Structural and Functional MRI Evidence for Distinct Medial Temporal and Prefrontal Roles in Context-dependent Relational Memory

Abstract

Declarative memory is supported by distributed brain networks in which the medial-temporal lobes (MTLs) and pFC serve as important hubs. Identifying the unique and shared contributions of these regions to successful memory performance is an active area of research, and a growing literature suggests that these structures often work together to support declarative memory. Here, we present data from a context-dependent relational memory task in which participants learned that individuals belonged in a single room in each of two buildings. Room assignment was consistent with an underlying contextual rule structure in which male and female participants were assigned to opposite sides of a building and the side assignment switched between buildings. In two experiments, neural correlates of performance on this task were evaluated using multiple neuroimaging tools: diffusion tensor imaging (Experiment 1), magnetic resonance elastography (Experiment 1), and functional MRI (Experiment 2). Structural and functional data from each individual modality provided complementary and consistent evidence that the hippocampus and the adjacent white matter tract (i.e., fornix) supported relational memory, whereas the ventromedial pFC/OFC (vmPFC/OFC) and the white matter tract connecting vmPFC/OFC to MTL (i.e., uncinate fasciculus) supported memory-guided rule use. Together, these data suggest that MTL and pFC structures differentially contribute to and support contextually guided relational memory.

Standard‐space atlas of the viscoelastic properties of the human brain

“…This work represents the first detailed investigation of the mechanical properties of parcellations of the cerebral cortex, though initial MRE investigations into cortical structure-function relationships Schwarb et al, 2019), contributions to adolescent risk-taking behavior (McIlvain et al, 2020), and the mechanical integrity of the cortex in Alzheimer's disease (Hiscox, Johnson, McGarry, Marshall, et al, 2020) This MRE study is the first to report significant sex differences in viscoelasticity in a wide range of neuroanatomical structures which supplements the wealth of existing data that reports sex differences in neuroanatomy. Interestingly, we found that female brains are approximately 4% more viscous compared to males as indicated by significantly higher ξ in global WM, which contradicts an early study that reported female brains were 9% less viscous in large regions primarily comprising white matter (Sack, Streitberger, Krefting, Paul, & Braun, 2011).…”

“…This work represents the first detailed investigation of the mechanical properties of parcellations of the cerebral cortex, though initial MRE investigations into cortical structure–function relationships (Johnson et al, 2018; Schwarb et al, 2019), contributions to adolescent risk‐taking behavior (McIlvain et al, 2020), and the mechanical integrity of the cortex in Alzheimer's disease (Hiscox, Johnson, McGarry, Marshall, et al, 2020) have been reported. We show that separate regions of the cortex exhibit different viscoelastic properties and, remarkably in some cases, observe distinct viscoelastic properties which do not overlap in the range of values across participants.…”

“…There is evidence to suggest that the corona radiata possesses more myelin than the corpus callosum (Chopra et al, 2018), and thus myelin content could contribute to the higher stiffness reported (Weickenmeier et al, 2016(Weickenmeier et al, , 2017. Notably, the fornix, which is part of the limbic system and is critically involved in the formation of new memories (Douet & Chang, 2015;Schwarb et al, 2019), is particularly soft and exhibits greatest variability among participants for both MRE measures. The large variability reported here may suggest that fornix viscoelasticity could be promising for detecting individual differences that may relate to functional outcomes, especially as its integrity has been implicated in the transition from mild cognitive impairment to Alzheimer's disease (Nowrangi & Rosenberg, 2015;Oishi, Mielke, Albert, Lyketsos, & Mori, 2012).…”

“…Although in this study we utilize 1.6 and 2.0 mm isotropic MRE data to build the viscoelastic template, which are considered highresolution for brain MRE, insufficient resolution may affect the accuracy of measurements in some of the smallest brain structures (Johnson et al, 2014(Johnson et al, , 2016. Prior spatial information was also not incorporated within the nonlinear inversion algorithm, though it is used in many studies reported in the brain MRE literature (Hiscox, Johnson, McGarry, Schwarb, et al, 2020;Schwarb et al, 2019). Soft prior regularization (SPR) is a method in which homogeneity in predefined spatial regions, typically obtained through an anatomical scan, is enforced through a penalty term in the nonlinear inversion strategy (McGarry et al, 2013).…”

“…We used a 19.6 mm cubic subzone, which has been standardized and maintained across all published brain MRE studies from our group. To further maintain consistency with our previously published work, maps of the complex shear modulus G* were reformulated to provide quantitative maps of shear stiffness, μ = 2jG * j 2 /(G 0 +jG * j), and damping ratio, Note: Data from these studies have previously been published elsewhere, see Study A = Hiscox et al, 2018;Hiscox, Johnson, McGarry, Marshall, et al, 2020;Hiscox, Johnson, McGarry, Schwarb, et al, 2020;Study B = Schwarb, Johnson, McGarry, & Cohen, 2016;Schwarb et al, 2019Study C = Huesmann et al, depending upon neuronal density and neurogenesis (Freimann et al, 2013;Klein et al, 2014), degree of myelination (Schregel et al, 2012; Weickenmeier et al, 2016; Weickenmeier, de Rooij, Budday, Ovaert, & Kuhl, 2017), and inflammation (Riek et al, 2012), and is the parameter most commonly reported to be affected in neurological disorders (Murphy et al, 2019). Damping ratio, ξ, is a F I G U R E 1 Overview of the MRE imaging and analysis procedure.…”