Abstracts

Rationale: Abnormalities in mGLUR5, a post-synaptic glutamatergic receptor involved in memory consolidation, have been described in mesial temporal lobe epilepsy (MTLE). Whilst suggesting a role for this receptor in the epileptogenic process, little is known about the extent to which mGLUR5 function contributes to memory deficits associated with MTLE. Here we report the relationship between hippocampal [11C]ABP688 PET binding potential (BP) and performance on a verbal learning and memory task. We hypothesize that decreases in left (dominant) hippocampus BP will be correlated with poorer verbal memory performance in MTLE patients. Methods: We studied 15 right-handed patients classified into left (n=6) or right MTLE based on interictal/ictal EEG and visual hippocampal analysis in clinical MRI scans. [11C]ABP688 PET scans consisted of a 1 hour dynamic acquisition, with image reconstruction using filter-back projection and coregistration to each patient's MRI. BP maps were generated using a simplified reference tissue method with the cerebellum as reference region. Individual patient MRIs and BP maps were resampled to standard space. Volumes of interest were manually drawn and used for extraction of mean BP within the hippocampal head, the segment in which the most significant abnormalities are seen in epileptogenic hippocampi. All patients were administered the Rey Auditory Verbal Learning Test (RAVLT) as part of the routine clinical neuropsychological exam. With the assumption that integrity of the left hippocampus will reflect greater verbal learning and memory regardless of side of seizure focus, we analyzed all patients together for learning across repeated trials, immediate and delayed recall. Memory scores were correlated with left hippocampus BP (LH-BP) and left hippocampus volumes (LH-V). Results: MTLE groups differed significantly in left and right hippocampal BP as well as in LH-V. Despite these differences, performance of the two patient groups improved similarly across learning trials. The total number of words learned, however, was significantly correlated with LH-V. Immediate recall after interference was correlated with LH-BP and LH-V. The correlation between delayed recall and LH-BP tended towards significance. Conclusions: The present study reveals a link between verbal learning, retention and left hippocampal mGLUR5 availability, shedding light into molecular mechanisms underlying memory dysfunction in MTLE. These findings go beyond previous structural studies demonstrating a correlation between hippocampal size and memory deficits by providing mechanistic insights about the molecular underpinnings of cognitive function. mGLUR5 thus constitutes a potential biomarker for epileptogenesis and memory impairment in MTLE. Funding: Savoy Foundation for Epilepsy