Accelerated Forgetting in People with Epilepsy: Pathologic Memory Loss, Its Neural Basis, and Potential Therapies

While forgetting is vital to human functioning, delineating between normative and disordered forgetting can become incredibly complex. This thesis characterizes a pathologic form of forgetting in epilepsy, identifies a neural basis, and investigates the potential of stimulation as a therapeutic tool. Chapter 2 presents a behavioral characterization of the time course of Accelerated Long-Term Forgetting (ALF) in people with epilepsy (PWE). This chapter shows evidence of ALF on a shorter time scale than previous studies, with a differential impact on recall and recognition. Chapter 3 builds upon the work in Chapter 2 by extending ALF time points and investigating the role of interictal epileptiform activity (IEA) in ALF. These findings lend support for distinct forgetting patterns between recall and recognition memory. We also demonstrate the contribution of hippocampal IEA during slow-wave sleep to this aberrant forgetting. Chapter 4 investigates the potential of intracranial stimulation to ameliorate IEA burden. Our findings suggest that stimulation does not appear to have a direct effect on IEA rate. Further studies are necessary to explore the potential of stimulation as a therapeutic tool outside of seizure cessation. Overall, this thesis provides further evidence and classification of long-term memory impairment in epilepsy and identifies a neural correlate that can be targeted for future clinical intervention