Structure–Function Dissociations of Human Hippocampal Subfield Stiffness and Memory Performance

Abstract

Aging and neurodegenerative diseases lead to decline in thinking and memory ability. The subfields of the hippocampus (HCsf) play important roles in memory formation and recall. Imaging techniques sensitive to the underlying HCsf tissue microstructure can reveal unique structure–function associations and their vulnerability in aging and disease. The goal of this study was to use magnetic resonance elastography (MRE), a noninvasive MR imaging-based technique that can quantitatively image the viscoelastic mechanical properties of tissue to determine the associations of HCsf stiffness with different cognitive domains across the lifespan. Eighty-eight adult participants completed the study (age 23–81 years, male/female 36/51), in which we aimed to determine which HCsf regions most strongly correlated with different memory performance outcomes and if viscoelasticity of specific HCsf regions mediated the relationship between age and performance. Our results revealed that both interference cost on a verbal memory task and relational memory task performance were significantly related to cornu ammonis 1–2 (CA1–CA2) stiffness (p= 0.018 andp= 0.011, respectively), with CA1–CA2 stiffness significantly mediating the relationship between age and interference cost performance (p= 0.031). There were also significant associations between delayed free verbal recall performance and stiffness of both the dentate gyrus–cornu ammonis 3 (DG–CA3;p= 0.016) and subiculum (SUB;p= 0.032) regions. This further exemplifies the functional specialization of HCsf in declarative memory and the potential use of MRE measures as clinical biomarkers in assessing brain health in aging and disease.SIGNIFICANCE STATEMENTHippocampal subfields are cytoarchitecturally unique structures involved in distinct aspects of memory processing. Magnetic resonance elastography is a technique that can noninvasively image tissue viscoelastic mechanical properties, potentially serving as sensitive biomarkers of aging and neurodegeneration related to functional outcomes. High-resolutionin vivoimaging has invigorated interest in determining subfield functional specialization and their differential vulnerability in aging and disease. Applying MRE to probe subfield-specific cognitive correlates will indicate that measures of subfield stiffness can determine the integrity of structures supporting specific domains of memory performance. These findings will further validate our high-resolution MRE method and support the potential use of subfield stiffness measures as clinical biomarkers in classifying aging and disease states.

Hippocampal subfield viscoelasticity in amnestic mild cognitive impairment evaluated with MR elastography

“…When estimating the HCsf property maps, NLI parameters were optimized to sensitively measure HCsf μ and ξ, using two inversion schemes with the following NLI parameter settings: μ – SPR: α = 10 -12 , spatial filtering (SF) width: 0.9 mm; ξ – SPR: α = 10 -12 , spatial filtering (SF) width: 1.5 mm. See our prior work for complete details of imaging and analysis protocols ( Delgorio et al, 2022 , 2021). Octahedral shear strain-based signal-to-noise ratio (OSS-SNR) was used to confirm data quality, with all data from all participants over the OSS-SNR threshold of 3.0 considered suitable for NLI ( Hannum et al, 2022 , McGarry et al, 2011 ).…”

“…However, as the HC and the HCsf are strongly affected by the Alzheimer’s pathology, it is important to examine viscoelastic changes in these regions in aMCI. Our group has previously shown the sensitivity of MRE in detecting structural differences of the HC in aging and neurodegeneration ( Delgorio et al, 2021 , Hiscox et al, 2018 , Johnson et al, 2016b ), and have recently developed a high-resolution, MRE protocol to reliably measure the viscoelasticity of individual HCsf ( Delgorio et al, 2022 , 2021), which can be potentially more sensitive to aMCI by examining the neural substrates first affected by the underlying pathology of aMCI.…”

Antenatal maternal intimate partner violence exposure is associated with sex-specific alterations in brain structure among young infants: Evidence from a South African birth cohort

“…To account for subject-specific and group-specific global differences in head size, subcortical volumes were normalized to the estimated total intracranial volume (eTIV). Corrections were performed by adjusting regional volumes using the analysis of covariance (ANCOVA) approach, which corrects regional measures based on the proportion of the difference between an individual’s global brain measure and the average global brain measure for the sample ( Delgorio et al, 2022 , Raz et al, 2005 ). The Shapiro-Wilk W test was used to test for a normal distribution, and the Cameron & Trivedi’s IM-test assessed for heteroscedasticity.…”

Mechanical Property Based Brain Age Prediction using Convolutional Neural Networks

“…Data collected at UIUC was previously pooled and used to create a standard-space atlas of brain mechanical properties . Additional data included in this work has been reported, in part, in several previous publications (Delgorio et al, 2022(Delgorio et al, , 2023McIlvain, Schneider, et al, 2022;Sanjana et al, 2021;Schneider et al, 2022). Readers are referred to prior works for additional information.…”