Abstracts

Rationale: Memory loss is the most debilitating co-morbidity associated with temporal lobe epilepsy (TLE) and patients with memory loss suffer from a decreased quality of life as a direct consequence. While the hippocampus has been shown to be important for normal memory function, the effect of temporal lobe disease on different kinds of memory is less clear. In addition to episodic memory (memory for autobiographical events), the hippocampus is thought to be important for statistical learning (SL); i.e., the ability to learn patterns of sensory input over time and space. Investigating EM and SL may lead to a comprehensive understanding of memory function in TLE and may provide memory related endpoints used to test the efficacy of novel treatments for memory loss.

Methods: We investigated SL and EM by combining novel, custom-designed, and unambiguous behavioral testing paradigms with quantitative structural and functional brain imaging in TLE, extra temporal lobe epilepsy (ETLE) and age and education matched healthy controls (HC). In a subset of TLE patients with intracranial electrodes (ICE) placed for seizure onset localization, we employed transiently disruptive direct electrical brain stimulation to understand the significance of different brain regions during SL and EM testing.

Results: TLE patients performed worse than ETLE and healthy controls in EM and SL. TLE patients also performed worse on SL compared to EM. Intriguingly, SL scores were worse in patients with poorly controlled epilepsy ( >4 seizures a month) for all patients. Lower SL scores were also correlated with a diminished total hippocampal (HPC) volume. Finally, in the patients studied with ICE, 1 Hz transient disruption of a more normally functioning hippocampus or entorhinal cortex led to decreased SL score.

Conclusions: Our findings suggest that SL in addition to EM is impaired in TLE. SL score reliably predicts poorly controlled epilepsy. We also find that the hippocampal circuitry (HPC and entorhinal cortex) is involved in SL. This study provides a comprehensive framework for investigating memory disorders in TLE, and sets the stage for novel treatment strategies for memory loss in TLE.

Funding: Please list any funding that was received in support of this abstract.: Swebilius foundation grant (Damisah); Xfinity NeuroNext (Damisah); Alzheimer’s Disease Research Center (Damisah).