Authors :
Presenting Author: Li Ding, MS – Vanderbilt University School of Medicine
Sneha Shankar, BS – University of Pennsylvania; Nicolette Driscoll, PhD – Massachusetts Institute of Technology; Chengwen Zhou, PhD – Vanderbilt University School of Medicine; Flavia Vitale, PhD – University of Pennsylvania; Tonia Rex, PhD – Vanderbilt University School of Medicine; Martin Gallagher, MD, PhD – Vanderbilt University School of Medicine / Dept. Veterans Affairs
Rationale: Mild traumatic brain injuries (mTBIs), those that produce loss of consciousness for less than thirty minutes, are the most common type of traumatic brain injury in civilians and military personnel. Little is known how mTBIs affect seizure networks in individuals with pre-existing generalized seizures or those with interictal spike-wave discharges (SWDs) but not clinical seizures (spike-wave trait). Recent studies demonstrated that altered awareness during SWDs is associated with SWD spike amplitude and thus it is necessary to determine how mTBI affects SWD morphology and connectivity and whether these changes alter behavior.
Methods: We used mice that heterozygously express a human epilepsy gene mutation (Gabra1(A322D)) and exhibit spontaneous SWDs and absence seizures. We first used two electrode continuous EEG monitoring to determine the effects of mTBI on SWD morphology. Mice (N = 9) underwent 24 hours of EEG monitoring (baseline) prior to receiving a 40-psi overpressure mTBI. Repeat 24-hour EEG monitoring was performed the same day as the mTBI as well as one week after the mTBI. SWDs were identified automatically using a support vector machine classifier. SWD peak amplitude and 7-9 Hz spectral power were calculated.
To determine the effects of mTBI on intracortical activity, mice were implanted with flexible 16 channel MXene based skull surface electrodes and underwent 16 channel high density EEG (HdEEG) recording for three hours before mTBI (N=8) or sham exposure (N=7). HdEEG monitoring was repeated four hours, one day, and one week post mTBI/sham. We identified SWDs and performed time frequency transforms to determine ictal weighted phase lag indices which were then used to calculate the ictal network node degree at each electrode.
Results: By one week after the injury, mTBI increased the median spike amplitude by 0.3±0.1 Z units (P=0.001) and the 7-9 Hz spectral power by 0.2±0.1 Z units (P=0.035). Network connectivity analysis demonstrated that mTBI increased the pre-ictal beta power network node degree (P = 0.002) with the most prominent increases localized in the frontal regions.
Conclusions: We conclude that mTBI increases SWD spike amplitude, a parameter previously associated with worsened SWD-associated impaired awareness and increased pre-ictal beta power network connectivity. Future studies will determine if these changes in SWDs following mTBI are associated with behavioral dysfunction
Funding: VA BLR&D (BX005316) to MJG, NIH R01NS121219-01 to FV, NIH U24 EY029893 to TSR