ECoG spiking activity and signal dimension are early predictive measures of epileptogenesis in a translational mouse model of traumatic brain injury.

The latency between traumatic brain injury (TBI) and the onset of epilepsy (PTE) represents an opportunity for counteracting epileptogenesis. Antiepileptogenesis trials are hampered by the lack of sensitive biomarkers that allow to enrich patient's population at-risk for PTE. We aimed to assess whether specific ECoG signals predict PTE in a clinically relevant mouse model with ∼60% epilepsy incidence. TBI was provoked in adult CD1 male mice by controlled cortical impact on the left parieto-temporal cortex, then mice were implanted with two perilesional cortical screw electrodes and two similar electrodes in the hemisphere contralateral to the lesion site. Acute seizures and spikes/sharp waves were ECoG-recorded during 1 week post-TBI. These early ECoG events were analyzed according to PTE incidence as assessed by measuring spontaneous recurrent seizures (SRS) at 5 months post-TBI. We found that incidence, number and duration of acute seizures during 3 days post-TBI were similar in PTE mice and mice not developing epilepsy (No SRS mice). Control mice with cortical electrodes (naïve, n = 5) or with electrodes and craniotomy (sham, n = 5) exhibited acute seizures but did not develop epilepsy. The daily number of spikes/sharp waves at the perilesional electrodes was increased similarly in PTE (n = 15) and No SRS (n = 8) mice vs controls (p < 0.05, n = 10) from day 2 post-injury. Differently, the daily number of spikes/sharp waves at both contralateral electrodes showed a progressive increase in PTE mice vs No SRS and control mice. In particular, spikes number was higher in PTE vs No SRS mice (p < 0.05) at 6 and 7 days post-TBI, and this measure predicted epilepsy development with high accuracy (AUC = 0.77, p = 0.03; CI 0.5830-0.9670). The cut-off value was validated in an independent cohort of TBI mice (n = 12). The daily spike number at the contralateral electrodes showed a circadian distribution in PTE mice which was not observed in No SRS mice. Analysis of non-linear dynamics at each electrode site showed changes in dimensionality during 4 days post-TBI. This measure yielded the best discrimination between PTE and No SRS mice (p < 0.01) at the cortical electrodes contralateral to injury. Data show that epileptiform activity contralateral to the lesion site has the the highest predictive value for PTE in this model reinforcing the hypothesis that the hemisphere contralateral to the lesion core may drive epileptogenic networks after TBI.

Unlocking Hidden Awareness: Repurposing fMRI to Detect Levels of Consciousness.

Determining the state of consciousness in patients with disorders of consciousness is a challenging task because for someone to be deemed conscious, both wakefulness and awareness are required. Awareness has traditionally been assessed by examining physical responsiveness but in 2010, Monti et al. explored how using fMRI to measure brain activity in humans could help reclassify the state of consciousness in these patients. The findings, published in The New England Journal of Medicine, show that some brain regions are active when patients respond to an imagery or communication task. This is a seminal study because it demonstrates that patients who behaviourally appear to be in a vegetative or minimally conscious state may still have residual brain functions that would not be apparent from a clinical examination alone. Notably, it exemplified how fMRI can be repurposed as a communication tool for this subset of aware, but 'locked in', patients who appear unresponsive. From an educator's perspective, this paper is valuable because it is relevant to a broad audience, both introductory and advanced level undergraduate students. It introduces key concepts in cognitive and clinical neuroscience and encourages students to consider the connections between social issues and technology development in neuroscience. Finally, educators may use this paper to discuss and debate the nature of consciousness and the ethical implications that the use of fMRI for determining consciousness may have on medical ethics.