Abstracts

Rationale: Memory impairment is a primary cognitive complaint in temporal lobe epilepsy. Prior work indicates that higher hippocampal sharp wave ripple (SWR) rates predict improved performance on an associative memory task and offline gains in speed on a motor sequence typing task. In contrast, hippocampal and temporal epileptic spikes impaired performance on an associative memory and auditory naming task. The combined contributions of SWR and epileptic spikes to human memory performance remain poorly understood. We evaluated the impact of hippocampal SWR and temporal and hippocampal spikes on wakeful learning using a motor sequence typing task.


Methods: Subjects with intracranial electrodes targeting the hippocampus were prospectively recruited. All subjects were trained on a motor sequence typing (MST) task using the hand(s) contralateral to hippocampal recording. The task required typing a 5-digit sequence as quickly and accurately as possible for twelve 30s trials (online) separated by 30s of rest (offline) (Figure 1A). Typing speed was quantified as the inverse of the average interval between adjacent key presses within each correctly typed sequence (Figure 1B). Offline gains were defined as the difference in typing speed between the last correct sequence of one trial and the first correct sequence of the next. Electrode locations were manually labeled by co-registering the preimplantation MRI with the post-implantation CT. SWRs in hippocampal electrodes and epileptic spikes in hippocampal and temporal neocortical electrodes were detected using automated approaches (Figure 1C). A linear mixed-effect model was fitted to evaluate the effects of offline hippocampal SWR rate and offline and online neocortical temporal and hippocampal spike rate on offline gains in typing speed per subject with a subject-specific intercept to account for multiple trials per subject.


Results: 15 epilepsy patients (22 hemispheres evaluated with intracranial recordings; 8 females; mean age 33 years, range 17-60 years) were enrolled. Hippocampal SWR rate during brief periods of rest during the task predicted gains in learning in the contralateral hand during rest (increase in correct typing speed of 7.3 keys/s for each increase in 1 ripple/s, p=0.004) (Figure 2A). Offline and online spike rates from temporal and hippocampal regions did not predict offline gains (p = 0.6) (Figure 2B).


Conclusions: These data indicate that hippocampal SWRs during brief periods of rest support wakeful learning even in the setting of epileptic spikes. Preliminary analysis suggests that the impact of temporal spikes on learning is more complex – further analysis will focus on spike location and timing during the task.


Funding: None