Necessary Role of PFC-MTL Interactions in Memory Tested in Humans Using TMS

Project 1 (Cohen): Year 2 Plan, with Proposed Expansion of Scope: Neuropsychological, neuroimaging, neuromodulatory, and eye-tracking studies of PFC-MTL functional interactions in humans Overview. During Year 2, we will continue to make progress on the experiments of PFC-MTL interactivity in human memory proposed in our original application. These will include lesion-deficit studies of the context-dependent association-learning paradigm in brain-damaged individuals, conducted at the University of Illinois and our patient-supplying performance site, the University of Iowa, together with fMRI experiments in healthy individuals, conducted at the University of Illinois. In addition, we propose an expansion of scope in order to conduct neuromodulatory experiments at a new performance site, Northwestern University Feinberg School of Medicine. These neuromodulatory experiments will use transcranial magnetic stimulation (TMS) to manipulate PFC-MTL interactions, while behavioral and fMRI measures will be used to assess the ramifications of manipulated interactions on memory and brain processing related to memory. The addition of TMS helps to overcome two of the challenges of the neuropsychological lesion-deficit approach: (1) Whereas natural lesion locations are variable and often encompass large areas with heterogeneous functions, TMS can be used to temporarily depress or facilitate regions with relatively high spatial precision, permitting us to better test the functional roles of specific PFC subdivisions; and (2) whereas natural brain lesions and their effects are static, making it difficult to pinpoint the particular stage(s) during learning when a particular region makes a critical contribution, TMS’s temporary manipulation of function can be targeted to specific stages of learning, permitting us to resolve the timecourse of PFC-MTL involvement and interactions. In this way, our proposed expansion of scope will enhance our ability to address our original specific aims, while also bringing this project into better correspondence with the animal-model-based projects, thereby serving to enhance the overarching Center goals of determining the roles of PFC, MTL, and their interactions in specific aspects of learning. TMS is a noninvasive technique for inducing electrical activity in focal neuronal populations in humans that is often used to achieve disruptive effects on local neural processing and task performance (Walsh & Cowey 2000, Todd et al. 2009). We will use repetitive TMS (rTMS) to temporarily disrupt PFC function during particular stages of the context-dependent association.