Hippocampal Subfields Research Articles

Structural and covariance network alterations of the hippocampus and amygdala in congenital hearing loss children

ObjectiveThe hippocampus and amygdala, as important components of the limbic system, play crucial roles in central remodeling in congenital hearing loss. This study aimed to investigate the morphological integrity and network properties of the subfields of hippocampus and amygdala in children with congenital hearing loss. MethodsA total of 24 children with congenital hearing loss and 17 age- and sex- matched healthy controls (HC) are included in the study. T1-weighted images are analyzed by segmenting the brain into cortical and subcortical regions. Intergroup difference of volumes were explored. Structural covariance networks for the whole brain and hippocampus-amygdala subregions were constructed. Between-group differences of network property are investigated by comparing area under a range of network sparsity. ResultsPatients with congenital hearing loss exhibited significantly larger volumes in the right dentate gyrus and CA3 of the hippocampus. However, there were no significant differences in total hippocampal or showed decreased global efficiency and increased characteristic path length, indicating reduced network integration. Lower betweenness centrality was observed in the left hippocampal fissure in the hearing loss group. The changes in volume and network topological properties are not affected by age and sex. ConclusionChildren with congenital hearing loss display specific volumetric increases in hippocampal subregions, suggesting compensatory adaptations to auditory deprivation. The hippocampus-amygdala network shows significant reorganization, potentially underpinning cognitive and behavioral development issues associated with congenital hearing loss. These findings highlight the importance of targeted neural substrates in understanding and addressing the developmental challenges faced by children with congenital hearing loss.

The HOPE4MCI study: AGB101 treatment slows progression of entorhinal cortex atrophy in APOE ε4 non‐carriers with mild cognitive impairment due to Alzheimer's disease

AbstractIntroductionHippocampal hyperactivity is a hallmark of prodromal Alzheimer's disease (AD) that predicts progression in patients with amnestic mild cognitive impairment (aMCI). AGB101 is an extended‐release formulation of levetiracetam in the dose range previously demonstrated to normalize hippocampal activity and improve cognitive performance in aMCI. The HOPE4MCI study was a 78‐week trial to assess the progression of MCI due to AD. As reported in Mohs et al., the decline in the Clinical Dementia Rating Sum of Boxes score (CDR‐SB) was reduced by 40% in apolipoprotein E (APOE) ε4 non‐carriers over the 78‐week duration of the study with a negligible effect in carriers. Here we report an exploratory analysis of the effects of AGB101 on neuroimaging and biomarker measures in the 44 APOE ε4 non‐carriers who completed the 78‐week protocol.MethodsStructural magnetic resonance imaging scans obtained at baseline and after 78 weeks were analyzed using the Automated Segmentation of Hippocampal Subfields software providing volume measures of key structures of the medial temporal lobe relevant to AD progression. Blood samples collected at 78 weeks in the study were analyzed for plasma biomarkers.ResultsTreatment with AGB101 significantly reduced atrophy of the left entorhinal cortex (ERC) compared to placebo. This reduction in atrophy was correlated with less decline in the CDR‐SB score over 78 weeks and with lower neurofilament light chain (NfL), a marker of neurodegeneration.DiscussionThe HOPE4MCI study showed that APOE ε4 non‐carriers treated with AGB101 demonstrated a substantially more favorable treatment effect compared to carriers. Here we report that treatment with AGB101 in non‐carriers of APOE ε4 significantly reduced atrophy of the left ERC over 78 weeks. That reduction in atrophy was closely coupled with the change in CDR‐SB and with plasma NfL indicative of neurodegeneration in the brain. These exploratory analyses are consistent with a reduction in neurodegeneration in APOE ε4 non‐carriers treated with AGB101 before a clinical diagnosis of dementia.Highlights AGB101 slows entorhinal cortex (ERC) atrophy in apolipoprotein E (APOE) ε4 non‐carriers with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). Slowing ERC atrophy by AGB101 is associated with less Clinical Dementia Rating Sum of Boxes decline. Slowing ERC atrophy by AGB101 is associated with lower neurofilament light chain. AGB101 treatment reduces neurodegeneration in APOE ε4 non‐carriers with MCI due to AD.

Combined cognitive assessment and automated MRI volumetry improves the diagnostic accuracy of detecting MCI due to Alzheimer's disease

BackgroundMild cognitive impairment (MCI) confers a high annual risk of 10–15 % of conversion to Alzheimer's disease (AD) dementia. MRI atrophy patterns derived from automated ROI analysis, particularly hippocampal subfield volumes, were reported to be useful in diagnosing early clinical stages of Alzheimer's disease. ObjectiveThe aim of the present study was to combine automated ROI MRI morphometry of hippocampal subfield volumes and cortical thickness estimates using FreeSurfer 6.0 with cognitive measures to predict disease progression and time to conversion from MCI to AD dementia. MethodsBaseline (Neuropsychology, MRI) and clinical follow-up data from 62 MCI patients were analysed retrospectively. Individual cortical thickness and volumetric measures were obtained from T1-weighted MRI. Linear discriminant analysis (LDA) of both, cognitive measures and MRI measures (hippocampal subfields, temporal and parietal lobe volumes), were performed to differentiate MCI converters from stable MCI patients. ResultsOut of 62 MCI patients 21 (34 %) converted to AD dementia within a mean follow-up time of 74.7 ± 36.8 months (mean ± SD, range 12 to 130 months). LDA identified temporal lobe atrophy and hippocampal subfield volumes in combination with cognitive measures of verbal memory, verbal fluency and executive functions to correctly classify 71.4.% of MCI subjects converting to AD dementia and 92.7 % with stable MCI. Lower baseline GM volume of the subiculum and the superior temporal gyrus was associated with faster disease progression of MCI converters. ConclusionCombining cognitive assessment with automated ROI MRI morphometry is superior to using a single test in order to distinguish MCI due to AD from non converting MCI patients.

Abnormal developmental of hippocampal subfields and amygdalar subnuclei volumes in young adults with heavy cannabis use: A three-year longitudinal study

BackgroundDifferences in the volumes of the hippocampus and amygdala have consistently been observed between young adults with heavy cannabis use relative to their non-using counterparts. However, it remains unclear whether the subfields of these functionally and structurally heterogenous regions exhibit similar patterns of change in young adults with long-term heavy cannabis use disorder (CUD). ObjectivesThis study aims to investigate the effects of long-term heavy cannabis use in young adults on the subregional structures of the hippocampus and amygdala, as well as their longitudinal alterations. MethodsThe study sample comprised 20 young adults with heavy cannabis use and 22 matched non-cannabis using healthy volunteers. All participants completed the Cannabis Use Disorder Identification Test (CUDIT) and underwent two T1-structural magnetic resonance imaging (MRI) scans, one at baseline and another at follow-up 3 years later. The amygdala, hippocampus, and their subregions were segmented on T1-weighted anatomical MRI scans, using a previously validated procedure. ResultsAt baseline, young adults with heavy CUD exhibited significantly larger volumes in several hippocampal (bilateral presubiculum, subiculum, Cornu Ammonis (CA) regions CA1, CA2-CA3, and right CA4-Dentate Gyrus (DG)) and amygdala (bilateral paralaminar nuclei, right medial nucleus, and right lateral nucleus) subregions compared to healthy controls, but these differences were attenuated at follow-up. Longitudinal analysis revealed an accelerated volumetric decrease in these subregions in young adults with heavy CUD relative to controls. Particularly, compared to healthy controls, significant accelerated volume decreases were observed in the right hippocampal subfields of the parasubiculum, subiculum, and CA4-DG. In the amygdala, similar trends of accelerated volumetric decreases were observed in the left central nucleus, right paralaminar nucleus, right basal nucleus, and right accessory basal nucleus. ConclusionsThe current findings suggest that long-term heavy cannabis use impacts maturational process of the amygdala and hippocampus, especially in subregions with high concentrations of cannabinoid type 1 receptors (CB1Rs) and involvement in adult neurogenesis.

Progression of hippocampal subfield atrophy and asymmetry in Alzheimer's disease.

Alzheimer's disease (AD) affects the hippocampus during its progression, but the specific observable changes of hippocampal subfields during disease progression remain poorly understood. In this study, we employed an event-based model (EBM) to determine the sequence of occurrence of hippocampal subfield atrophy in mild cognitive impairment (MCI) and AD cohorts. Subjects (207) were included: 86 MCI, 53 AD, and 68 healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants underwent structural magnetic resonance imaging (MRI) scans to analyse the hippocampal subfields. We assigned each patient to a specific EBM stage, based on the number of their abnormal subfields. A combination of 2-year follow-up MRI scans were applied to demonstrate the longitudinal consistency and utility of the model's staging system. The model estimated that the earliest atrophy occurs in the hippocampal fissure, then spreading to other subregions in both MCI and AD. We identified a marked divergence between the sequences of left and right hippocampal subfields atrophy, so inter-hemispheric asymmetry pattern was further analysed. The sequence of asymmetry index (AI) increases beginning in the molecular and granule cell layers of the dentate gyrus (GC-ML-DG), cornus ammonis (CA) 4, and the molecular layer (ML). Longitudinal analysis confirms the efficacy of the model. In addition, the model stages were significantly correlated with patients' memory scores (p < .05). Collectively, we used a data-driven method to provide new insight into AD hippocampal progression. The present model could aid in understanding of the disease stages, as well as tracking memory decline.

Hypoxemia during rapid eye movement sleep mediates memory impairment in older adults at risk for dementia via CA1 hippocampal volume loss.

Obstructive sleep apnea is associated with increased dementia risk. Nocturnal hypoxemia, which can be more severe during rapid eye movement (REM) sleep, may be a key mechanism. This study examines how REM hypoxemia affects memory and explores whether hippocampal vulnerability to hypoxemia mediates this effect in older adults at risk for dementia. Older adults aged ≥50 years (N = 338) with subjective or mild cognitive impairment (i.e., objective impairment) underwent neuropsychological, mood, and medical assessment, magnetic resonance imaging scanning (n = 135), and overnight polysomnography. Verbal learning and memory were assessed with the Rey Auditory Verbal Learning Test. REM sleep hypoxemia was measured using the Oxygen Desaturation Index-3% (REM-ODI). Hippocampal subfield (CA1, CA3, subiculum, and dentate gyrus) volumes were derived from T1 and high-resolution hippocampus T2 scans. We determined whether the relationship between REM-ODI and learning and memory was mediated by hippocampal subfield volume. Analyses were repeated in non-REM sleep to determine whether the effects were REM-specific. Although there was not a direct effect of REM-ODI on verbal learning (p > 0.05) or memory (p > 0.05), mediation analyses showed a significant indirect effect of high REM-ODI on poorer verbal learning (β = -0.09, 95% confidence interval [CI] = -0.238 to -0.005) and memory (β = -0.100, 95% CI = -0.255 to -0.005), which was mediated by CA1 volume. These associations were absent in non-REM sleep (p > 0.05). Hypoxemia during REM sleep may impair memory in people at risk for dementia by reducing CA1 hippocampal volume. Research is needed to explore whether interventions targeting REM sleep hypoxemia are protective against memory decline.

Morphometry of medial temporal lobe subregions using high-resolution T2-weighted MRI in ADNI3: Why, how, and what's next?

This paper for the 20th anniversary of the Alzheimer's Disease Neuroimaging Initiative (ADNI) provides an overview of magnetic resonance imaging (MRI) of medial temporal lobe (MTL) subregions in ADNI using a dedicated high-resolution T2-weighted sequence. A review of the work that supported the inclusion of this imaging modality into ADNI Phase 3 is followed by a brief description of the ADNI MTL imaging and analysis protocols and a summary of studies that have used these data. This review is supplemented by a new study that uses novel surface-based tools to characterize MTL neurodegeneration across biomarker-defined AD stages. This analysis reveals a pattern of spreading cortical thinning associated with increasing levels of tau pathology in the presence of elevated amyloid beta, with apparent epicenters in the transentorhinal region and inferior hippocampal subfields. The paper concludes with an outlook for high-resolution imaging of the MTL in ADNI Phase 4. HIGHLIGHTS: As of Phase 3, the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) protocol includes a high-resolution T2-weighted MRI scan optimized for imaging hippocampal subfields and medial temporal lobe (MTL) subregions. These scans are processed by the ADNI core to obtain automatic segmentations of MTL subregions and to derive morphologic measurements. More detailed granular examination of MTL neurodegeneration in response to disease progression is achieved by applying surface-based modeling techniques. Surface-based analysis of gray matter loss in MTL subregions reveals increasing and spatially expanding patterns of neurodegeneration with advancing stages of Alzheimer's disease (AD), as defined based on amyloid and tau positron emission tomography biomarkers in accordance with recently proposed criteria. These patterns closely align with post mortem literature on spread of pathological tau in AD, supporting the role of tau pathology in the presence of elevated levels of amyloid beta as the driver of neurodegeneration.

Amygdala atrophies in specific subnuclei in preclinical Alzheimer's disease.

Magnetic resonance imaging (MRI) segmentation algorithms make it possible to study detailed medial temporal lobe (MTL) substructures as hippocampal subfields and amygdala subnuclei, offering opportunities to develop biomarkers for preclinical Alzheimer's disease (AD). We identified the MTL substructures significantly associated with tau-positron emission tomography (PET) signal in 581 non-demented individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI-3). We confirmed our results in our UCLouvain cohort including 110 non-demented individuals by comparing volumes between individuals with different visual Braak's stages and clinical diagnosis. Four amygdala subnuclei (cortical, central, medial, and accessory basal) were associated with tau in amyloid beta-positive (Aβ+) clinically normal (CN) individuals, while the global amygdala and hippocampal volumes were not. Using UCLouvain data, we observed that both Braak I-II and Aβ+ CN individuals had smaller volumes in these subnuclei, while no significant difference was observed in the global structure volumes or other subfields. Measuring specific amygdala subnuclei, early atrophy may serve as a marker of temporal tauopathy in preclinical AD, identifying individuals at risk of progression. Amygdala atrophy is not homogeneous in preclinical Alzheimer's disease (AD). Tau pathology is associated with atrophy of specific amygdala subnuclei, specifically, the central, medial, cortical, and accessory basal subnuclei. Hippocampal and amygdala volume is not associated with tau in preclinical AD. Hippocampus and CA1-3 volume is reduced in preclinical AD, regardless of tau.

Glucose metabolism and smaller hippocampal volume in elderly people with normal cognitive function

We investigated associations of glycemic measures, and insulin resistance and secretion measures with hippocampal and subfield volumes. In this cross-sectional study, 7400 community-dwelling participants underwent brain MRI and health checkups between 2016 and 2018. Hemoglobin A1c (HbA1c), glycated albumin (GA), homeostasis model assessment for insulin resistance (HOMA-IR), and HOMA of percent β-cell function (HOMA-β) were evaluated. The associations of each measure with a smaller volume of the hippocampus and twelve hippocampal subfields were investigated. As a result, higher HbA1c or GA and lower HOMA-β levels were significantly associated with smaller volumes in multiple hippocampal subfields. Furthermore, even when we analyzed non-diabetic individuals, substantial associations remained between higher GA or lower HOMA-β levels and smaller volumes of the whole hippocampus or the fimbria. Our findings indicate that postprandial glucose fluctuations, postprandial hyperglycemia, and low insulin secretion have a specific effect on the development of smaller hippocampal volume, suggesting that primary prevention of diabetes and/or sufficient glucose control are important for the prevention of dementia.

Delineating structural and metabolic abnormalities in amygdala and hippocampal subfields for different seizure-onset patterns via stereotactic electroencephalography.

We aimed to investigate mesial temporal lobe abnormalities in mesial temporal lobe epilepsy (MTLE) patients with hypersynchronous (HYP) and low-voltage fast rhythms (LVF) onset identified by stereotactic electroencephalography (SEEG) and evaluate their diagnostic and prognostic value. Fifty-one MTLE patients were categorized as HYP or LVF by SEEG. High-resolution MRI volume-based analysis and 18F-FDG-PET standard uptake values of hippocampal and amygdala subfields were quantified and compared with 57 matched controls. Further analyses were conducted to delineate the distinct pathological characteristics differentiating the two groups. Diagnostic and prognostic prediction performance of these biomarkers were assessed using receiver operating characteristic curves. LVF-onset individuals demonstrated ipsilateral amygdala enlargement (p = 0.048) and contralateral hippocampus hypermetabolism (p = 0.042), pathological results often accompany abnormalities in the temporal lobe cortex, while HYP-onset subjects had significant atrophy (p < 0.001) and hypometabolism (p = 0.013) in ipsilateral hippocampus and its subfields, as well as amygdala atrophy (p < 0.001), pathological results are highly correlated with hippocampal sclerosis. Severe fimbria atrophy was observed in cases of HYP-onset MTLE with poor prognosis (AUC = 0.874). Individuals with different seizure-onset patterns display specific morphological and metabolic abnormalities in the amygdala and hippocampus. Identifying these subfield abnormalities can improve diagnostic and prognostic precision, guiding surgical strategies for MTLE.

Hippocampal, thalamic, and amygdala subfield morphology in major depressive disorder: an ultra-high resolution MRI study at 7-Tesla.

Morphological changes in the hippocampal, thalamic, and amygdala subfields have been suggested to form part of the pathophysiology of major depressive disorder (MDD). However, the use of conventional MRI scanners and acquisition techniques has prevented in-depth examinations at the subfield level, precluding a fine-grained understanding of these subfields and their involvement in MDD pathophysiology. We uniquely employed ultra-high field MRI at 7.0 Tesla to map hippocampal, thalamic, and amygdala subfields in MDD. Fifty-six MDD patients and 14 healthy controls (HCs) were enrolled in the final analysis. FreeSurfer protocols were used to segment hippocampal, thalamic, and amygdala subfields. Bayesian analysis was then implemented to assess differences between groups and relations with clinical features. While no effect was found for MDD diagnosis (i.e., case-control comparison), clinical characteristics of MDD patients were associated with subfield volumes of the hippocampus, thalamus, and amygdala. Specifically, the severity of depressive symptoms, insomnia, and childhood trauma in MDD patients related to lower thalamic subfield volumes. In addition, MDD patients with typical MDD versus those with atypical MDD showed lower hippocampal, thalamic, and amygdala subfield volumes. MDD patients with recurrent MDD versus those with first-episode MDD also showed lower thalamic subfield volumes. These findings allow uniquely fine-grained insights into hippocampal, thalamic, and amygdala subfield morphology in MDD, linking some of them to the clinical manifestation of MDD.

Propagation of sharp wave-ripple activity in the mouse hippocampal CA3 subfield in vitro.

Sharp wave-ripple complexes (SPW-Rs) are spontaneous oscillatory events that characterize hippocampal activity during resting periods and slow-wave sleep. SPW-Rs are related to memory consolidation - the process during which newly acquired memories are transformed into long-lasting memory traces. To test the involvement of SPW-Rs in this process, it is crucial to understand how SPW-Rs originate and propagate throughout the hippocampus. SPW-Rs can originate in CA3, and they typically spread from CA3 to CA1, but little is known about their formation within CA3. To investigate the generation and propagation of SPW-Rs in CA3, we recorded from mouse hippocampal slices using multi-electrode arrays and patch-clamp electrodes. We characterized extracellular and intracellular correlates of SPW-Rs and quantified their propagation along the pyramidal cell layer of CA3. We found that a hippocampal slice can be described by a speed and a direction of propagation of SPW-Rs. The preferred propagation direction was from CA3c (the subfield closer to the dentate gyrus) toward CA3a (the subfield at the boundary to CA2). In patch-clamp recordings from CA3 pyramidal neurons, propagation was estimated separately for excitatory and inhibitory currents associated with SPW-Rs. We found that propagation speed and direction of excitatory and inhibitory currents were correlated. The magnitude of the speed of propagation of SPW-Rs within CA3 was consistent with the speed of propagation of action potentials in axons of CA3 principal cells. KEY POINTS: Hippocampal sharp waves are considered important for memory consolidation; therefore, it is of interest to understand the mechanisms of their generation and propagation. Here, we used two different approaches to study the propagation of sharp waves in mouse CA3 in vitro: multi-electrode arrays and multiple single-cell recordings. We find a preferred direction of propagation of sharp waves from CA3c toward CA3a - both in the local field potential and in sharp wave-associated excitatory and inhibitory synaptic activity. The speed of sharp wave propagation is consistent with the speed of action potential propagation along the axons of CA3 pyramidal neurons. These new insights into the dynamics of sharp waves in the CA3 network will inform future experiments and theoretical models of sharp-wave generation mechanisms.

Differential increase of hippocampal subfield volume after socio-affective mental training relates to reductions in diurnal cortisol

The hippocampus is a central modulator of the HPA-axis, impacting the regulation of stress on brain structure, function, and behavior. The current study assessed whether three different types of 3 months mental Training Modules geared towards nurturing (a) attention-based mindfulness, (b) socio-affective, or (c) socio-cognitive skills may impact hippocampal organization by reducing stress. We evaluated mental training-induced changes in hippocampal subfield volume and intrinsic functional connectivity, by combining longitudinal structural and resting-state fMRI connectivity analysis in 332 healthy adults. We related these changes to changes in diurnal and chronic cortisol levels. We observed increases in bilateral cornu ammonis volume (CA1-3) following the 3 months compassion-based module targeting socio-affective skills (Affect module), as compared to socio-cognitive skills (Perspective module) or a waitlist cohort with no training intervention. Structural changes were paralleled by relative increases in functional connectivity of CA1-3 when fostering socio-affective as compared to socio-cognitive skills. Furthermore, training-induced changes in CA1-3 structure and function consistently correlated with reductions in cortisol output. Notably, using a multivariate approach, we found that other subfields that did not show group-level changes also contributed to changes in cortisol levels. Overall, we provide a link between a socio-emotional behavioural intervention, changes in hippocampal subfield structure and function, and reductions in cortisol in healthy adults.

Differential increase of hippocampal subfield volume after socio-affective mental training relates to reductions in diurnal cortisol.

The hippocampus is a central modulator of the HPA-axis, impacting the regulation of stress on brain structure, function, and behavior. The current study assessed whether three different types of 3 months mental Training Modules geared towards nurturing (a) attention-based mindfulness, (b) socio-affective, or (c) socio-cognitive skills may impact hippocampal organization by reducing stress. We evaluated mental training-induced changes in hippocampal subfield volume and intrinsic functional connectivity, by combining longitudinal structural and resting-state fMRI connectivity analysis in 332 healthy adults. We related these changes to changes in diurnal and chronic cortisol levels. We observed increases in bilateral cornu ammonis volume (CA1-3) following the 3 months compassion-based module targeting socio-affective skills (Affect module), as compared to socio-cognitive skills (Perspective module) or a waitlist cohort with no training intervention. Structural changes were paralleled by relative increases in functional connectivity of CA1-3 when fostering socio-affective as compared to socio-cognitive skills. Furthermore, training-induced changes in CA1-3 structure and function consistently correlated with reductions in cortisol output. Notably, using a multivariate approach, we found that other subfields that did not show group-level changes also contributed to changes in cortisol levels. Overall, we provide a link between a socio-emotional behavioural intervention, changes in hippocampal subfield structure and function, and reductions in cortisol in healthy adults.

Upregulated solute-carrier family genes in the hippocampus of schizophrenia can be rescued by antipsychotic medications

Background and hypothesisOur previous studies have found that functional changes in the hippocampal circuit from dentate gyrus (DG) to cornu ammonis 3 and 1 (CA3, CA1) are highly associated with schizophrenia (SZ). However, no studies have explored the genetic expression across the three and two human hippocampal subfields (DG-CA3-CA1 and CA3-CA1) between subjects with SZ and healthy controls (CT). Study designWe matched cohorts between CT (n = 13) and SZ (n = 13). Among SZ, 6 subjects were on antipsychotics (AP) while 7 were off AP. We combined RNA-seq data from all three and two hippocampal subfields and performed differentially expressed gene analyses across DG-CA3-CA1 and CA3-CA1 affected by either SZ or AP. Study resultsWe found that differentially expressed genes (DEGs) from effects of SZ and AP across DG-CA3-CA1 and CA3-CA1 were highly associated with gene ontology terms related to hormonal and immune signaling, cellular mitosis and apoptosis, ion and amino acid transports, and protein modification and degradation. Additionally, we found that multiple genes related to solute-carrier family and immune signaling were significantly upregulated across DG-CA3-CA1 and CA3-CA1 in patients with SZ relative to CT, and AP consistently and robustly repressed the expression of these upregulated genes in the DG-CA3-CA1 and CA3-CA1 from subjects with SZ. ConclusionsTogether, these data suggest that the upregulated solute-carrier family genes in the hippocampus might have important roles in the pathophysiology of SZ, and that AP may reduce the symptoms of psychosis in SZ via rescuing the solute-carrier gene expression.

Objective Sleep Function is Associated with Hippocampal Subfield Volumes in Community-Dwelling Adults.

Sleep patterns often shift as people age, a phenomenon frequently associated with the onset of neurodegenerative conditions. Additionally, distinct alterations occur in brain structure as individuals grow older, particularly within the hippocampus, a region known for its role in cognition and sleep regulation. Yet, how exactly do changes in sleep relate to specific subfields within the hippocampus is still unclear. We conducted a study involving non-demented healthy adults from the Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) cohort. Participants underwent objective sleep measurements using wrist Actiwatch and WatchPAT devices. Further, all participants underwent the same Magnetic Resonance Imaging (MRI) protocol, including a 3D high resolution T1-weighted sequence, on the same 3.0 Tesla MRI scanner using an eight-channel head coil. The study aimed to examine the relationship between objectively measured sleep metrics and the morphology of twenty-two distinct hippocampal subregions. In total, 75 non-demented participants with 63 mean years of age were included in the study. Results indicated that a higher frequency of awakenings during sleep was associated with increased volume in the right presubiculum body (beta = 0.630, p False Discovery Rate (FDR) <0.036). Longer sleep duration showed a tendency to be associated with smaller volumes of the right presubiculum body, hinting at a possible negative impact of prolonged sleep on this brain region. Similar trends were observed regarding sleep apnea and the presubiculum body volume. Further analysis based on age stratification revealed that in younger participants, longer sleep duration was linked to decreased volume of the presubiculum body, while a greater number of awakenings was correlated with increased volume of the same region. Among older participants, higher frequencies of awakenings were associated with larger volumes in various hippocampal subfields. These findings shed light on the complex relationship between sleep characteristics and brain structure, highlighting potential age-related differences. The study provides valuable insights into how sleep disruptions may impact hippocampal morphology and cognitive function of cognitively healthy adults. Further research is warranted to elucidate the underlying mechanisms and implications for neurodegenerative diseases.

The developing hippocampus: Microstructural evolution through childhood and adolescence.

The hippocampus is a structure in the medial temporal lobe which serves multiple cognitive functions. While important, the development of the hippocampus in the formative period of childhood and adolescence has not been extensively investigated, with most contemporary research focusing on macrostructural measures of volume. Thus, there has been little research on the development of the micron-scale structures (i.e., microstructure) of the hippocampus, which engender its cognitive functions. The current study examined age-related changes of hippocampal microstructure using diffusion MRI data acquired with an ultra-strong gradient (300 mT/m) MRI scanner in a sample of children and adolescents (N=88; 8-19 years). Surface-based hippocampal modelling was combined with established microstructural approaches, such as Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion Density Imaging (NODDI), and a more advanced gray matter diffusion model Soma And Neurite Density Imaging (SANDI). No significant changes in macrostructural measures (volume, gyrification, and thickness) were found between 8-19 years, while significant changes in microstructure measures related to neurites (from NODDI and SANDI), soma (from SANDI), and mean diffusivity (from DTI) were found. In particular, there was a significant increase across age in neurite MR signal fraction and a significant decrease in extracellular MR signal fraction and mean diffusivity across the hippocampal subfields and long-axis. A significant negative correlation between age and MR apparent soma radius was found in the subiculum and CA1 throughout the anterior and body of the hippocampus. Further surface-based analyses uncovered variability in age-related microstructural changes between the subfields and long-axis, which may reflect ostensible developmental differences along these two axes. Finally, correlation of hippocampal surfaces representing age-related changes of microstructure with maps derived from histology allowed for postulation of the potential underlying microstructure that diffusion changes across age may be capturing. Overall, distinct neurite and soma developmental profiles in the human hippocampus during late childhood and adolescence are reported for the first time.

Precise Definition of Porcine Hippocampal Cornu Ammonis 2: High Histoarchitectural Similarity to Humans but Unequal Sensitivity to Hypoxia

Experimental animal studies of hypoxic–ischemic injury of the hippocampus of pigs are limited due to the unprecise definition of hippocampal subfields, cornu ammonis 1 to 4, compared to humans. Given that the pig model closely mirrors human physiology and serves as an important model for critical care research, a more precise description is necessary to draw valid conclusions applicable to human diseases. In our study, we were able to precisely define the CA2 and its adjacent regions in a domestic pig model by arginine vasopressin receptor 1B (AVPR1B) and calbindin-D28K like (CaBP-Li) expression patterns. Our findings demonstrate that the histoarchitecture of the porcine cornu ammonis subfields closely resembles that of the human hippocampus. Notably, we identified unusually strong neuronal damage in regions of the pig hippocampus following global ischemia, which are typically not susceptible to hypoxic–ischemic damage in humans.

Can a nature walk change your brain? Investigating hippocampal brain plasticity after one hour in a forest

In cities, the incidence of mental disorders is higher, while visits to nature have been reported to benefit mental health and brain function. However, there is a lack of knowledge about how exposure to natural and urban environments affects brain structure. To explore the causal relationship between exposure to these environments and the hippocampal formation, 60 participants were sent on a one hour walk in either a natural (forest) or an urban environment (busy street), and high-resolution hippocampal imaging was performed before and after the walks. We found that the participants who walked in the forest had an increase in subiculum volume, a hippocampal subfield involved in stress response inhibition, while no change was observed after the urban walk. However, this result did not withstand Bonferroni correction for multiple comparisons. Furthermore, the increase in subiculum volume after the forest walk was associated with a decrease in self-reported rumination. These results indicate that visits to nature can lead to observable alterations in brain structure, with potential benefits for mental health and implications for public health and urban planning policies.

Distinct patterns of hippocampal subfieldvolumes predict coping strategies, emotion regulation, and impulsivity in healthy adults.

Recent studies have suggested that the hippocampus (HC) is involved in cognitive and behavioral functions beyond memory.We aimed to investigate how the volume of each subfield of the HC is associated with distinct patterns of coping strategies, emotion regulation, and impulsivity in a healthy population. We studied a total of 218 healthy subjects using the Leipzig mind-brain-body dataset. Participants were assessed for coping strategies, emotion regulation, and impulsivity using the Cognitive Emotion Regulation Questionnaire(CERQ), Coping Orientations to Problems Experienced (COPE), Impulsive Behavior Scale (UPPS), and Behavioral Activation and Inhibition System (BAS/BIS). The associations between HC subfield volumes including CA1, CA2/3, CA4/DG, SR-SL-SM, and subiculum, and behavioral scores were examined using multiple linear regression models adjusted for possible confounders, including age, sex, years of education, handedness, total intracranial volume (ICV), and HC volume. The use of emotional support, venting, and positive reframing coping strategies were significantly and positively correlated with total, total right, and total left HC volumes. Venting was significantly associated with CA1 after adjusting for age, sex, handedness, and education (P=0.001, B = 0.265, P-FDR = 0.005).No significant association was observed between CERQ subscales and HC subfieldvolumesafter controlling for confounders and multiple analyses. However,sensation-seeking subscale of the UPPS-P was positively correlated with total and right CA2-CA3 volumes after adjustments for age, sex, handedness, ICV, and HC volumes(P=0.002, B = 0.266, P-FDR = 0.035).BAS and BIS subscales did not showsignificant relationshipwith HC subfield volumes. Patterns ofHC subfieldsvolumes are associated with copingstrategies, impulsivity, and emotion regulation.In particular, using emotional support, positive reframing, venting, and sensation seeking aresignificantly associated with certain HC subfield volumes.These findings suggest that the hippocampus may play a crucial role in modulating emotional responses and behavioral adaptations, offering potential targets for therapeutic interventions.