Hippocampal Subregions Research Articles

Longitudinal volumetric evaluation of hippocampus and amygdala subregions in recent trauma survivors.

The hippocampus and the amygdala play a central role in post-traumatic stress disorder (PTSD) pathogenesis. While alternations in volumes of both regions have been consistently observed in individuals with PTSD, it remains unknown whether these reflect pre-trauma vulnerability traits or acquired post-trauma consequences of the disorder. Here, we conducted a longitudinal panel study of adult civilian trauma survivors admitted to a general hospital emergency department (ED). One hundred eligible participants (mean age = 32.97 ± 10.97, n = 56 females) completed both clinical interviews and structural MRI scans at 1-, 6-, and 14-months after ED admission (alias T1, T2, and T3). While all participants met PTSD diagnosis at T1, only n = 29 still met PTSD diagnosis at T3 (a "non-Remission" Group), while n = 71 did not (a "Remission" Group). Bayesian multilevel modeling analysis showed robust evidence for smaller right hippocampus volume (P+ of ~0.014) and moderate evidence for larger left amygdala volume (P+ of ~0.870) at T1 in the "non-Remission" group, compared to the "Remission" group. Subregion analysis further demonstrated robust evidence for smaller volume in the subiculum and right CA1 hippocampal subregions (P+ of ~0.021-0.046) in the "non-Remission" group. No time-dependent volumetric changes (T1 to T2 to T3) were observed across all participants or between groups. Results support the "vulnerability trait" hypothesis, suggesting that lower initial volumes of specific hippocampus subregions are associated with non-remitting PTSD. The stable volume of all hippocampal and amygdala subregions does not support the idea of consequential, progressive, stress-related atrophy during the first critical year following trauma exposure.

Hypertension Status Moderated the Relationship between the Hippocampal Subregion of the Left GC-ML-DG and Cognitive Performance in Subjective Cognitive Decline

Background To investigate the relationship between hypertension status, hippocampus/hippocampal subregion structural alteration, and cognitive performance in subjective cognitive decline (SCD). Methods All participants were divided into two groups according to blood pressure status: SCD without hypertension and SCD with hypertension. The cognitive assessments and T1-MPRAGE brain MRI were performed to measure the cognitive function and the volume of the hippocampus and hippocampal subregions. Association and mediating/moderating effects were analyzed between the volume of hippocampus/hippocampal subregions and cognitive scores. Results Compared to the SCD without hypertension, we found (1) increased reaction time (RT) of the Go/No go test, compatible test, and divided attention visual task and (2) decreased volume of the left whole hippocampal/left subiculum/left CA1/left presubiculum/left parasubiculum/left molecular layer HP/left GC-ML-DG/left HATA in SCD with hypertension. There was a significant negative association between the volume of the left GC-ML-DG and Go/No go test RT in SCD without hypertension. A significant moderating effect of hypertension status on the relationship between the volume of the left GC-ML-DG and Go/No go test RT was found. Conclusion The results suggested that hypertension status affects inhibitory control function and visual divided attention which may be related to the reduction of hippocampus/hippocampal subregion volume in SCD. Limitations. The study has several limitations. First, this study does not include a healthy control group. In further studies, healthy controls may need to assess the interaction between hypertension status and disease status on cognitive function. Second, we defined the hypertension status using with or without hypertension disease. More detailed parameters of hypertension status need to be further studied. Third, our study was a small number of participants/single-center and cross-sectional study, which may hinder its generalization. A large-sample/multicenter, longitudinal study is helpful to comprehensively understand the relationship between hypertension status and cognitive function in SCD patients.

The Influence of Environmental Enrichment on Affective and Neural Consequences of Social Isolation Across Development.

Social stress is associated with depression and anxiety, physiological disruptions, and altered brain morphology in central stress circuitry across development. Environmental enrichment strategies may improve responses to social stress. Socially monogamous prairie voles exhibit analogous social and emotion-related behaviors to humans, with potential translational insight into interactions of social stress, age, and environmental enrichment. This study explored the effects of social isolation and environmental enrichment on behaviors related to depression and anxiety, physiological indicators of stress, and dendritic structural changes in amygdala and hippocampal subregions in young adult and aging prairie voles. Forty-nine male prairie voles were assigned to one of six groups divided by age (young adult vs. aging), social structure (paired vs. isolated), and housing environment (enriched vs. non-enriched). Following 4 weeks of these conditions, behaviors related to depression and anxiety were investigated in the forced swim test and elevated plus maze, body and adrenal weights were evaluated, and dendritic morphology analyses were conducted in hippocampus and amygdala subregions. Environmental enrichment decreased immobility duration in the forced swim test, increased open arm exploration in the elevated plus maze, and reduced adrenal/body weight ratio in aging and young adult prairie voles. Age and social isolation influenced dendritic morphology in the basolateral amygdala. Age, but not social isolation, influenced dendritic morphology in the hippocampal dentate gyrus. Environmental enrichment did not influence dendritic morphology in either brain region. These data may inform interventions to reduce the effects of social stressors and age-related central changes associated with affective behavioral consequences in humans.

Cdc42 signaling regulated by dopamine D2 receptor correlatively links specific brain regions of hippocampus to cocaine addiction

BackgroundHippocampus plays critical roles in drug addiction. Cocaine-induced modifications in dopamine receptor function and the downstream signaling are important regulation mechanisms in cocaine addiction. Rac regulates actin filament accumulation while Cdc42 stimulates the formation of filopodia and neurite outgrowth. Based on the region specific roles of small GTPases in brain, we focused on the hippocampal subregions to detect the regulation of Cdc42 signaling in long-term morphological and behavioral adaptations to cocaine. MethodsGenetically modified mouse models of Cdc42, dopamine receptor D1 (D1R) and D2 (D2R) and expressed Cdc42 point mutants that are defective in binding to and activation of its downstream effector molecules PAK and N-WASP were generated, respectively, in CA1 or dentate gyrus (DG) subregion. ResultsCocaine induced upregulation of Cdc42 signaling activity. Cdc42 knockout or mutants blocked cocaine-induced increase in spine plasticity in hippocampal CA1 pyramidal neurons, leading to a decreased conditional place preference (CPP)-associated memories and spatial learning and memory in water maze. Cdc42 knockout or mutants promoted cocaine-induced loss of neurogenesis in DG, leading to a decreased CPP-associated memories and spatial learning and memory in water maze. Furthermore, by using D1R knockout, D2R knockout, and D2R/Cdc42 double knockout mice, we found that D2R, but not D1R, regulated Cdc42 signaling in cocaine-induced neural plasticity and behavioral changes. ConclusionsCdc42 acts downstream of D2R in the hippocampus and plays an important role in cocaine-induced neural plasticity through N-WASP and PAK-LIMK-Cofilin, and Cdc42 signaling pathway correlatively links specific brain regions (CA1, dentate gyrus) to cocaine-induced CPP behavior.

Cannabidiol inhibits microglia activation and mitigates neuronal damage induced by kainate in an in-vitro seizure model

BackgroundEpilepsy is one of the most common brain disorder and, despite the possible use of several therapeutic options, many patients continue to have seizures for their entire lifespan and they need new therapeutic approaches. In the last years the interest on the non-psychoactive compounds present in Cannabis sativa has massively increased, and cannabidiol (CBD) has been shown to be effective in the treatment of different types of neurological disorders and neurodegenerative diseases such as epilepsy, ischemia, multiple sclerosis and Alzheimer's Disease. MethodsWe investigated the effects of the selected cannabinoids, Δ9-tetrahydrocannabinol (THC), CBD and cannabigerol (CBG) in rat organotypic hippocampal slices exposed to kainate, an in vitro seizure model. Cell death in the cornu Ammonis 3 (CA3) hippocampal subregion was quantified by propidium iodide fluorescence. Morphological analysis and tissue organization were examined by immunohistochemistry and confocal microscopy and microglia activation and polarization was evaluated using flow cytometry and morphology analysis. ResultsWhen present in the incubation medium, cannabidiol reduced dose-dependent CA3 injury induced by kainate. Conversely, incubation with THC exacerbated hippocampal damage. The neuroprotective effects of cannabidiol were blocked by TRPV1, TRPV2, 5-HT1A, and PPARγ antagonists. Confocal microscopy confirmed that CBD but not THC had a significant protective effect against neuronal damage and tissue disorganization caused by kainate. Cannabidiol incubation significantly block the microglia activation from the M0 to M1 phenotype observed in the kainate in-vitro seizure model, pushing toward a transition from M0 to M2. ConclusionsOur results suggest that CBD mitigated neuronal damage induced by kainate and blocked the transition from the M0 to the M1 phenotype.

Mechanical properties of murine hippocampal subregions investigated by atomic force microscopy and in vivo magnetic resonance elastography

The hippocampus is a very heterogeneous brain structure with different mechanical properties reflecting its functional variety. In particular, adult neurogenesis in rodent hippocampus has been associated with specific viscoelastic properties in vivo and ex vivo. Here, we study the microscopic mechanical properties of hippocampal subregions using ex vivo atomic force microscopy (AFM) in correlation with the expression of GFP in presence of the nestin promoter, providing a marker of neurogenic activity. We further use magnetic resonance elastography (MRE) to investigate whether in vivo mechanical properties reveal similar spatial patterns, however, on a much coarser scale. AFM showed that tissue stiffness increases with increasing distance from the subgranular zone (p = 0.0069), and that stiffness is 39% lower in GFP than non-GFP regions (p = 0.0004). Consistently, MRE showed that dentate gyrus is, on average, softer than Ammon´s horn (shear wave speed = 3.2 ± 0.2 m/s versus 4.4 ± 0.3 m/s, p = 0.01) with another 3.4% decrease towards the subgranular zone (p = 0.0001). The marked reduction in stiffness measured by AFM in areas of high neurogenic activity is consistent with softer MRE values, indicating the sensitivity of macroscopic mechanical properties in vivo to micromechanical structures as formed by the neurogenic niche of the hippocampus.

Heritability of hippocampal functional and microstructural organisation

The hippocampus is a uniquely infolded allocortical structure in the medial temporal lobe that consists of the microstructurally and functionally distinct subregions: subiculum, cornu ammonis, and dentate gyrus. The hippocampus is a remarkably plastic region that is implicated in learning and memory. At the same time it has been shown that hippocampal subregion volumes are heritable, and that genetic expression varies along a posterior to anterior axis. Here, we studied how a heritable, stable, hippocampal organisation may support its flexible function in healthy adults. Leveraging the twin set-up of the Human Connectome Project with multimodal neuroimaging, we observed that the functional connectivity between hippocampus and cortex was heritable and that microstructure of the hippocampus genetically correlated with cortical microstructure. Moreover, both functional and microstructural organisation could be consistently captured by anterior-to-posterior and medial-to-lateral axes across individuals. However, heritability of functional, relative to microstructural, organisation was found reduced, suggesting individual variation in functional organisation may be explained by experience-driven factors. Last, we demonstrate that structure and function couple along an inherited macroscale organisation, suggesting an interplay of stability and plasticity within the hippocampus. Our study provides new insights on the heritability of the hippocampal of the structure and function within the hippocampal organisation.

Gut metagenomic characteristics of ADHD reveal low Bacteroides ovatus-associated host cognitive impairment

ABSTRACT Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can have three phenotypical presentations: inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD). Environmental factors correlated with the gut microbiota community have been implicated in the development of ADHD. However, whether different ADHD symptomatic presentations are associated with distinct microbiota compositions and whether patients could benefit from the correction of aberrant bacterial colonization are still largely unclear. We carried out metagenomic shotgun analysis with 207 human fecal samples to characterize the gut microbial profiles of patients with ADHD grouped according to their phenotypical presentation. Then, we transplanted the candidate low-abundance bacteria identified in patient subgroups into ADHD rats and evaluated ADHD-associated behaviors and neuronal activation in these rats. Patients with C-ADHD had a different gut microbial composition from that of healthy controls (HCs) (p = .02), but not from that of I-ADHD patients. Eight species became progressively attenuated or enriched when comparing the compositions of HCs to those of I-ADHD and C-ADHD; in particular, the abundance of Bacteroides ovatus was depleted in patients with C-ADHD. In turn, Bacteroides ovatus supplementation ameliorated spatial working memory deficits and reversed θ electroencephalogram rhythm alterations in ADHD rats. In addition, Bacteroides ovatus induced enhanced neuronal activation in the hippocampal CA1 subregion. These findings indicate that gut microbial characteristics that are unique to patients with C-ADHD may be masked when considering a more heterogeneous group of patients. We link the gut microbiota to brain function in an ADHD animal model, suggesting the relevance of testing a potential bacteria-based intervention for some aspects of ADHD.

Aberrant intrinsic hippocampal and orbitofrontal connectivity in drug-naive adolescent patients with major depressive disorder.

Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.

Hippocampal responses to electrical stimulation of the major input pathways are modulated by dentate spikes.

Dentate gyrus (DG) is important for pattern separation and spatial memory, and it is thought to gate information flow to the downstream hippocampal subregions. Dentate spikes (DSs) are high-amplitude, fast, positive local-field potential events taking place in the DG during immobility and sleep, and they have been connected to memory consolidation in rodents. DSs are a result of signaling from the entorhinal cortex (EC) to the DG, and they suppress firing of pyramidal cells in the CA3 and CA1. To study the effects of DSs to signaling in the hippocampal tri-synaptic loop, we electrically stimulated the afferent fibers of the DG, CA3, and CA1 in adult male Sprague-Dawley rats at different delays from DSs. Responses to stimulation were increased in the EC-DG synapse during DSs, and the effect was amplified after theta-burst stimulation. We concluded that DSs strengthen the excitatory signal from the EC to the DG, which is reinforced by synapse potentiation and increased excitability of granule cells after theta-burst stimulation. This signal boosting may function in enhancing plastic changes in the DG-CA3 synapse. As responses in the CA3 and CA1 remained unaffected by the DS, the DS-contingent silencing of pyramidal cells seems to be a result of a decrease in excitatory input rather than a decrease in the excitability of the pyramidal cells themselves. In addition, we found that the DSs occur asynchronously in the left and right hippocampi, giving novel evidence of lateralization of the rodent hippocampus.

Shared and distinct functional connectivity of hippocampal subregions in schizophrenia, bipolar disorder, and major depressive disorder.

Schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) share etiological and pathophysiological characteristics. Although neuroimaging studies have reported hippocampal alterations in SZ, BD, and MDD, little is known about how different hippocampal subregions are affected in these conditions because such subregions, namely, the cornu ammonis (CA), dentate gyrus (DG), and subiculum (SUB), have different structural foundations and perform different functions. Here, we hypothesize that different hippocampal subregions may reflect some intrinsic features among the major psychiatric disorders, such as SZ, BD, and MDD. By investigating resting functional connectivity (FC) of each hippocampal subregion among 117 SZ, 103 BD, 96 MDD, and 159 healthy controls, we found similarly and distinctly changed FC of hippocampal subregions in the three disorders. The abnormal functions of middle frontal gyrus might be the core feature of the psychopathological mechanisms of SZ, BD, and MDD. Anterior cingulate cortex and inferior orbital frontal gyrus might be the shared abnormalities of SZ and BD, and inferior orbital frontal gyrus is also positively correlated with depression and anxiety symptoms in SZ and BD. Caudate might be the unique feature of SZ and showed a positive correlation with the cognitive function in SZ. Middle temporal gyrus and supplemental motor area are the differentiating features of BD. Our study provides evidence for the different functions of different hippocampal subregions in psychiatric pathology.

Corticosterone induces discrete epigenetic signatures in the dorsal and ventral hippocampus that depend upon sex and genotype: focus on methylated NR3C1 gene

Brief Summary: This mouse study identified sex and genotype-dependent effects of oral corticosterone on behavioral and physiological outcomes as well as on gene expression and epigenetics in hippocampal subregions.

Effects of Tibetan medicine metacinnabar (β-HgS) combined with imipramine or sertraline on depression-like symptoms in mice.

Depression is a common mood disorder that has exhibited an increased incidence rate worldwide, but the overall clinical efficacy of antidepressants remains unsatisfactory. In traditional Ayurveda and Tibetan medicines, β-HgS-containing medicines have been used to treat neurological diseases for thousands of years, and our previous study found that β-HgS ameliorated depression-like behaviors in chronic restraint stress (CRS)-treated or chronic unpredictable mild stress (CUMS)-treated mice. Hence, present study investigated the effects of β-HgS combined with the clinical first-line antidepressants, imipramine (IMI) and sertraline (SER), on depression-like symptoms in CRS- and CUMS-co-treated mice. Our results revealed that β-HgS promoted the antidepressant effect of SER on depression-like behavior in mice, and enhanced its effects on promoting glucocorticoid receptor (GR) expression and neuronal proliferation in key hippocampal subregions, as well as increasing interleukin 10 (IL-10) levels and decreasing malondialdehyde levels in the sera of stress-stimulated mice. As for IMI, β-HgS enhanced its effects on preventing atrophy and severe structural damage in the hippocampus, as well as in promoting hippocampal GR levels and neuronal proliferation and serum IL-10 and superoxide dismutase (SOD) levels. Additionally, combination therapy resulted in the increased diversity of important intestinal microbiota compared to that of monotherapy, which may help sustain the health of the digestive tract and reduce inflammation to further enhance the antidepressant effects of IMI and SER in mice.

Stable functional compensation within hippocampal-subregion networks in patients with temporal glioma before and after surgery.

ObjectiveTo identify whether tumor invasion of the temporal lobe induces functional compensation of the hippocampal-subregion (HIPsub) network connectivity before surgery, and to further validate the stability of this functional compensation within the HIPsub network in patients with temporal glioma tumor (TTumor) after surgical resection of the tumor.MethodsIn the first cohort, analysis of HIPsub functional connectivity (FC) was conducted to identify the functional compensation of the altered HIPsub connectivity pattern in TTumor through a pattern classification approach. Then, the second cohort investigated whether functional compensation in TTumor patients changed after surgical resection of the tumor.ResultsIn the first cohort, this study identified altered HIPsub network connectivity patterns and its functional compensation regions (i.e., left parahippocampal gyrus and bilateral cerebellum anterior lobe) in TTumor patients. Second, the altered HIPsub network connectivity patterns had the power to discriminate TTumor patients from healthy controls (CN) on an individual subject basis, with an AUC of 97.0%, sensitivity of 93.5%, and specificity of 90.3%. Finally, in the second cohort, we found that functional connectivities of functional compensation regions within the HIPsub network in TTumor patients did not change between before and after surgery.ConclusionThis study provides novel evidence regarding functional compensation within the HIPsub network in TTumor patients. It has been suggested that the fine hippocampal subregion was more sensitive, which reveals functional compensation induced by tumor invasion of the temporal lobe. Furthermore, this study verified the stability and persistence of this functional compensation in TTumor patients after surgical resection of the tumor.

Providing height to pullets does not influence hippocampal dendritic morphology or brain-derived neurotrophic factor at the end of the rearing period

Pullets reared with diverse behavioral experiences are faster to learn spatial cognition tasks and acclimate more successfully to laying environments with elevated structures. However, the neural underpinnings of the improved spatial abilities are unclear. The objective of this study was to determine whether providing structural height in the rearing environment affected the development of the hippocampus and whether hippocampal neural metrics correlated with individual behavior on spatial cognition tasks. Female Dekalb White pullets were reared in a floor pen (FL), single-tiered aviary (ST), or two-tiered aviary (TT; 5 pens/treatment). Pullets completed floor-based Y-maze and elevated visual cliff tasks to evaluate depth perception at 15 and 16 wk, respectively. At 16 wk, brains were removed for Golgi-Cox staining (n = 12 for FL, 13 for ST, 13 total pullets for TT; 2 to 3 pullets/pen) and qPCR to measure gene expression of brain-derived neurotrophic factor (BDNF; n = 10 for FL, 11 for ST, and 9 pullets for TT). Rearing environment did not affect various morphometric outcomes of dendritic arborization, including Sholl profiles; mean dendritic length; sum dendritic length; number of dendrites, terminal tips, or nodes; soma size; or BDNF mRNA expression (P > 0.05). Hippocampal subregion did affect dendritic morphology, with multipolar neurons from the ventral subregion differing in several characteristics from multipolar neurons in the dorsomedial or dorsolateral subregions (P < 0.05). Neural metrics did not correlate with individual differences in behavior during the spatial cognition tasks. Overall, providing height during rearing did not affect dendritic morphology or BDNF at 16 wk of age, but other metrics in the hippocampus or other brain regions warrant further investigation. Additionally, other structural or social components or the role of animal personality are areas of future interest for how rearing environments influence pullet behavior.

Abnormal resting-state functional connectivity of hippocampal subregions in children with primary nocturnal enuresis.

ObjectivePrevious neuroimaging studies have shown abnormal brain-bladder control network in children with primary nocturnal enuresis (PNE). The hippocampus, which has long been considered to be an important nerve center for memory and emotion, has also been confirmed to be activating during micturition in several human imaging studies. However, few studies have explored hippocampus-related functional networks of PNE in children. In this study, the whole resting-state functional connectivity (RSFC) of hippocampus was investigated in children with PNE.MethodsFunctional magnetic resonance imaging data of 30 children with PNE and 29 matched healthy controls (HCs) were analyzed in our study. We used the seed-based RSFC method to evaluate the functional connectivity of hippocampal subregions defined according to the Human Brainnetome Atlas. Correlation analyses were also processed to investigate their relationship with disease duration time, bed-wetting frequency, and bladder volume.ResultsCompared with HCs, children with PNE showed abnormal RSFC of the left rostral hippocampus (rHipp) with right fusiform gyrus, right Rolandic operculum, left inferior parietal lobule, and right precentral gyrus, respectively. Moreover, decreased RSFC of the left caudal hippocampus (cHipp) with right fusiform gyrus and right supplementary motor area was discovered in the PNE group. There were no significant results in the right rHipp and cHipp seeds after multiple comparison corrections. In addition, disease duration time was negatively correlated with RSFC of the left rHipp with right Rolandic operculum (r = −0.386, p = 0.035, uncorrected) and the left cHipp with right fusiform gyrus (r = −0.483, p = 0.007, uncorrected) in the PNE group, respectively. In the Receiver Operating Characteristic (ROC) analysis, all the above results of RSFC achieved significant performance.ConclusionsTo our knowledge, this is the first attempt to examine the RSFC patterns of hippocampal subregions in children with PNE. These findings indicated that children with PNE have potential dysfunctions in the limbic network, sensorimotor network, default mode network, and frontoparietal network. These networks may become less efficient with disease duration time, inducing impairments in brain-bladder control, cognition, memory, and emotion. Further prospective research with dynamic observation of brain imaging, bladder function, cognition, memory, and emotion is warranted.

Body mass index related to executive function and hippocampal subregion volume in subjective cognitive decline.

ObjectiveThis study aims to explore whether body mass index (BMI) level affects the executive function and hippocampal subregion volume of subjective cognitive decline (SCD).Materials and methodsA total of 111 participants were included in the analysis, including SCD (38 of normal BMI, 27 of overweight and obesity) and normal cognitive control (NC) (29 of normal BMI, 17 of overweight and obesity). All subjects underwent the Chinese version of the Stroop Color-Word Test (SCWT) to measure the executive function and a high-resolution 3D T1 structural image acquisition. Two-way ANOVA was used to examine the differences in executive function and gray matter volume in hippocampal subregions under different BMI levels between the SCD and NC.ResultThe subdimensions of executive function in which different BMI levels interact with SCD and NC include inhibition control function [SCWT C-B reaction time(s): F(1,104) = 5.732, p = 0.018], and the hippocampal subregion volume of CA1 [F(1,99) = 8.607, p = 0.004], hippocampal tail [F(1,99) = 4.077, p = 0.046], and molecular layer [F(1,99) = 6.309, p = 0.014]. After correction by Bonferroni method, the population × BMI interaction only had a significant effect on the CA1 (p = 0.004). Further analysis found that the SCWT C-B reaction time of SCD was significantly longer than NC no matter whether it is at the normal BMI level [F(1,104) = 4.325, p = 0.040] or the high BMI level [F(1,104) = 21.530, p < 0.001], and the inhibitory control function of SCD was worse than that of NC. In the normal BMI group, gray matter volume in the hippocampal subregion (CA1) of SCD was significantly smaller than that of NC [F(1,99) = 4.938, p = 0.029]. For patients with SCD, the high BMI group had worse inhibitory control function [F(1,104) = 13.499, p < 0.001] and greater CA1 volume compared with the normal BMI group [F(1,99) = 7.619, p = 0.007].ConclusionThe BMI level is related to the inhibition control function and the gray matter volume of CA1 subregion in SCD. Overweight seems to increase the gray matter volume of CA1 in the elderly with SCD, but it is not enough to compensate for the damage to executive function caused by the disease. These data provide new insights into the relationship between BMI level and executive function of SCD from the perspective of imaging.

Activation of liver X receptors protects oligodendrocytes in CA3 of stress-induced mice

Depression is a complex disorder that is associated with various structural abnormalities. Oligodendrocyte (OL) dysfunction is associated with the pathogenesis of depression and the promotion of hippocampal oligodendrocyte maturation and myelination could be a novel therapeutic strategy for ameliorating depressive behaviors. Recent studies have shown that activation of liver X receptors (LXRs) by GW3965 improves depressive phenotypes, but the effects of GW3965 on OL function and myelination in the hippocampus of depression remain relatively unclear. To address this issue, we investigated the effects of GW3965 on mature OL in the hippocampus and on the myelin sheaths of mice subjected to chronic unpredictable stress (CUS). Behavioral tests were performed to assess depressive behaviors. Then, the number of mature OLs (CC1+) in each hippocampal subregion was precisely quantified with immunohistochemical and stereological methods, and the density of newborn mature OLs (BrdU+/Olig2+/CC1+ cells) in each hippocampal subregion was quantified with immunofluorescence. In addition, myelin basic protein (MBP) staining intensity in the cornu ammonis 3 (CA3) region was assessed by using immunofluorescence. We found that both the number of CC1+ OLs and the density of BrdU+/Olig2+/CC1+ cells were obviously decreased in each hippocampal subregion of mice subjected to CUS, and 4 weeks of GW3965 treatment reversed these effects only in the CA3 region. Furthermore, the decreased MBP expression in the CA3 region of mice subjected to CUS was ameliorated by GW3965 treatment. Collectively, these results suggested that improvement of OL maturation and enhancement of myelination may be structural mechanisms underlying the antidepressant effects of LXR agonists.

Abnormal Dynamic Functional Connectivity of the Left Rostral Hippocampus in Predicting Antidepressant Efficacy in Major Depressive Disorder.

Objective Some pharmacological treatments are ineffective in parts of patients with major depressive disorder (MDD), hence this needs prediction of effective treatment responses. The study aims to examine the relationship between dynamic functional connectivity (dFC) of the hippocampal subregion and antidepressant improvement of MDD patients and to estimate the capability of dFC to predict antidepressant efficacy. Methods The data were from 70 MDD patients and 43 healthy controls (HC); the dFC of hippocampal subregions was estimated by sliding-window approach based on resting-state functional magnetic resonance imaging (R-fMRI). After 3 months treatment, 36 patients underwent second R-fMRI scan and were then divided into the response group and non-response group according to clinical responses. Results The result manifested that MDD patients exhibited lower mean dFC of the left rostral hippocampus (rHipp.l) compared with HC. After 3 months therapy, the response group showed lower dFC of rHipp.l compared with the non-response group. The dFC of rHipp.l was also negatively correlated with the reduction rate of Hamilton Depression Rating Scale. Conclusion These findings highlighted the importance of rHipp in MDD from the dFC perspective. Detection and estimation of these changes might demonstrate helpful for comprehending the pathophysiological mechanism and for assessment of treatment reaction of MDD.

Socioeconomic disadvantage and episodic memory ability in the ABCD sample: Contributions of hippocampal subregion and subfield volumes

Socioeconomic disadvantage is associated with volumetric differences in stress-sensitive neural structures, including the hippocampus, and deficits in episodic memory. Rodent studies provide evidence that memory deficits arise via stress-related structural differences in hippocampal subdivisions; however, human studies have only provided limited evidence to support this notion. We used a sample of 10,695 9–13-year-old participants from two timepoints of the Adolescent Brain and Cognitive Development (ABCD) Study to assess whether socioeconomic disadvantage relates to episodic memory performance through hippocampal volumes. We explored associations among socioeconomic disadvantage, measured via the Area Deprivation Index (ADI), concurrent subregion (anterior, posterior) and subfield volumes (CA1, CA3, CA4/DG, subiculum), and episodic memory, assessed via the NIH Toolbox Picture Sequence Memory Test at baseline and 2-year follow-up (Time 2). Results showed that higher baseline ADI related to smaller concurrent anterior, CA1, CA4/DG, and subiculum volumes and poorer Time 2 memory performance controlling for baseline memory. Moreover, anterior, CA1, and subiculum volumes mediated the longitudinal association between the ADI and memory. Results suggest that greater socioeconomic disadvantage relates to smaller hippocampal subregion and subfield volumes and less age-related improvement in memory. These findings shed light on the neural mechanisms linking socioeconomic disadvantage and cognitive ability in childhood.