Articles Exam #2 PDF

Reader Article #6: “Structure–Function Dissociations of Human Hippocampal Subfield Stiffness and Memory Performance” by Delgorio et. al - Motivation - Trying to find if the “stiffness” of hippocampal subfields (HCsf) is linked to different memory domains, aiming to de...

Reader Article #6: “Structure–Function Dissociations of Human Hippocampal Subfield Stiffness and Memory Performance” by Delgorio et. al - Motivation - Trying to find if the “stiffness” of hippocampal subfields (HCsf) is linked to different memory domains, aiming to determine if it can explain age-related memory decline. - Stiffness: how much the tissue resists deformation when subjected to external forces, like vibrations applied during MRE - How firm or elastic is the tissue - u = viscoelastic shear stiffness, which is calculated from their MRE method - Damping ratio = how damped or cushioned brain tissue response is to stress - Higher damping ratio = more viscous - Lower damping ratio = more elastic - HCsf tissue = individual subfields of the hippocampus - Include dental gyrus, CA1-CA3, SUB - Hypothesis - CA1-CA2, dentate gyrus-CA3 (DG-CA3), and subiculum (SUB) will each contribute uniquely to specific memory tasks, reflecting their differential roles in memory processes. - Task - Participants performed tasks targeting different memory types: - CVLT for verbal memory and interference management - California verbal learning test - LM for episodic memory recall - Logical memory - SR for assessing spatial memory - Spatial reconstruction - Helped determine which hippocampal subfields support specific memory types and whether stiffness changes in these regions mediate memory decline with age. - Dependent Variables: - Stiffness and damping ratio of hippocampal subfields (CA1-CA2, DG-CA3, SUB)  - Memory performance scores (CVLT, LM, SR) - Independent Variables: - Age - Hippocampal subfield type - Population/Participants - Wide age range (23-81 years) of 88 participants (36 males, 51 females), broad examination of age-related changes in hippocampal stiffness and memory across the lifespan. Participants were healthy adults, enhancing the generalizability of findings to the general aging population. - All participants completed a 1-hour MRI session, using a 3T Siemens Prisma scanner to capture high-resolution MRE data. - Methods - Big Picture: The study used MRE (magnetic resonance elastography) to measure the viscoelastic properties (stiffness and dampness ratio) of HCsf in 88 adults aged 23-81, correlating these properties with verbal, logical, and spatial memory performance. - MRE = a test that combines magnetic resonance imaging (MRI) with low-frequency vibrations to create a visual map called an elastogram - Fine Details: High-resolution MRE was conducted to assess subfield stiffness. Memory performance was measured using: - California Verbal Learning Test (CVLT) for verbal memory and interference cost - Logical Memory (LM) for immediate and delayed recall - Spatial Reconstruction (SR) for spatial memory. - Mediation analyses were used to assess whether subfield stiffness explained age-related changes in memory performance. - Key Takeaways - Strong evidence that hippocampal subfield stiffness → contributes to specific memory functions and mediates part of the age-related decline in memory. - Underscores the potential of MRE as a non-invasive tool to assess brain health. Helps in understanding the structural underpinnings of memory and aging. - Hippocampal subfield stiffness is associated with specific memory types  - suggesting that different subfields contribute uniquely to memory functions - Age-related declines in memory are partially explained by reductions in hippocampal stiffness - making it a potential clinical biomarker. - Can help in developing interventions targeting hippocampal integrity to mitigate age-related memory decline Figure 1. MRE Protocol & Subfield Segmentation - 1A. → MRE setup. - 50 Hz Resoundant pneumatic actuator placed on a passive pillow driver → induces micron-level vibrations in the brain → measures tissue deformation in the hippocampal subfields (HCsf). - The setup establishes a foundation for extracting stiffness and damping metrics - 1B. - 1.25 mm isotropic resolution multiband MRE sequence → image shear waves generated by the actuator - Captures detailed deformation patterns across the HCsf regions. - Cooler colors → less displacement (how much it's moving)  - 1C. - Describes segmentation and analysis of the HCsf regions (DG-CA3, CA1-CA2, SUB), using automated segmentation software (ASHS) - Nonlinear inversion (NLI) techniques are applied to calculate shear stiffness and damping ratio for each subfield - enabling precise measurements of viscoelastic properties; color map → stiffness ratio (4 is stiff, 1 is less stiff) Figure 2. Correlations of stiffness with Memory Performance → better stiffness = better memory performance - 2A-C. - [Bivariate correlations between stiffness (m) of each HCsf region and performance on the California Verbal Learning Test (CVLT) interference cost task.]  - CA1-CA2 stiffness shows the strongest positive correlation, indicating its role in verbal memory suppression. - 2D-F. - [Correlations between stiffness and delayed recall on the CVLT.] - The DG-CA3 region shows a significant positive correlation, suggesting a role in delayed verbal recall performance. - 2G-I. - [Show positive correlations between HCsf stiffness and Logical Memory (LM) delayed recall.] - CA1-CA2 and SUB stiffness are significant predictors → importance in episodic memory retention. - 2J-L. - [Illustrate correlations between HCsf stiffness and Spatial Reconstruction (SR) task performance] - CA1-CA2 stiffness is a significant predictor → role in spatial memory integration Figure 3. Correlations of Damping Ratio with Memory Performance  - 3A-C. - [Show correlations between the damping ratio (j) of HCsf regions and CVLT interference cost performance.] - No significant correlations → damping properties may not strongly influence this memory domain. - 3D-F. - [Displays correlations of damping ratio with delayed recall in the CVLT.] - No significant correlations are found → damping may not impact verbal recall performance. - 3G-I. - [Correlations of damping ratio with LM delayed recall] - again showing no significant associations - 3J-L. - [The damping ratio correlates significantly with SR performance across all HCsf regions] - Lower damping (i.e., less energy dissipation) is linked to better spatial memory performance Figure 4. Bivariate Correlations between Memory & Age  - 4A-D. → Summarize the relationship between memory and age - 4A. Negative correlation between age and CVLT for interference cost - older people have more difficulty suppressing interference (interference of giving 2 lists and whether they can remember). - 4B. Negative correlation between age and CVLT delayed recall - older people recall fewer words over time. - 4C. Similar negative correlation between age and LM delayed recall - as age increases, performance on delayed recall tasks from the Logical Memory test decreases → declines in the brain’s ability to support episodic memory over time - 4D. Strong negative correlation between age and SR performance - demonstrating a substantial age-related decline in spatial memory​ Figure 5. Bivariate Correlations between Stiffness, Damping, and Age  - 5A-C. - Negative correlations between the stiffness of each HCsf region and age - confirming that hippocampal stiffness declines with increasing age. - 5D-F. - Positive correlations between damping ratio and age for all hippocampal subfields - As age increases → the damping ratio in each hippocampal subfield also increases. - The hippocampal tissue becomes less capable of dissipating energy with aging (less stiff and more energy-absorbing). Figure 6. Mediation Analysis of Age Effects on Memory by HCsf Stiffness - 6A. - Mediation model where CA1-CA2 stiffness → mediates the relationship between age and CVLT interference cost performance. - Age has a strong negative effect on CA1-CA2 stiffness (-0.56, p < 0.001).  - CA1-CA2 stiffness positively correlates with CVLT interference cost → higher stiffness is associated with better interference suppression. - The indirect effect of age through CA1-CA2 stiffness is significant (-0.15, p = 0.031) - 6B-C. - DG-CA3 and SUB stiffness → mediate the relationship between age and LM delayed recall - stiffness declines in these subfields → episodic memory declines over time. - 6B. - Age negatively affects DG-CA3 stiffness (-0.43, p < 0.001). - DG-CA3 stiffness positively influences Logical Memory delayed recall (0.29, p < 0.05) → greater stiffness supports episodic memory. - The indirect effect is marginally significant (-0.13, p = 0.050) → DG-CA3 stiffness plays a partial role in mediating age-related declines in episodic memory. - 6C. - Age negatively correlates with subiculum stiffness (-0.47, p < 0.001). - Subiculum stiffness has a positive effect on Logical Memory delayed recall (0.27, p < 0.05), meaning higher stiffness is linked to better recall. - The indirect effect is marginally significant (-0.13, p = 0.054), suggesting that subiculum stiffness partially mediates age-related declines in episodic memory, similar to DG-CA3. - 6D. - Age strongly decreases CA1-CA2 stiffness (-0.56, p < 0.001). - However, CA1-CA2 stiffness does not significantly affect SR performance (0.18, not significant). - The indirect effect is not significant (-0.099, p = 0.073) → CA1-CA2 stiffness does not mediate the relationship between age and spatial memory - other factors contribute more to spatial memory decline with aging. Tables 3 & 4 - 3 → stiffness ⇒ important predictor on importance on tasks - 4 → damping ration ⇒ not a good predictor Summary - Appears that: - Higher stiffness in HC = better performance and stiffness decreases over lifespan - The lower damping ratio in HC = better performance and the damping ratio increases over the lifespan - But based on ridge regression, stiffness seems to be much more important than damping ratio in predicting cognitive function (along with age!) - CA1-CA2 viscoelasticity is the strongest predictor for two types of memory performance: recall following inference and short-delay relational memory - Aging affects HCsf integrity (viscoelasticity) and memory performance