Structure-Function Dissociations of Human Hippocampal Subfield Stiffness and Memory Performance.

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 and p = 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 STATEMENT Hippocampal 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-resolution in vivo imaging 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.

Sex differences in the severity and natural recovery of child PTSD symptoms: a longitudinal analysis of children exposed to acute trauma.

BACKGROUND: Higher levels of PTSD symptoms are present among trauma-exposed females v. males in adulthood; however, much less is known about the emergence of this sex difference during development. METHODS: In a multi-study sample of 7-18-year-olds (n = 3397), we examined the effect of sex and age on the severity of PTSD symptoms after a single incident trauma at 1 month (T1), and on symptom change after a natural recovery period of 3 (T2) and 6 months (T3). PTSD scores were harmonised across measurement types, and linear regressions were used to determine sex and age effects, adjusting for study level variance and trauma type. RESULTS: A sex × age interaction was observed at T1 (p < 0.001) demonstrating that older age was associated with greater PTSD symptom severity in females (ß = 0.008, p = 0.047), but less severe symptoms in males (ß = -0.011, p = 0.014). The same pattern was observed at T2 and T3, with sex differences beginning to emerge by age 12 years. PTSD symptoms decreased naturally by ~25% at T2 with little further improvement by T3. Further, females showed a greater reduction in symptoms at T3 than males, although the same effect was not observed at T2. CONCLUSIONS: Sex differences in PTSD symptoms become apparent during adolescence, due to opposing changes in susceptibility occurring in females and males with age. Understanding the factors contributing to these findings is likely to provide wider insight into sex-specific psychological vulnerability to trauma-related psychopathology.

Sex-Based Contributors to and Consequences of Post-traumatic Stress Disorder.

PURPOSE OF REVIEW: Women are twice as likely to develop post-traumatic stress disorder (PTSD) compared to men after a traumatic experience. The purpose of this mini review was to explore recent research on biological contributors to this sex difference. RECENT FINDINGS: We identified 51 studies published since 2019. Studies found that beyond the influence of sex on the prevalence and symptoms of PTSD, there is evidence for and against sex-based differences in genetic and epigenetic factors (n = 8), brain structure and function (n = 11), neuroendocrine and inflammatory responses (n = 5), and in the role of sleep on emotional memory processing (n = 1). Sex differences were also observed in recovery and during PTSD treatment (n = 16). Finally, there is emerging evidence of sex-differentiated risk for medical and psychiatric comorbidities in PTSD (n = 10). Rapid advances are being made using integrated multidisciplinary approaches to understand why females are at a heightened risk for developing PTSD.

Effect of Aging on the Viscoelastic Properties of Hippocampal Subfields Assessed with High-Resolution MR Elastography.

Age-related memory impairments have been linked to differences in structural brain parameters, including the integrity of the hippocampus (HC) and its distinct hippocampal subfields (HCsf). Imaging methods sensitive to the underlying tissue microstructure are valuable in characterizing age-related HCsf structural changes that may relate to cognitive function. Magnetic resonance elastography (MRE) is a noninvasive MRI technique that can quantify tissue viscoelasticity and may provide additional information about aging effects on HCsf health. Here, we report a high-resolution MRE protocol to quantify HCsf viscoelasticity through shear stiffness, µ, and damping ratio, ξ, which reflect the integrity of tissue composition and organization. HCsf exhibit distinct mechanical properties-the subiculum had the lowest µ and both subiculum and entorhinal cortex had the lowest ξ. Both measures correlated with age: HCsf µ was lower with age (P < 0.001) whereas ξ was higher (P = 0.002). The magnitude of age-related differences in ξ varied across HCsf (P = 0.011), suggesting differential patterns of brain aging. This study demonstrates the feasibility of using MRE to assess HCsf microstructural integrity and suggests incorporation of these metrics to evaluate HC health in neurocognitive disorders.

Aging brain mechanics: Progress and promise of magnetic resonance elastography.

Neuroimaging techniques that can sensitivity characterize healthy brain aging and detect subtle neuropathologies have enormous potential to assist in the early detection of neurodegenerative conditions such as Alzheimer's disease. Magnetic resonance elastography (MRE) has recently emerged as a reliable, high-resolution, and especially sensitive technique that can noninvasively characterize tissue biomechanical properties (i.e., viscoelasticity) in vivo in the living human brain. Brain tissue viscoelasticity provides a unique biophysical signature of neuroanatomy that are representative of the composition and organization of the complex tissue microstructure. In this article, we detail how progress in brain MRE technology has provided unique insights into healthy brain aging, neurodegeneration, and structure-function relationships. We further discuss additional promising technical innovations that will enhance the specificity and sensitivity for brain MRE to reveal considerably more about brain aging as well as its potentially valuable role as an imaging biomarker of neurodegeneration. MRE sensitivity may be particularly useful for assessing the efficacy of rehabilitation strategies, assisting in differentiating between dementia subtypes, and in understanding the causal mechanisms of disease which may lead to eventual pharmacotherapeutic development.

Standard-space atlas of the viscoelastic properties of the human brain.

Standard anatomical atlases are common in neuroimaging because they facilitate data analyses and comparisons across subjects and studies. The purpose of this study was to develop a standardized human brain atlas based on the physical mechanical properties (i.e., tissue viscoelasticity) of brain tissue using magnetic resonance elastography (MRE). MRE is a phase contrast-based MRI method that quantifies tissue viscoelasticity noninvasively and in vivo thus providing a macroscopic representation of the microstructural constituents of soft biological tissue. The development of standardized brain MRE atlases are therefore beneficial for comparing neural tissue integrity across populations. Data from a large number of healthy, young adults from multiple studies collected using common MRE acquisition and analysis protocols were assembled (N = 134; 78F/ 56 M; 18-35 years). Nonlinear image registration methods were applied to normalize viscoelastic property maps (shear stiffness, µ, and damping ratio, ξ) to the MNI152 standard structural template within the spatial coordinates of the ICBM-152. We find that average MRE brain templates contain emerging and symmetrized anatomical detail. Leveraging the substantial amount of data assembled, we illustrate that subcortical gray matter structures, white matter tracts, and regions of the cerebral cortex exhibit differing mechanical characteristics. Moreover, we report sex differences in viscoelasticity for specific neuroanatomical structures, which has implications for understanding patterns of individual differences in health and disease. These atlases provide reference values for clinical investigations as well as novel biophysical signatures of neuroanatomy. The templates are made openly available (github.com/mechneurolab/mre134) to foster collaboration across research institutions and to support robust cross-center comparisons.

Acute effects of high-intensity exercise on brain mechanical properties and cognitive function.

Previous studies have shown that engagement in even a single session of exercise can improve cognitive performance in the short term. However, the underlying physiological mechanisms contributing to this effect are still being studied. Recently, with improvements to advanced quantitative neuroimaging techniques, brain tissue mechanical properties can be sensitively and noninvasively measured with magnetic resonance elastography (MRE) and regional brain mechanical properties have been shown to reflect individual cognitive performance. Here we assess brain mechanical properties before and immediately after engagement in a high-intensity interval training (HIIT) regimen, as well as one-hour post-exercise. We find that immediately after exercise, subjects in the HIIT group had an average global brain stiffness decrease of 4.2% (p < 0.001), and an average brain damping ratio increase of 3.1% (p = 0.002). In contrast, control participants who did not engage in exercise showed no significant change over time in either stiffness or damping ratio. Changes in brain mechanical properties with exercise appeared to be regionally dependent, with the hippocampus decreasing in stiffness by 10.4%. We also found that one-hour after exercise, brain mechanical properties returned to initial baseline values. The magnitude of changes to brain mechanical properties also correlated with improvements in reaction time on executive control tasks (Eriksen Flanker and Stroop) with exercise. Understanding the neural changes that arise in response to exercise may inform potential mechanisms behind improvements to cognitive performance with acute exercise.

Vascular determinants of hippocampal viscoelastic properties in healthy adults across the lifespan.

Arterial stiffness and cerebrovascular pulsatility are non-traditional risk factors of Alzheimer's disease. However, there is a gap in understanding the earliest mechanisms that link these vascular determinants to brain aging. Changes to mechanical tissue properties of the hippocampus (HC), a brain structure essential for memory encoding, may reflect the impact of vascular dysfunction on brain aging. We tested the hypothesis that arterial stiffness and cerebrovascular pulsatility are related to HC tissue properties in healthy adults across the lifespan. Twenty-five adults underwent measurements of brachial blood pressure (BP), large elastic artery stiffness, middle cerebral artery pulsatility index (MCAv PI), and magnetic resonance elastography (MRE), a sensitive measure of HC viscoelasticity. Individuals with higher carotid pulse pressure (PP) exhibited lower HC stiffness (ß = -0.39, r = -0.41, p = 0.05), independent of age and sex. Collectively, carotid PP and MCAv PI significantly explained a large portion of the total variance in HC stiffness (adjusted R2 = 0.41, p = 0.005) in the absence of associations with HC volumes. These cross-sectional findings suggest that the earliest reductions in HC tissue properties are associated with alterations in vascular function.

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.

Maternal psychological distress during pregnancy has been linked to adverse outcomes in children with evidence of sex-specific effects on brain development. Here, we investigated whether in utero exposure to intimate partner violence (IPV), a particularly severe maternal stressor, is associated with brain structure in young infants from a South African birth cohort. Exposure to IPV during pregnancy was measured in 143 mothers at 28-32 weeks' gestation and infants underwent structural and diffusion magnetic resonance imaging (mean age 3 weeks). Subcortical volumetric estimates were compared between IPV-exposed (n = 63; 52% female) and unexposed infants (n = 80; 48% female), with white matter microstructure also examined in a subsample (IPV-exposed, n = 28, 54% female; unexposed infants, n = 42, 40% female). In confound adjusted analyses, maternal IPV exposure was associated with sexually dimorphic effects in brain volumes: IPV exposure predicted a larger caudate nucleus among males but not females, and smaller amygdala among females but not males. Diffusivity alterations within white matter tracts of interest were evident in males, but not females exposed to IPV. Results were robust to the removal of mother-infant pairs with pregnancy complications. Further research is required to understand how these early alterations are linked to the sex-bias in neuropsychiatric outcomes later observed in IPV-exposed children.

Influence of mild cognitive impairment and body mass index on white matter integrity assessed by diffusion tensor imaging.

Mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease, is characterized by decreased memory and cognition, which are linked to degenerative changes in the brain. To assess whether white matter (WM) integrity is compromised in MCI, we collected diffusion-weighted images from 60 healthy older adults (OA) (69.16 ± 0.7) and 20 older adults with amnestic MCI (72.45 ± 1.9). WM integrity differences were examined using Tract-Based Spatial Statistics (TBSS). We hypothesized that those with MCI would have diminished WM integrity relative to OA. In a whole-brain comparison, those with MCI showed higher axial diffusivity in the splenium (SCC) and body of the corpus callosum (BCC), superior corona radiata (SCR), and the retrolenticular part of the internal capsule (RLIC) (p's < .05 TFCE-corrected). Additionally, significant between-group connectivity differences were observed using probabilistic tractography between the SCC, chosen from the TBSS results, and forceps major and minor (p-value's < .05). To further relate a physical health indicator to WM alterations, linear regression showed significant interactions between cognitive status and body mass index (BMI) on diffusivity outcome measures from probabilistic tractography (p-value-'s < .05). Additionally, we examined the association between relational memory, BMI, and WM integrity. WM integrity was positively associated with relational memory performance. These findings suggest that these regions may be more sensitive to early markers of neurodegenerative disease and health behaviors, suggesting that modifiable lifestyle factors may affect white matter integrity.

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

Hippocampal subfields (HCsf) are brain regions important for memory function that are vulnerable to decline with amnestic mild cognitive impairment (aMCI), which is often a preclinical stage of Alzheimer's disease. Studies in aMCI patients often assess HCsf tissue integrity using measures of volume, which has little specificity to microstructure and pathology. We use magnetic resonance elastography (MRE) to examine the viscoelastic mechanical properties of HCsf tissue, which is related to structural integrity, and sensitively detect differences in older adults with aMCI compared to an age-matched control group. Group comparisons revealed HCsf viscoelasticity is differentially affected in aMCI, with CA1-CA2 and DG-CA3 exhibiting lower stiffness and CA1-CA2 exhibiting higher damping ratio, both indicating poorer tissue integrity in aMCI. Including HCsf stiffness in a logistic regression improves classification of aMCI beyond measures of volume alone. Additionally, lower DG-CA3 stiffness predicted aMCI status regardless of DG-CA3 volume. These findings showcase the benefit of using MRE in detecting subtle pathological tissue changes in individuals with aMCI via the HCsf particularly affected in the disease.

5-HTTLPR-environment interplay and its effects on neural reactivity in adolescents.

It is not known how 5-HTTLPR genotype x childhood adversity (CA) interactions that are associated with an increased risk for affective disorders in population studies operate at the neural systems level. We hypothesized that healthy adolescents at increased genetic and environmental risk for developing mood disorders (depression and anxiety) would demonstrate increased amygdala reactivity to emotional stimuli compared to those with only one such risk factor or those with none. Participants (n=67) were classified into one of 4 groups dependent on being homozygous for the long or short alleles within the serotonin-transporter-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene and exposure to CA in the first 11 years of life (present or absent). A functional magnetic resonance imaging investigation was undertaken which involved viewing emotionally-salient face stimuli. In addition, we assessed the role of other variables hypothesized to influence amygdala reactivity, namely recent negative life-events (RNLE) assessed at ages 14 and 17, current anxiety symptoms and psychiatric history. We replicated prior findings demonstrating moderation by gene variants in 5-HTTLPR, but found no support for an effect of CA on amygdala reactivity. We also found a significant effect of RNLE aged 17 with amygdala reactivity demonstrating additive, but not interactive effects with 5-HTTLPR. A whole-brain analysis found a 5-HTTLPR×CA interaction in the lingual gyrus whereby CA appears to differentially modify neural reactivity depending on genotype. These results demonstrate that two different forms of environmental adversities interplay with 5-HTTLPR and thereby differentially impact amygdala and cortical reactivity.

Evaluation of cerebral cortex viscoelastic property estimation with nonlinear inversion magnetic resonance elastography.

Objective. Magnetic resonance elastography (MRE) of the brain has shown promise as a sensitive neuroimaging biomarker for neurodegenerative disorders; however, the accuracy of performing MRE of the cerebral cortex warrants investigation due to the unique challenges of studying thinner and more complex geometries.Approach. A series of realistic, whole-brain simulation experiments are performed to examine the accuracy of MRE to measure the viscoelasticity (shear stiffness,µ, and damping ratio, ξ) of cortical structures predominantly effected in aging and neurodegeneration. Variations to MRE spatial resolution and the regularization of a nonlinear inversion (NLI) approach are examined.Main results. Higher-resolution MRE displacement data (1.25 mm isotropic resolution) and NLI with a low soft prior regularization weighting provided minimal measurement error compared to other studied protocols. With the optimized protocol, an average error inµand ξ was 3% and 11%, respectively, when compared with the known ground truth. Mid-line structures, as opposed to those on the cortical surface, generally display greater error. Varying model boundary conditions and reducing the thickness of the cortex by up to 0.67 mm (which is a realistic portrayal of neurodegenerative pathology) results in no loss in reconstruction accuracy.Significance. These experiments establish quantitative guidelines for the accuracy expected ofin vivoMRE of the cortex, with the proposed method providing valid MRE measures for future investigations into cortical viscoelasticity and relationships with health, cognition, and behavior.

Examining harmful impacts of the COVID-19 pandemic and school closures on parents and carers in the United Kingdom: A rapid review.

Background: As a result of the COVID-19 pandemic, school closures meant that for many households, home and school environments became intertwined. Parents and carers found themselves taking on the role as de-facto educators, as well as balancing working from home and caring for additional members of the household. Understanding the full extent of the effects incurred by parents and carers during school closures is vital to identifying and supporting vulnerable families. This rapid review aimed to appraise the available evidence on the potential effects of the COVID-19 pandemic on UK parents and carers. Methods: Searches for academic literature were conducted using Proquest Central, Scopus, and Google Scholar between 21st and 28th April 2021 using search terms describing "parents and carers", "COVID-19" and the "UK". Additional literature was identified on relevant parents and carers' organisations websites including charity reports. Results: Thirty-two articles were found relating to harms affecting parents and carers in the UK High levels of psychological distress, including anxiety and depression, were consistently identified in the general parent population, and especially in parents caring for a child with special educational needs and/or neurodevelopmental disorders (SEN/ND). Charity reports indicated that many parents, especially those from an ethnic minority background and kinship carers, were worse off financially and with food insecurities, whereas empirical evidence showed that mothers were more likely to initiate furlough for themselves compared with fathers or childless women. Domestic abuse support services also reported a sharp rise in demand during lockdown restrictions, and practitioners reported an increase in child and adolescent violence towards parents. Conclusions: Given the known impacts of parental stress, mental health problems, domestic violence and financial hardship on children's development, it is critical that these findings are taken into account in case of future pandemics to minimise harms both to parents and their families.

Sex differences in post-traumatic stress disorder in a high adversity cohort of South African adolescents: an examination of depressive symptoms, age, and trauma type as explanatory factors.

Background: Evidence from high-income countries (HICs) has documented a higher rate of post-traumatic stress disorder (PTSD) in females than males. However, data are limited on sex differences in PTSD from low- and middle-income countries (LMICs), despite particularly high levels of trauma experienced by LMIC youth. Objectives: In a sample of adolescents from an impoverished South African community, we examined sex differences in PTSD, as well as co-occurring depression, adolescent age, and the type and extent of trauma exposure as potential contributors to female vulnerability. Methods: Participants were recruited from high schools in the Khayelitsha area of Cape Town. Self-reported trauma exposure, PTSD and depressive symptoms were measured in 797 adolescents (62% female) aged 13-17 years. Poisson regressions were used to examine Risk Ratios (RR) based on probable PTSD diagnoses, and linear regressions were applied to assess posttraumatic stress symptom (PTSS) severity. Results: 92% of adolescents reported trauma exposure, of whom 28% had probable PTSD. Prevalence of PTSD was higher for females than for males, even when controlling for total trauma exposure (RR = 1.71, p < .001) and co-occurring depressive symptoms (RR = 1.45, p = .005). By contrast, sex differences in depression were eliminated after controlling for co-occurring PTSS. There was little evidence of age effects on the emergence of sex differences. At lower thresholds of interpersonal trauma, females showed higher levels of PTSS compared to males, but no sex differences were found at high levels of exposure. Conclusion: Higher PTSD rates are observed in adolescent females in a high adversity-LMIC sample suggesting sex differences are robust across international contexts. Sex differences in PTSD are unlikely to be explained by co-occurring depression and in this context sex differences in depression may be secondary to trauma and PTSD. However, exposure to significant interpersonal trauma appears to overrule any specific female vulnerability.

Antecedentes: La evidencia de una tasa más alta del trastorno de estrés postraumático (TEPT) ha sido documentada en países de ingresos altos (PIAs). Sin embargo, la evidencia respecto a las diferencias según el sexo es limitada en países con ingresos bajos o medios (PIBMs) a pesar de los niveles altos de trauma que experimenta su población joven.Objetivos: Evaluamos las diferencias según género en el TEPT, además de la depresión comórbida, la edad del adolescente y el tipo y la duración de la exposición al trauma como potenciales contribuyentes a la vulnerabilidad femenina en una muestra de adolescentes de una comunidad pobre de Sudáfrica.Métodos: Se reclutaron a los participantes de los colegios de secundaria del área de Khayelitsha de la Ciudad del Cabo. Se midieron la exposición autorreportada al trauma, los síntomas del TEPT y los síntomas de la depresión en 797 adolescentes (62% mujeres) entre los 13 y los 17 años. Se emplearon las regresiones de Poisson para evaluar el riesgo relativo (RR) basado en los diagnósticos probables del TEPT y se emplearon regresiones lineales para evaluar la severidad de los síntomas de estrés postraumático (SEPTs).Resultados: El 92% de los adolescentes reportó exposición al trauma, del cual un 28% tenía un probable TEPT. La prevalencia del TEPT era más alta en mujeres que en varones, incluso luego de controlar el efecto de la exposición total al trauma (RR = 1.71, p < .001) y de los síntomas de la depresión comórbida (RR = 1.45, p = .005). Por el contrario, las diferencias según el sexo en la depresión fueron eliminadas luego de controlar el efecto de los SEPTs comórbidos. Había poca evidencia de que la edad tenga efecto sobre el origen de la diferencia según el sexo. Al emplear puntos de corte más bajos para medir el trauma interpersonal, las mujeres mostraron niveles más altos de SEPTs en comparación con los hombres; no obstante, no se encontraron diferencias según el sexo con niveles más elevados de exposición.Conclusión: Se observan tasas del TEPT más altas en mujeres adolescentes en una muestra alta en exposición a la adversidad en un PIBM, lo que sugiere que las diferencias según el sexo son robustas y transversales a los contextos internacionales. Es poco probable que las diferencias según el sexo en el TEPT se expliquen por la depresión comórbida y, en este contexto, la depresión podría ser secundaria al trauma y al TEPT. Sin embargo, la exposición a un trauma interpersonal significativo impresiona anular cualquier vulnerabilidad femenina específica.

Calibration of a Heterogeneous Brain Model Using a Subject-Specific Inverse Finite Element Approach.

Central to the investigation of the biomechanics of traumatic brain injury (TBI) and the assessment of injury risk from head impact are finite element (FE) models of the human brain. However, many existing FE human brain models have been developed with simplified representations of the parenchyma, which may limit their applicability as an injury prediction tool. Recent advances in neuroimaging techniques and brain biomechanics provide new and necessary experimental data that can improve the biofidelity of FE brain models. In this study, the CAB-20MSym template model was developed, calibrated, and extensively verified. To implement material heterogeneity, a magnetic resonance elastography (MRE) template image was leveraged to define the relative stiffness gradient of the brain model. A multi-stage inverse FE (iFE) approach was used to calibrate the material parameters that defined the underlying non-linear deviatoric response by minimizing the error between model-predicted brain displacements and experimental displacement data. This process involved calibrating the infinitesimal shear modulus of the material using low-severity, low-deformation impact cases and the material non-linearity using high-severity, high-deformation cases from a dataset of in situ brain displacements obtained from cadaveric specimens. To minimize the geometric discrepancy between the FE models used in the iFE calibration and the cadaveric specimens from which the experimental data were obtained, subject-specific models of these cadaveric brain specimens were developed and used in the calibration process. Finally, the calibrated material parameters were extensively verified using independent brain displacement data from 33 rotational head impacts, spanning multiple loading directions (sagittal, coronal, axial), magnitudes (20-40 rad/s), durations (30-60 ms), and severity. Overall, the heterogeneous CAB-20MSym template model demonstrated good biofidelity with a mean overall CORA score of 0.63 ± 0.06 when compared to in situ brain displacement data. Strains predicted by the calibrated model under non-injurious rotational impacts in human volunteers (N = 6) also demonstrated similar biofidelity compared to in vivo measurements obtained from tagged magnetic resonance imaging studies. In addition to serving as an anatomically accurate model for further investigations of TBI biomechanics, the MRE-based framework for implementing material heterogeneity could serve as a foundation for incorporating subject-specific material properties in future models.

Blood lipid markers are associated with hippocampal viscoelastic properties and memory in humans.

Age-related memory loss shares similar risk factors as cardiometabolic diseases including elevated serum triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C). The mechanisms linking these aberrant blood lipids to memory loss are not completely understood but may be partially mediated by reduced integrity of the hippocampus (HC), the primary brain structure for encoding and recalling memories. In this study, we tested the hypothesis that blood lipid markers are independently associated with memory performance and HC viscoelasticity-a noninvasive measure of brain tissue microstructural integrity assessed by high-resolution magnetic resonance elastography (MRE). Twenty-six individuals across the adult lifespan were recruited (14 M/12 F; mean age: 42 ± 15 y; age range: 22-78 y) and serum lipid profiles were related to episodic memory and HC viscoelasticity. All subjects were generally healthy without clinically abnormal blood lipids or memory loss. Episodic memory was negatively associated with the TG/HDL-C ratio. HC viscoelasticity was negatively associated with serum TGs and the TG/HDL-C ratio, independent of age and in the absence of associations with HC volume. These data, although cross-sectional, suggest that subtle differences in blood lipid profiles in healthy adults may contribute to a reduction in memory function and HC tissue integrity.

Mechanical property alterations across the cerebral cortex due to Alzheimer's disease.

Alzheimer's disease is a personally devastating neurodegenerative disorder and a major public health concern. There is an urgent need for medical imaging techniques that better characterize the early stages and monitor the progression of the disease. Magnetic resonance elastography (MRE) is a relatively new and highly sensitive MRI technique that can non-invasively assess tissue microstructural integrity via measurement of brain viscoelastic mechanical properties. For the first time, we use high-resolution MRE methods to conduct a voxel-wise MRE investigation and state-of-the-art post hoc region of interest analysis of the viscoelastic properties of the cerebral cortex in patients with Alzheimer's disease (N = 11) compared with cognitively healthy older adults (N = 12). We replicated previous findings that have reported significant volume and stiffness reductions at the whole-brain level. Significant reductions in volume were also observed in Alzheimer's disease when white matter, cortical grey matter and subcortical grey matter compartments were considered separately; lower stiffness was also observed in white matter and cortical grey matter, but not in subcortical grey matter. Voxel-based morphometry of both cortical and subcortical grey matter revealed localized reductions in volume due to Alzheimer's disease in the hippocampus, fusiform, middle, superior temporal gyri and precuneus. Similarly, voxel-based MRE identified lower stiffness in the middle and superior temporal gyri and precuneus, although the spatial distribution of these effects was not identical to the pattern of volume reduction. Notably, MRE additionally identified stiffness deficits in the operculum and precentral gyrus located within the frontal lobe; regions that did not undergo volume loss identified through voxel-based morphometry. Voxel-based-morphometry and voxel-based MRE results were confirmed by a complementary post hoc region-of-interest approach in native space where the viscoelastic changes remained significant even after statistically controlling for regional volumes. The pattern of reduction in cortical stiffness observed in Alzheimer's disease patients raises the possibility that MRE may provide unique insights regarding the neural mechanisms which underlie the development and progression of the disease. The measured mechanical property changes that we have observed warrant further exploration to investigate the diagnostic usefulness of MRE in cases of Alzheimer's disease and other dementias.

Hippocampal viscoelasticity and episodic memory performance in healthy older adults examined with magnetic resonance elastography.

Episodic memory is particularly sensitive to normative aging; however, studies investigating the structure-function relationships that support episodic memory have primarily been limited to gross volumetric measures of brain tissue health. Magnetic resonance elastography (MRE) is an emerging non-invasive, high-resolution imaging technique that uniquely quantifies brain viscoelasticity, and as such, provides a more specific measure of neural microstructural integrity. Recently, a significant double dissociation between orbitofrontal cortex-fluid intelligence and hippocampal-relational memory structure-function relationships was observed in young adults, highlighting the potential of sensitive MRE measures for studying brain health and its relation to cognitive function. However, the structure-function relationship observed by MRE has not yet been explored in healthy older adults. In this study, we examined the relationship between hippocampal (HC) viscoelasticity and episodic memory in cognitively healthy adults aged 66-73 years (N = 11), as measured with the verbal-paired associates (VPA) subtest from the Wechsler Memory Scale (WMS-R). Given the particular dependence of verbal memory tasks on the left HC, unilateral HC MRE measurements were considered for the first time. A significant negative correlation was found between left HC damping ratio, ξ and VPA recall score (rs = -0.77, p = 0.009), which is consistent with previous findings of a relationship between HC ξ and memory performance in young adults. Conversely, correlations between right HC ξ with VPA recall score were not significant. These results highlight the utility of MRE to study cognitive decline and brain aging and suggest its possible use as a sensitive imaging biomarker for memory-related impairments.

Network analysis of canine brain morphometry links tumour risk to oestrogen deficiency and accelerated brain ageing.

Structural 'brain age' is a valuable but complex biomarker for several brain disorders. The dog is an unrivalled comparator for neurological disease modeling, however canine brain morphometric diversity creates computational and statistical challenges. Using a data-driven approach, we explored complex interactions between patient metadata, brain morphometry, and neurological disease. Twenty-four morphometric parameters measured from 286 canine brain magnetic resonance imaging scans were combined with clinical parameters to generate 9,438 data points. Network analysis was used to cluster patients according to their brain morphometry profiles. An 'aged-brain' profile, defined by a small brain width and volume combined with ventriculomegaly, was revealed in the Boxer breed. Key features of this profile were paralleled in neutered female dogs which, relative to un-neutered females, had an 11-fold greater risk of developing brain tumours. Boxer dog and geriatric dog groups were both enriched for brain tumour diagnoses, despite a lack of geriatric Boxers within the cohort. Our findings suggest that advanced brain ageing enhances brain tumour risk in dogs and may be influenced by oestrogen deficiency-a risk factor for dementia and brain tumours in humans. Morphometric features of brain ageing in dogs, like humans, might better predict neurological disease risk than patient chronological age.