Project AbstractLesions to the human medial temporal result in striking and often long-lasting deficits indelayed verbal memory termed medial temporal lobe amnesia. While models of medialtemporal lobe function such as declarative memory theory hypothesize a restricted rolefor the medial temporal lobe in memory function a growing consensus in cognitiveneuroscience suggests that such deficits also include impairments in representationsimportant to other areas of cognition such as perception attention working memorylanguage and spatial navigation. Here we propose a novel model to better account forthe range of cognitive deficits that accompany medial temporal lobe lesions. Our modelhypothesizes that human medial temporal lobe function can best be described asinvolving both representational precision and binding predicting increasing deficits astask-demands increase along these two critical dimensions. Experiments in Aim 1 testour model with a particular focus on testing representational precision in the context ofmemory and navigation to allow us to compare the outcomes from these experimentsagainst those predicted by declarative memory theory. Experiments will include testingwith bilateral medial temporal lobe patients including those with lesions primarilyrestricted to the hippocampus and high-resolution fMRI studies in healthy participants tobetter determine the mechanistic basis of hippocampal contributions to precision andbinding. Aim 2 will determine the predictive capacity of our model in conjunction withfMRI-based network modeling to explain deficits accompanying unilateral medialtemporal lesions that occur as a result of surgical resections during treatment ofpharmacologically intractable epilepsy. The anticipated outcomes from the proposal are:1) a more complete account of the consequences of medial temporal lobe lesionsparticularly to the hippocampus on cognition than can be provided byneuropsychological measures alone 2) a more complete predictive model of the effectsof unilateral temporal lobe resection on cognitive outcomes post-resection possiblyallowing greater flexibility in determining which patients should undergo responsiveneurostimulation (RNS) vs. resection 3) modeling whether and how extra-medialtemporal lobe cortical networks can compensate for lost function following resection 4)potentially inspiration for novel therapies involving cognitive interventions orneurostimulation targeting intact cortical tissue in patients with amnestic-like symptoms.