Faculty Bibliography

Benign Rolandic epilepsy (benign epilepsy with centrotemporal spikes; recently renamed self-limited epilepsy with centrotemporal spikes) is associated with widespread deficits in cognition and behavior, suggesting abnormalities in networks that extend beyond the centrotemporal region. To assess functional connectivity in children with benign Rolandic epilepsy, we assessed EEG spectral power and coherence during awake and sleep records in 27 children with centrotemporal spikes. Coherence represents the consistency of the phase difference between two EEG signals when compared over time and serves as a measure of synchronization between two EEG signals based mainly on phase consistency. Epochs of EEG with and without centrotemporal spikes were compared during both waking and sleep. During the spike epochs, there was an increase in spectral power at all frequencies, although statistical significance was seen primarily in the delta, theta and alpha bandwidths. This increase in absolute power was seen at all electrode sites and was similar in left and right-sided electrodes. During centrotemporal spikes, there were significant changes in coherence compared to the EEG segments without spikes. In the theta, alpha and beta bandwidths, there were significant increases in coherence. The increases in coherences were widespread and bilateral, and involved electrode pairs outside the central and temporal regions. To determine if there was a relationship between location of the spikes and coherence values, right-sided, left-sided and bilateral centrotemporal spikes were compared. There was no relationship between location of the centrotemporal spikes and power or coherence values. These findings indicate that benign Rolandic epilepsy results in generalized changes in spectral power and connectivity and raises the suggestion that from a functional standpoint, benign Rolandic epilepsy resembles a generalized rather than focal seizure disorder.

Survivors of sepsis often experience long-term cognitive and functional decline. Previous studies utilizing lipopolysaccharide injection and cecal ligation and puncture in rodent models of sepsis have demonstrated changes in depressive-like behavior and learning and memory after sepsis, as well as evidence of myeloid inflammation and cytokine expression in the brain, but the long-term course of neuroinflammation after sepsis remains unclear. Here, we utilize cecal ligation and puncture with greater than 80% survival as a model of sepsis. We found that sepsis survivor mice demonstrate deficits in extinction of conditioned fear, but no acquisition of fear conditioning, nearly two months after sepsis. These cognitive changes occur in the absence of neuronal loss or changes in synaptic density in the hippocampus. Sepsis also resulted in infiltration of monocytes and neutrophils into the CNS at least two weeks after sepsis in a CCR2 independent manner. Cellular inflammation is accompanied by long-term expression of pro-inflammatory cytokine and chemokine genes, including TNFα and CCR2 ligands, in whole brain homogenates. Gene expression analysis of microglia revealed that while microglia do express anti-microbial genes and damage-associated molecular pattern molecules of the S100A family of genes at least 2 weeks after sepsis, they do not express the cytokines observed in whole brain homogenates. Our results indicate that in a naturalistic model of infection, sepsis results in long-term neuroinflammation, and that this sustained inflammation is likely due to interactions among multiple cell types, including resident microglia and peripherally derived myeloid cells.