Investigations of Spatial Recognition Memory to Improve Cognitive Outcomes in Epilepsy Surgery - Epilepsy is a common neurologic disorder that cannot be controlled with medication in a third of patients. The most common form of epilepsy, and the most difficult to control, is medial temporal lobe epilepsy. Patients with epilepsy and their caregivers note substantial cognitive difficulties that are not well correlated with neuropsychological testing. Emerging evidence suggests this discrepancy is due to the lack of neuropsychological tests for core deficits in epilepsy. These deficits are primarily related to episodic memory. Emerging psychological theory places 'scenes' - integrated spatial and object representations - at the core of episodic memory, recollective experience, and imagining future scenarios. These memory processes appear to be at the heart of cognitive difficulties in epilepsy and overlap with disturbances in recognition memory that encompasses both familiarity judgments, including hyperfamiliarity and recollection. Our long-term goal is to delineate core memory circuits, particularly in relation to the deficits in epilepsy and after epilepsy surgery, and then develop better means to test these processes and avoid morbidity. To this end, we have updated a unique paradigm that now includes photorealistic dynamic scenes that can independently assay familiarity and distinguish this from validated recall. This paradigm addresses core features of memory and memory disturbances by including objects, spatial features, and temporal dynamics; it can be used to assay familiarity, recollection, and potentially memory generalization. We hypothesize that coordination between two distinct memory networks for encoding is required to perform this task during study scenes. During test scenes, recollective experience is necessary for the task and can overlap with encoding. This coincidence of recollective experience and encoding is a possible feature of deja vu, which, interestingly, can be elicited by this paradigm. We will use this approach and other behavioral measures to study a unique and large cohort of patients with epilepsy surgery-related focal lesions of pertinent brain regions. We will also prospectively test patients before and after surgery. This is followed by electrophysiological studies with paradigm modifications, including event- related potentials (in control subjects) and human intracranial electrophysiology (in pre-surgical epilepsy patients). These approaches will enable us to delineate the precise timing and neural circuits underlying these phenomena. Our rationale is that through these studies, we can design better tests for memory problems, avoid surgical injury to memory, and ultimately contribute to developing new memory treatments. We anticipate that our proposed studies will have impacts that extend beyond epilepsy in the clinical sphere and be highly informative for psychological theory and computational memory models. These studies will, therefore, significantly impact our understanding, classification, scoring, and treatment of memory disorders. Innovative approaches are employed in these studies, and we expect impacts on theory and memory models.
