Hippocampus-amygdala Transition Area Research Articles

Subsegmentation of the hippocampus in subgroups of migraine with aura patients: advanced structural neuroimaging study

BackgroundThis study investigated for a possible contributing role of hippocampus in the different clinical phenotypic manifestations of migraine aura.MethodsHerein, patients were categorized as those with pure visual aura (MwAv), those who reported additional somatosensory and dysphasic symptoms (MwAvsd), and healthy controls (HCs). Neuroimaging data obtained using FreeSurfer-based segmentation of hippocampal subfields were compared between HCs and patients with migraine with aura, as well as between HCs and those with MwAv and MwAvsd. The average migraine aura complexity score (MACS) was calculated for each patient to investigate the correlation between hippocampal subfield volume and migraine aura complexity.ResultsHerein, 46 patients with migraine with aura (28 MwAvsd and 18 MwAv) and 31 HCs were included. There were no significant differences in the hippocampal subfields between HCs and patients with migraine with aura. The average MACS negatively correlated with the volumes of the left and right hippocampi, Cornu Ammonis (CA) 1, CA3, CA4, molecular layer, left granule cell layer of the dentate gyrus, hippocampal fissure, and hippocampus-amygdala transition area. The MwAvsd subgroup had significantly smaller whole hippocampal volumes in both hemispheres, as well as in both subicula, compared with the MwAv subgroup and HCs. In addition, the left molecular layer, right CA1, and hippocampal fissures were significantly smaller in the MwAvsd group than in the MwAv subgroup and HCs.ConclusionsSmaller left and right hippocampal volumes, particularly of the subiculum/CA1 area, may play an important role in the pathophysiology of somatosensory and dysphasic symptoms in migraine with aura.

Associations between parental rearing style and amygdala and hippocampal subfield abnormalities in drug-naive females with anorexia nervosa

BackgroundAltered volumes in the hippocampus and amygdala have been linked to anorexia nervosa (AN). This study aimed to investigate amygdala and hippocampal subfields volume abnormalities in AN patients, and their associations with parental rearing practices and clinical psychological characteristics.MethodsThis study included twenty-nine drug-naive females with AN from West China Hospital of Sichuan University, China, and fifty-nine age- and gender-matched healthy controls (HCs) recruited through advertisement. All participants underwent T1-weighted imaging. Amygdala and hippocampal subfields volume was calculated using FreeSurfer 7.0. The Core Self-Evaluation Scale (CSES) and Rosenberg Self-Esteem Scale (RSES) were used to assess the psychological characteristics of AN patients. The Egna Minnen av Barndoms Uppfostran (EMBU) was employed to evaluate parental rearing practices. Group differences in brain volumes were analyzed with covariates like age and total intracranial volume (TIV). Partial correlation analysis explored the correlations between brain region volumes and clinical psychological characteristics.ResultsAN patients exhibited lower RSES and CSES scores, and more adverse parental rearing style than healthy norms. After adjusting for covariates, AN patients showed decreased gray matter volume (GMV) in the left medial (Me) and cortical (Co) nucleus, as well as in the right hippocampal-amygdala transition area (HATA). GMV in the left Me was correlated with years of education among HCs but not among AN patients. GMV in the right HATA was positively correlated with paternal penalty and severity, as well as maternal overinterference.ConclusionThis study supports structure abnormalities in amygdala and hippocampus in AN patients and suggests that parental rearing practices may be associated with hippocampal abnormalities, potentially contributing to the pathophysiology of AN. Addressing appropriate parental rearing styles may offer a positive impact on AN.

Resting-state neural activity and cerebral blood flow alterations in type 2 diabetes mellitus: Insights from hippocampal subfields.

In this study, multimodal magnetic resonance imaging (MRI) imaging was used to deeply analyze the changes of hippocampal subfields perfusion and function in patients with type 2 diabetes mellitus (T2DM), aiming to provide image basis for the diagnosis of hippocampal-related nerve injury in patients with T2DM. We recruited 35 patients with T2DM and 40 healthy control subjects (HCs). They underwent resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL) scans, and a series of cognitive tests. Then, we compared the differences of two groups in the cerebral blood flow (CBF) value, amplitude of low-frequency fluctuation (ALFF) value, and regional homogeneity (ReHo) value of the bilateral hippocampus subfields. The CBF values of cornu ammonis area 1 (CA1), dentate gyrus (DG), and subiculum in the right hippocampus of T2DM group were significantly lower than those of HCs. The ALFF values of left hippocampal CA3, subiculum, and bilateral hippocampus amygdala transition area (HATA) were higher than those of HCs in T2DM group. The ReHo values of CA3, DG, subiculum, and HATA in the left hippocampus of T2DM group were higher than those of HCs. In the T2DM group, HbAc1 and FINS were negatively correlated with imaging characteristics in some hippocampal subregions. This study indicates that T2DM patients had decreased perfusion in the CA1, DG, and subiculum of the right hippocampus, and the right hippocampus subiculum was associated with chronic hyperglycemia. Additionally, we observed an increase in spontaneous neural activity within the left hippocampal CA3, subiculum, and bilateral HATA regions, as well as an enhanced local neural coordination in the left hippocampal CA3, DG, HATA, and subiculum among patients with type 2 diabetes, which may reflect an adaptive compensation for cognitive decline. However, this compensation may decline with the exacerbation of metabolic disorders.

Hippocampal Structures Among Japanese Adolescents Before and After the COVID-19 Pandemic

Few studies have used a large-sample, longitudinal, population-based cohort study to examine whether the COVID-19 pandemic as a global major life event is associated with structural plasticity of the adolescent hippocampus. To examine whether Japan's first state of emergency (SoE) during the COVID-19 pandemic was associated with alterations in the macrostructures and microstructures of the hippocampus during its development. The population-neuroscience Tokyo TEEN Cohort study is a prospective cohort study with 4 consecutive waves in Tokyo, Japan. Due to the SoE, data collection was suspended between March 27, 2020, and July 30, 2020. Analyzed data, comprising 1149 brain structural scans obtained from 479 participants, of whom 336 participants had undergone 2 or more scans, were collected between October 2013 and November 2021. Data were analyzed from August 2022 to December 2023. Japan's first SoE (April 7 to May 25, 2020). Hippocampal volume, 12 hippocampal subfield volumes, and 7 microstructural measures of the hippocampus. A total of 1060 brain scans from 459 participants (214 female participants [47%]) including 246 participants from wave 1 (median [IQR] age, 11.3 [11.1-11.7] years), 358 from wave 2 (median [IQR] age, 13.8 [13.3-14.5] years), 304 from wave 3 (median [IQR] age, 15.9 [15.4-16.5] years), and 152 from wave 4 (median [IQR] age, 17.9 [17.5-18.4] years) were included in the final main analysis. The generalized additive mixed model showed a significant associations of the SoE with the mean hippocampal volume (β = 102.19; 95% CI, 0.61-203.77; P = .049). The generalized linear mixed models showed the main associations of the SoE with hippocampal subfield volume (granule cell and molecular layer of the dentate gyrus: β = 18.19; 95% CI, 2.97-33.41; uncorrected P = .02; CA4: β = 12.75; 95% CI, 0.38-25.12; uncorrected P = .04; hippocampus-amygdala transition area: β = 5.67; 95% CI, 1.18-10.17; uncorrected P = .01), and fractional anisotropy (β = 0.03; 95% CI, 0.00-0.06; uncorrected P = .04). After the first SoE, a volumetric increase in the hippocampus and trend increase in 3 subfield volumes and microstructural integration of the hippocampus were observed, suggesting that the transient plasticity of the adolescent hippocampus was affected by a major life event along with the typical developmental trajectory.

Atrophy of hippocampal subfields relates to memory decline during the pathological progression of Alzheimer's disease.

It has been well documented that atrophy of hippocampus and hippocampal subfields is closely linked to cognitive decline in normal aging and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, evidence is still sparce regarding the atrophy of hippocampus and hippocampal subfields in normal aging adults who later developed MCI or AD. To examine whether atrophy of hippocampus and hippocampal subfields has occurred in normal aging before a diagnosis of MCI or AD. We analyzed structural magnetic resonance imaging (MRI) data of cognitively normal (CN, n = 144), MCI (n = 90), and AD (n = 145) participants obtained from the Alzheimer's Disease Neuroimaging Initiative. The CN participants were categorized into early dementia converters (CN-C) and non-converters (CN-NC) based on their scores of clinical dementia rating after an average of 36.2 months (range: 6-105 months). We extracted the whole hippocampus and hippocampal subfields for each participant using FreeSurfer, and analyzed the differences in volumes of hippocampus and hippocampal subfields between groups. We then examined the associations between volume of hippocampal subfields and delayed recall scores in each group separately. Hippocampus and most of the hippocampal subfields demonstrated significant atrophy during the progression of AD. The CN-C and CN-NC groups differed in the left hippocampus-amygdala transition area (HATA). Furthermore, the volume of presubiculum was significantly correlated with delayed recall scores in the CN-NC and AD groups, but not in the CN-C and MCI groups. Hippocampal subfield atrophy (i.e., left HATA) had occurred in cognitively normal elderly individuals before clinical symptoms were recognized. Significant associations of presubiculum with delayed recall scores in the CN-NC and AD groups highlight the essential role of the hippocampal subfields in both early dementia detection and AD progression.

Volumetric alterations of the hippocampal subfields in major depressive disorder with and without suicidal ideation

Major depressive disorder (MDD) is often accompanied with suicidal ideation (SI). Previous studies suggested that MDD patients who experienced suicidal attempts (SA) exhibited smaller hippocampal volume than those without SA. The hippocampus consists of several subfields that are histologically and functionally unique respectively. However, few studies have been designed to investigate the relationship between suicide and volumetric changes of the hippocampal subfields in MDD. A total of 92 participants, including 24 MDD patients with SI (MDD-SI), 30 MDD patients without SI (MDD-nSI), and 38 healthy controls (HC) were recruited in this study. High-resolution structural magnetic resonance images (MRI) were obtained and analyzed by using the automated hippocampal substructure module in FreeSurfer 7.3.2 Analyses of variance (ANOVA) were performed to obtain hippocampal subfields with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. Finally, the relationships between volumes of the hippocampal subfields and clinical characteristics were assessed using correlation analyses. The ANOVA revealed significant volumetric differences of the hippocampal subfields among three groups in the bilateral cornu ammonis (CA) 1 head, CA4 body, granule cell layer of the dentate gyrus (GC-ML-DG), molecular layer (ML), the right hippocampus-amygdala transition area (HATA), the right subiculum (Sub) body, and the left CA4 head. Relative to HC, both groups of MDD showed decreased volumes in the CA1 head, CA4, GC-ML-DG head, ML head, and whole hippocampal head of the left hippocampus, the right HATA, and bilateral whole hippocampal body, and whole hippocampus. Meanwhile, the MDD-SI group further exhibited diminished volume in the CA1 head, GC-ML-DG head, ML head, CA4 body, Sub body, and whole hippocampal head of the right hippocampus, as well as bilateral GC-ML-DG body and ML body. Additionally, the MDD-SI group also showed decreased volumes in the right GC-ML-DG body, ML body, and Sub body when compared to MDD-nSI group. However, no significant association was observed between hippocampal subfield volumes and clinical features in MDD. The present findings suggested that SI in MDD might be attributed to subfield abnormalities in the subiculum and DG-dominant circuit of the right hippocampus.

Associations between hippocampal subfield volume and cognitive performance

AbstractBackgroundIt is well demonstrated that hippocampal atrophy is associated with cognitive impairment. Existing studies have associated smaller hippocampal volumes with dementia, and hippocampal volume reduction has been established as a biomarker for the conversion of mild cognitive impairment to Alzheimer’s Disease. Although some studies have examined correlations between hippocampal subfield volumes and cognitive domains such as memory, further research is needed to clarify the associations between the volume of each subfield and the various cognitive domains. So far a few studies have been conducted among Asian populations. A more specific understanding of these relationships is crucial given the functional and histological differences in the subfields and their distinct patterns of atrophy, which imply that the hippocampal subfields may affect cognition differentially. This study aimed to investigate the associations between the volumes of 12 hippocampal subfields on cognitive performance in a Singaporean sample.Method448 patients at a memory clinic in Singapore (97 with no cognitive impairment, 177 with CIND, and 174 with dementia) underwent magnetic resonance imaging (MRI) and a neuropsychological assessment. MRI was processed through free surfer (v.6.1) to extract volumes of 12 hippocampal subfields—the tail, subiculum, presubiculum, parasubiculum, CA1, CA3, CA4, fimbria, fissure, molecular layer, the molecular and granule cell layers of the of the dentate gyrus (GCMLDG), and the hippocampus‐amygdala transition area (HATA). Cognition was assessed using NINDS–Canadian Stroke Network harmonization neuropsychological battery.ResultGlobal cognition was associated with the subiculum, presubiculum, CA1, CA3, CA4, molecular layer, and GCMLDG (all p‐values < .0005). Except for the fissure, all hippocampal subfields were associated with visuospatial skills (all p‐values < .05) and memory (all p‐values < .035). The fimbria was associated with the most cognitive domains, including executive dysfunction (p = .011), language (p = .006), visuomotor function (p = .003), visuospatial skills (p < .001), and memory (p < .001).ConclusionThe current study builds on existing research on the associations between hippocampal subfield volumes and cognitive dysfunction. Longitudinal studies are required to investigate the volumetric reduction of hippocampal subfields as a biomarker of cognitive decline.

Volume changes of hippocampal and amygdala subfields in patients with mild cognitive impairment and Alzheimer's disease.

Automated segmentation of hippocampal and amygdala subfields could improve classification accuracy of Mild Cognitive Impairments (MCI) and Alzheimer's Disease (AD) individuals. We applied T1-weighted magnetic resonance imaging (MRI) for 21 AD, 39 MCI and 32 normalcontrol(NC) participants at 3-Tesla MRI. Twelve hippocampal subfields and 9 amygdala subfields in each hemisphere were analyzed using FreeSurfer 6.0. Smaller volumes were observed in right/left whole hippocampus, right/left hippocampal tail, right/left subiculum, right Cornu ammonis 1(CA1), right/left molecular layer, right granule cell-molecular layer-dentate gyrus (GC-ML-DG), right CA4, right fimbria, right whole amygdala, right/left accessory basal, right anterior amygdala area, left central, left medial and right/left cortical nucleus of AD group compared to both MCI and NC groups (p < 0.001). The volumes of right presubiculum, right CA3, right hippocampus-amygdala-transition-area (HATA), right lateral, right basal, right central, right medial, right cortico-amygdaloid transition (CAT) and right paralaminar nucleus were significantly larger in NC than AD group (p ≤ 0.001), while the volumes of right subiculum, right CA1, right molecular layer, right whole hippocampus, right whole amygdala, right basal and right accessory basal were significantly larger in NC than MCI group (p ≤ 0.002). Trend analysis showed that most hippocampus and amygdala subfields have a trend of atrophy with the decline of cognitive function. Six core components were identified by the hierarchical clustering. The combined Receiver operating characteristic (ROC) analysis achieved the diagnostic performances (AUC: 0.81) in differentiating AD from MCI; (AUC: 0.79) in differentiating MCI from NC and (AUC: 0.97) in differentiating AD from NC. Volumetric differences of hippocampus and amygdala were at a finer subfields scale, and the volumes of right basal nucleus, left parasubiculum, left medial nucleus, left GC-ML-DG, left hippocampal fissure, and right fimbria can be employed as neuroimaging biomarkers to assist the clinical diagnosis of MCI and AD.

Structural plasticity of the contralesional hippocampus and its subfields in patients with glioma.

To characterize the structural plasticity of the contralesional hippocampus and its subfields in patients with unilateral glioma. 3D T1-weighted MRI images were collected from 55 patients with tumors infiltrating the left (HipL, n = 27) or right (HipR, n = 28) hippocampus, along with 30 age- and sex-matched healthy controls (HC). Gray matter volume differences of the contralesional hippocampal regions and three control regions (superior frontal gyrus, caudate nucleus, and superior occipital gyrus) were evaluated using voxel-based morphometry (VBM) analyses. Volumetric differences in the hippocampus and its subregional volume were measured using the FreeSurfer software. Compared with HC, patients with unilateral hippocampal glioma exhibited significantly larger gray matter volume in the contralesional hippocampus and parahippocampal regions (cluster = 571 voxels for HipL; cluster 1 = 538 voxels and cluster 2 = 88 voxels for HipR; family-wise error corrected p < 0.05). No significant alterations were found in control regions. Volumetric analyses showed the same trend in the contralesional hippocampal subregions for both patient groups, including the CA1 head, CA3 head, hippocampus amygdala transition area (HATA), fimbria, and the granule cell molecular layer of the dentate gyrus head (GC-ML-DG head). Notably, the differences of the contralesional HATA (HipL: η2 = 0.418, corrected p = 0.002; HipR: η2 = 0.313, corrected p = 0.052) and fimbria (HipL: η2 = 0.450, corrected p < 0.001; HipR: η2 = 0.358, corrected p = 0.012) still held after the Bonferroni correction. Our findings provide evidence for macrostructural plasticity of the contralateral hippocampus in patients with unilateral hippocampal glioma. Specifically, HATA and fimbria exhibit great potential in this process. • Glioma infiltration of the hippocampal regions induces a significant increase in gray matter volume on the contralateral side. • Specifically, the HATA and fimbria regions exhibit favorable plastic potential in the process of lesion-induced structural remolding.

Hippocampal subfield alterations in schizophrenia and major depressive disorder: a systematic review and network meta-analysis of anatomic MRI studies.

Hippocampal disturbances are important in the pathophysiology of both schizophrenia and major depressive disorder (MDD). Imaging studies have shown selective volume deficits across hippocampal subfields in both disorders. We aimed to investigate whether these volumetric alterations in hippocampal subfields are shared or divergent across disorders. We searched PubMed and Embase from database inception to May 8, 2021. We identified MRI studies in patients with schizophrenia, MDD or both, in which hippocampal subfield volumes were measured. We excluded nonoriginal, animal or postmortem studies, and studies that used other imaging modalities or overlapping data. We conducted a network meta-analysis to estimate and contrast alterations in subfield volumes in the 2 disorders. We identified 45 studies that met the initial criteria for systematic review, of which 15 were eligible for network metaanalysis. Compared to healthy controls, patients with schizophrenia had reduced volumes in the bilateral cornu ammonis (CA) 1, granule cell layer of the dentate gyrus, subiculum, parasubiculum, molecular layer, hippocampal tail and hippocampus-amygdala transition area (HATA); in the left CA4 and presubiculum; and in the right fimbria. Patients with MDD had decreased volumes in the left CA3 and CA4 and increased volumes in the right HATA compared to healthy controls. The bilateral parasubiculum and right HATA were smaller in patients with schizophrenia than in patients with MDD. We did not investigate medication effects because of limited information. Study heterogeneity was noteworthy in direct comparisons between patients with MDD and healthy controls. The volumes of multiple hippocampal subfields are selectively altered in patients with schizophrenia and MDD, with overlap and differentiation in subfield alterations across disorders. Rigorous head-to-head studies are needed to validate our findings.

Baduanjin exercise modulates the hippocampal subregion structure in community-dwelling older adults with cognitive frailty.

Regular Baduanjin exercise intervention was proven to be beneficial in improving the cognitive ability and physical performance of older adults with different health conditions but was unclear to influence the structural plasticity of the hippocampus. This study aimed to explore the modulation of hippocampal subregions as a mechanism by which Baduanjin exercise improves cognitive frailty in older adults. A total of 102 community-dwelling older adults with cognitive frailty were recruited and randomly allocated to the Baduanjin exercise training group and usual physical activity control group. The participants in the Baduanjin exercise training group participated in a 24-week Baduanjin exercise intervention program with an exercise frequency of 60 min per day, 3 days per week. Cognitive ability and physical frailty were assessed, and MRI scans were performed on all participants at baseline and after 24 weeks of intervention. The structural MRI data were processed with MRIConvert (version 2.0 Rev. 235) and FreeSurfer (version 6.0.0) software. Data analyses were performed using the independent sample t tests/Mann-Whitney U tests with the Bonferroni correction, mixed linear model, correlation, or mediation analysis by the SPSS 24.0 software (IBM Corp, Armonk, NY, United States). After 24 weeks of intervention, a statistically significant increase was found for the Montreal Cognitive Assessment (MoCA) scores (p = 0.002) with a large effect size (Cohen's d = 0.94) and the significant interaction effect (P goup × time < 0.05), Memory Quotient (MQ) scores (p = 0.019) with a medium effect size (Cohen's d = 0.688) and the significant interaction effect (P goup × time < 0.05), and other parameters of WMS-RC test including pictures (p = 0.042), recognition (p = 0.017), and association (p = 0.045) test with a medium effect size (Cohens' d = 0.592, 0.703, and 0.581) for the Baduanjin training group, while significant decrease for the Edmonton Frailty Scale (EFS) score (p = 0.022), with a medium effect size (Cohen's d = -0.659) and the significant interaction effect (P goup × time < 0.05) for the Baduanjin training group. The differences in the left parasubiculum, Hippocampal Amygdala Transition Area (HATA), right Cornu Ammonis Subfield 1 (CA1) and presubiculum volumes from baseline to 24 weeks after intervention in the Baduanjin training group were significantly greater than those in the control group (p < 0.05/12). Further analysis showed that the changes in right CA1 volume were positively correlated with the changes in MoCA and MQ scores (r = 0.510, p = 0.015; r = 0.484, p = 0.022;), the changes in right presubiculum and left parasubiculum volumes were positively correlated with the changes in MQ (r = 0.435, p = 0.043) and picture test scores (r = 0.509, p = 0.016), respectively, and the changes in left parasubiculum and HATA volumes were negatively correlated with the changes in EFS scores (r = -0.534, p = 0.011; r = -0.575, p = 0.005) in the Baduanjin training group, even after adjusting for age, sex, years of education and marital status; furthermore, the volume changes in left parasubiculum and left HATA significantly mediated the Baduanjin exercise training-induced decrease in the EFS scores (β = 0.376, 95% CI 0.024 ~ 0.947; β = 0.484, 95% CI 0.091 ~ 0.995); the changes of left parasubiculum and right CA1 significantly mediated the Baduanjin exercise training-induced increase in the picture and MO scores (β = -0.83, 95% CI-1.95 ~ -0.002; β = -2.44, 95% CI-5.99 ~ -0.32). A 24-week Baduanjin exercise intervention effectively improved cognitive ability and reduced physical frailty in community-dwelling older adults with cognitive frailty, and the mechanism might be associated with modulating the structural plasticity of the hippocampal subregion.

Hippocampal adaptation to high altitude: a neuroanatomic profile of hippocampal subfields in Tibetans and acclimatized Han Chinese residents.

The hippocampus is highly plastic and vulnerable to hypoxia. However, it is unknown whether and how it adapts to chronic hypobaric hypoxia in humans. With a unique sample of Tibetans and acclimatized Han Chinese individuals residing on the Tibetan plateau, we aimed to build a neuroanatomic profile of the altitude-adapted hippocampus by measuring the volumetric differences in the whole hippocampus and its subfields. High-resolution T1-weighted magnetic resonance imaging was performed in healthy Tibetans (TH, n = 72) and healthy Han Chinese individuals living at an altitude of more than 3,500 m (HH, n = 27). In addition, healthy Han Chinese individuals living on a plain (HP, n = 72) were recruited as a sea-level reference group. Whereas the total hippocampal volume did not show a significant difference across groups when corrected for age, sex, and total intracranial volume, subfield-level differences within the hippocampus were found. Post hoc analyses revealed that Tibetans had larger core hippocampal subfields (bilateral CA3, right CA4, right dentate gyrus); a larger right hippocampus-amygdala transition area; and smaller bilateral presubiculum, right subiculum, and bilateral fimbria, than Han Chinese subjects (HH and/or HP). The hippocampus and all its subfields were found to be slightly and non-significantly smaller in HH subjects than in HP subjects. As a primary explorational study, our data suggested that while the overall hippocampal volume did not change, the core hippocampus of Tibetans may have an effect of adaptation to chronic hypobaric hypoxia. However, this adaptation may have required generations rather than mere decades to accumulate in the population.

Hippocampal subfield morphology in regular hemodialysis patients.

Hippocampal alterations have been implicated in the pathophysiology of cognitive impairment in hemodialysis patients. The hippocampus consists of several distinct subfields, and the molecular mechanisms underlying cognition might be associated with specific hippocampal subfield volume changes. However, this has not yet been investigated in hemodialysis patients. This study aimed to explore volumetric abnormalities in hippocampal subfields in regular hemodialysis patients. High-resolution T1-weighted structural images were collected in 61 subjects including 36 hemodialysis patients and 25 healthy controls. A state-of-the-art hippocampal segmentation approach was adopted to segment the hippocampal subfields. Group differences in hippocampal subfield volumes were assessed in Python with a statsmodels module using an ordinary least squares regression with age and sex as nuisance effects. Hemodialysis patients had significantly smaller volumes in the bilateral hippocampus (P<.05/2, Bonferroni corrected), cornu ammonis 1 (CA1), CA4, granule cell and molecular layer of the dentate gyrus, hippocampus-amygdala transition area and molecular layer of the hippocampus than healthy controls (P<.05/24, Bonferroni corrected). Hemodialysis patients also had lower volumes in the left hippocampal tail and right fimbria than healthy controls (P<.05/24, Bonferroni corrected). Hippocampal subfield volumes were associated with neuropsychological test scores, the duration of disease and hemoglobin levels. We found smaller hippocampal subfield volumes in hemodialysis patients, which were associated with impaired cognition, supporting their role in memory disturbance in the hemodialysis population. However, multiple clinical factors may have confounded the results, and therefore, the interpretation of these results needs to be cautious.

Genetic Specificity of Hippocampal Subfield Volumes, Relative to Hippocampal Formation, Identified in 2148 Young Adult Twins and Siblings.

The hippocampus is a complex brain structure with key roles in cognitive and emotional processing and with subregion abnormalities associated with a range of disorders and psychopathologies. Here we combine data from two large independent young adult twin/sibling cohorts to obtain the most accurate estimates to date of genetic covariation between hippocampal subfield volumes and the hippocampus as a single volume. The combined sample included 2148 individuals, comprising 1073 individuals from 627 families (mean age = 22.3 years) from the Queensland Twin IMaging (QTIM) Study, and 1075 individuals from 454 families (mean age = 28.8 years) from the Human Connectome Project (HCP). Hippocampal subfields were segmented using FreeSurfer version 6.0 (CA4 and dentate gyrus were phenotypically and genetically indistinguishable and were summed to a single volume). Multivariate twin modeling was conducted in OpenMx to decompose variance into genetic and environmental sources. Bivariate analyses of hippocampal formation and each subfield volume showed that 10%-72% of subfield genetic variance was independent of the hippocampal formation, with greatest specificity found for the smaller volumes; for example, CA2/3 with 42% of genetic variance being independent of the hippocampus; fissure (63%); fimbria (72%); hippocampus-amygdala transition area (41%); parasubiculum (62%). In terms of genetic influence, whole hippocampal volume is a good proxy for the largest hippocampal subfields, but a poor substitute for the smaller subfields. Additive genetic sources accounted for 49%-77% of total variance for each of the subfields in the combined sample multivariate analysis. In addition, the multivariate analyses were sufficiently powered to identify common environmental influences (replicated in QTIM and HCP for the molecular layer and CA4/dentate gyrus, and accounting for 7%-16% of total variance for 8 of 10 subfields in the combined sample). This provides the clearest indication yet from a twin study that factors such as home environment may influence hippocampal volumes (albeit, with caveats).

Volume of hippocampus-amygdala transition area predicts outcomes of electroconvulsive therapy in major depressive disorder: high accuracy validated in two independent cohorts.

Although many previous studies reported structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy (ECT) in major depressive disorder (MDD), yet the exact roles of both areas for antidepressant effects are still controversial. In the current study, segmentation of amygdala and hippocampal sub-regions was used to investigate the longitudinal changes of volume, the relationship between volume and antidepressant effects, and prediction performances for ECT in MDD patients before and after ECT using two independent datasets. As a result, MDD patients showed selectively and consistently increased volume in the left lateral nucleus, right accessory basal nucleus, bilateral basal nucleus, bilateral corticoamygdaloid transition (CAT), bilateral paralaminar nucleus of the amygdala, and bilateral hippocampus-amygdala transition area (HATA) after ECT in both datasets, whereas marginally significant increase of volume in bilateral granule cell molecular layer of the head of dentate gyrus, the bilateral head of cornu ammonis (CA) 4, and left head of CA 3. Correlation analyses revealed that increased volume of left HATA was significantly associated with antidepressant effects after ECT. Moreover, volumes of HATA in the MDD patients before ECT could be served as potential biomarkers to predict ECT remission with the highest accuracy of 86.95% and 82.92% in two datasets (The predictive models were trained on Dataset 2 and the sensitivity, specificity and accuracy of Dataset 2 were obtained from leave-one-out-cross-validation. Thus, they were not independent and very likely to be inflated). These results not only suggested that ECT could selectively induce structural plasticity of the amygdala and hippocampal sub-regions associated with antidepressant effects of ECT in MDD patients, but also provided potential biomarkers (especially HATA) for effectively and timely interventions for ECT in clinical applications.

Hippocampal Volume and Plasma Brain-Derived Neurotrophic Factor Levels in Patients With Depression and Healthy Controls.

The aim of the present study was to investigate associations between hippocampal subfield volumes and plasma levels of brain-derived neurotrophic factor (BDNF) in patients experiencing a first episode of major depression (MD) (n = 30) as compared to healthy controls (HC) (n = 49). Covariate-adjusted linear regression was performed to compare the MD and healthy groups, adjusting for age, sex, and total estimated intracranial volume. We demonstrated that there were no differences in total hippocampal volume between the MD and HC groups. However, the volumes of the hippocampus-amygdala-transition-area (HATA) on the left side of the brain as well as the parasubiculum, presubiculum, and fimbria on the right side were statistically significantly smaller in the MD group than in the HC group. Furthermore, the volume of the hippocampal fissure on the right side was statistically significantly smaller in the HC group than in the MD group. In the MD group, we found a positive linear correlation between hippocampal volume and plasma BDNF concentrations in the CA4 area on the left side (p = 0.043). In contrast, in the HC group, we found a negative linear correlation between parasubiculum volume on the right side and plasma BDNF concentrations (p = 0.04). These results suggest that some hippocampal subfields may already be atrophic at the start of MD. In addition, our findings suggest that the sensitivity of the right parasubiculum region to BDNF may differ between MD and HC groups. These findings guide future research directions and, if confirmed, may ultimately inform medical guidelines.

An aberrant hippocampal subregional network, rather than structure, characterizes major depressive disorder

BackgroundBehavioral and neuroimaging studies have implicated the hippocampus as a cardinal neural structure in major depressive disorder (MDD) pathogenesis. The hippocampal subregion-specific structural and functional abnormalities in MDD remain unknown. MethodsMultimodal magnetic resonance imaging (MRI) was acquired in 140 patients with MDD and 44 age- and sex-matched healthy controls (HCs). We quantified hippocampal subregional volumes and fractional anisotropy (FA) following a structural and diffusion MRI data analysis processing stream. Hippocampal subregional networks were established using seed-based functional connectivity (FC) analysis. Univariate analysis was used to investigate the differences between the two groups. Significant subfield metrics were correlated with depression severity. ResultsCompared with HCs, we did not find significant differences in subregional volumes or FA metrics in the MDD group. The MDD group exhibited a significantly weaker connectivity of the right hippocampal subregional networks with the temporal cortex (extending to the insula) and basal ganglia but showed increased connectivity of the right subiculum to the bilateral lingual gyrus. The FC between the right cornu ammonis 1 and right fusiform, between the right hippocampal amygdala transition area and the bilateral basal ganglia, were negatively correlated with depression severity (r = −0.224, p = 0.010; r = −0.196, p = 0.025, respectively) in the MDD group. LimitationsThis study did not consider the longitudinal changes in the structure and functional connectivity of the hippocampal subregion. ConclusionThese findings advance our understanding of the neurobiological basis of depression by identifying the hippocampal subregional structural and functional abnormalities.

Structural Alteration of Medial Temporal Lobe Subfield in the Amnestic Mild Cognitive Impairment Stage of Alzheimer's Disease.

Objective Volume reduction and structural abnormality is the most replicated finding in neuroimaging studies of Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is the early stage of AD development. Thus, it is necessary to investigate the link between atrophy of regions of interest (ROIs) in medial temporal lobe, the variation trend of ROI densities and volumes among patients with cognitive impairment, and the distribution characteristics of ROIs in the aMCI group, Alzheimer's disease (AD) group, and normal control (NC) group. Methods 30 patients with aMCI, 16 patients with AD, and 30 NC are recruited; magnetic resonance imaging (MRI) brain scans are conducted. Voxel-based morphometry was employed to conduct the quantitative measurement of gray matter densities of the hippocampus, amygdala, entorhinal cortex, and mammillary body (MB). FreeSurfer was utilized to automatically segment the hippocampus into 21 subregions and the amygdala into 9 subregions. Then, their subregion volumes and total volume were calculated. Finally, the ANOVA and multiple comparisons were performed on the above-mentioned data from these three groups. Results AD had lower GM densities than MCI, and MCI had lower GM densities than NC, but not all of the differences were statistically significant. In the comparisons of AD-aMCI-NC, AD-aMCI, and AD-NC, the hippocampus, amygdala, and entorhinal cortex showed differences in the gray matter densities (p < 0.05); the differences of mammillary body densities were not significant in the random comparison between these three groups (p > 0.05). The hippocampus densities and volumes of the subjects from the aMCI group and the AD group were bilaterally symmetric. The gray matter densities of the right side of the entorhinal cortex inside each group and the hippocampus from the NC group were higher than those of the left side (p < 0.05), and the gray matter densities of the amygdala and mammillary body were bilaterally symmetric in the three groups (p > 0.05). There were no gender differences of four ROIs in the AD, aMCI, and NC groups (p > 0.05). The volume differences of the hippocampus presubiculum-body and parasubiculum manifest no statistical significance (p > 0.05) in the random comparison between these three groups. Volume differences of the left amygdala basal nucleus, the left lateral nucleus, the left cortical amygdala transitional area, the left paravamnion nucleus, and bilateral hippocampal amygdala transition area (HATA) had statistical differences only between the AD group and the NC group (p < 0.05). Conclusion Structural defects of medial temporal lobe subfields were revealed in the aMCI and AD groups. Decreased gray matter densities of the hippocampus, entorhinal cortex, and amygdala could distinguish patients with early stage of AD between aMCI and NC. Volume decline of the hippocampus and amygdala subfields could only distinguish AD between NC.

Hippocampal Subfield Volumes and Cognitive Function in Schizophrenia and Mood Disorders

Introduction: The hippocampus is relevant to cognitive function in schizophrenia (SCZ) and mood disorder patients. Although not anatomically uniform, it is clearly divided into subfields. This study aimed to elucidate the relationship between hippocampal subfield volume and cognitive function in patients with SCZ, bipolar disorder (BP), and major depressive disorder (MDD). Methods: The study included 21 patients with SCZ, 22 with BP, and 21 with MDD and 25 healthy controls (HCs). Neurocognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. We obtained hippocampal subfield volumes using FreeSurfer 6.0. We compared the volumes of the hippocampal subfield between the 4 groups and ascertained correlation between the cognitive composite score and hippocampal subfield volume in each group. Results: The SCZ group had significantly lower cognitive composite score than the BP, MDD, and HC groups. In the SCZ group, the left and right hippocampus-amygdala transition area and right subiculum and right presubiculum volumes were significantly reduced compared to those in the HC group. The left presubiculum volumes in the SCZ group were significantly reduced compared to those in the MDD group. Subfield volumes did not significantly differ between the BP, MDD, and HC groups. Interestingly, in the SCZ group, volumes of the right CA1, right molecular layer of the hippocampus, and right granule cell and molecular layer of the dentate gyrus were significantly correlated with the cognitive composite score. Conclusion: Patients with SCZ had poorer cognitive function, which is related to their hippocampal pathology, than those with mood disorders.

Treatment-Specific Hippocampal Subfield Volume Changes With Antidepressant Medication or Cognitive-Behavior Therapy in Treatment-Naive Depression.

Background: Hippocampal atrophy has been consistently reported in major depressive disorder with more recent focus on subfields. However, literature on hippocampal volume changes after antidepressant treatment has been limited. The first-line treatments for depression include antidepressant medication (ADM) or cognitive-behavior therapy (CBT). To understand the differential effects of CBT and ADM on the hippocampus, we investigated the volume alterations of hippocampal subfields with treatment, outcome, and chronicity in treatment-naïve depression patients.Methods: Treatment-naïve depressed patients from the PReDICT study were included in this analysis. A total of 172 patients who completed 12 weeks of randomized treatment with CBT (n = 45) or ADM (n = 127) were included for hippocampal subfield volume analysis. Forty healthy controls were also included for the baseline comparison. Freesurfer 6.0 was used to segment 26 hippocampal substructures and bilateral whole hippocampus from baseline and week 12 structural MRI scans. A generalized linear model with covariates of age and gender was used for group statistical tests. A linear mixed model for the repeated measures with covariates of age and gender was used to examine volumetric changes over time and the contributing effects of treatment type, outcome, and illness chronicity.Results: Of the 172 patients, 85 achieved remission (63/127 ADM, 22/45 CBT). MDD patients showed smaller baseline volumes than healthy controls in CA1, CA3, CA4, parasubiculum, GC-ML-DG, Hippocampal Amygdala Transition Area (HATA), and fimbria. Over 12 weeks of treatment, further declines in the volumes of CA1, fimbria, subiculum, and HATA were observed regardless of treatment type or outcome. CBT remitters, but not ADM remitters, showed volume reduction in the right hippocampal tail. Unlike ADM remitters, ADM non-responders had a decline in volume in the bilateral hippocampal tails. Baseline volume of left presubiculum (regardless of treatment type) and right fimbria and HATA in CBT patients were correlated with a continuous measure of clinical improvement. Chronicity of depression had no effect on any measures of hippocampal subfield volumes.Conclusion: Two first-line antidepressant treatments, CBT and ADM, have different effects on hippocampal tail after 12 weeks. This finding suggests that remission achieved via ADM may protect against progressive hippocampal atrophy by altering neuronal plasticity or supporting neurogenesis. Studies with multimodal neuroimaging, including functional and structural analysis, are needed to assess further the impact of two different antidepressant treatments on hippocampal subfields.