Jesse Rissman, Ph.D. - US grants

DESCRIPTION (provided by applicant): The long-term objective of this research plan is to further our understanding of the neural basis of working memory (WM). Specifically, the goals of this proposal are to characterize the network of functionally connected brain regions mediating visual WM maintenance and determine the behavioral significance of their interactions. Many theories of visual WM postulate the prefrontal cortex (PFC) provides top-down signals to posterior visual association areas in order to keep behaviorally relevant perceptual information activated when it is no longer accessible in the environment. However, evidence for the existence of this interaction is limited and indirect. The experiments outlined in this proposal will use event-related functional magnetic resonance imaging to measure activity levels throughout the brain as subjects perform WM tasks. A recently developed multivariate analysis procedure will then be applied to the data to examine inter-regional interactions during the component stages of WM. The first experiment will seek to determine whether the strength and nature of these interactions is related to behavioral performance. The second and third experiments will assess the mechanisms by which the WM system can dynamically adapt its functional connectivity profile to accommodate increased memory load or overcome distraction.

[unreadable] DESCRIPTION (provided by candidate): The broad aim of the proposed research is to investigate how declarative memory processes within the medial temporal lobe (MIL) circuit are modulated by cognitive goals that bias processing toward the learning or the retrieval of information. Experiment 1 will use high-resolution functional MRI (fMRI) to test whether the MIL subregions that show novelty effects (greater activity to new vs. old stimuli) during encoding also exhibit recollection effects (greater activity to remembered old stimuli vs. new stimuli) during episodic retrieval. Such a finding would support a conceptualization of MIL function in which MTL processing of sensory stimuli is not dictated by their mnemonic history, but rather by one's mnemonic goals at the time of encounter. Experiment 2 will use high-resolution fMRI to assess whether there are circumstances in which MIL cortical regions-which typically show a diminished response to previously encountered relative to novel stimuli-can invert this response pattern and actively contribute to the recollection of sensory details associated with prior stimulus encounters. Given the distinct sensory inputs to the perirhinal and parahippocampal cortices, the engagement of these regions during episodic recollection is predicted to depend critically on the whether object-based or spatially-based information is being recollected. Experiment 3 will bear on the hypothesis that the ability to modulate the response profile of MTL regions in accordance with mnemonic goals depends on control mechanisms subserved by prefrontal cortex. Moreover, posterior parietal cortex is hypothesized to monitor mnemonic signals emerging from MTL or to direct attention to the internally-represented contents of retrieved memories. Experiment 3 will use whole-brain fMRI and functional connectivity analyses to examine how prefrontal and parietal regions interact with MTL to facilitate novelty encoding and episodic recollection. Delineating the manner in which MTL responses are influenced by top- down control signals will advance mechanistic accounts of declarative memory and provide insights into how mnemonic control processes break down when PFC and/or MTL function is compromised by schizophrenia, attention-deficit hyperactivity disorder, depression, aging, or dementia. Relevance: This research will use functional MRI to examine how our behavioral goals influence the neural processing of sensory information, serving either to promote new learning or the retrieval of relevant details from long-term memory. Characterizing how these control processes influence specific mechanisms within the medial temporal lobes will help us better understand the nature of memory impairments in clinical conditions that affect these structures, such as schizophrenia, depression, and dementia. [unreadable] [unreadable] [unreadable]

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. While the brain responds differently when it experiences a novel sensory stimulus as compared to a previously encountered stimulus, conventional functional magnetic resonance imaging (fMRI) data analysis approaches, utilizing univariate statistics to compare voxel activity levels across task conditions, cannot reliably capture these mnemonic effects on single trials. We sought to exploit the wealth of information represented in distributed fMRI activity patterns, using a multi-voxel pattern analysis approach to decode the mnemonic status of individual stimuli. Prior to scanning, participants studied 200 color photographs of human faces. Subsequently, participants were scanned while they made recognition memory decisions about the 200 studied faces intermixed with 200 novel faces. For each test face, participants indicated whether they 1) recollected having studied the face, 2) were highly confident they studied it, 3) thought they studied it, 4) thought they did not study it, or 5) were highly confident they did not study it.