Hippocampal Subfield Volumes Research Articles

More extensive structural damage in temporal lobe epilepsy with hippocampal sclerosis type 1

ObjectiveTo explore clinical and structural differences between mesial temporal lobe epilepsy (mTLE) patients with different hippocampal sclerosis (HS) subtypes. MethodsHigh-resolution T1-weighted MRI and diffusion tensor imaging data were obtained in 41 refractory mTLE patients and 52 age- and sex-matched healthy controls. Postoperative histopathological examination confirmed HS type 1 in 30 patients and HS type 2 in eleven patients. Clinical features, postoperative seizure outcomes, hippocampal subfields volumes, fractional anisotropy (FA) values of white matter regions and graph theory parameters were explored and compared between the HS type 1 and HS type 2 groups. ResultsNo significant differences in clinical features and postsurgical seizure outcomes were found between the HS type 1 and type 2 groups. However, the HS type 1 group showed extra atrophy in ipsilateral parasubiculum than healthy controls and more severe atrophy in contralateral hippocampal fissure than the HS type 2 group. More extensive FA decrease were also observed in the HS type 1 group, involving ipsilateral optic radiation, superior fronto-occipital fasciculus, contralateral uncinate fasciculus, tapetum, bilateral hippocampal cingulum, corona radiata, etc. Furthermore, in spite of similar impairments in characteristic path length, global efficiency and local efficiency in two HS groups, the HS type 1 group showed additional decrease of clustering coefficient than healthy controls. ConclusionsHS type 1 and 2 groups had similar clinical characteristics and postoperative seizure outcomes. More widespread neuronal cell loss in the HS type 1 group contributed to more extensive structural damage and connectivity abnormality. These results shed new light on the imaging correlates of different HS pathology.

Hippocampal subfield abnormalities and biomarkers of pathologic brain changes: from SARS-CoV-2 acute infection to post-COVID syndrome.

Cognitive deficits are among the main disabling symptoms in COVID-19 patients and post-COVID syndrome (PCS). Within brain regions, the hippocampus, a key region for cognition, has shown vulnerability to SARS-CoV-2 infection. Therefore, invivo detailed evaluation of hippocampal changes in PCS patients, validated on post-mortem samples of COVID-19 patients at the acute phase, would shed light into the relationship between COVID-19 and cognition. Hippocampal subfields volume, microstructure, and perfusion were evaluated in 84 PCS patients and compared to 33 controls. Associations with blood biomarkers, including glial fibrillary acidic protein (GFAP), myelin oligodendrocyte glycoprotein (MOG), eotaxin-1 (CCL11) and neurofilament light chain (NfL) were evaluated. Besides, biomarker immunodetection in seven hippocampal necropsies of patients at the acute phase were contrasted against eight controls. Invivo analyses revealed that hippocampal grey matter atrophy is accompanied by altered microstructural integrity, hypoperfusion, and functional connectivity changes in PCS patients. Hippocampal structural and functional alterations were related to cognitive dysfunction, particularly attention and memory. GFAP, MOG, CCL11 and NfL biomarkers revealed alterations in PCS, and showed associations with hippocampal volume changes, in selective hippocampal subfields. Moreover, post mortem histology showed the presence of increased GFAP and CCL11 and reduced MOG concentrations in the hippocampus in post-mortem samples at the acute phase. The current results evidenced that PCS patients with cognitive sequalae present brain alterations related to cognitive dysfunction, accompanied by a cascade of pathological alterations in blood biomarkers, indicating axonal damage, astrocyte alterations, neuronal injury, and myelin changes that are already present from the acute phase. Nominative Grant FIBHCSC 2020 COVID-19. Department of Health, Community of Madrid. Instituto de Salud Carlos III through the project INT20/00079, co-funded by European Regional Development Fund "A way to make Europe" (JAMG). Instituto de Salud Carlos III (ISCIII) through Sara Borrell postdoctoral fellowship Grant No. CD22/00043) and co-funded by the European Union (MDC). Instituto de Salud Carlos III through a predoctoral contract (FI20/000145) (co-funded by European Regional Development Fund "A way to make Europe") (MVS). Fundación para el Conocimiento Madri+d through the project G63-HEALTHSTARPLUS-HSP4 (JAMG, SOM).

Altered hippocampal subfield volumes in major depressive disorder with and without anhedonia

BackgroundPrevious neuroimaging findings have demonstrated the association between anhedonia and the hippocampus. However, few studies have focused on the structural changes in the hippocampus in major depressive disorder (MDD) patients with anhedonia. Meanwhile, considering that multiple and functionally specialized subfields of the hippocampus have their own signatures, the present study aimed to investigate the volumetric alterations of the hippocampus as well as its subfields in MDD patients with and without anhedonia.MethodsA total of 113 subjects, including 30 MDD patients with anhedonia, 40 MDD patients without anhedonia, and 43 healthy controls (HCs), were recruited in the study. All participants underwent high-resolution brain magnetic resonance imaging (MRI) scans, and the automated hippocampal substructure module in FreeSurfer 6.0 was used to evaluate the volumes of hippocampal subfields. We compared the volumetric differences in hippocampal subfields among the three groups by analysis of variance (ANOVA, post hoc Bonferroni), and partial correlation was used to explore the association between hippocampal subregion volumes and clinical characteristics.ResultsANOVA showed significant volumetric differences in the hippocampal subfields among the three groups in the left hippocampus head, mainly in the cornu ammonis (CA) 1, granule cell layer of the dentate gyrus (GC-ML-DG), and molecular layer (ML). Compared with HCs, both groups of MDD patients showed significantly smaller volumes in the whole left hippocampus head. Interestingly, further exploration revealed that only MDD patients with anhedonia had significantly reduced volumes in the left CA1, GC-ML-DG and ML when compared with HCs. No significant difference was found in the volumes of the hippocampal subfields between MDD patients without anhedonia and HCs, either the two groups of MDD patients. However, no association between hippocampal subfield volumes and clinical characteristics was found in either the subset of patients with anhedonia or in the patient group as a whole.ConclusionsThese preliminary findings suggest that MDD patients with anhedonia exhibit unique atrophy of the hippocampus and that subfield abnormalities in the left CA1 and DG might be associated with anhedonia in MDD.

Volumes of hippocampal subfields suggest a continuum between schizophrenia, major depressive disorder and bipolar disorder.

There is considerable debate as to whether the continuum of major psychiatric disorders exists and to what extent the boundaries extend. Converging evidence suggests that alterations in hippocampal volume are a common sign in psychiatric disorders; however, there is still no consensus on the nature and extent of hippocampal atrophy in schizophrenia (SZ), major depressive disorder (MDD) and bipolar disorder (BD). The aim of this study was to verify the continuum of SZ - BD - MDD at the level of hippocampal subfield volume and to compare the volume differences in hippocampal subfields in the continuum. A total of 412 participants (204 SZ, 98 MDD, and 110 BD) underwent 3 T MRI scans, structured clinical interviews, and clinical scales. We segmented the hippocampal subfields with FreeSurfer 7.1.1 and compared subfields volumes across the three diagnostic groups by controlling for age, gender, education, and intracranial volumes. The results showed a gradual increase in hippocampal subfield volumes from SZ to MDD to BD. Significant volume differences in the total hippocampus and 13 of 26 hippocampal subfields, including CA1, CA3, CA4, GC-ML-DG, molecular layer and the whole hippocampus, bilaterally, and parasubiculum in the right hemisphere, were observed among diagnostic groups. Medication treatment had the most effect on subfields of MDD compared to SZ and BD. Subfield volumes were negatively correlated with illness duration of MDD. Positive correlations were found between subfield volumes and drug dose in SZ and MDD. There was no significant difference in laterality between diagnostic groups. The pattern of hippocampal volume reduction in SZ, MDD and BD suggests that there may be a continuum of the three disorders at the hippocampal level. The hippocampus represents a phenotype that is distinct from traditional diagnostic strategies. Combined with illness duration and drug intervention, it may better reflect shared pathophysiology and mechanisms across psychiatric disorders.

Brain but not serum BDNF levels are associated with structural alterations in the hippocampal regions in patients with drug-resistant mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy is the most common type of focal epilepsy, imposing a significant burden on the health care system worldwide. Approximately one-third of patients with this disease who do not adequately respond to pharmacotherapy are considered drug-resistant subjects. Despite having some clues of how such epileptic activity and resistance to therapy emerge, coming mainly from preclinical models, we still witness a scarcity of human data. To narrow this gap, in this study, we aimed to estimate the relationship between hippocampal and serum levels of brain-derived neurotrophic factor (BDNF), one of the main and most widely studied neurotrophins, and hippocampal subfield volumes in patients with drug-resistant mesial temporal epilepsy undergoing neurosurgical treatment. We found that hippocampal (but not serum) BDNF levels were negatively correlated with the contralateral volumes of the CA1 and CA4 subfields, presubiculum, subiculum, dentate gyrus, and molecular layer of the hippocampus. Taken together, these findings are generally in accordance with existing data, arguing for a proepileptic nature of BDNF effects in the hippocampus and related brain structures.

In vivo analyses reveal hippocampal subfield volume reductions in adolescents with schizophrenia, but not with major depressive disorder

BackgroundAdult studies have reported atypicalities in the hippocampus and subfields in patients with schizophrenia (SCZ) and major depressive disorder (MDD). Both affective and psychotic disorders typically onset in adolescence, when human brain develops rapidly and shows increased susceptibility to adverse environments. However, few in vivo studies have investigated whether hippocampus subfield abnormalities occur in adolescence and whether they differ between SCZ and MDD cases. MethodsWe recruited 150 adolescents (49 SCZ patients, 67 MDD patients, and 34 healthy controls) and obtained their structural images. We used FreeSurfer to automatically segment hippocampus into 12 subfields and analyzed subfield volumetric differences between groups by analysis of covariance, covarying for age, sex, and intracranial volume. Composite measures by summing subfield volumes were further compared across groups and analyzed in relation to clinical characteristic. ResultsSCZ adolescents showed significant volume reductions in subfields of CA1, molecular layer, subiculum, parasubiculum, dentate gyrus and CA4 than healthy controls, and almost significant reductions, as compared to the MDD group, in left molecular layer, dentate gyrus, CA2/3 and CA4. Composite analyses showed smaller volumes in SCZ group than in healthy controls in all bilateral composite measures, and reduced volumes in comparison to MDD group in all left composite measures only. ConclusionsSCZ adolescents exhibited both hippocampal subfield and composite volumes reduction, and also showed greater magnitude of deviance than those diagnosed with MDD, particularly in core CA regions. These results indicate a hippocampal disease process, suggesting a potential intervention marker of early psychotic patients and risk youths.

Altered Sex Differences in Hippocampal Subfield Volumes in Schizophrenia.

The hippocampus is a heterogenous brain structure that differs between the sexes and has been implicated in the pathophysiology of psychiatric illnesses. Here, we explored sex and diagnostic group differences in hippocampal subfield volumes, in individuals with schizophrenia spectrum disorder (SZ), bipolar disorders (BD), and healthy controls (CTL). One thousand and five hundred and twenty-one participants underwent T1-weighted magnetic resonance imaging (SZ, n = 452, mean age 30.7 ± 9.2 [SD] years, males 59.1%; BD, n = 316, 33.7 ± 11.4, 41.5%; CTL, n = 753, 34.1 ± 9.1, 55.6%). Total hippocampal, subfield, and intracranial volumes were estimated with Freesurfer (v6.0.0). Analysis of covariance and multiple regression models were fitted to examine sex-by-diagnostic (sub)group interactions in volume. In SZ and BD, separately, associations between volumes and clinical as well as cognitive measures were examined between the sexes using regression models. Significant sex-by-group interactions were found for the total hippocampus, dentate gyrus, molecular layer, presubiculum, fimbria, hippocampal-amygdaloid transition area, and CA4, indicating a larger volumetric deficit in male patients relative to female patients when compared with same-sex CTL. Subgroup analyses revealed that this interaction was driven by males with schizophrenia. Effect sizes were overall small (partial η < 0.02). We found no significant sex differences in the associations between hippocampal volumes and clinical or cognitive measures in SZ and BD. Using a well-powered sample, our findings indicate that the pattern of morphological sex differences in hippocampal subfields is altered in individuals with schizophrenia relative to CTL, due to higher volumetric deficits in males.

A fast and robust hippocampal subfields segmentation: HSF revealing lifespan volumetric dynamics.

The hippocampal subfields, pivotal to episodic memory, are distinct both in terms of cyto- and myeloarchitectony. Studying the structure of hippocampal subfields in vivo is crucial to understand volumetric trajectories across the lifespan, from the emergence of episodic memory during early childhood to memory impairments found in older adults. However, segmenting hippocampal subfields on conventional MRI sequences is challenging because of their small size. Furthermore, there is to date no unified segmentation protocol for the hippocampal subfields, which limits comparisons between studies. Therefore, we introduced a novel segmentation tool called HSF short for hippocampal segmentation factory, which leverages an end-to-end deep learning pipeline. First, we validated HSF against currently used tools (ASHS, HIPS, and HippUnfold). Then, we used HSF on 3,750 subjects from the HCP development, young adults, and aging datasets to study the effect of age and sex on hippocampal subfields volumes. Firstly, we showed HSF to be closer to manual segmentation than other currently used tools (p < 0.001), regarding the Dice Coefficient, Hausdorff Distance, and Volumetric Similarity. Then, we showed differential maturation and aging across subfields, with the dentate gyrus being the most affected by age. We also found faster growth and decay in men than in women for most hippocampal subfields. Thus, while we introduced a new, fast and robust end-to-end segmentation tool, our neuroanatomical results concerning the lifespan trajectories of the hippocampal subfields reconcile previous conflicting results.

Cross-sectional field study comparing hippocampal subfields in patients with post-traumatic stress disorder, major depressive disorder, post-traumatic stress disorder with comorbid major depressive disorder, and adjustment disorder using routine clinical data.

The hippocampus is a central brain structure involved in stress processing. Previous studies have linked stress-related mental disorders, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), with changes in hippocampus volume. As PTSD and MDD have similar symptoms, clinical diagnosis relies solely on patients reporting their cognitive and emotional experiences, leading to an interest in utilizing imaging-based data to improve accuracy. Our field study aimed to determine whether there are hippocampal subfield volume differences between stress-related mental disorders (PTSD, MDD, adjustment disorders, and AdjD) using routine clinical data from a military hospital. Participants comprised soldiers (N = 185) with PTSD (n = 50), MDD (n = 70), PTSD with comorbid MDD (n = 38), and AdjD (n = 27). The hippocampus was segmented and volumetrized into subfields automatically using FreeSurfer. We used ANCOVA models with estimated total intracranial volume as a covariate to determine whether there were volume differences in the hippocampal subfields cornu ammonis 1 (CA1), cornu ammonis 2/3 (CA2/3), and dentate gyrus (DG) among patients with PTSD, MDD, PTSD with comorbid MDD, and AdjD. Furthermore, we added self-reported symptom duration and previous psychopharmacological and psychotherapy treatment as further covariates to examine whether there were associations with CA1, CA2/3, and DG. No significant volume differences in hippocampal subfields between stress-related mental disorders were found. No significant associations were detected between symptom duration, psychopharmacological treatment, psychotherapy, and the hippocampal subfields. Hippocampal subfields may distinguish stress-related mental disorders; however, we did not observe any subfield differences. We provide several explanations for the non-results and thereby inform future field studies.

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 &lt; .0005). Except for the fissure, all hippocampal subfields were associated with visuospatial skills (all p‐values &lt; .05) and memory (all p‐values &lt; .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 &lt; .001), and memory (p &lt; .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.

Posterior hippocampal CA2/3 volume is associated with autobiographical memory recall ability in lower performing individuals

People vary substantially in their capacity to recall past experiences, known as autobiographical memories. Here we investigated whether the volumes of specific hippocampal subfields were associated with autobiographical memory retrieval ability. We manually segmented the full length of the two hippocampi in 201 healthy young adults into DG/CA4, CA2/3, CA1, subiculum, pre/parasubiculum and uncus, in the largest such manually segmented subfield sample yet reported. Across the group we found no evidence for an association between any subfield volume and autobiographical memory recall ability. However, when participants were assigned to lower and higher performing groups based on their memory recall scores, we found that bilateral CA2/3 volume was significantly and positively associated with autobiographical memory recall performance specifically in the lower performing group. We further observed that this effect was attributable to posterior CA2/3. By contrast, semantic details from autobiographical memories, and performance on a range of laboratory-based memory tests, did not correlate with CA2/3 volume. Overall, our findings highlight that posterior CA2/3 may be particularly pertinent for autobiographical memory recall. They also reveal that there may not be direct one-to-one mapping of posterior CA2/3 volume with autobiographical memory ability, with size mattering perhaps only in those with poorer memory recall.

Household socioeconomic status relates to specific hippocampal subfield volumes across development.

The hippocampus is composed of cytoarchitecturally distinct subfields that support specific memory functions. Variations in total hippocampal volume across development have been linked to socioeconomic status (SES), a proxy for access to material resources, medical care, and quality education. High childhood household SES is associated with greater cognitive abilities in adulthood. Currently, it is not known whether household SES differentially impacts specific hippocampal subfield volumes. We assessed susceptibility of subfields to variations in household SES across development in a sample of 167 typically developing 5- to 25-year-old. Bilateral cornu ammonis (CA) 1-2, combined CA3-dentate gyrus (DG), and subiculum (Sub) volumes were measured by highly reliable manual segmentation of high-resolution T2-weighted images and adjusted for intracranial volume. A summary component score of SES measures (paternal education, maternal education, and income-to-needs ratio) was used to examine variability in volumes across ages. We did not identify age-related differences in any of the regional volumes, nor did age modify SES-related effects. Controlling for age, larger volumes of CA3-DG and CA1-2 were associated with lower SES, while Sub volume was not. Overall, these findings support the specific impact of SES on CA3-DG and CA1-2 and highlight the importance of considering environmental influences on hippocampal subfield development.

Neurobiological and genetic correlates of the dissociative subtype of posttraumatic stress disorder.

Approximately 10%-30% of individuals with posttraumatic stress disorder (PTSD) exhibit a dissociative subtype of the condition defined by symptoms of depersonalization and derealization. This study examined the psychometric evidence for the dissociative subtype of PTSD in a sample of young, primarily male post-9/11-era Veterans (n = 374 at baseline and n = 163 at follow-up) and evaluated its biological correlates with respect to resting state functional connectivity (default mode network [DMN]; n = 275), brain morphology (hippocampal subfield volume and cortical thickness; n = 280), neurocognitive functioning (n = 337), and genetic variation (n = 193). Multivariate analyses of PTSD and dissociation items suggested a class structure was superior to dimensional and hybrid ones, with 7.5% of the sample comprising the dissociative class; this group showed stability over 1.5 years. Covarying for age, sex, and PTSD severity, linear regression models revealed that derealization/depersonalization severity was associated with: decreased DMN connectivity between bilateral posterior cingulate cortex and right isthmus (p = .015; adjusted-p [padj] = .097); increased bilateral whole hippocampal, hippocampal head, and molecular layer head volume (p = .010-.034; padj = .032-.053); worse self-monitoring (p = .018; padj = .079); and a candidate genetic variant (rs263232) in the adenylyl cyclase 8 gene (p = .026), previously associated with dissociation. Results converged on biological structures and systems implicated in sensory integration, the neural representation of spatial awareness, and stress-related spatial learning and memory, suggesting possible mechanisms underlying the dissociative subtype of PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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

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

Volumetric Analysis of Hippocampal Subregions and Subfields in Left and Right Predominant Semantic Dementia (P11-6.002)

<h3>Objective:</h3> To assess relative volume loss of hippocampal subregions/subfields in semantic dementia(SMD) compared to controls and determine whether subfield volumes differ between left-predominant(lpSMD) and right-predominant(rpSMD) SMD. <h3>Background:</h3> Semantic dementia is characterized by conceptual knowledge loss, with lpSMD associating more with impairment of verbal knowledge and rpSMD with behavioral changes and loss of non-verbal knowledge. The hippocampus participates in semantic memory preservation. <h3>Design/Methods:</h3> Thirty-four SMD and 15 controls from the Neurodegenerative Research Group that had completed 3T volumetric MRI and [¹⁸F]-fluorodeoxyglucose-PET scans were included. Participants were classified as lpSMD or rpSMD based on temporal lobe hypometabolism. Volumetric analysis of hippocampal subfields (CA1, CA3, CA4, dentate gyrus, molecular layer, fimbria, hippocampal-amgydaloid transition area [HATA], pre/parasubiculum and subiculum) were performed using FreeSurfer 7. Subfield volumes were measured separately from the head and body subregions. We fit a linear mixed effects model with log-transformed hippocampal subfield volume as the dependent variable; age, sex, total intracranial volume, hemisphere and a group-by-hemisphere interaction as fixed effects; and subfield nested within hemisphere as a random effect. <h3>Results:</h3> Twenty-seven participants (79%) were lpSMD, 7(21%) rpSMD. Compared to controls, lpSMD showed 21%–41% smaller volumes across all subregions/subfields of the dominant (predominantly involved) hemisphere and no differences in the non-dominant (spared) hemisphere. Contrarily, rpSMD showed 30%–50% volume reductions across all dominant hemisphere subregions/subfields <i>versus</i> controls, with the non-dominant hemisphere also showing 16–21% less volumes of the fimbria, HATA, parasubiculum, and presubiculum/subiculum of the head subregion. Comparison of dominant hemispheres showed 28% less volume of the parasubiculum in rpSMD; comparison of non-dominant hemispheres revealed 15% volume loss in entire CA3 and HATA in rpSMD <i>versus</i> lpSMD. Absolute degree of asymmetry across regions was similar in both groups. <h3>Conclusions:</h3> All hippocampal subregional/subfield volumes are affected in SMD, with subregional/subfield volumes being more affected in some regions in both dominant and non-dominant hemispheres in rpSMD than in lpSMD. <b>Disclosure:</b> Arenn Faye Carlos, MD has nothing to disclose. Stephen Weigand has nothing to disclose. The institution of Rene Utianski has received research support from NIH. The institution of Joseph Duffy has received research support from NIH. Joseph Duffy has received publishing royalties from a publication relating to health care. Heather Clark has received personal compensation for serving as an employee of Mayo Clinic. The institution of Heather Clark has received research support from NIH. Heather Clark has received publishing royalties from a publication relating to health care. The institution of Dr. Machulda has received research support from NIH. Nha Trang Thu Pham has received personal compensation for serving as an employee of Mayo Clinic. Christopher Schwarz has received personal compensation for serving as an employee of Mayo Clinic. The institution of Christopher Schwarz has received research support from NIH. The institution of Dr. Jack has received research support from NIH. The institution of Dr. Jack has received research support from Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic. Dr. Whitwell has nothing to disclose. Dr. Josephs has nothing to disclose.

Lack of correlation between hippocampal substructure atrophy and attention dysfunction in deficit schizophrenia

Hippocampal abnormalities are an established finding in the neuroimaging study of schizophrenia. However, no studies have examined the possibility of regional hippocampal abnormalities specific to deficit schizophrenia (DS) and associations with the unique symptoms of this schizophrenia subtype. This study compared 33 DS and 39 non-deficit schizophrenia (NDS) patients and 38 healthy subjects for hippocampal subfield volumetry. Clinical symptoms were assessed by PANSS, cognition by the neurocognitive battery on the day of the MRI scan. The automatic hippocampal segmentation were preprocesses use FreeSurfer 7.2.0. Unfortunately, the associations between neurocognitive scores and hippocampal subfield volumes in the DS group were not significant after the Bonferroni correction. Our results did not support a causal relationship between hippocampal subregional atrophy and cognitive deficits in DS.

Oxidative stress impairs cognitive function by affecting hippocampal fimbria volume in drug-naïve, first-episode schizophrenia.

The aim of the present study was to explore influencing factors of cognitive impairments and their interrelationships in drug-naïve, first-episode schizophrenia (SCZ). Patients with drug naïve, first episode SCZ and healthy controls (HCs) were enrolled. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Serum levels of oxidative stress indices, including folate, superoxide dismutase (SOD), uric acid (UA) and homocysteine (Hcy), were determined after an overnight fast. Hippocampal subfield volumes were measured using FreeSurfer. Mediation models were conducted using the SPSS PROCESS v3.4 macro. A false discovery rate (FDR) correction was applied for multiple comparisons. Sixty-seven patients with SCZ and 65 HCs were enrolled in our study. The patient group had significantly lower serum levels of folate and SOD and higher serum levels of HCY compared with the HCs (all p < 0.05). The patient group had a significantly smaller volume of the whole hippocampus than the HC group (p < 0.05). We also found significant volume differences between the two groups in the following subfields: CA1, molecular layer, GC-ML-DG and fimbria (all p < 0.05, uncorrected). The partial correlation analysis controlling for age and sex showed that the fimbria volume in the patient group was significantly positively associated with NAB scores (r = 0.382, pFDR = 0.024); serum levels of SOD in the patient group showed a significantly positive correlation with fimbria volume (r = 0.360, pFDR = 0.036). Mediation analyses controlling for age and sex showed that the serum levels of SOD in patients with SCZ had significant indirect effects on the NAB scores which were mediated by the fimbria volume [indirect effect = 0.0565, 95% CI from the bootstrap test excluding zero (0.0066 to 0.0891)]. Oxidative stress, a reduction in hippocampal subfield volumes and cognitive impairments occur in early SCZ. Oxidative stress impairs cognitive function by affecting hippocampal subfield volumes.

Larger left hippocampal presubiculum is associated with lower risk of antisocial behavior in healthy adults with childhood conduct history

Conduct Disorder (CD) is defined as aggressive, antisocial, and rule-breaking behavior during childhood. It is a major risk factor for developing antisocial personality disorder (ASPD) in adulthood. However, nearly half the CDs do not develop ASPD. Identification of reversion factors seems crucial for proper interventions. We identified 40 subjects with childhood history of CD (CC) and 1166 control subjects (HC) from Human Connectome Project. Their psychiatric, emotional, impulsivity, and personality traits were extracted. An emotion recognition task-fMRI analysis was done. We also did subregion analysis of hippocampus and amygdala in 35 CC and 69 demographically matched HCs. CC subjects scored significantly higher in antisocial-related evaluations. No differences in task-fMRI activation of amygdala and hippocampus were observed. CCs had larger subfields of the left hippocampus: presubiculum, CA3, CA4, and dentate gyrus. Further, an interaction model revealed a significant presubiculum volume × group association with antisocial, aggression, and agreeableness scores. Our study shows that healthy young adults with a prior history of CD still exhibit some forms of antisocial-like behavior with larger left hippocampal subfields, including presubiculum that also explains the variability in antisocial behavior. These larger left hippocampal subfield volumes may play a protective role against CD to ASPD conversion.

342. Pretreatment Hippocampal Subfield Volumes Predict Improved Neurocognitive Function Following Ketamine Treatment in Major Depression

342. Pretreatment Hippocampal Subfield Volumes Predict Improved Neurocognitive Function Following Ketamine Treatment in Major Depression

The impact of pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities in young adults

BackgroundUrbanicity refers to the conditions that are particular to urban areas and is a growing environmental challenge that may affect hippocampus and neurocognition. This study aimed to investigate the effects of the average pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities as well as the sensitive age windows of the urbanicity effects. Participants and methodsWe included 5,390 CHIMGEN participants (3,538 females; age: 23.69 ± 2.26 years, range: 18–30 years). Pre-adulthood urbanicity of each participant was defined as the average value of annual night-time light (NL) or built-up% from age 0–18, which were extracted from remote-sensing satellite data based on annual residential coordinates of the participants. The hippocampal subfield volumes were calculated based on structural MRI and eight neurocognitive measures were assessed. The linear regression was applied to investigate the associations of pre-adulthood NL with hippocampal subfield volumes and neurocognitive abilities, mediation models were used to find the underlying pathways among urbanicity, hippocampus and neurocognition, and distributed lag models were used to identify sensitive age windows of urbanicity effect. ResultsHigher pre-adulthood NL was associated with greater volumes in the left (β = 0.100, 95%CI: [0.075, 0.125]) and right (0.078, [0.052, 0.103]) fimbria and left subiculum body (0.045, [0.020, 0.070]) and better neurocognitive abilities in information processing speed (-0.212, [-0.240, −0.183]), working memory (0.085, [0.057, 0.114]), episodic memory (0.107, [0.080, 0.135]), and immediate (0.094, [0.065, 0.123]) and delayed (0.087, [0.058, 0.116]) visuospatial recall, and hippocampal subfield volumes and visuospatial memory showed bilateral mediations for the urbanicity effects. Urbanicity effects were greatest on the fimbria in preschool and adolescence, on visuospatial memory and information processing from childhood to adolescence and on working memory after 14 years. ConclusionThese findings improve our understanding of the impact of urbanicity on hippocampus and neurocognitive abilities and will benefit for designing more targeted intervention for neurocognitive improvement.