Lesions to the human medial temporal result in striking and often long-lasting deficits in delayed verbal memory, termed medial temporal lobe amnesia. While models of medial temporal lobe function, such as declarative memory theory, hypothesize a restricted role for the medial temporal lobe in memory function, a growing consensus in cognitive neuroscience suggests that such deficits also include impairments in representations important to other areas of cognition, such as perception, attention, working memory, language, and spatial navigation. Here, we propose a novel model to better account for the range of cognitive deficits that accompany medial temporal lobe lesions. Our model hypothesizes that human medial temporal lobe function can best be described as involving both representational precision and binding, predicting increasing deficits as task-demands increase along these two critical dimensions. Experiments in Aim 1 test our model with a particular focus on testing representational precision in the context of memory and navigation to allow us to compare the outcomes from these experiments against those predicted by declarative memory theory. Experiments will include testing with bilateral medial temporal lobe patients, including those with lesions primarily restricted to the hippocampus, and high-resolution fMRI studies in healthy participants to better determine the mechanistic basis of hippocampal contributions to precision and binding.
Aim 2 will determine the predictive capacity of our model, in conjunction with fMRI-based network modeling, to explain deficits accompanying unilateral medial temporal lesions that occur as a result of surgical resections during treatment of pharmacologically intractable epilepsy. The anticipated outcomes from the proposal are: 1) a more complete account of the consequences of medial temporal lobe lesions, particularly to the hippocampus, on cognition than can be provided by neuropsychological measures alone 2) a more complete predictive model of the effects of unilateral temporal lobe resection on cognitive outcomes post-resection, possibly allowing greater flexibility in determining which patients should undergo responsive neurostimulation (RNS) vs. resection 3) modeling whether and how extra-medial temporal lobe cortical networks can compensate for lost function following resection 4) potentially, inspiration for novel therapies involving cognitive interventions or neurostimulation targeting intact cortical tissue in patients with amnestic-like symptoms.
While there is widespread consensus that lesions to the human medial temporal lobes result in a profound loss of long-term verbal memory, there is now growing consensus in the field of cognitive neuroscience that the impairments following such lesions extend outside of this domain into perception, working memory, attention, language, and navigation. Yet how such deficits might arise cannot be accounted for by most contemporary models of medial temporal lobe function. Here, we propose to test a novel model that accounts for such representational impairments based on two dimensions: precision and binding. The expected outcomes of this grant are: 1) a more complete account of the patterns of cognitive deficits accompanying bilateral medial temporal lobe lesions, particularly those localized to the hippocampus (Aim 1), and, 2) more accurate modeling and prediction of the cognitive deficits accompanying unilateral temporal lobe resections to treat pharmacologically-intractable epilepsy (Aim 2).
