Abstracts

Rationale: Theta oscillations (4-8 Hz) in the hippocampus and the neocortex have been suggested to play a role in the encoding of new memories and long-term plasticity. Intracranial electrode field potential recordings provide high temporal and spatial resolution for studying these oscillations in humans during cognitive tasks. In humans, theta oscillations have been observed in many structures, including the hippocampus, during memory encoding and recall [1] and virtual maze navigation [2]. The amplitude of these oscillations was correlated to successful memory retrieval in a verbal memory task [3]. Here we characterize the encoding of memory signals at multiple temporal scales and different locations in patients with epilepsy during two complex memory tasks involving retaining sequential episodic information. We show selective modulation of theta activity for successfully recalled memories. This effort lays the groundwork for diagnostic memory testing in epilepsy patients based on quantifying a physiologic brain rhythm.Methods: Epileptic patients implanted with subdural electrodes for seizure localization were tested on two tasks. The first one was a classic multi-item short-term memory task [4]. In the second task, the subjects were shown a series of 4-6 images. After a short delay, the patients were instructed to arrange the previously presented objects in the order in which they appeared using the buttons on a key-pad. Results: In both tests, an increase in the amplitude of theta power with respect to the pre-task baseline was observed during the stimulus presentation period in the medial temporal lobe electrodes (Figure 1A). In contrast, electrodes in the frontal and parietal regions showed a decrease in theta power during the task compared to theta levels pre-trial (Figure 1B). Furthermore, there was a significant increase in theta power in the medial temporal lobe during successful trials (p<0.01, Wilcoxon s rank sum test, with respect to pre-task baseline, e.g. Figure 1A, top), while in the unsuccessful trials theta power dropped to levels pre-trial (Figure 1A, bottom). This result was consistent across 3 patients tested on both the tasks (29/70 electrodes in the temporal lobe and 15/25 electrodes in the frontal and parietal lobes). Conclusions: These results suggest a role of temporal theta oscillations in the encoding of successfully recalled memories, perhaps related to hippocampal theta oscillations implicated in memory formation. This physiologically based quantitative assay of memory function may prove valuable in predicting postoperative memory outcomes in patients undergoing seizure surgery. 1. U. Rutishauser, et al. (2010), Human memory strength is predicted by theta-frequency phase-locking of single neurons. Nature (464), 903-907. 2. M.J. Kahana, et al. (1999), Human theta oscillations exhibit task dependence during virtual maze navigation. Nature (399), 781-784. 3. W. Klimesch, et al. (1996), Theta band power in the human scalp EEG and the encoding of new information. Neuroreport, 7(7), 1235-1240. 4. S. Sternberg, (1966) High-speed scanning in human memory. Science, 153, 652-654.