Abby…Normal? a New Gold Standard for Identifying Normal High Frequency Oscillations

Commentary High frequency oscillations (HFOs) have garnered considerable attention in epilepsy research over the past 15 years. Originally discovered within normal brain tissue (1), HFOs are brief (<100 ms), low amplitude discharges composed of frequencies above the gamma range (>60 Hz). The role of HFOs in normal cognitive processing is still an active area of research, as they represent higher order cortical processing and are seen throughout the brain. Later work has demonstrated that HFOs are increased in epileptic tissue (2), and over the ensuing years considerable evidence has shown that HFOs are a potential biomarker of epilepsy (3). Thus, HFOs paradoxically appear to be markers of both normal and epileptic brain processes, which has been one of the primary barriers to using them in epilepsy care. Most prior research has been unable to distinguish normal from epileptic HFOs, which confounds the analysis considerably: there is no known reliable method to ascertain which HFOs are uniquely associated with epilepsy. In this work, Kucewicz et al. took the opposite approach and instead developed a method to identify HFOs that are associated with cortical visual processing—in other words, they found a way to isolate the normal HFOs. While their results provide important insights into the role of HFOs in normal cognition, the method itself is a major breakthrough, as it is capable of accurately identifying normal HFOs within a patient that has both normal and epileptic EEG waveforms. After decades of recordings limited to gamma and theta rhythms, HFOs are a relatively new entity, and there is hope that they may provide novel insights into brain physiology. Part of their intriguing novelty is that they exist on a smaller spatiotemporal scale than traditional EEG recordings, demonstrating the brief activity of cortical columns and possibly of individual cells. For instance, in the hippocampus during memory consolidation, individual neuron firing during HFOs can follow a highly organized order related to the original memory High Frequency Oscillations Are Associated With Cognitive Processing in Human Recognition Memory.