Pathological high frequency oscillations in epileptic networks, their influence on spatial coding and on physiological ripple oscillations

In epilepsy, neural networks in the brain generate pathological high frequency oscillations (pHFOs) during inter-ictal periods. These transient, fast oscillations occur in seizure-genic zones, and therefore serve as a biomarker for locating the seizure focus during tissue resection surgery. Complicating matters, there are some brain networks, like the hippocampus in the temporal lobe, that generate normal high frequency oscillations, which are fundamental for cognition. Therefore, in temporal lobe epilepsy, a major challenge is to properly separate and classify normal and pathological high frequency oscillations for proper treatment of patients. To aid classification, a better understanding on how pHFOs are distinct from normal oscillations in overlapping frequency bands and how they may alter ongoing brain activity is needed. To answer these questions, we performed high-density single unit and local field potential recordings from the hippocampi of behaving rats. In animals with epilepsy we observed two types of fast oscillations, which we could classify as putative ‘ripple-like’ or ‘pHFO’ using a clustering analysis based on the frequency and amplitude of their associated slow wave. Validating our classifier, ripple-like events had a similar brain state dependence as ripples recorded in control animals, occurring selectively during periods of slow wave activity. However, pHFOs had abnormal brain state dependence, occurring during both theta and slow wave states. Most neurons that were modulated by high frequency oscillations were only active during one event type suggesting that sub-networks in hippocampus are pathological. Generally, spatial representations of hippocampal neurons were disrupted, having spatial firing fields that were less precise and stable. However, when neurons had spikes that occurred during pHFOs, those spikes had a negative impact on the spatial information of the neuron. Our findings highlight that pHFOs can have negative impacts on an already largely compromised hippocampal code, corroborating the need for proper classification of pHFOs so that treatments can be developed to selectively target them.

Laura EWELL – Institute of Experimental Epileptology and Cognition Research, Bonn, Allemagne

Invité par Julie KOENIG

Inmed, salle de conférence, lundi 10 septembre 2018 à 11h