Hippocampal Volume Changes Research Articles

Effects of exergaming on hippocampal volume and brain-derived neurotrophic factor levels in Parkinson's disease.

Cognitive impairment is among the most burdensome non-motor symptoms in Parkinson's disease (PD) and has been associated with hippocampal atrophy. Exercise has been reported to enhance neuroplasticity in the hippocampus in correlation with an improvement of cognitive function. We present data from the Training-PD study, which was designed to evaluate effects of an "" training protocol on neuronal plasticity in PD. We initiated a 6-week exergaming training program, combining visually stimulating computer games with physical exercise in 17 PD patients and 18matched healthy controls. Volumetric segmentation of hippocampal subfields on T1- and T2-weighted magnetic resonance imaging and brain-derived neurotrophic factor (BDNF) serum levels were analyzed before and after the training protocol. The PD group showed a group-dependent significant volume increase of the left hippocampal subfields CA1, CA4/dentate gyrus (DG) and subiculum after the 6-week training protocol. The effect was most pronounced in the left DG of PD patients, who showed a significantly smaller percentage volume compared to healthy controls at baseline, but not at follow-up. Both groups had a significant increase in serum BDNF levels after training. The results of the present study indicate that exergaming might be a suitable approach to induce hippocampal volume changes in PD patients. Further and larger studies are needed to verify our findings.

RADT-35. CHANGE IN HIPPOCAMPAL VOLUME AS A FUNCTION OF RADIATION DOSE: RESULTS FROM A PROSPECTIVE TRIAL WITH STANDARDIZED IMAGING AND MORPHOMETRIC EVALUATION

Abstract PURPOSE/OBJECTIVES MRIs in pediatric and adult brain tumor patients (Age< 35) were prospectively collected at baseline and during follow-up to measure volumetric changes in multiple brain substructures with neurocognitive, laboratory, and quality-of-life assessments. In this planned interim analysis, we model early outcomes for change in hippocampal volume at 6 months following radiotherapy. MATERIALS AND METHODS As of 5/15/2021, 50 patients enrolled on this prospective study and 41 completed 6-month post-treatment assessments after fractionated intensity-modulated proton therapy. Left and right hippocampus volumes were independently measured on T1 sagittal precontrast MRI at baseline and 6-months after radiotherapy using both automated software and physician-delineated contours. The relationship between mean hippocampus dose and change in volume was assessed by Pearson’s correlation coefficient. A linear mixed-effects model was applied to evaluate other predictors associated with change in hippocampal volume, assuming random effects of subjects. RESULTS Mean hippocampus dose was strongly correlated with change in hippocampal volume at 6 months following radiotherapy (r=−0.727, 95% CI [-0.820,-0.596], p< 0.001). Changes in hippocampal volumes over time were similar between software and physician contours. Hippocampal volume was significantly reduced for mean doses ≥10 Gy (mean Δ -10.8% ± 5.5%, p< 0.001), while no significant volume change was observed with mean doses < 10 Gy (mean Δ +0.7% ± 3.9%). In the mixed-effects model, only mean hippocampus dose was significantly associated with hippocampal volume change (p< 0.001). The final model predicted a -3.4% change in hippocampal volume for every 10 Gy increase in mean dose. CONCLUSIONS Change in hippocampal volume was correlated with hippocampus mean dose at 6 months following radiotherapy. Future analyses will assess volume change in the hippocampus and other brain substructures over time as a function of radiation dose and correlate with measured neurocognitive and other effects.

Change in Hippocampus Volume as a Function of Radiation Dose: Early Results From a Prospective Trial with Standardized Imaging and Morphometric Evaluation

<h3>Purpose/Objective(s)</h3> Pediatric brain tumor patients are at high risk of developing neurocognitive deficits following treatment. The perihippocampal subventricular zone contains a niche of radiosensitive neural progenitor cells linked to memory development, and radiotherapy (RT) to this brain substructure has been associated with neurocognitive impairment in randomized trials. In this prospective study, 3D volumetric MRIs were obtained in pediatric brain tumor patients at baseline and during follow-up to measure volumetric changes in multiple brain substructures along with neurocognitive, endocrine, quality-of-life, and exploratory biomarker assessments. In this planned interim analysis, we model early outcomes for change in hippocampal volume at 6 months following RT. <h3>Materials/Methods</h3> As of 2/26/2021, 47 patients had enrolled on this prospective study and 36 had completed their 6-month follow-up assessments after fractionated intensity-modulated proton therapy (IMPT) for primary brain and skull base tumors. Left and right hippocampus volumes were independently measured on T1 sagittal precontrast MRI using automated software at baseline and 6-months after RT and were compared to manual physician contours. The relationship between mean hippocampus dose and change in volume was assessed by Pearson's correlation coefficient. The effect of mean hippocampus dose on change in volume was assessed for mean doses < 10 Gy and ≥10 Gy by t-test. A linear mixed-effects (LME) model was applied to evaluate other predictors associated with change in hippocampus volume, assuming random effects of subjects. Potential factors considered were age, gender, tumor location, focal vs. whole brain RT, prior craniotomy, and chemotherapy. <h3>Results</h3> Mean hippocampus dose was strongly correlated with change in hippocampus volume at 6 months following RT (r = −0.727, 95% CI [-0.820 -0.596], <i>P</i> < 0.001). Hippocampus volumes and observed changes over time were similar between the software and physician-delineated contours. A significant reduction in hippocampus volume was observed for mean doses ≥10 Gy (mean Δ -10.8% ± 5.5%, <i>P</i> < 0.001), while no significant change in volume was observed for mean doses < 10 Gy (mean Δ +0.7% ± 3.9%). The LME model demonstrated that only mean hippocampus dose was significantly associated with change in hippocampus volume (<i>P</i> < 0.001). The final model predicted a -3.4% change in hippocampus volume for every 10 Gy increase in mean dose. Regression diagnostics showed no evidence of lack-of-fit and no patterns in residuals. <h3>Conclusion</h3> Change in hippocampus volume was correlated with hippocampus mean dose at 6 months following RT. A significant reduction in hippocampus volume was observed for mean doses ≥10 Gy compared to no significant change at mean doses < 10 Gy. Future analyses from this study will assess volume change in this and other brain substructures over time as a function of radiation dose and will correlate these findings with measured neurocognitive and other late effects.

Neurodegeneration Over 3 Years Following Ischaemic Stroke: Findings From the Cognition and Neocortical Volume After Stroke Study.

Background: Stroke survivors are at high risk of dementia, associated with increasing age and vascular burden and with pre-existing cognitive impairment, older age. Brain atrophy patterns are recognised as signatures of neurodegenerative conditions, but the natural history of brain atrophy after stroke remains poorly described. We sought to determine whether stroke survivors who were cognitively normal at time of stroke had greater total brain (TBV) and hippocampal volume (HV) loss over 3 years than controls. We examined whether stroke survivors who were cognitively impaired (CI) at 3 months following their stroke had greater brain volume loss than cognitively normal (CN) stroke participants over the next 3 years.Methods: Cognition And Neocortical Volume After Stroke (CANVAS) study is a multi-centre cohort study of first-ever or recurrent adult ischaemic stroke participants compared to age- and sex-matched community controls. Participants were followed with MRI and cognitive assessments over 3 years and were free of a history of cognitive impairment or decline at inclusion. Our primary outcome measure was TBV change between 3 months and 3 years; secondary outcomes were TBV and HV change comparing CI and CN participants. We investigated associations between group status and brain volume change using a baseline-volume adjusted linear regression model with robust standard error.Results: Ninety-three stroke (26 women, 66.7 ± 12 years) and 39 control participants (15 women, 68.7 ± 7 years) were available at 3 years. TBV loss in stroke patients was greater than controls: stroke mean (M) = 20.3 cm3 ± SD 14.8 cm3; controls M = 14.2 cm3 ± SD 13.2 cm3; [adjusted mean difference 7.88 95%CI (2.84, 12.91) p-value = 0.002]. TBV decline was greater in those stroke participants who were cognitively impaired (M = 30.7 cm3; SD = 14.2 cm3) at 3 months (M = 19.6 cm3; SD = 13.8 cm3); [adjusted mean difference 10.42; 95%CI (3.04, 17.80), p-value = 0.006]. No statistically significant differences in HV change were observed.Conclusions: Ischaemic stroke survivors exhibit greater neurodegeneration compared to stroke-free controls. Brain atrophy is greater in stroke participants who were cognitively impaired early after their stroke. Early cognitive impairment was associated greater subsequent atrophy, reflecting the combined impacts of stroke and vascular brain burden. Atrophy rates could serve as a useful biomarker for trials testing interventions to reduce post-stroke secondary neurodegeneration.Clinical Trail Registration: http://www.clinicaltrials.gov, identifier: NCT02205424.

Longitudinal Effects of Physical Activity Change on Hippocampal Volumes over up to 12Years in Middle and Older Age Community-Dwelling Individuals.

The objectives of this study were to investigate the long-term associations between changes in physical activity levels and hippocampal volumes over time, while considering the influence of age, sex, and APOE-ε4 genotype. We investigated the effects of change in physical activity on hippocampal volumes in 411 middle age (mean age = 47.2years) and 375 older age (mean age = 63.1years) adults followed up to 12years. An annual volume decrease was observed in the left (middle age: 0.46%; older age: 0.51%) but not in the right hippocampus. Each additional 10 metabolic equivalents (METs, ~2h of moderate exercise) increase in weekly physical activity was associated with 0.33% larger hippocampal volume in middle age (equivalent to ~1year of typical aging). In older age, each additional MET was associated with 0.05% larger hippocampal volume; however, the effects declined with time by 0.005% per year. For older age APOE-ε4 carriers, each additional MET was associated with a 0.10% increase in hippocampal volume. No sex effects of physical activity change were found. Increasing physical activity has long-term positive effects on hippocampal volumes and appears especially beneficial for older APOE-ε4 carriers. To optimize healthy brain aging, physical activity programs should focus on creating long-term exercise habits.

The analysis of structural magnetic resonance imaging manifestation of hippocampus based on voxel and spherical harmonic surface morphometry in mesial temporal lobe epilepsy

Objective: To compare the hippocampal volume and local surface morphology changes in patients with mesial temporal lobe (mTLE) using the voxel-based morphometry and spherical harmonic methods respectively. Methods: A total of 66 patients (31 males and 35 females, age range from 17 to 48 (28±8) years) with mTLE and 80 age-and gender-matched controls (38 males and 42 females, age range from 19 to 46 (27±7) years) were retrospectively collected from July 2009 to February 2019 at Jinling hospital.. High resolution structural MRI of the whole brain, three-dimensional T1-weighted data(3DT1) were acquired from each subject. The changes of hippocampal volume and surface morphology were evaluated between mTLE groups and controls for observing the hippocampal atrophy pattern by using voxel-based morphometry and spherical harmonic shape descriptions point distribution model respectively. Pearson correlation analysis was conducted for observing the relationship between the morphological changes of hippocampus and disease duration. Results: Compared with the controls, hippocampal volume on the affected side in patients with mTLE was significantly reduced (Z-score:-1.55±0.57 vs 0.38±0.58, P<0.001) and negatively correlated with disease duration (r=-0.297, P=0.016). Furthermore, surface morphology analysis subtly showed that the atrophy of the affected hippocampus in patients with mTLE mainly located in the head, mesial lateral part and posterior tail of the hippocampus. Their displacement values were negatively correlated with disease duration (r=-0.336, P=0.006) and positively associated with the hippocampal grey matter volume (r=0.336, P=0.006). Conclusions: Voxel-based morphometry analysis reveals a global reduction in hippocampal volume, while the morphological measurement method based on surface shape can describe the local morphological changes of hippocampal atrophy.

Seizure control does not predict hippocampal subfield volume change in children with focal drug-resistant epilepsy.

Background and purposeRecurrent seizures have been reported to induce neuronal loss in the hippocampus. It is unclear whether seizure control influences hippocampal volume. The aims of this study were to determine if there was a change in total or subfield hippocampal volume over time in children with focal drug-resistant epilepsy, and whether seizure control influenced total or subfield hippocampal volumes.MethodsUsing FreeSurfer’s automated segmentation of brain magnetic resonance imaging scans, we calculated the total and subfield (including CA1, CA3, CA4, subiculum, presubiculum, parasubiculum, molecular layer and dentate gyrus) hippocampal volumes of children with non-lesional focal epilepsy. Seizure frequency and hippocampal volumes were assessed at baseline and follow-up. Patients were classified into those who were seizure free or have improvement in seizures (group 1) and those with no improvement in seizures (group 2) at follow-up.ResultsThirty-seven patients were included, with mean age 10.31 ± 3.68 years at baseline. The interval between the two magnetic resonance imaging scans was 2.59 ± 1.25 years. There was no significant difference in the total and subfield hippocampal volumes for the whole cohort at follow-up compared to baseline (all P > 0.002). Seizure control of the two groups did not predict total or subfield hippocampal volume, after controlling for baseline volume, age, severity of seizure frequency at baseline and time interval between the magnetic resonance imaging scans (all P > 0.002).ConclusionWe have found that total and subfield hippocampal volumes did not change, and seizure control did not predict hippocampal volumes at follow-up in children with drug-resistant epilepsy.

High resolution diffusion tensor imaging of the hippocampus across the healthy lifespan.

The human hippocampus is difficult to image given its small size, location, shape, and complex internal architecture. Structural magnetic resonance imaging (MRI) has shown age-related hippocampal volume changes that vary along the anterior-posterior axis. Diffusion tensor imaging (DTI) provides complementary measures related to microstructure, but there are few hippocampus DTI studies investigating change with age in healthy participants, and all have been limited by low spatial resolution. The current study uses high resolution 1 mm isotropic DTI of 153 healthy volunteers aged 5-74 years to investigate diffusion and volume trajectories of the hippocampus (whole, head, body, and tail) and correlations with memory. Hippocampal volume showed age-related changes that differed between head (peaking at midlife), body (no changes), and tail (decreasing across the age span). Fractional anisotropy (FA) and mean, axial, and radial diffusivities (MD, AD, RD) yielded peaks or minima, respectively, at ~30-35 years in all three subregions of the hippocampus. Greater magnitude changes were observed during development than in aging. Age trajectories for both volume and DTI were similar between males and females. Correlations between tests of memory and FA and/or volume were significant in younger subjects (5-17 years), but not in 18-49 year olds or 50-74 year olds. MD was significantly correlated with memory performance in 18-49 year olds, but not in other age groups. Given the diffusion-weighted image contrast and resolution, head digitations could be examined revealing that the majority of subjects had 3-4 (48%) or 2 (32%) bilaterally with no effect of age. One millimeter isotropic DTI yielded high quality diffusion-weighted maps of the human hippocampus that showed regionally specific age effects and cognitive correlations along the anterior-posterior axis from 5 to 74 years.

Presumed small vessel disease, imaging and cognition markers in the Alzheimer's Disease Neuroimaging Initiative.

MRI-derived features of presumed cerebral small vessel disease are frequently found in Alzheimer’s disease. Influences of such markers on disease-progression measures are poorly understood. We measured markers of presumed small vessel disease (white matter hyperintensity volumes; cerebral microbleeds) on baseline images of newly enrolled individuals in the Alzheimer’s Disease Neuroimaging Initiative cohort (GO and 2) and used linear mixed models to relate these to subsequent atrophy and neuropsychological score change. We also assessed heterogeneity in white matter hyperintensity positioning within biomarker abnormality sequences, driven by the data, using the Subtype and Stage Inference algorithm. This study recruited both sexes and included: controls: [n = 159, mean(SD) age = 74(6) years]; early and late mild cognitive impairment [ns = 265 and 139, respectively, mean(SD) ages =71(7) and 72(8) years, respectively]; Alzheimer’s disease [n = 103, mean(SD) age = 75(8)] and significant memory concern [n = 72, mean(SD) age = 72(6) years]. Baseline demographic and vascular risk-factor data, and longitudinal cognitive scores (Mini-Mental State Examination; logical memory; and Trails A and B) were collected. Whole-brain and hippocampal volume change metrics were calculated. White matter hyperintensity volumes were associated with greater whole-brain and hippocampal volume changes independently of cerebral microbleeds (a doubling of baseline white matter hyperintensity was associated with an increase in atrophy rate of 0.3 ml/year for brain and 0.013 ml/year for hippocampus). Cerebral microbleeds were found in 15% of individuals and the presence of a microbleed, as opposed to none, was associated with increases in atrophy rate of 1.4 ml/year for whole brain and 0.021 ml/year for hippocampus. White matter hyperintensities were predictive of greater decline in all neuropsychological scores, while cerebral microbleeds were predictive of decline in logical memory (immediate recall) and Mini-Mental State Examination scores. We identified distinct groups with specific sequences of biomarker abnormality using continuous baseline measures and brain volume change. Four clusters were found; Group 1 showed early Alzheimer’s pathology; Group 2 showed early neurodegeneration; Group 3 had early mixed Alzheimer’s and cerebrovascular pathology; Group 4 had early neuropsychological score abnormalities. White matter hyperintensity volumes becoming abnormal was a late event for Groups 1 and 4 and an early event for 2 and 3. In summary, white matter hyperintensities and microbleeds were independently associated with progressive neurodegeneration (brain atrophy rates) and cognitive decline (change in neuropsychological scores). Mechanisms involving white matter hyperintensities and progression and microbleeds and progression may be partially separate. Distinct sequences of biomarker progression were found. White matter hyperintensity development was an early event in two sequences.

What Can We Tell About the Effect of Electroconvulsive Therapy on the Human Hippocampus?

Electroconvulsive therapy (ECT) is the most effective antidepressant treatment, although its mechanisms of action remain unclear. Since 2010, several structural magnetic resonance imaging studies based on a neuroplastic hypothesis have consistently reported increases in the hippocampal volume following ECT. Moreover, volume increases in the human dentate gyrus, where neurogenesis occurs, have also been reported. These results are in line with the preclinical findings of ECT-induced neuroplastic changes, including neurogenesis, gliogenesis, synaptogenesis, and angiogenesis, in rodents and nonhuman primates. Despite this robust evidence of an effect of ECT on hippocampal plasticity, the clinical relevance of these human hippocampal changes continues to be questioned. This narrative review summarizes recent findings regarding ECT-induced hippocampal volume changes. Furthermore, this review also discusses methodological considerations and future directions in this field.

1271Green tea consumption is associated with annual changes in hippocampal volumes: a longitudinal study

Abstract Background To investigate the association between green tea consumption and the annual rate of change of gray matter (GM), white matter (WM), and hippocampal volumes in middle-aged and older Japanese community-dwellers. Methods A prospective cohort study with two years of follow-up was conducted with 1693 participants (aged 40–89 years). Green tea consumption (mL/day) data were collected with a 3-day dietary record. Volumes of GM, WM, and the hippocampus were estimated by T1-weighted brain magnetic resonance imaging and FreeSurfer software. The GM ratio, WM ratio, and hippocampal ratio (HR) were calculated as the percentages of total intracranial volume, respectively. Results The mean (SD) annual rate of change of hippocampal volume [(HR at baseline - HR at follow-up)/HR at baseline/follow-up years×100%] was 0.499 (1.128) (%). In the multivariable-adjusted general linear model, green tea consumption at baseline was negatively associated only with the annual rate of change of hippocampal volume (%) [β (95% CI) for each 1 mL/day increase in green tea consumption = -20.2E-5 (-35.0E-5 to -5.3E-5); P-value = 0.008]. No associations were observed for the annual rate of change of GM or WM volumes. The results remained significant when the analysis was limited to those with stable green tea consumption and were especially evident among individuals aged 65 years and older and among women. Conclusions In this study, each additional 100 mL/day of green tea intake was related to a reduction of approximately 5% in annual hippocampal atrophy. This association was especially evident among older individuals and among women. Key messages A negative association between green tea consumption and brain atrophy has been suggested; however, this relationship has not yet been investigated in humans. In this study, for the first time, a negative association between green tea consumption and annual hippocampal atrophy was observed in community-dwelling middle-aged and older individuals.

DeepAtrophy: Teaching a neural network to detect progressive changes in longitudinal MRI of the hippocampal region in Alzheimer's disease

Measures of change in hippocampal volume derived from longitudinal MRI are a well-studied biomarker of disease progression in Alzheimer's disease (AD) and are used in clinical trials to track therapeutic efficacy of disease-modifying treatments. However, longitudinal MRI change measures based on deformable registration can be confounded by MRI artifacts, resulting in over-estimation or underestimation of hippocampal atrophy. For example, the deformation-based-morphometry method ALOHA (Das et al., 2012) finds an increase in hippocampal volume in a substantial proportion of longitudinal scan pairs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, unexpected, given that the hippocampal gray matter is lost with age and disease progression. We propose an alternative approach to quantify disease progression in the hippocampal region: to train a deep learning network (called DeepAtrophy) to infer temporal information from longitudinal scan pairs. The underlying assumption is that by learning to derive time-related information from scan pairs, the network implicitly learns to detect progressive changes that are related to aging and disease progression. Our network is trained using two categorical loss functions: one that measures the network's ability to correctly order two scans from the same subject, input in arbitrary order; and another that measures the ability to correctly infer the ratio of inter-scan intervals between two pairs of same-subject input scans. When applied to longitudinal MRI scan pairs from subjects unseen during training, DeepAtrophy achieves greater accuracy in scan temporal ordering and interscan interval inference tasks than ALOHA (88.5% vs. 75.5% and 81.1% vs. 75.0%, respectively). A scalar measure of time-related change in a subject level derived from DeepAtrophy is then examined as a biomarker of disease progression in the context of AD clinical trials. We find that this measure performs on par with ALOHA in discriminating groups of individuals at different stages of the AD continuum. Overall, our results suggest that using deep learning to infer temporal information from longitudinal MRI of the hippocampal region has good potential as a biomarker of disease progression, and hints that combining this approach with conventional deformation-based morphometry algorithms may lead to improved biomarkers in the future.

Sub-regional hippocampal volumes in first-episode drug-naïve major depression disorder

Hippocampal volume reduction was reported to underlie depressive symptomatology, however, the evidence to date remains inconsistent. For the complex intrinsic organization of hippocampus, the hippocampal volumes can be further divided into subfields or axial parts. The current study aimed to explore the alterations of hippocampal sub-regional volumes in first episode drug-naïve major depressive disorder (MDD) by two segmentation methods. Thirty-five first-episode drug-naïve MDD and 35 age- and gender-matched healthy controls (HC) were recruited. Volumes of three sub-regions of hippocampus along the longitudinal axis (head, body and tail) were analyzed manually and eight transverse subfields were automatically determined using FreeSurfer. An asymmetric index (AI) of volumes was defined as (∣Left − Right∣/∣Left + Right∣) * 100. There were significant reductions in the volumes of bilateral hippocampal head in MDD compared to HC. The volumes of eight subfields were not different between groups. MDD patients had higher AI values in the subfield of cornu ammonis 4/dentate gyrus than HC. The change in hippocampal sub-regional volumes might be an imaging biomarker in the first-episode, drug-naïve patients with MDD. Current findings may contribute to developing new diagnostic and therapeutic strategies for major depression.

From reaction kinetics to dementia: A simple dimer model of Alzheimer's disease etiology.

Oligomers of the amyloid β-protein (Aβ) have been implicated in the pathogenesis of Alzheimer’s disease (AD) through their toxicity towards neurons. Understanding the process of oligomerization may contribute to the development of therapeutic agents, but this has been difficult due to the complexity of oligomerization and the metastability of the oligomers thus formed. To understand the kinetics of oligomer formation, and how that relates to the progression of AD, we developed models of the oligomerization process. Here, we use experimental data from cell viability assays and proxies for rate constants involved in monomer-dimer-trimer kinetics to develop a simple mathematical model linking Aβ assembly to oligomer-induced neuronal degeneration. This model recapitulates the rapid growth of disease incidence with age. It does so through incorporation of age-dependent changes in rates of Aβ monomer production and elimination. The model also describes clinical progression in genetic forms of AD (e.g., Down’s syndrome), changes in hippocampal volume, AD risk after traumatic brain injury, and spatial spreading of the disease due to foci in which Aβ production is elevated. Continued incorporation of clinical and basic science data into the current model will make it an increasingly relevant model system for doing theoretical calculations that are not feasible in biological systems. In addition, terms in the model that have particularly large effects are likely to be especially useful therapeutic targets.

When Fear Shrinks the Brain: A Computational Model of the Effects of Posttraumatic Stress on Hippocampal Volume.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder often characterized by the unwanted re-experiencing of a traumatic event through nightmares, flashbacks, and/or intrusive memories. This paper presents a neurocomputational model using the ACT-R cognitive architecture that simulates intrusive memory retrieval following a potentially traumatic event (PTE) and predicts hippocampal volume changes observed in PTSD. Memory intrusions were captured in the ACT-R rational analysis framework by weighting the posterior probability of re-encoding traumatic events into memory with an emotional intensity term I to capture the degree to which an event was perceived as dangerous or traumatic. It is hypothesized that (1) increasing the intensity I of a PTE will increase the odds of memory intrusions, and (2) increased frequency of intrusions will result in a concurrent decrease in hippocampal size. A series of simulations were run and it was found that I had a significant effect on the probability of experiencing traumatic memory intrusions following a PTE. The model also found that I was a significant predictor of hippocampal volume reduction, where the mean and range of simulated volume loss match results of existing meta-analyses. The authors believe that this is the first model to both describe traumatic memory retrieval and provide a mechanistic account of changes in hippocampal volume, capturing one plausible link between PTSD and hippocampal volume.

Role of hippocampal location and radiation dose in glioblastoma patients with hippocampal atrophy

BackgroundThe hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma.MethodsAll patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy.ResultsRegardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall.ConclusionsThere was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved.Trial registration Retrospectively registered.

Green tea consumption is associated with annual changes in hippocampal volumes: A longitudinal study in community-dwelling middle-aged and older Japanese individuals

BackgroundTo investigate the association between green tea consumption and the annual rate of change of gray matter (GM), white matter (WM), and hippocampal volumes in community-dwelling middle-aged and older Japanese individuals. MethodsA prospective cohort study with two years of follow-up was conducted as part of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) project. A total of 1693 participants (862 men and 831 women, aged 40–89 years) were included. Green tea consumption (mL/day) data were collected with a 3-day dietary record. Volumes of GM, WM, and the hippocampus were estimated by T1-weighted brain magnetic resonance imaging and FreeSurfer software. The GM ratio, WM ratio, and hippocampal ratio (HR) were calculated as the percentages of total intracranial volume, respectively. ResultsThe mean (SD) annual rate of change of hippocampal volume [(HR at baseline - HR at follow-up)/HR at baseline/follow-up years×100%] was 0.499 (1.128) (%). In the multivariable-adjusted general linear model, green tea consumption was negatively associated only with the annual rate of change of hippocampal volume (%) [β (95% CI) for each 1 mL/day increase in green tea consumption = -20.2E-5 (-35.0E-5 to -5.3E-5); P-value = 0.008]. No associations were observed for the annual rate of change of GM or WM volumes. The results remained significant when the analysis was limited to those with stable green tea consumption and were especially evident among individuals aged 65 years and older and among women. ConclusionsIn this study, higher green tea consumption was associated with less annual hippocampal atrophy, and each additional 100 mL/day of green tea intake was related to a reduction of approximately 5% in annual hippocampal atrophy. This association was especially evident among older individuals and among women. Further study in different settings is needed to confirm this association.

The Effects of Mean of Visit-to-Visit Blood Pressure on Incident Brain Vascular Lesions and Functional-Cognitive Decline.

Cerebrovascular disease (CeVD) is an underlying cause of cognitive impairment and dementia. Hypertension is a known risk factor of CeVD, but the effects of mean of visit-to-visit blood pressure (BP) on incident CeVD and functional-cognitive decline remains unclear. To determine the association between mean of visit-to-visit BP with the incidence and progression of CeVD [white matter hyperintensities (WMH), infarcts (cortical infarcts and lacunes), cerebral microbleeds (CMBs), intracranial stenosis, and hippocampal volume] as well as functional-cognitive decline over 2 years of follow-up. 373 patients from a memory-clinic underwent BP measurements at baseline, year 1, and year 2. The mean of visit-to-visit systolic BP, diastolic BP, pulse pressure, and mean arterial pressure were calculated. Baseline and year 2 MRI scans were graded for WMH, infarcts, CMBs, intracranial stenosis, and hippocampal volume. Functional-cognitive decline was assessed using locally validated protocol. Logistic and linear regression models with odds ratios, mean difference, and 95%confidence interval were constructed to analyze associations of visit-to-visit BP on CeVD incidence and progression as well as functional-cognitive decline. Higher mean of visit-to-visit diastolic BP was associated with WMH progression. Higher tertiles of diastolic BP was associated with WMH progression and incident CMBs. There was no association between mean of visit-to-visit BP measures with incident cerebral infarcts, intracranial stenosis, change in hippocampal volume, and functional-cognitive decline. These findings suggest the possibility of hypertension-related vascular brain damage. Careful monitoring and management of BP in elderly patients is essential to reduce the incidence and progression of CeVD.

Quality control strategies for brain MRI segmentation and parcellation: Practical approaches and recommendations - insights from the Maastricht study

Quality control of brain segmentation is a fundamental step to ensure data quality. Manual quality control strategies are the current gold standard, although these may be unfeasible for large neuroimaging samples. Several options for automated quality control have been proposed, providing potential time efficient and reproducible alternatives. However, those have never been compared side to side, which prevents consensus in the appropriate quality control strategy to use. This study aimed to elucidate the changes manual editing of brain segmentations produce in morphological estimates, and to analyze and compare the effects of different quality control strategies on the reduction of the measurement error.Structural brain MRI from 259 participants of The Maastricht Study were used. Morphological estimates were automatically extracted using FreeSurfer 6.0. Segmentations with inaccuracies were manually edited, and morphological estimates were compared before and after editing. In parallel, 12 quality control strategies were applied to the full sample. Those included: two manual strategies, in which images were visually inspected and either excluded or manually edited; five automated strategies, where outliers were excluded based on the tools “MRIQC” and “Qoala-T”, and the metrics “morphological global measures”, “Euler numbers” and “Contrast-to-Noise ratio”; and five semi-automated strategies, where the outliers detected through the mentioned tools and metrics were not excluded, but visually inspected and manually edited. In order to quantify the effects of each quality control strategy, the proportion of unexplained variance relative to the total variance was extracted after the application of each strategy, and the resulting differences compared.Manually editing brain surfaces produced particularly large changes in subcortical brain volumes and moderate changes in cortical surface area, thickness and hippocampal volumes. The performance of the quality control strategies depended on the morphological measure of interest. Overall, manual quality control strategies yielded the largest reduction in relative unexplained variance. The best performing automated alternatives were those based on Euler numbers and MRIQC scores. The exclusion of outliers based on global morphological measures produced an increase of relative unexplained variance.Manual quality control strategies are the most reliable solution for quality control of brain segmentation and parcellation. However, measures must be taken to prevent the subjectivity associated with these strategies. The detection of inaccurate segmentations based on Euler numbers or MRIQC provides a time efficient and reproducible alternative. The exclusion of outliers based on global morphological estimates must be avoided.

Longitudinal hippocampal volumetric changes in mice following brain infarction

Hippocampal atrophy is increasingly described in many neurodegenerative syndromes in humans, including stroke and vascular cognitive impairment. However, the progression of brain volume changes after stroke in rodent models is poorly characterized. We aimed to monitor hippocampal atrophy occurring in mice up to 48-weeks post-stroke. Male C57BL/6J mice were subjected to an intraluminal filament-induced middle cerebral artery occlusion (MCAO). At baseline, 3-days, and 1-, 4-, 12-, 24-, 36- and 48-weeks post-surgery, we measured sensorimotor behavior and hippocampal volumes from T2-weighted MRI scans. Hippocampal volume—both ipsilateral and contralateral—increased over the life-span of sham-operated mice. In MCAO-subjected mice, different trajectories of ipsilateral hippocampal volume change were observed dependent on whether the hippocampus contained direct infarction, with a decrease in directly infarcted tissue and an increase in non-infarcted tissue. To further investigate these volume changes, neuronal and glial cell densities were assessed in histological brain sections from the subset of MCAO mice lacking hippocampal infarction. Our findings demonstrate previously uncharacterized changes in hippocampal volume and potentially brain parenchymal cell density up to 48-weeks in both sham- and MCAO-operated mice.