Hippocampal Interictal Spikes Disrupt Cognition in Rats

Objective: Cognitive impairment is common in epilepsy, particularly in memory function. Interictal spikes (IlSs) are thought to disrupt cognition, but it is difficult to delineate their contribution from general impairments in memory produced by etiology and seizures. We investigated the transient impact of focal IlSs on the hippocampus, a structure crucial for learning and memory and yet highly prone to IlSs in temporal lobe epilepsy (TLE). Methods: Bilateral hippocampal depth electrodes were implanted into 14 Sprague-Dawley rats, followed by intrahippocampal pilocarpine or saline infusion unilaterally. Rats that developed chronic spikes were trained in a hippocampal-dependent operant behavior task, delayed-match-to-sample. Depth-electroencephalogram (EEG) was recorded during 5,562 trials among five rats, and within-subject analyses evaluated the impact of hippocampal spikes on short-term memory operations. Results: Hippocampal spikes that occurred during memory retrieval strongly impaired performance (p < 0.001). However, spikes that occurred during memory encoding or memory maintenance did not affect performance in those trials. Hippocampal spikes also affected response latency, adding approximately 0.48 seconds to the time taken to respond (p < 0.001). Interpretation: We found that focal IIS-related interference in cognition extends to structures in the limbic system, which required intrahippocampal recordings. Hippocampal spikes seem most harmful if they occur when hippocampal function is critical, extending human studies showing that cortical spikes are most disruptive during active cortical functioning. The cumulative effects of spikes could therefore impact general cognitive functioning. These results strengthen the argument that suppression of IlSs may improve memory and cognitive performance in patients with epilepsy. ANN NEUROL 2010;67:250-257