Neuronal mechanisms in prefrontal and temporal lobe cortical areas underlying perceptual and mnemonic processes

The medial temporal lobe (MTL) cortical areas, including hippocampus, perirhinal and entorhinal cortex and parahippocampal cortex, are known to support recognition memory. Inferotemporal cortex (IT) is involved in processing visual stimulus during recognition memory, and reciprocally projects to some regions of MTL (e.g. perirhinal cortex). Many neuroimaging, neuropsychological and neurophysiological studies have also emphasized the role of the prefrontal cortex (PFC) in maintaining information during working memory. Although the function of MTL was traditionally viewed as containing a system of structures exclusively involved in memory, a recent perceptual-mnemonic debate over MTL indicates some MTL structures (e.g. perirhinal cortex and hippocampus) contribute to perceptual discrimination. Various versions of cognitive tasks have been implemented to investigate different roles of MTL, IT and PFC in memory and perception, such as cognitive tasks with either mnemonic (i.e. memory tasks with delays) or perceptual demands (i.e. simultaneous discrimination tasks without delays). However, it’s still unknown i) whether sub-areas of MTL, sub-regions of PFC or IT operate in the same or different manner when contributing to memory tasks with delays versus simultaneous discrimination tasks without delays; and ii) how any of these areas interact when supporting these tasks; and iii) whether the neural mechanisms in NHPs and in humans differ or not when they perform homologous memory tasks. The motivating idea for the body of work in this thesis is that some of the same brain regions in MTL, IT and PFC may interact differently to underlie mnemonic or perceptual 2 processes, and/or that different combinations of brain areas (networks and sub-networks) may be recruited for different cognitive processes. To investigate interactions both within MTL, IT and PFC and between these areas in a battery of task variants, I recorded neural activities in a range of perceptual and mnemonic tasks using a simultaneous multi-area, multi-electrode recording paradigm in three awake macaques. Then to generalize the neural mechanism of recognition memory from NHPs to humans, I applied a series of homologous behavioral paradigms to both primates to investigate recollection and familiarity, which are two recognition memory processes based on dual-process theory. To bridge the species divide, I implemented NHP electrophysiological recordings and targeted transcranial magnetic stimulation (TMS) in humans in several homologous recognition memory tasks to investigate both the neural substrates and time course of recollection and familiarity processes, as these two processes are key considerations pertaining to human functional anatomy of MTL and PFC regions. Finally, I investigated the interaction between frontopolar cortex (FPC) and other brain regions during resting state using circumscribed FPC lesions in NHPs and network cluster analyses of whole brain functional connectivity analyses, to illustrate NHP FPC might help implement long-standing diverse neural network dynamics.

Advisor: Buckley, M