Abstracts

Rationale: Posttraumatic epilepsy is currently a major public health problem. A noninvasive method to predict epilepsy following head injury is needed for earlier therapeutic intervention in at-risk patients. We studied resting functional connectivity fMRI in the rat lateral fluid percussion injury (LFPI) model as a potential biomarker of epileptogenesis. Resting functional connectivity refers to correlations in low frequency fMRI signals between spatially remote brain regions at rest. Our goal is to find a noninvasive method for assessment of posttraumatic epileptogenesis that can ultimately be applied to therapeutic trials of human posttraumatic epilepsy. Methods: EEG-fMRI at 9.4T were performed on sprague-Dawley rats (n=7) 4 months after injury and sham controls (n=6) to measure resting functional connectivity in the interictal period. For fMRI analysis, four pairs of regions of interests (ROIs) were made: bilateral frontal and parietal cortex, hippocampus, and thalamus. We applied high-pass (0.01Hz) and low-pass (0.08Hz) filters to fMRI data, and correlations were calculated over time between each ROI. Group statistics comparing LFPI and sham controls were performed by ANOVA. A week after fMRI, rats were implanted with tripolar EEG electrodes in the frontal and parietal cortex. After recovery from electrode implantation, all rats were injected with a subseizure threshold dose (25 mg/kg body weight) of pentylenetetrazol (PTZ) to measure EEG. Latency to first interictal epileptiform discharge (IED) and frequency of IED were calculated for 60 minutes of post-PTZ EEG data.Results: At the group level, we found significantly decreased connectivity between bilateral parietal cortex and between parietal cortex and hippocampus on the side of injury in LFPI rats compared to controls. We also found abnormal negative connectivity in LFPI rats between parietal cortex in both hemispheres and other regions. On EEG, we found significantly decreased latency and significantly increased number of IED in LFPI rats compared to controls. Conclusions: Our results are important for better understanding of epileptogenesis in posttraumatic epilepsy noninvasively. With further investigation, abnormal connectivity on fMRI may serve as a noninvasive imaging biomarker in human posttraumatic epilepsy. Grant/Other Support: 5R01NS055829-04 and R01 NS-049307 (to HB), Veterans Affairs (SGW), and American Epilepsy Foundation (AM). Religious Conflict: Saturday