The prevailing model of amnesia holds that it depends on damage to a group of loosely related structures, collectively called the medial temporal lobe (MTL). One influential theory holds that these areas work together as a single functional unit. According to this theory, the structures in the MTL store the memory of specific objects, facts and events. We have developed a competing hypothesis, which holds that different structures within the MTL have specialized functions, and that their collective functions extend beyond those assigned to the MTL by the prevailing model. Human functional imaging studies by other groups have identified a distributed network of cortical brain regions that display temporally coordinated activity during wakeful rest, commonly termed the default mode network (DMN). The DMN is largely conserved across species and includes a number of subsystems that converge onto primary DMN core hubs in medial prefrontal and posterior cingulate cortices. The interactions between these hubs and subsystems, and their contribution to the overall integrity of DMN functional connectivity, remain relatively unexplored. Because the hippocampus is vulnerable to a variety of neurodegenerative conditions that affect memory, we aimed to directly test the effects of damage to the hippocampus on DMN dynamics. In the last year we have made some headway towards developing imaging protocols to examine network dynamics in subjects with hippocampal damage. Pilot studies were carried out to optimize imaging sequences. The anesthesia protocol induces a level of anesthesia that preserves blood-oxygen-level dependent (BOLD) signal. Imaging sequences include structural scans, arterial spin label (ASL) to examine cerebral blood flow, and resting state scans. Imaging, post-acquisition pre-processing and analysis are ongoing. Preliminary results indicate a pattern of activity temporally correlated with a seed region in the posterior cingulate cortex distributed across frontal and cingulate cortices comparable to previous descriptions of the default mode network. Analyses in progress will assess whether damage to the hippocampus significantly disrupts distributed cortical network dynamics.

Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
2016
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
Zip Code
Murray, Elisabeth A; Wise, Steven P; Graham, Kim S (2018) Representational specializations of the hippocampus in phylogenetic perspective. Neurosci Lett 680:4-12
Yang, Tianming; Bavley, Rachel L; Fomalont, Kevin et al. (2014) Contributions of the hippocampus and entorhinal cortex to rapid visuomotor learning in rhesus monkeys. Hippocampus 24:1102-11
Murray, Elisabeth A; Wise, Steven P (2012) Why is there a special issue on perirhinal cortex in a journal called hippocampus? The perirhinal cortex in historical perspective. Hippocampus 22:1941-51
Tu, Hsiao-Wei; Hampton, Robert R; Murray, Elisabeth A (2011) Perirhinal cortex removal dissociates two memory systems in matching-to-sample performance in rhesus monkeys. J Neurosci 31:16336-43
Murray, Elisabeth A; Wise, Steven P (2010) What, if anything, can monkeys tell us about human amnesia when they can't say anything at all? Neuropsychologia 48:2385-405
Shamy, J L; Carpenter, D M; Fong, S G et al. (2010) Alterations of white matter tracts following neurotoxic hippocampal lesions in macaque monkeys: a diffusion tensor imaging study. Hippocampus 20:906-10
Basile, Benjamin M; Hampton, Robert R; Suomi, Stephen J et al. (2009) An assessment of memory awareness in tufted capuchin monkeys (Cebus apella). Anim Cogn 12:169-80