Ripple While You Walk, and You May Get Lost: Pathological High-Frequency Activity Can Alter Spatial Navigation Circuits

Abstract

The Impact of Pathological High-frequency Oscillations on Hippocampal Network Activity in Rats With Chronic Epilepsy. Ewell LA, Fischer KB, Leibold C, Leutgeb S, Leutgeb JK. eLIFE. 2019;8:pii: e42148. doi: 10.7554/eLife.42148. PMID: 30794155 In epilepsy, brain networks generate pathological high-frequency oscillations (pHFOs) during interictal periods. To understand how pHFOs differ from normal oscillations in overlapping frequency bands and potentially perturb hippocampal processing, we performed high-density single unit and local field potential recordings from hippocampi of behaving rats with and without chronic epilepsy. In epileptic animals, we observed 2 types of co-occurring fast oscillations that by comparison to control animals could be classified as “ripple-like” or “pHFO.” We compared their spectral characteristics, brain state dependence, and cellular participants. Strikingly, pHFO occurred irrespective of brain state, were associated with interictal spikes, engaged distinct subnetworks of principal neurons compared to ripple-like events, increased the sparsity of network activity, and initiated both general and immediate disruptions in spatial information coding. Taken together, our findings suggest that events that result in pHFOs have an immediate impact on memory processes, corroborating the need for proper classification of pHFOs to facilitate therapeutic interventions that selectively target pathological activity.

Epilepsy disrupts hippocampal phase precision and impairs working memory

“…Previous work suggests that transient epileptic activity may induce WM‐related TCI by disrupting hippocampal activity 44 . HFOs occurring in the rodent hippocampi have also been shown to disrupt hippocampal network function and impair WM‐related spatial coding via the induction of spurious, uninformative action potentials and transient reduction of hippocampal theta power 45,46 . Notably, in the current work, we demonstrated that transient epileptic activity distal to the human hippocampi can interfere with hippocampal activity.…”

“…44 HFOs occurring in the rodent hippocampi have also been shown to disrupt hippocampal network function and impair WM-related spatial coding via the induction of spurious, uninformative action potentials and transient reduction of hippocampal theta power. 45,46 Notably, in the current work, we demonstrated that transient epileptic activity distal to the human hippocampi can interfere with hippocampal activity. We showed that the occurrence of HFO or IED in the epileptogenic zone was associated with disrupted hippocampal phase resetting, which would normally serve as a neural syntax for information processing and potentiation.…”

The Oscillatory Basis of Working Memory Function and Dysfunction in Epilepsy

“…The neurophysiological underpinnings of HFO-induced WM impairment remain elusive. However, it is conceivable that their pathophysiological mechanisms resemble those of IEDs, encompassing disruptions of oscillatory network activity ( Brennan and Ahmed, 2019 ).…”