Abstracts

Rationale: Status epilepticus (SE) can often result in significant cognitive impairment. Recently we showed that SE produces a phase misalignment in the circadian rhythm of CA1 local field potentials (Talathi et al., Neurosci. Lett. 2009, 455:145-9; Fisher et al., Biol. Cybern. 2010, 102:427-40). In order to study the cognitive implications of these findings, we have tracked the circadian modulation of hippocampal gamma rhythms, which are known to constitute a fundamental mechanism for sensory information processing and cognition. Here we report preliminary evidence of a circadian phase shift in hippocampal gamma oscillations following SE. We discuss the implications of this phase shift in terms of cognitive impairment in epilepsy.Methods: Adult male Sprague Dawley rats were surgically implanted with a twisted Teflon-coated stimulating electrode in the ventral hippocampus and microwire recording electrodes in the bilateral hippocampal subfields. Rats were housed in a 24-hour symmetric light-dark cycle with continuous 24-hour video/EEG. Following a baseline recording period of at least one week, self-sustaining SE was electrically induced. Monitoring and recording then continued for 1-3 weeks post-stimulus. A full account of the experimental protocol can be found in Talathi et al (2009).Results: The continuous EEG data recorded from a single microwire in the ipsilateral CA1 subfield was split into frequency component modes using empirical mode decomposition (EMD). Examining the mean frequencies of the EMD modes, we observed that two modes fell within the gamma range (22-65 Hz). These gamma-range modes were divided into in 6-hr 90% overlapping epochs (Fig 1a). The mean peak-to-peak EMD amplitude from each epoch was extracted and plotted as function of time, with each data point representing a single 6-hr epoch (shown in red trace in Fig 1b). The trace in black is the baseline mean peak-to-peak amplitude estimated from 48-hr epochs. In each of the 4 rats analyzed, we observed that at least one of the gamma EMD modes exhibited a circadian phase shift > 900 immediately following SE stimulation. This phase shift is illustrated for a single rat in Figure 1b (insets). The circadian phases of all 4 rats were estimated by least squares curve fitting to sinusoidal functions and are summarized in Figure 2. Conclusions: Our preliminary observations show that a circadian phase misalignment in gamma rhythms emerges following SE. Recent literature has shown that several circadian abnormalities are associated with significant cognitive deficit. Given that gamma rhythms play a role in memory consolidation during REM sleep, we suggest that cognitive decline following SE may be partly circadian in nature and related to this gamma rhythm phase shift.