neuroimage 109:368-77 |
| Mishra, Asht Mangal; Bai, Xiaoxiao; Sanganahalli, Basavaraju G et al. (2014) Decreased resting functional connectivity after traumatic brain injury in the rat. PLoS One 9:e95280 |
| Dezsi, Gabi; Ozturk, Ezgi; Stanic, Davor et al. (2013) Ethosuximide reduces epileptogenesis and behavioral comorbidity in the GAERS model of genetic generalized epilepsy. Epilepsia 54:635-43 |
| Bailey, Christopher J; Sanganahalli, Basavaraju G; Herman, Peter et al. (2013) Analysis of time and space invariance of BOLD responses in the rat visual system. Cereb Cortex 23:210-22 |
| Mishra, Asht M; Bai, Xiaoxiao; Motelow, Joshua E et al. (2013) Increased resting functional connectivity in spike-wave epilepsy in WAG/Rij rats. Epilepsia 54:1214-22 |
| van Luijtelaar, Gilles; Mishra, Asht M; Edelbroek, Peter et al. (2013) Anti-epileptogenesis: Electrophysiology, diffusion tensor imaging and behavior in a genetic absence model. Neurobiol Dis 60:126-38 |
| Blumenfeld, Hal (2011) Epilepsy and the consciousness system: transient vegetative state? Neurol Clin 29:801-23 |
| Mishra, Asht Mangal; Ellens, Damien J; Schridde, Ulrich et al. (2011) Where fMRI and electrophysiology agree to disagree: corticothalamic and striatal activity patterns in the WAG/Rij rat. J Neurosci 31:15053-64 |
| Mishra, Asht Mangal; Bai, Harrison; Gribizis, Alexandra et al. (2011) Neuroimaging biomarkers of epileptogenesis. Neurosci Lett 497:194-204 |
| Danielson, Nathan B; Guo, Jennifer N; Blumenfeld, Hal (2011) The default mode network and altered consciousness in epilepsy. Behav Neurol 24:55-65 |
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