Cognitive impairment in temporal lobe epilepsy: Role of online and offline processing of single cell information

Abstract

Cognitive impairment is a common comorbidity in temporal lobe epilepsy (TLE) and is often considered more detrimental to quality of life than seizures. While it has been previously shown that the encoding of memory during behavior is impaired in the pilocarpine model of TLE in rats, how this information is consolidated during the subsequent sleep period remains unknown. In this study, we first report marked deficits in spatial memory performance and severe cell loss in the CA1 layer of the hippocampus lower spatial coherence of firing in TLE rats. We then present the first evidence that the reactivation of behavior-driven patterns of activity of CA1 place cells in the hippocampus is intact in TLE rats. Using a template-matching method, we discovered that real-time (3–5 s) reactivation structure was intact in TLE rats. Furthermore, we estimated the entropy rate of short time scale (~250 ms) bursting activity using block entropies and found that significant, extended temporal correlations exist in both TLE and Control rats. Fitting a first order Markov Chain model to these bursting time series, we found that long sequences derived from behavior were significantly enriched in the Markov model over corresponding models fit on randomized data confirming the presence of replay in shorter time scales. We propose that the persistent consolidation of poor spatial information in both real-time and during bursting activity may contribute to memory impairments in TLE rats.

Third International Congress on Epilepsy, Brain, and Mind: Part 2

“…This is in line with an earlier pilot study of forgetting in epilepsy [111] and further supported by animal studies, as rat models of TLE show normal replay of behavior-driven sequences of single cell hippocampal activity during sleep [112]. In contrast, these three studies suggest that activity during periods of wakefulness following learning, possibly within the first few hours [113], may be more closely linked to ALF, as would be predicted by interference-based models of amnesia (e.g., [114,115]).…”

Long-Term Effects of Anterior Thalamic Nucleus Deep Brain Stimulation on Spatial Learning in the Pilocarpine Model of Temporal Lobe Epilepsy

“…Previous studies have shown that TLE rats have poor spatial memory performance accompanied by decreased place field stability and increased out‐of‐field firing of hippocampal place cells . This suggests that while spatial coding by place cells in the hippocampus is disrupted, temporal coding remains intact . Thus, it has been proposed that while the integration of place cells into spatial processing networks in TLE rats is intact, the original representation is unreliable .…”

NMDAR-independent hippocampal long-term depression impairment after status epilepticus in a lithium-pilocarpine model of temporal lobe epilepsy

“…Although lesions are found in many brain areas, this type of epilepsy is usually associated with significant hippocampal damage (Bartolomei et al, ; Blümcke et al, ; Coras & Blümcke, ). Unsurprisingly, temporal lobe epilepsy often provokes cognitive decline and memory deficits in both human patients (Dinkelacker, Xin, Baulac, Samson, & Dupont, ; Giovagnoli & Avanzini, ; Halgren et al, ; Hennion et al, ; Rayner, Jackson, & Wilson, ; Titiz, Mahoney, Testorf, Holmes, & Scott, ) and animal models (Armstrong et al, ; Faure et al, ; Häussler, Rinas, Kilias, Egert, & Haas, ; Kalemenev et al, ; Zhang, Thamattoor, LeRoy, & Buckmaster, ). Unfortunately, the mechanisms of these deficits and dysfunctions are not yet fully understood and no effective treatment for seizure prevention exists at present.…”