Changes In Hippocampal Subfields Research Articles

Hippocampal subfields volume changes and its correlation with memory functions in patients with mild cognitive impairment

BackgroundThis study examined hippocampal subfields volumes in patients with mild cognitive impairment (MCI) as potential non-invasive predictive neuroimaging markers of cognitive decline. MethodsT1-weighted images and Addenbrooke's cognitive examination III (ACE-III) data were obtained from 36 healthy controls and 27 MCI patients. The hippocampal subfields volumes were extracted using Freesurfer software, and group differences and correlation were assessed using general linear model (GLM) with age, sex, and total intracranial volume (TIV) as covariates. ResultsMCI participants exhibited significant decrease in memory scores and notable volumetric changes in hippocampal subfields, including the bilateral hippocampal tail, subiculum, CA1, CA3, molecular layer, as well as the left presubiculum, parasubiculum, CA4, GC-ML-DG, and HATA. Moreover, the left presubiculum, left parasubiculum, and left GC-ML-DG showed significant positive correlations with ACE memory scores in MCI patients. ConclusionsThe alterations in hippocampal subfields in MCI patients may indicate underlying neurodegenerative processes associated with Alzheimer's disease (AD) pathology.

P173: Structural Changes in the Hippocampal Subfields in Early-Onset Mild Cognitive Impairment

Objective:The aim of this study was to examine the structural change in the hippocampal subfields in early-onset (EO) mild cognitive impairment (MCI) patients associated with the APOE ε4 carrier state.Methods:This study had 50 subjects aged 55-63 years, all of whom were diagnosed with amnestic MCI at baseline via the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet (CERAD-K). The EO-MCI patients were divided into the MCI continued (MCIcont) and Alzheimer’s disease (AD) converted (ADconv) groups 2 years later. The volumes of hippocampal subfields were measured for all the subjects. The calculations were based on the change of the volumes between the 2-year-interval brain Magnetic resonance image (MRI) scans between MCIcont and ADconv groups according to the Apolipoprotein ε4 (APOE ε4) carrier state.Results:There was a significant correlation between APOE ε4 allele and structural changes in several hippocampal subfields. The volume reduction in cornus ammonis 1 (CA1) field and subiculum, especially in the APOE ε4 carriers. The significance was more prominent in ADconv group.Conclusion:These results suggest that the possession of APOE ε4 allele may lead to significantly greater predilection for the structural changes in hippocampal subfields, showing significant changes, especially in the ADconv patients compared with MCIcont patients.

Using 7T MRI to study hippocampal structures in Alzheimer’s disease and post‐SARS‐CoV2 infection

AbstractBackground7T MRI allows implementation of high‐resolution quantitative susceptibility mapping (QSM) which can be used to assess the cerebral microvascular/hypoperfusion pathogenic hypothesis in Alzheimer’s disease (AD) and in the post‐SARS‐CoV2 setting to explore if there may be similarities in brain changes in these two conditions. The magnetic susceptibility (reflective of tissue iron) of hippocampal subfields was assessed in patients with 1) CSF‐Amyloidß‐status AD; 2) mild COVID‐19 over 6 months previously (Cv); 3) severe COVID‐19 with ICU admission >6 months previously (ICU‐Cv); and 4) age‐matched healthy controls (HC).Methods33 participants (10 HC, 14 Cv, 9 ICU‐Cv) for the COVID study and 24 participants (14 AD, 11HC) from AD patients with confirmed CSF‐Amyloidß levels, aged 42‐79, were scanned on a 7T scanner with the following protocol T2* GRE for the AD groups (0.7×0.7×0.7mm3,TE/TR = 20/31ms) and T2* multi‐echo GRE for the Cv groups (0.38×0.38×0.75mm3,TE1/TE2/TR = 8.2/18.4/24ms). Data were processed using QSMbox1 to produce susceptibility maps. PSIR (0.55×0.55×0.55mm3,TE/TR = 3.1/6.9ms) and T2‐weighted FSE (0.38×0.39×1.5mm3, TE/TR = 117/5900ms) images were used to segment the hippocampal subfields (Figure 1)2. One‐way analyses were used in SPSS for comparison between the HC group and each of the Cv, ICU‐Cv, and AD groups.ResultsThere was no change in susceptibility for the whole hippocampus between AD and HC, but there was a significant difference for the DG subfield (p = 0.045), Figure 2. For COVID patients, there was a significant difference between the susceptibility of the whole hippocampus in the ICU‐Cv group (p = 0.035), but not in the Cv group (p = 0.788), Figure 3, compared to HC. In subfield analyses there was a trend towards decreased susceptibility in the subiculum, an area known to be affected by Alzheimer pathology, in the ICU‐Cv group (p = 0.032) compared to HC.ConclusionThe lower susceptibility within the hippocampal structures observed in AD and ICU‐Cv patients may reflect less iron either from cerebral hypoperfusion or vascular injuries in AD or additionally result from sequelae of hypoxaemia in ICU‐Cv. The study provides preliminary evidence of detectable in vivo microstructural changes in hippocampal subfields in both AD and post‐COVID settings. Funding: Medical Research Council, UK (MR/T005580/1); National Institute of Health, USA (1R56AG074467‐01)

High blood lead level correlates with selective hippocampal subfield atrophy and neuropsychological impairments

BackgroundLead contamination is a major public health concern. Previous studies have demonstrated that lead exposure could affect the hippocampus, which is a complex and heterogeneous structure composed of 12 subregions. Here, we explored volumetric and functional changes in hippocampal subfields and neuropsychological alterations after lead exposure. MethodsWe performed a cross-sectional study at a smelting company between September 2020 and December 2021. Blood lead level was recorded, and neuropsychological functions were assessed by Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). The hippocampus was segmented into 12 subfields in each hemisphere in magnetic resonance images (MRIs). Then, the effect of altered hippocampal subfield volumes on brain functions were studied by seed-based functional connectivity (FC) analysis. Finally, the relationships between the lead level with hippocampal subfield volumes and neuropsychological functions were investigated. Baseline characteristics, hippocampal subfield volumes, and FC analysis were compared between lead-exposed (≥ 300 μg/L) and the control group (≤ 100 μg/L). ResultsIn 76 participants, lead level positively correlated with SDS(r = 0.422) and negatively correlated with MoCA(r = −0.414), MMSE(r = −0.251), Concentration(r = −0.331), Recall(r = −0.319), Orientation(r = −0.298) and Executive Function/Visuospatial abilities(r = −0.231). Lead group (26 participants) had lower MoCA and MMSE and higher SDS than control group (23 participants). A significantly decreased volume in the left CA4 and GC-ML-DG subfields was found in the lead group compared with the control group. The left GC-ML-DG of the lead group showed a decreased FC with the bilateral postcentral gyrus. The left CA4(r = −0.409) and left GC-ML-DG (r = −0.383) volumes negatively correlated with lead level. The FC between left GC-ML-DG and left postcentral gyrus positively correlated with MoCA(r = 0.318), MMSE(r = 0.379) and Recall(r = 0.311). The FC between left GC-ML-DG and right postcentral gyrus positively correlated with MoCA(r = 0.326), Executive Function/Visuospatial abilities(r = 0.307) and Concentration(r = 0.297). ConclusionHigh blood lead level was associated with neuropsychological alterations, hippocampal structural and functional changes. The left GC-ML-DG and CA4 atrophy might serve as predictive imaging markers for neurological damage associated with high lead exposure.

Relationships Between Memory Impairments and Hippocampal Structure in Patients With Subcortical Ischemic Vascular Disease.

Background and PurposePatients with subcortical ischemic vascular disease (SIVD) suffer from memory disorders that are thought to be associated with the hippocampus. We aimed to explore changes in hippocampal subfields and the relationship between different hippocampal subfield volumes and different types of memory dysfunction in SIVD patients.MethodsA total of 77 SIVD patients with cognitive impairment (SIVD-CI, n = 39) or normal cognition (HC-SIVD, n = 38) and 41 matched healthy controls (HCs) were included in this study. Memory function was measured in all subjects, and structural magnetic resonance imaging (MRI) was performed. Then, the hippocampus was segmented and measured by FreeSurfer 6.0 software. One-way ANOVA was used to compare the volume of hippocampal subfields among the three groups while controlling for age, sex, education and intracranial volume (ICV). Then, post hoc tests were used to evaluate differences between each pair of groups. Finally, correlations between significantly different hippocampal subfield volumes and memory scores were tested in SIVD patients.ResultsAlmost all hippocampal subfields were significantly different among the three groups except for the bilateral hippocampal fissure (p = 0.366, p = 0.086, respectively.) and left parasubiculum (p = 0.166). Furthermore, the SIVD-CI patients showed smaller volumes in the right subiculum (p < 0.001), CA1 (p = 0.002), presubiculum (p = 0.002) and molecular layer of the hippocampus (p = 0.017) than the HC-SIVD patients. In addition, right subiculum volumes were positively related to Rey’s Auditory Verbal Learning Test (RAVLT) word recognition (r = 0.230, p = 0.050), reverse digit span test (R-DST) (r = 0.326, p = 0.005) and Rey–Osterrieth Complex Figure Test (ROCF) immediate recall (r = 0.247, p = 0.035) scores, right CA1 volumes were positively correlated with RAVLT word recognition (r = 0.261, p = 0.026), and right presubiculum volumes showed positive relationships with R-DST (r = 0.254, p = 0.030) and ROCF immediate recall (r = 0.242, p = 0.039) scores.ConclusionSIVD might lead to general reductions in volume in multiple hippocampal subfields. However, SIVD-CI patients showed atrophy in specific subfields, which might be associated with memory deficits.

Variations in response to trauma and hippocampal subfield changes

Models of posttraumatic stress disorder (PTSD) suggest that the hippocampus is key to the persistence of traumatic memory. Yet very little is known about the precise changes that take place in this structure, nor their relation with PTSD symptoms. Previous studies have mostly used magnetic resonance imaging (MRI) at low resolutions, making it impossible to identify sensitive anatomical landmarks, or compared groups often unequally matched in terms of traumatic exposure. The present cross-sectional study included 92 individuals who had all been exposed to the terrorist attacks in Paris on November 13, 2015 (53 of whom subsequently developed PTSD) and 56 individuals who had not been exposed. Hippocampal subfield volumes were estimated using cross-validated automatic segmentation of high-resolution MRI images. Results revealed changes in CA1 and CA2-3/dentate gyrus (DG) volumes in individuals with PTSD, but not in resilient (i.e., exposed but without PTSD) individuals, after controlling for potential nuisance variables such as previous traumatic exposure and substance abuse. In line with current models of hippocampal subfield functions, CA1 changes were linked to the uncontrollable re-experiencing of intrusive memories, while CA2-3/DG changes, potentially exacerbated by comorbid depression, fostered the overgeneralization of fear linked to avoidance and hypervigilance behaviors. Additional analyses revealed that CA1 integrity was linked to optimum functioning of the memory control network in resilient individuals. These findings shed new light on potential pathophysiological mechanisms in the hippocampus subtending the development of PTSD and the failure to recover from trauma.

Modeling longitudinal changes in hippocampal subfields and relations with memory from early- to mid-childhood

The hippocampus has been suggested to show protracted postnatal developmental growth across childhood. Most previous studies during this developmental period have been cross-sectional in nature and have focused on age-related differences in either hippocampal subregions or subfields, but not both, potentially missing localized changes. This study capitalized on a latent structural equation modeling approach to examine the longitudinal development of hippocampal subfields (cornu ammonis (CA) 2-4/dentate gyrus (DG), CA1, subiculum) in both the head and the body of the hippocampus, separately, in 165 typically developing 4- to 8-year-old children. Our findings document differential development of subfields within hippocampal head and body. Specifically, within hippocampal head, CA1 volume increased between 4−5 years and within hippocampal body, CA2-4/DG and subiculum volume increased between 5−6 years. Additionally, changes in CA1 volume in the head and changes in subiculum in the body between 4−5 years related to improvements in memory between 4−5 years. These findings demonstrate the protracted development of subfields in vivo during early- to mid-childhood, illustrate the importance of considering subfields separately in the head and body of the hippocampus, document co-occurring development of brain and behavior, and highlight the strength of longitudinal data and latent modeling when examining brain development.

Hippocampal circuits underlie improvements in self-reported anxiety following mindfulness training.

IntroductionMindfulness meditation has successfully been applied to cultivate skills in self‐regulation of emotion, as it employs the unbiased present moment awareness of experience. This heightened attention to and awareness of sensory experience has been postulated to create an optimal therapeutic exposure condition and thereby improve extinction learning. We recently demonstrated increased connectivity in hippocampal circuits during the contextual retrieval of extinction memory following mindfulness training.MethodsHere, we examine the role of structural changes in hippocampal subfields following mindfulness training in a randomized controlled longitudinal study using a two‐day fear‐conditioning and extinction protocol.ResultsWe demonstrate an association between mindfulness training‐related increases in subiculum and decreased hippocampal connectivity to lateral occipital regions during contextual retrieval of extinguished fear. Further, we demonstrate an association between decreased connectivity and decreases in self‐reported anxiety following mindfulness training.ConclusionsThe results highlight the role of the subiculum in gating interactions with contextual stimuli during memory retrieval and, also, the mechanisms through which mindfulness training may foster resilience.

Structural Changes in Hippocampal Subfields in Patients with Continuous Remission of Drug-Naive Major Depressive Disorder.

Objective: Hippocampal volume is reduced in patients with major depressive disorder (MDD) compared with healthy controls. The hippocampus is a limbic structure that has a critical role in MDD. The aim of the present study was to investigate the changes in the volume of the hippocampus and its subfields in MDD patients who responded to antidepressants and subsequently were in continuous remission. Subjects and Methods: Eighteen patients who met the following criteria were enrolled in the present study: the DSM-IV-TR criteria for MDD, drug-naïve at least 8 weeks or more, scores on the 17-items of Hamilton Rating Scale for Depression (HAMD) of 14 points or more, and antidepressant treatment response within 8 weeks and continuous remission for at least 6 months. All participants underwent T1-weighted structural MRI and were treated with antidepressants for more than 8 weeks. We compared the volumes of the hippocampus, including its subfields, in responders at baseline to the volumes at 6 months. The volumes of the whole hippocampus and the hippocampal subfields were measured using FreeSurfer v6.0. Results: The volumes of the left cornu Ammonis (CA) 3 (p = 0.016) and the granule cell layer of the dentate gyrus (GC-DG) region (p = 0.021) were significantly increased after 6 months of treatment compared with those at baseline. Conclusions: Increases in volume was observed in MDD patients who were in remission for at least 6 months.

Hippocampal subfield transcriptome analysis in schizophrenia psychosis.

We have previously demonstrated functional and molecular changes in hippocampal subfields in individuals with schizophrenia (SZ) psychosis associated with hippocampal excitability. In this study, we use RNA-seq and assess global transcriptome changes in the hippocampal subfields, DG, CA3, and CA1 from individuals with SZ psychosis and controls to elucidate subfield-relevant molecular changes. We also examine changes in gene expression due to antipsychotic medication in the hippocampal subfields from our SZ ON- and OFF-antipsychotic medication cohort. We identify unique subfield-specific molecular profiles in schizophrenia postmortem samples compared with controls, implicating astrocytes in DG, immune mechanisms in CA3, and synaptic scaling in CA1. We show a unique pattern of subfield-specific effects by antipsychotic medication on gene expression levels with scant overlap of genes differentially expressed by SZ disease effect versus medication effect. These hippocampal subfield changes serve to confirm and extend our previous model of SZ and can explain the lack of full efficacy of conventional antipsychotic medication on SZ symptomatology. With future characterization using single-cell studies, the identified distinct molecular profiles of the DG, CA3, and CA1 in SZ psychosis may serve to identify further potential hippocampal-based therapeutic targets.

Curved multiplanar reformatting provides improved visualization of hippocampal anatomy.

There is a growing body of literature studying changes in hippocampal subfields in a variety of different neurological conditions, but this work has mainly focused on the hippocampal body given challenges in visualization of hippocampal anatomy in the head and tail when sectioned in the typical coronal image plane. Curved multiplanar reformatting (CMPR) is an image reconstruction method that can improve visualization of complex three‐dimensional structures. The objective of this study was to determine whether CMPR could facilitate visualization of the human hippocampal anatomy along the entire caudal–rostral axis. CMPR was applied to high‐resolution magnetic resonance imaging acquired ex vivo on four cadaveric hippocampal specimens at 4.7 T (T2‐weighted, 0.2 × 0.2 × 0.5 mm3). CMPR provided clear visualization of the classic “interlocking C” appearance of the dentate gyrus and cornu ammonis along the entire caudal–rostral axis including the head and tail, which otherwise show complex anatomy on the standard coronal slices. CMPR facilitated visualization of hippocampal anatomy providing the impetus to develop simplified approaches to delineate subfields along the entire hippocampus including the usually neglected head and tail.

Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease.

ObjectiveParkinson's disease (PD) episodic memory impairments are common; however, it is not known whether these impairments are due to hippocampal pathology. Hippocampal Lewy-bodies emerge by Braak stage 4, but are not uniformly distributed. For instance, hippocampal CA1 Lewy-body pathology has been specifically associated with pre-mortem episodic memory performance in demented patients. By contrast, the dentate gyrus (DG) is relatively free of Lewy-body pathology. In this study, we used ultra-high field 7-Tesla to measure hippocampal subfields in vivo and determine if these measures predict episodic memory impairment in PD during life.MethodsWe studied 29 participants with PD (age 65.5 ± 7.8 years; disease duration 4.5 ± 3.0 years) and 8 matched-healthy controls (age 67.9 ± 6.8 years), who completed comprehensive neuropsychological testing and MRI. With 7-Tesla MRI, we used validated segmentation techniques to estimate CA1 stratum pyramidale (CA1-SP) and stratum radiatum lacunosum moleculare (CA1-SRLM) thickness, dentate gyrus/CA3 (DG/CA3) area, and whole hippocampus area. We used linear regression, which included imaging and clinical measures (age, duration, education, gender, and CSF), to determine the best predictors of episodic memory impairment in PD.ResultsIn our cohort, 62.1% of participants with PD had normal cognition, 27.6% had mild cognitive impairment, and 10.3% had dementia. Using 7-Tesla MRI, we found that smaller CA1-SP thickness was significantly associated with poorer immediate memory, delayed memory, and delayed cued memory; by contrast, whole hippocampus area, DG/CA3 area, and CA1-SRLM thickness did not significantly predict memory. Age-adjusted linear regression models revealed that CA1-SP predicted immediate memory (beta[standard error]10.895[4.215], p < .05), delayed memory (12.740[5.014], p < .05), and delayed cued memory (12.801[3.991], p < .05). In the fully-adjusted models, which included all five clinical measures as covariates, only CA1-SP remained a significant predictor of delayed cued memory (13.436[4.651], p < .05).ConclusionsIn PD, we found hippocampal CA1-SP subfield thickness estimated on 7-Tesla MRI scans was the best predictor of episodic memory impairment, even when controlling for confounding clinical measures. Our results imply that ultra-high field imaging could be a sensitive measure to identify changes in hippocampal subfields and thus probe the neuroanatomical underpinnings of episodic memory impairments in patients with PD.

Reduced GluN1 in mouse dentate gyrus is associated with CA3 hyperactivity and psychosis-like behaviors

Recent findings from in vivo-imaging and human post-mortem tissue studies in schizophrenic psychosis (SzP), have demonstrated functional and molecular changes in hippocampal subfields that can be associated with hippocampal hyperexcitability. In this study, we used a subfield-specific GluN1 knockout mouse with a disease-like molecular perturbation expressed only in hippocampal dentate gyrus (DG) and assessed its association with hippocampal physiology and psychosis-like behaviors. First, we used whole-cell patch-clamp recordings to measure the physiological changes in hippocampal subfields and cFos immunohistochemistry to examine cellular excitability. DG-GluN1 KO mice show CA3 cellular hyperactivity, detected using two approaches: (1) increased excitatory glutamate transmission at mossy fibers (MF)-CA3 synapses, and (2) an increased number of cFos-activated pyramidal neurons in CA3, an outcome that appears to project downstream to CA1 and basolateral amygdala (BLA). Furthermore, we examined psychosis-like behaviors and pathological memory processing; these show an increase in fear conditioning (FC), a reduction in prepulse inhibition (PPI) in the KO animal, along with a deterioration in memory accuracy with Morris Water Maze (MWM) and reduced social memory (SM). Moreover, with DREADD vectors, we demonstrate a remarkably similar behavioral profile when we induce CA3 hyperactivity. These hippocampal subfield changes could provide the basis for the observed increase in human hippocampal activity in SzP, based on the shared DG-specific GluN1 reduction. With further characterization, these animal model systems may serve as targets to test psychosis mechanisms related to hippocampus and assess potential hippocampus-directed treatments.

Hippocampal lipid differences in Alzheimer's disease: a human brain study using matrix-assisted laser desorption/ionization-imaging mass spectrometry.

IntroductionAlzheimer's disease (AD), the leading cause of dementia, is pathologically characterized by β‐amyloid plaques and tau tangles. However, there is also evidence of lipid dyshomeostasis‐mediated AD pathology. Given the structural diversity of lipids, mass spectrometry is a useful tool for studying lipid changes in AD. Although there have been a few studies investigating lipid changes in the human hippocampus in particular, there are few reports on how lipids change in each hippocampal subfield (e.g., Cornu Ammonis [CA] 1–4, dentate gyrus [DG] etc.). Since each subfield has its own function, we postulated that there could be lipid changes that are unique to each.MethodsWe used matrix‐assisted laser desorption/ionization‐imaging mass spectrometry to investigate specific lipid changes in each subfield in AD. Data from the hippocampus region of six age‐ and gender‐matched normal and AD pairs were analyzed with SCiLS lab 2015b software (SCiLS GmbH, Germany; RRID:SCR_014426), using an analysis workflow developed in‐house. Hematoxylin, eosin, and luxol fast blue staining were used to precisely delineate each anatomical hippocampal subfield. Putative lipid identities, which were consistent with published data, were assigned using MS/MS.ResultsBoth positively and negatively charged lipid ion species were abundantly detected in normal and AD tissue. While the distribution pattern of lipids did not change in AD, the abundance of some lipids changed, consistent with trends that have been previously reported. However, our results indicated that the majority of these lipid changes specifically occur in the CA1 region. Additionally, there were many lipid changes that were specific to the DG.ConclusionsMatrix‐assisted laser desorption/ionization‐imaging mass spectrometry and our analysis workflow provide a novel method to investigate specific lipid changes in hippocampal subfields. Future work will focus on elucidating the role that specific lipid differences in each subfield play in AD pathogenesis.

Hippocampal subfield volumetry in patients with subcortical vascular mild cognitive impairment.

Memory impairment is a typical characteristic of patients with subcortical vascular mild cognitive impairment (svMCI) or with amnestic mild cognitive impairment (aMCI). The hippocampus, which plays an important role in the consolidation of information from short-term memory to long-term memory, is a heterogeneous structure that consists of several anatomically and functionally distinct subfields. However, whether distinct hippocampal subfields are differentially and selectively affected by svMCI pathology and whether these abnormal changes in hippocampal subfields are different between svMCI and aMCI patients are largely unknown. A total of 26 svMCI patients, 26 aMCI patients and 26 healthy controls matched according to age, gender and years of education were enrolled in this study. We utilized an automated hippocampal subfield segmentation method provided by FreeSurfer to estimate the volume of several hippocampal subfields, including the cornu ammonis (CA) areas, the dentate gyrus (DG), the subiculum and the presubiculum. Compared with controls, the left subiculum and presubiculum and the right CA4/DG displayed significant atrophy in patients with svMCI. Interestingly, we also found significant differences in the volume of the right CA1 between the svMCI and aMCI groups. Taken together, our results reveal region-specific vulnerability of hippocampal subfields to svMCI pathology and identify distinct hippocampal subfield atrophy patterns between svMCI and aMCI patients.

Hippocampal Subfield Volumetry and 3D Surface Mapping in Subjective Cognitive Decline.

Subjective cognitive decline (SCD) may be the first clinical sign of Alzheimer's disease (AD). SCD individuals with normal cognition may already have significant hippocampal atrophy, a well-known feature of AD. To test the hypothesis that SCD, compared to healthy individuals without SCD, have a pattern of hippocampal subfield atrophy similar to that measured in the AD pathology. 17 SCD, 21 AD, and 40 matched controls underwent a standard T1-weighted MRI and a dedicated high-resolution MRI proton-density hippocampal sequence. For each participant, three hippocampal regions-of-interest were manually delineated on the proton-density hippocampal sequence corresponding to the CA1, subiculum, and other (including CA2-3-4 and dentate gyrus) subfields. Total intracranial volume (TIV)-normalized subfield volumes were compared between-group. Voxelwise group comparisons assessed from the standard T1 MRI were also projected on 3D hippocampal surface views. Both patient groups showed significant TIV-normalized volume decrease in hippocampus global volume and in CA1 and subiculum subfields as well as in the other subfield in AD compared to controls. Significant differences were observed between SCD and AD in hippocampus global TIV-normalized volume. Atrophy maps on hippocampal surface showed major involvement of the lateral part (CA1) in both SCD and AD, with larger overlap of other regions in AD. The findings indicate topographically similar hippocampal subfield changes in SCD individuals as those found in AD. This further highlights the relevance of SCD recruited from a memory clinic in assessing pre-dementia AD stages.

Hippocampal subfield changes in mild cognitive impairment patients with Alzheimer's disease pathology

Hippocampal subfield changes in mild cognitive impairment patients with Alzheimer's disease pathology

Hippocampal subfield changes in mild cognitive impairment patients with Alzheimer's disease pathology

Hippocampal subfield changes in mild cognitive impairment patients with Alzheimer's disease pathology

Structural Changes in Hippocampal Subfields in Major Depressive Disorder: A High-Field Magnetic Resonance Imaging Study

Magnetic resonance imaging (MRI) has shown lower hippocampal volume in major depressive disorder (MDD). Preclinical and postmortem studies show that chronic stress and MDD may affect hippocampal subfields differently, but MRI spatial resolution has previously been insufficient to measure subfield volumes. Twenty MDD participants (9 unmedicated and 11 medicated, both > 6 months) and 27 healthy control subjects were studied. We used T2-weighted two-dimensional fast spin echo and T1-weighted three-dimensional magnetization prepared rapid acquisition gradient-echo sequences at 4.7 T to compare hippocampal subfield volumes at .09 μL voxel volume. Unmedicated MDD participants had a lower dentate gyrus volume than control subjects or medicated MDD participants and a lower cornu ammonis (CA1-3) volume in the hippocampal body subregion than control subjects. Hippocampal volumes in unmedicated MDD showed evidence of localization to specific subfields and subregions, findings that appear, on the surface, consistent with preclinical evidence for localized mechanisms of hippocampal neuroplasticity. Strengths include in vivo measurement of entire hippocampal subfields and separation between unmedicated and medicated MDD. Limitations include power to control for multiple comparisons and that MRI landmarks approximate the subfields defined by cellular microstructure.

Measurement of hippocampal subfields and age-related changes with high resolution MRI at 4tesla

Normal aging and Alzheimer's disease (AD) are both associated with loss of hippocampal neurons. However, histological studies suggest that hippocampal neuronal loss is different in normal aging and AD. While in AD neuron loss is most pronounced in CA1, normal aging is thought to predominantely impact the hilus and subiculum, although this is controversal. The aims of this study were: 1. To test if hippocampal subfields can be identified and reliably traced using anatomical landmarks on MR images with submillimeter resolution. 2. To test if age-related volume changes of subfields can be detected. 14 subjects (12 healthy controls mean age 47.3, range: 24-77 years werestudied on a 4T system with using a T2 weighted high resolution turbo-spin-echo sequence (TR/TE: 3500/19 ms, turbofactor 15, 18.6 ms echo spacing, 160° flip angle, FOV 200, 512x384 matrix, 2 mm slice thickness, 24, interleaved slices without gap). Using anatomical landmarks, entorhinal cortex (ERC), subiculum, CA1, CA2 and CA3/dentate compound (CA3, CA4, dentate gyrus) on both sides were traced twice by two raters. Intraclass correlation coefficients (ICC) were calculated to assess reliablity of markings within and between raters. The mean ICC for rater 1 was 0.96 (range 0.83- 0.99) and for rater 2 the mean ICC was 0.87 (range 0.66-0.98).The between rater ICC for the different subfields ranged between 0.67 and 0.93 and was above 0.87 for the CA1 sectors In the group of healthy subjects, there was a significant correlation between age and the left and right CA1 (left: r= -0.63, p=0.02; right: r= -0.53, p=0.04). These preliminary results suggest that it is possible to reliably identify and mark hippocampal subfields on high resolution MRIs of the hippocampus. The major finding was a significant correlation between age and the CA1 but not other subfields. This contrasts with some histological data suggesting that age is primarily associated with atrophy of the hilus and subiculum. Further studies on a larger group of subjects are needed to assess the changes in hippocampal subfields in normal aging and AD and to determine the value of these measurements for the early detection of AD.