Hippocampal Subfield Volumes Research Articles

Volume of hippocampal subfields and cognitive deficits in neuromyelitis optica spectrum disorders.

Aquaporin-4 (AQP4) water channel is involved in hippocampal plasticity and is the target of neuromyelitis optica spectrum disorders (NMOSD) autoimmunity. We measured volumes of hippocampal subfields and their association with cognitive performance in AQP4-seropositive NMOSD patients. Global and regional hippocampal volumes were derived from 28 AQP4-seropositive NMOSD patients and 101 healthy controls (HC) from 3D-T1-weighted images. Normalized brain volumes were also calculated. A neuropsychological evaluation, including the Brief Repeatable Battery of Neuropsychological Tests, was performed in patients. Based on HC data, we estimated mean z-scores of volumes in the whole NMOSD group and compared them according to the status of global and domain-selective cognitive impairment. Global cognitive impairment was detected in 46.4% of NMOSD patients, with attentive (60.7%) and executive (21.4%) domains being the most affected. NMOSD patients had left hippocampal atrophy at global (p=0.012) and regional level (fimbria, Cornu Ammonis [CA] 3, molecular layer, dentate gyrus [DG], and subicular complex, p values ranging between 0.033 and <0.001). On the right side the fimbria and hippocampal tail were atrophic (p=0.024 for both). Cognitively impaired patients showed atrophy in the left CA3 and CA4 (p=0.025-0.028), while patients presenting verbal and visual memory impairment had significant CA3 and DG atrophy. Those patients with attentive or executive impairment had preserved brain and hippocampal volumes. NMOSD patients showed hippocampal atrophy associated with verbal and visual memory impairment. Such damage did not explain attention and executive function alterations, which were the most common cognitive deficits in this population.

Impact of Frailty on Hippocampal Volume in Patients with Chronic Obstructive Pulmonary Disease.

Brain frailty may be related to the pathophysiology of poor clinical outcomes in chronic obstructive pulmonary disease (COPD). This study examines the relationship between hippocampal subfield volumes and frailty and depressive symptoms, and their combined association with quality of life (QOL) in patients with COPD. The study involved 40 patients with COPD. Frailty, depressive symptoms and QOL were assessed using Kihon Checklist (KCL), Hospital Anxiety and Depression Scale (HADS), and World Health Organization Quality of Life Assessment (WHO/QOL-26). Anatomical MRI data were acquired, and volumes of the hippocampal subfields were obtained using FreeSurfer (version 6.0). Statistically, HADS score had significant association with WHO/QOL-26 and KCL scores. KCL scores were significantly associated with volumes of left and right whole hippocampi, presubiculum and subiculum, but HADS score had no significant association with whole hippocampi or hippocampal subfield volumes. Meanwhile, WHO/QOL-26 score was significantly associated with volume of the left CA1. There was a significant association between frailty, depression, and QOL. Hippocampal pathology was related to frailty and, to some extent, with QOL in patients with COPD. Our results suggest the impact of frailty on hippocampal volume and their combined associations with poor QOL in COPD.

Hippocampal subfield volumes and memory discrimination in the developing brain

The ability to keep distinct memories of similar events is underpinned by a type of neural computation called pattern separation (PS). Children typically report coarse-grained memories narratives lacking specificity and detail. This lack of memory specificity is illustrative of an immature or impaired PS. Despite its importance for the ontogeny of memory, data regarding the maturation of PS during childhood is still scarce. PS is known to rely on the hippocampus, particularly on hippocampal subfields DG and CA3. In this study, we used a memory discrimination task, a behavioral proxy for PS, and manually segmented hippocampal subfields volumes in the hippocampal body in a cohort of 26 children aged from 5 to 12 years. We examined the association between subfields volumes and memory discrimination performance. The main results were: (1) we showed age-related differences of memory discrimination suggesting a continuous increase of memory performance during early to late childhood. (2) We evidenced distinct associations between age and the volumes of hippocampal subfield, suggesting distinct developmental trajectories. (3) We showed a relationship between memory discrimination performance and the volumes of CA3 and subiculum. Our results further confirm the role of CA3 in memory discrimination, and suggest to scrutinize more closely the role of the subiculum. Overall, we showed that hippocampal subfields contribute distinctively to PS during development.

Comparison of Hippocampal Subfield Segmentation Agreement between 2 Automated Protocols across the Adult Life Span.

The hippocampus is a frequent focus of quantitative neuroimaging research, and structural hippocampal alterations are related to multiple neurocognitive disorders. An increasing number of neuroimaging studies are focusing on hippocampal subfield regional involvement in these disorders using various automated segmentation approaches. Direct comparisons among these approaches are limited. The purpose of this study was to compare the agreement between two automated hippocampal segmentation algorithms in an adult population. We compared the results of 2 automated segmentation algorithms for hippocampal subfields (FreeSurfer v6.0 and volBrain) within a single imaging data set from adults (n = 176, 89 women) across a wide age range (20-79 years). Brain MR imaging was acquired on a single 3T scanner as part of the IXI Brain Development Dataset and included T1- and T2-weighted MR images. We also examined subfield volumetric differences related to age and sex and the impact of different intracranial volume and total hippocampal volume normalization methods. Estimated intracranial volume and total hippocampal volume of both protocols were strongly correlated (r = 0.93 and 0.9, respectively; both P < .001). Hippocampal subfield volumes were correlated (ranging from r = 0.42 for the subiculum to r = 0.78 for the cornu ammonis [CA]1, all P < .001). However, absolute volumes were significantly different between protocols. volBrain produced larger CA1 and CA4-dentate gyrus and smaller CA2-CA3 and subiculum volumes compared with FreeSurfer v6.0. Regional age- and sex-related differences in subfield volumes were qualitatively and quantitatively different depending on segmentation protocol and intracranial volume/total hippocampal volume normalization method. The hippocampal subfield volume relationship to demographic factors and disease states should undergo nuanced interpretation, especially when considering different segmentation protocols.

Nonclinical psychotic-like experiences and schizotypy dimensions: Associations with hippocampal subfield and amygdala volumes.

Schizotypy and psychotic‐like experiences (PLE) form part of the wider psychosis continuum and may have brain structural correlates in nonclinical cohorts. This study aimed to compare the effects of differential schizotypy dimensions, PLE, and their interaction on hippocampal subfields and amygdala volumes in the absence of clinical psychopathology. In a cohort of 367 psychiatrically healthy individuals, we assessed schizotypal traits using the Oxford‐Liverpool Inventory of Life Experiences (O‐LIFE) and PLE using the short form of the Prodromal Questionnaire (PQ‐16). Based on high‐resolution structural MRI scans, we used automated segmentation to estimate volumes of limbic structures. Sex and total intracranial volume (Step 1), PLE and schizotypy dimensions (Step 2), and their interaction terms (Step 3) were entered as regressors for bilateral amygdala and hippocampal subfield volumes in hierarchical multiple linear regression models. Positive schizotypy, but not PLE, was negatively associated with left amygdala and subiculum volumes. O‐LIFE Impulsive Nonconformity, as well as the two‐way interaction between positive schizotypy and PLE, were associated with larger left subiculum volumes. None of the estimators for right hemispheric hippocampal subfield volumes survived correction for multiple comparisons. Our findings support differential associations of hippocampus subfield volumes with trait dimensions rather than PLE, and support overlap and interactions between psychometric positive schizotypy and PLE. In a healthy cohort without current psychosis risk syndromes, the positive association between PLE and hippocampal subfield volume occurred at a high expression of positive schizotypy. Further studies combining stable, transient, and genetic parameters are required.

Association between lifetime depression history, hippocampal volume and memory in non-amnestic mild cognitive impairment.

Hippocampal subfield volume loss in older adults with amnestic mild cognitive impairment (aMCI) and depression history are associated with amyloid beta and tau pathology, thereby increasing the risk for Alzheimer's disease (AD). However, no studies have exclusively examined distinct alterations in hippocampal subfields in non-amnestic MCI (naMCI) in relation to depression history. Here, we used both longitudinal and transverse hippocampal segmentation methods using the automated FreeSurfer software to examine whether a lifetime depression history is associated with differences in hippocampal head/body/tail (H/B/T) and key subfield volumes (CA1, subiculum, dentate gyrus) in older adults with naMCI. Further, we explored whether differences in hippocampal H/B/T and subfield volumes were associated with structured and unstructured verbal encoding and retention, comparing those with and without a depression history. The naMCI with a depression history group demonstrated larger or relatively preserved right CA1 volumes, which were associated with better unstructured verbal encoding and as well as structured verbal memory retention. This association between memory encoding and hippocampal CA1 and total head volume was significantly different to those with no depression history. The relationship between right CA1 volume and memory retention was also moderated by depression history status F (5,143)=7.84, p<0.001, R2 =0.22. Those participants taking antidepressants had significantly larger hippocampal subiculum (p=0.008), and right hippocampal body (p=0.004) and better performance on structured encoding (p=0.011) and unstructured memory retention (p=0.009). These findings highlight the importance of lifetime depression history and antidepressant use on the hippocampus and encoding and memory retention in naMCI.

A neurostructural biomarker of dissociative amnesia: a hippocampal study in dissociative identity disorder.

Little is known about the neural correlates of dissociative amnesia, a transdiagnostic symptom mostly present in the dissociative disorders and core characteristic of dissociative identity disorder (DID). Given the vital role of the hippocampus in memory, a prime candidate for investigation is whether total and/or subfield hippocampal volume can serve as biological markers of dissociative amnesia. A total of 75 women, 32 with DID and 43 matched healthy controls (HC), underwent structural magnetic resonance imaging (MRI). Using Freesurfer (version 6.0), volumes were extracted for bilateral global hippocampus, cornu ammonis (CA) 1-4, the granule cell molecular layer of the dentate gyrus (GC-ML-DG), fimbria, hippocampal-amygdaloid transition area (HATA), parasubiculum, presubiculum and subiculum. Analyses of covariance showed volumetric differences between DID and HC. Partial correlations exhibited relationships between the three factors of the dissociative experience scale scores (dissociative amnesia, absorption, depersonalisation/derealisation) and traumatisation measures with hippocampal global and subfield volumes. Hippocampal volumes were found to be smaller in DID as compared with HC in bilateral global hippocampus and bilateral CA1, right CA4, right GC-ML-DG, and left presubiculum. Dissociative amnesia was the only dissociative symptom that correlated uniquely and significantly with reduced bilateral hippocampal CA1 subfield volumes. Regarding traumatisation, only emotional neglect correlated negatively with bilateral global hippocampus, bilateral CA1, CA4 and GC-ML-DG, and right CA3. We propose decreased CA1 volume as a biomarker for dissociative amnesia. We also propose that traumatisation, specifically emotional neglect, is interlinked with dissociative amnesia in having a detrimental effect on hippocampal volume.

Automated volumetry of hippocampal subfields in temporal lobe epilepsy

IntroductionHippocampal sclerosis is the most frequent pathological substrate in drug resistant temporal lobe epilepsy (TLE). Recently 4 types of hippocampal sclerosis (HS) have been defined in a task force by the International League Against Epilepsy (ILAE), based on patterns of cell loss in specific hippocampal subfields. Type 1 HS is most frequent and has the most favorable outcome after epilepsy surgery. We hypothesized that volume loss in specific hippocampal subfields determined by automated volumetry of high resolution MRI would correspond to cell loss in histological reports. Material and MethodsIn a group of well characterized patients with drug resistant TLE (N = 26 patients, 14 with right-sided focus, 12 with left-sided focus) volumes of the right and left hippocampus and the hippocampal subfields CA1, CA2 + 3, CA4 and dentate gyrus (DG) were estimated automatically using FreeSurfer version 6.0 from high-resolution cerebral MRI and compared to a large group of healthy controls (N = 121). HS subtype classification was attempted based on histological reports. ResultsVolumes of the whole hippocampus and all investigated hippocampal subfields (CA1, CA2 + 3, CA4 and DG) were significantly lower on the ipsilateral compared the contralateral side (p < 0.001) and compared to the healthy controls (p < 0.001). Conversely, whole hippocampal and hippocampal subfield volumes were not significantly different from healthy control values on the contralateral side.In 12 of 20 patients the pattern of hippocampal volume loss in specific subfields was in accordance with HS types from histology. The highest overlap between automated MRI and histology was achieved for type 1 HS (in 10 of 12 cases). ConclusionThe automated volumetry of hippocampal subfields, based on high resolution MRI, may have the potential to predict the pattern of cell loss in hippocampal sclerosis before operation.

Relationship between hippocampal subfields and Verbal and Visual memory function in Mesial Temporal Lobe Epilepsy patients

ObjectiveHigh-resolution protocols used in magnetic resonance imaging (MRI) currently enable the detailed analysis of the hippocampus along with its subfield segmentation. The relationship between episodic memory and the hippocampus is well established, and there is growing evidence that some specific memory processing steps are associated with individual hippocampal segments, but there are inconsistencies in the literature. We focused our analysis on hippocampal subfield volumetry and neuropsychological visual and verbal memory tests in patients with temporal lobe epilepsy (TLE) presenting with unilateral hippocampal atrophy. MethodsThe study involved a cohort of 62 patients with unilateral TLE, including unilateral hippocampal atrophy (29 on the left side) based on MRI and unequivocal ipsilateral ictal onsets based on surface video electroencephalography recordings. The hippocampal subfield volumes were evaluated using FreeSurfer version 7.1. We used the Rey-Auditory Verbal Learning Test to evaluate short-term (A1), learning (ΣA1-A5), immediate (A6), and delayed (A7) recall of episodic verbal memory. We used the Rey-Osterrieth Complex Figure Test to evaluate the immediate and delayed recall of visual memory. We analyzed the correlations between the asymmetry index scores for the hippocampal subfield volumes of thecornu ammonis (CA)1, CA2/3, and CA4 and memory test performance. ResultsModerate associations were established between the CA2/3 asymmetry index scores and visual memory in TLE (both right and left hippocampal atrophy), as well as visual memory and CA4 in the right atrophy cases. The CA1 asymmetry index scores did not correlate with any of the memory test results. We did not find any significant correlation between verbal memory tests and specific hippocampal subfields. ConclusionsThe use of high-resolution MRI protocols andin vivo automated segmentation processing revealed moderate associations between hippocampal subfields and memory parameters. Further investigations are needed to establish the utility of these results for clinical decisions.

Differential involvement of hippocampal subfields in Niemann-Pick type C disease: a case-control study.

Hippocampal brain regions are strongly implicated in Niemann Pick type C disease (NPC), but little is known regarding distinct subregions of the hippocampal complex and whether these are equally or differentially affected. To address this gap, we compared volumes of five hippocampal subfields between NPC and healthy individuals using MRI. To this end, 9 adult-onset NPC cases and 9 age- and gender-matched controls underwent a 3T T1-weighted MRI scan. Gray matter volumes of the cornu ammonis (CA1, CA2 and CA3), dentate gyrus (DG), subiculum, entorhinal cortex and hippocampal-amygdalar transition area were calculated by integrating MRI-based image intensities with microscopically defined cytoarchitectonic probabilities. Compared to healthy controls, NPC patients showed smaller volumes of the CA1-3 and DG regions bilaterally, with the greatest difference localized to the left DG (Cohen's d = 1.993, p = 0.008). No significant associations were shown between hippocampal subfield volumes and key clinical features of NPC, including disease duration, symptom severity and psychosis. The pattern of hippocampal subregional atrophy in NPC differs from those seen in other dementias, which may indicate unique cytoarchitectural vulnerabilities in this earlier-onset disorder. Future MRI studies of hippocampal subfields may clarify its potential as a biomarker of neurodegeneration in NPC.

The DRD2 Taq1A polymorphism moderates the effect of PTSD symptom severity on the left hippocampal CA3 volume: a pilot study

Rationale and objectivesThe hippocampus, especially the CA1, CA3, and dentate gyrus (DG) subfields, is reported to be associated with post-traumatic stress disorder (PTSD) after trauma. However, neuroimaging studies of the associations between PTSD and hippocampal subfield volumes have failed to yield consistent findings. The aim of this study is to examine whether the dopamine D2 receptor (DRD2) Taq1A polymorphism, which is associated with both hippocampal function and PTSD, moderated the association between PTSD severity and hippocampal CA1, CA3 and DG volumes.MethodsT1-weighted images were acquired from 142 trauma survivors from the 2008 Wenchuan earthquake using a 3.0-T magnetic resonance imaging system. Hippocampal subfield segmentations were performed with FreeSurfer v6.0. We used the simple moderation model from the PROCESS v3.4 tool for SPSS 23.0 to examine the association between the rs1800497 polymorphism, PTSD severity, and hippocampal CA3 and DG volumes.ResultsA significant genotype × PTSD symptom severity interaction was found for the left CA3 volume (ΔF = 5.01, p = 0.008, ΔR2 = 0.05). Post hoc, exploratory analyses deconstructing the interaction revealed that severe PTSD symptomatology were associated with reduced left CA3 volume among TC heterozygotes (t = − 2.86, p = 0.005).ConclusionsThis study suggests that DRD2 Taq1A polymorphism moderates the association between PTSD symptomatology and left CA3 volume, which promotes an etiological understanding of the hippocampal atrophy at the subfield level. This highlights the complex effect of environmental stress, and provides possible mechanism for the relationship between the dopaminergic system and hippocampal function in PTSD.

Variations in response to trauma and hippocampal subfield changes

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

Genetic Influences on Hippocampal Subfields: An Emerging Area of Neuroscience Research.

There is clear evidence that hippocampal subfield volumes have partly distinct genetic determinants associated with specific biological processes. The identification of genetic correlates of hippocampal subfield volumes may help to elucidate the mechanisms of neurologic diseases, as well as aging and neurodegenerative processes. However, despite the emerging interest in this area of research, the current knowledge of the genetic architecture of hippocampal subfields has not yet been consolidated. We aimed to provide a review of the current evidence from genetic studies of hippocampal subfields, highlighting current priorities and upcoming challenges. The limited number of studies investigating the influential genetic effects on hippocampal subfields, a lack of replicated results and longitudinal designs, and modest sample sizes combined with insufficient standardization of protocols are identified as the most pressing challenges in this emerging area of research.

Volumetric and shape analysis of the hippocampus in temporal lobe epilepsy with GAD65 antibodies compared with non-immune epilepsy

Glutamic acid decarboxylase 65 antibodies (anti-GAD65) have been found in patients with late-onset chronic temporal lobe epilepsy (TLE). No prior neuroimaging studies have addressed how they affect hippocampal volume and shape and how they relate to cognitive abnormalities. We aimed to investigate both brain structure and function in patients with isolated TLE and high anti-GAD65 levels (RIA ≥ 2000 U/ml) compared to 8 non-immune mesial TLE (niTLE) and 8 healthy controls (HC). Hippocampal subfield volume properties were correlated with the duration of the disease and cognitive test scores. The affected hippocampus of GAD-TLE patients showed no volume changes to matched HC whereas niTLE volumes were significantly smaller. Epilepsy duration in GAD-TLE patients correlated negatively with volumes in the presubiculum, subiculum, CA1, CA2–3, CA4, molecular layer and granule cell-molecular layer of the dentate nucleus. We found differences by advanced vertex-wise shape analysis in the anterior hippocampus of the left GAD-TLE compared to HC whereas left niTLE showed bilateral posterior hippocampus deformation. Verbal deficits were similar in GAD-TLE and niTLE but did not correlate to volume changes. These data might suggest a distinct expression of hippocampal structural and functional abnormalities based on the immune response.

Understanding the role of aerobic fitness, spatial learning, and hippocampal subfields in adolescent males

Physical exercise during adolescence, a critical developmental window, can facilitate neurogenesis in the dentate gyrus and astrogliogenesis in Cornu Ammonis (CA) hippocampal subfields of rats, and which have been associated with improved hippocampal dependent memory performance. Recent translational studies in humans also suggest that aerobic fitness is associated with hippocampal volume and better spatial memory during adolescence. However, associations between fitness, hippocampal subfield morphology, and learning capabilities in human adolescents remain largely unknown. Employing a translational study design in 34 adolescent males, we explored the relationship between aerobic fitness, hippocampal subfield volumes, and both spatial and verbal memory. Aerobic fitness, assessed by peak oxygen utilization on a high-intensity exercise test (VO2 peak), was positively associated with the volumetric enlargement of the hippocampal head, and the CA1 head region specifically. Larger CA1 volumes were also associated with spatial learning on a Virtual Morris Water Maze task and verbal learning on the Rey Auditory Verbal Learning Test, but not recall memory. In line with previous animal work, the current findings lend support for the long-axis specialization of the hippocampus in the areas of exercise and learning during adolescence.

Perceived Stress Associations With Hippocampal Subfield Volume and Hippocampal-Dependent Behavior

Smaller hippocampal volume is seen in depression, PTSD, and healthy individuals with elevated perceived stress. These structural alterations may compromise the information processing function of pattern separation that involves the dentate gyrus (DG) and CA3. The concurrent assessment of perceived stress, pattern separation behavior, and DG/CA3 volume may illuminate mechanisms of stress-related psychopathology.

Hippocampal shape across the healthy lifespan and its relationship with cognition

The study of the hippocampus across the healthy adult lifespan has rendered inconsistent findings. While volumetric measurements have often been a popular technique for analysis, more advanced morphometric techniques have demonstrated compelling results that highlight the importance and improved specificity of shape-based measures. Here, the MAGeT Brain algorithm was applied on 134 healthy individuals aged 18–81 years old to extract hippocampal subfield volumes and hippocampal shape measurements, namely: local surface area (SA) and displacement. We used linear-, second- or third-order natural splines to examine the relationships between hippocampal measures and age. In addition, partial least squares analyses were performed to relate volume and shape measurements with cognitive and demographic information. Volumetric results indicated a relative preservation of the right cornus ammonis 1 with age and a global volume reduction linked with older age, female sex, lower levels of education and cognitive performance. Vertex-wise analysis demonstrated an SA preservation in the anterior hippocampus with a peak during the sixth decade, while the posterior hippocampal SA gradually decreased across lifespan. Overall, SA decrease was linked to older age, female sex and, to a lesser extent lower levels of education and cognitive performance. Outward displacement in the lateral hippocampus and inward displacement in the medial hippocampus were enlarged with older age, lower levels of cognition and education, indicating an accentuation of the hippocampal “C” shape with age. Taken together, our findings suggest that vertex-wise analyses have higher spatial specifity and that sex, education, and cognition are implicated in the differential impact of age on hippocampal subregions throughout its anteroposterior and medial-lateral axes. This article is part of the Virtual Special Issue titled COGNITIVE NEU- ROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.

Hippocampal and Hippocampal-Subfield Volumes From Early-Onset Major Depression and Bipolar Disorder to Cognitive Decline.

Background: The hippocampus and its subfields (HippSub) are reported to be diminished in patients with Alzheimer's disease (AD), bipolar disorder (BD), and major depressive disorder (MDD). We examined these groups vs healthy controls (HC) to reveal HippSub alterations between diseases.Methods: We segmented 3T-MRI T2-weighted hippocampal images of 67 HC, 58 BD, and MDD patients from the AFFDIS study and 137 patients from the DELCODE study assessing cognitive decline, including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and AD, via Free Surfer 6.0 to compare volumes across groups.Results: Groups differed significantly in several HippSub volumes, particularly between patients with AD and mood disorders. In comparison to HC, significant lower volumes appear in aMCI and AD groups in specific subfields. Smaller volumes in the left presubiculum are detected in aMCI and AD patients, differing from the BD group. A significant linear regression is seen between left hippocampus volume and duration since the first depressive episode.Conclusions: HippSub volume alterations were observed in AD, but not in early-onset MDD and BD, reinforcing the notion of different neural mechanisms in hippocampal degeneration. Moreover, duration since the first depressive episode was a relevant factor explaining the lower left hippocampal volumes present in groups.

Association between hippocampal structure and serum Brain-Derived Neurotrophic Factor (BDNF) in healthy adults: A registered report

The hippocampus is a highly plastic brain structure supporting functions central to human cognition. Morphological changes in the hippocampus have been implicated in development, aging, as well as in a broad range of neurological and psychiatric disorders. A growing body of research suggests that hippocampal plasticity is closely linked to the actions of brain-derived neurotrophic factor (BDNF). However, evidence on the relationship between hippocampal volume (HCV) and peripheral BDNF levels is scarce and limited to elderly and patient populations. Further, despite evidence that BDNF expression differs throughout the hippocampus and is implicated in adult neurogenesis specifically in the dentate gyrus, no study has so far related peripheral BDNF levels to the volumes of individual hippocampal subfields. Besides its clinical implications, BDNF-facilitated hippocampal plasticity plays an important role in regulating cognitive and affective processes. In the current registered report, we investigated how serum BDNF (sBDNF) levels relate to volumes of the hippocampal formation and its subfields in a large sample of healthy adults (N = 279, 160 f) with a broad age range (20–55 years, mean 40.5) recruited in the context of the ReSource Project. We related HCV to basal sBDNF and, in a subsample (n = 103, 57 f), to acute stress-reactive change in sBDNF. We further tested the role of age as a moderator of both associations. Contrary to our hypotheses, neither basal sBDNF levels nor stress-reactive sBDNF change were associated with total HCV or volume of the dentate gyrus/cornu ammonis 4 (DG/CA4) subfield. We also found no evidence for a moderating effect of age on any of these associations. Our null results provide a first point of reference on the relationship between sBDNF and HCV in healthy mid-age, in contrast to patient or aging populations. We suggest that sBDNF levels have limited predictive value for morphological differences of the hippocampal structure when notable challenge to its neuronal integrity or to neurotrophic capacity is absent.

Stability of hippocampal subfield volumes after trauma and relationship to development of PTSD symptoms

BackgroundThe hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus’ functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample to also investigate reliability of hippocampal subfield volumes using both cross-sectional and longitudinal pipelines available in FreeSurfer v6.0. MethodsTwo-hundred and fifteen traumatically injured individuals were recruited from an urban Emergency Department. Two-weeks post-injury, participants underwent two consecutive days of neuroimaging (time 1: T1, and time 2: T2) with magnetic resonance imaging (MRI) and completed self-report assessments. Six-months later (time 3: T3), participants underwent an additional scan and were administered a structured interview assessing PTSD symptoms. First, we calculated reliability of hippocampal measurements at T1 and T2 (automatically segmented with FreeSurfer v6.0). We then examined the prospective (T1 subfields) and cross-sectional (T3 subfields) relationship between volumes and PTSD. Finally, we tested whether change in subfield volumes between T1 and T3 explained PTSD symptom variability. ResultsAfter controlling for sex, age, and total brain volume, none of the subfield volumes (T1) were prospectively related to T3 PTSD symptoms nor were subfield volumes (T3) associated with current PTSD symptoms (T3). Tl – T2 reliability of all hippocampal subfields ranged from good to excellent (intraclass correlation coefficient (ICC) values > 0.83), with poorer reliability in the hippocampal fissure. ConclusionOur study was a novel examination of the prospective relationship between hippocampal subfield volumes in relation to PTSD in a large trauma-exposed urban sample. There was no significant relationship between subfield volumes and PTSD symptoms, however, we confirmed FreeSurfer v6.0 hippocampal subfield segmentation is reliable when applied to a traumatically-injured sample, using both cross-sectional and longitudinal analysis pipelines. Although hippocampal subfield volumes may be an important marker of individual variability in PTSD, findings are likely conditional on the timing of the measurements (e.g. acute or chronic post-trauma periods) and analysis strategy (e.g. cross-sectional or prospective).