Hippocampal Head Research Articles

Involvement of hippocampal subfields and anterior-posterior subregions in encoding and retrieval of item, spatial, and associative memories: Longitudinal versus transverse axis

The functional role of the hippocampal formation in episodic memory has been studied using functional magnetic resonance imaging (fMRI) for many years. The hippocampus can be segmented into three major anteroposterior sections, called head, body and tail, and into the Cornu Ammonis (CA), dentate gyrus (DG), and subiculum (Sub) subfields based on its transverse axis. However, the exact role of these subregions and subfields in memory processes is less understood. In the present study we combined ultra-high-resolution structural Magnetic Resonance Imaging (MRI) at 4.7 T with an event-related high-resolution fMRI paradigm based on the ‘Designs’ subtest of the Wechsler Memory Scale to investigate how the hippocampal subfields and longitudinal subregions are involved in encoding and retrieval of item, spatial, and associative memories. Our results showed that during memory encoding, regardless of the type of memory being learned, all subregions and all subfields were active. During the retrieval phase, on the other hand, we observed an anterior to posterior gradient in hippocampal activity for all subfields and all types of memory. Our findings also confirmed presence of an anterior to posterior gradient in hippocampal activity during spatial learning. Comparing subfield activities to each other revealed that the DG was more active than the CA1-3 and Sub during both encoding and retrieval. Finally, our results showed that for every subfield, encoding vs. retrieval activity differences were larger in the hippocampal head than in the hippocampal body and tail. Furthermore, these encoding vs. retrieval activity differences were similar in all subfields, highlighting the importance of studying both the longitudinal and transverse axis specialization simultaneously. Current findings further elucidate the structure–function relationship between the human hippocampus and episodic memory.

In vivo metabotropic glutamate receptor type 5 abnormalities localize the epileptogenic zone in mesial temporal lobe epilepsy.

Surgical specimens from patients with mesial temporal lobe epilepsy (MTLE) show abnormalities in tissue concentrations of metabotropic glutamate receptor type 5 (mGluR5). To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), we characterized in vivo whole-brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [11 C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site. Thirty-one unilateral MTLE patients and 30 healthy controls underwent [11 C]ABP688 PET. We compared partial volume corrected [11 C]ABP688 nondisplaceable binding potentials (BPND ) between groups using region-of-interest and whole-brain voxelwise analyses. [18 F]Fluorodeoxyglucose (FDG) PET was acquired in 15 patients, for whom we calculated asymmetry indices of [11 C]ABP688 BPND and [18 F]FDG uptake to compare lateralization and localization differences. [11 C]ABP688 BPND was focally reduced in the epileptogenic hippocampal head and amygdala (p < 0.001). Patients with hippocampal atrophy showed more extensive abnormalities, including the ipsilateral temporal neocortex (p = 0.006). [11 C]ABP688 BPND showed interhemispheric differences of higher magnitude and discriminated the epileptogenic structures more accurately when compared to [18 F]FDG uptake, which showed more widespread hypometabolism. Among 23 of 25 operated patients with >1 year of follow-up, 13 were seizure-free (Engel Ia) and showed significantly lower [11 C]ABP688 BPND in the ipsilateral entorhinal cortex. [11 C]ABP688 PET provides a focal biomarker for the EZ in MTLE with higher spatial accuracy compared to [18 F]FDG PET. Focally reduced mGluR5 availability in the EZ might reflect receptor internalization or conformational changes in response to excessive extracellular glutamate, supporting a potential role for mGluR5 as therapeutic target in human MTLE. Ann Neurol 2019; 1-11 ANN NEUROL 2019;85:218-228.

Limbic and paralimbic structures driving ictal central apnea.

To precisely identify cortical regions that modulate breathing, and delineate a network of cortical structures that underpin ictal central apnea (ICA) during epileptic seizures. We electrically stimulated multiple cortical structures in patients undergoing stereotactic EEG (SEEG) evaluation before epilepsy surgery. Structures investigated were orbitofrontal cortex, anterior and posterior cingulate and subcallosal gyri, insula, hippocampus, parahippocampal gyrus, amygdala, temporo-polar cortex, antero-mesial fusiform gyrus, and lateral and basal temporal cortices. Chest/abdominal excursions using thoracic/abdominal belts, peripheral capillary oxygen saturation, end tidal and transcutaneous carbon dioxide, and airflow were continuously monitored. Nineteen consecutive adult patients (10 female) aged 18-69 years were investigated. Transient central apnea was elicited in 13/19 patients with amygdala, hippocampus head and body, anterior parahippocampal gyrus, and antero-mesial fusiform gyrus. Insula, cingulate, subcallosal, orbitofrontal, lateral, and basal temporal cortices stimulation did not induce apnea. Apnea duration was associated with stimulus duration (p < 0.001) and current intensity (p = 0.004). These findings suggest a limbic/paralimbic mesial temporal breathing modulation network that includes amygdala, hippocampus, anterior parahippocampal, and antero-mesial fusiform gyri. These structures likely represent anatomical and functional substrates for ICA, a putative sudden unexpected death in epilepsy (SUDEP) breathing biomarker. Damage to such areas is known to occur in high SUDEP risk patients and SUDEP victims, and may underpin the prolonged ICA that is thought to be particularly dangerous. Furthermore, inclusive targeting of apnea-producing structures in SEEG implantations, peri-ictal breathing signal recordings, and stringent analysis of apneic sequences in seizure semiology may enhance accurate identification of symptomatogenic and seizure onset zones for epilepsy surgery.

Left Transsylvian Transcisternal and Transinferior Insular Sulcus Approach for Resection of Uncohippocampal Tumor: 3-Dimensional Operative Video.

The medial temporal lobe can be divided in anterior, middle, and posterior segments. The anterior segment is formed by the uncus and hippocampal head, and it has extra and intraventricular structures. There are 2 main approaches to the uncohippocampal region, the anteromedial temporal lobectomy (Spencer's technique) and the transsylvian selective amygdalohippocampectomy (Yasargil's technique).In this video, we present the case of a 29-yr-old man with new onset of generalized seizures and a contrast-enhancing lesion in the left anterior segment of the medial temporal lobe compatible with high-grade glioma. He had a medical history of cervical astrocytoma at age 8 requiring craniospinal radiation therapy and ventriculoperitoneal shunt placement.The tumor was approached using a combined transsylvian transcisternal and transinferior insular sulcus approach to the extra and intraventricular aspects of the uncohippocampal region. It was resected completely, and the patient was neurologically intact after resection with no further seizures at 6-mo follow-up. The diagnosis was glioblastoma IDH-wild type, for which he underwent adjuvant therapy.Surgical anatomy and technical nuances of this approach are illustrated using a 3-dimensional video and anatomic dissections. The selective approach, when compared to an anteromedial temporal lobectomy, has the advantage of preserving the anterolateral temporal cortex, which is particularly relevant in dominant-hemisphere lesions, and the related fiber tracts, including the inferior fronto-occipital and inferior longitudinal fascicles, and most of the optic radiation fibers. The transsylvian approach, however, is technically and anatomically more challenging and potentially carries a higher risk of vascular injury and vasospasm.Page 1 and figures from Fernández-Miranda JC et al, Microvascular Anatomy of the Medial Temporal Region: Part 1: Its Application to Arteriovenous Malformation Surgery, Operative Neurosurgery, 2010, Volume 67, issue 3, ons237-ons276, by permission of the Congress of Neurological Surgeons (1:26-1:37 in video).Page 1 from Fernández-Miranda JC et al, Three-Dimensio-nal Microsurgical and Tractographic Anatomy of the White Matter of the Human Brain, Neurosurgery, 2008, Volume 62, issue suppl_3, SHC989-SHC1028, by permission of the Congress of Neurological Surgeons (1:54-1:56 in video).

Manual Hippocampal Subfield Segmentation Using High-Field MRI: Impact of Different Subfields in Hippocampal Volume Loss of Temporal Lobe Epilepsy Patients.

In patients with temporal lobe epilepsy (TLE), presurgical magnetic resonance imaging (MRI) often reveals hippocampal atrophy, while neuropathological assessment indicates the different types of hippocampal sclerosis (HS). Different HS types are not discriminated in MRI so far. We aimed to define the volume of each hippocampal subfield on MRI manually and to compare automatic and manual segmentations for the discrimination of HS types. The T2-weighted images from 14 formalin-fixed age-matched control hippocampi were obtained with 4.7T MRI to evaluate the volume of each subfield at the anatomical level of the hippocampal head, body, and tail. Formalin-fixed coronal sections at the level of the body of 14 control cases, as well as tissue samples from 24 TLE patients, were imaged with a similar high-resolution sequence at 3T. Presurgical three-dimensional (3D) T1-weighted images from TLE went through a FreeSurfer 6.0 hippocampal subfield automatic assessment. The manual delineation with the 4.7T MRI was identified using Luxol Fast Blue stained 10-μm-thin microscopy slides, collected at every millimeter. An additional section at the level of the body from controls and TLE cases was submitted to NeuN immunohistochemistry for neuronal density estimation. All TLE cases were classified according to the International League Against Epilepsy's (ILAE's) HS classification. Manual volumetry in controls revealed that the dentate gyrus (DG)+CA4 region, CA1, and subiculum accounted for almost 90% of the hippocampal volume. The manual 3T volumetry showed that all TLE patients with type 1 HS (TLE-HS1) had lower volumes for DG+CA4, CA2, and CA1, whereas those TLE patients with HS type 2 (TLE-HS2) had lower volumes only in CA1 (p ≤ 0.038). Neuronal cell densities always decreased in CA4, CA3, CA2, and CA1 of TLE-HS1 but only in CA1 of TLE-HS2 (p ≤ 0.003). In addition, TLE-HS2 had a higher volume (p = 0.016) and higher neuronal density (p < 0.001) than the TLE-HS1 in DG + CA4. Automatic segmentation failed to match the manual or histological findings and was unable to differentiate TLE-HS1 from TLE-HS2. Total hippocampal volume correlated with DG+CA4 and CA1 volumes and neuronal density. For the first time, we also identified subfield-specific pathology patterns in the manual evaluation of volumetric MRI scans, showing the importance of manual segmentation to assess subfield-specific pathology patterns.

Radiation-induced gray matter atrophy in patients with nasopharyngeal carcinoma after intensity modulated radiotherapy: a MRI magnetic resonance imaging voxel-based morphometry study.

Gray matter (GM) damage after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients can result in cognitive impairment, while there may be no visible brain tissue change according to the conventional magnetic resonance imaging (MRI). This study investigated radiation-induced GM volume differences between NPC patients who received RT and those who did not. High-resolution brain structural MRI data from two groups of patients were acquired. The pre-RT group was composed of 56 newly diagnosed but not yet medically treated NPC patients, while the after-RT group consisted of 40 NPC patients who had completed RT more than 1 year ago. Voxel-based morphometry (VBM) was applied to assess GM volumes. Two sample t-test was used to analyze GM volumes voxel-by-voxel using the VBM8 toolbox built in the SPM software. Radiation-induced cortical volume alteration in all NPC patients after RT and dosimetry of 36 patients were analyzed. Compared to pre-treatment group, cortical volumes of GM were significantly smaller in the left hippocampus, the right pulvinar and the right middle temporal gyrus (MTG, P<0.001, AlphaSim correction, cluster size ≥157). The mean dose (Dmean) for bilateral hippocampal heads were significantly higher than other different parts of the brain (P<0.001). No significant correlations between the GM volume in any brain regions and the mean dose of corresponding position of these brain regions were observed (P>0.05). Radiation to the NPC patients can not only induce damage of the hippocampus, but also other secondary damages of GM.

Global Hippocampal Volume Reductions and Local CA1 Shape Deformations in Amyotrophic Lateral Sclerosis.

There is increasing evidence for hippocampal involvement in Amyotrophic Lateral Sclerosis (ALS). Recent neuroimaging studies have been focused on disease-related hippocampal volume alterations while changes in hippocampal shape have been investigated less frequently. Here, we aimed to characterize the patterns of hippocampal degeneration using both an automatic and manual volumetric and surface-based approach in a group of 31 patients with ALS and 29 healthy controls. Irrespective of the segmentation type, left, and right hippocampal volumes were significantly reduced in ALS compared to controls. Local shape alterations were identified in the hippocampal head region of patients with ALS that corresponds to the cornu ammonis field 1 (CA1), a region known to be involved in novelty detection, memory processing, and integration of hippocampal input and output information. The results suggest a global hippocampal volume loss in ALS that is complemented by local shape deformations in a highly interconnected region within the hippocampus.

Ablation dynamics during laser interstitial thermal therapy for mesiotemporal epilepsy.

IntroductionThe recent emergence of laser interstitial thermal therapy (LITT) as a frontline surgical tool in the management of brain tumors and epilepsy is a result of advances in MRI thermal imaging. A limitation to further improving LITT is the diversity of brain tissue thermoablative properties, which hinders our ability to predict LITT treatment-related effects. Utilizing the mesiotemporal lobe as a consistent anatomic model system, the goal of this study was to use intraoperative thermal damage estimate (TDE) maps to study short- and long-term effects of LITT and to identify preoperative variables that could be helpful in predicting tissue responses to thermal energy.MethodsFor 30 patients with mesiotemporal epilepsy treated with LITT at a single institution, intraoperative TDE maps and pre-, intra- and post-operative MRIs were co-registered in a common reference space using a deformable atlas. The spatial overlap of TDE maps with manually-traced immediate (post-ablation) and delayed (6-month) ablation zones was measured using the dice similarity coefficient (DSC). Then, motivated by simple heat-transfer models, ablation dynamics were quantified at amygdala and hippocampal head from TDE pixel time series fit by first order linear dynamics, permitting analysis of the thermal time constant (τ). The relationships of these measures to 16 independent variables derived from patient demographics, mesiotemporal anatomy, preoperative imaging characteristics and the surgical procedure were examined.ResultsTDE maps closely overlapped immediate ablation borders but were significantly larger than the ablation cavities seen on delayed imaging, particularly at the amygdala and hippocampal head. The TDEs more accurately predicted delayed LITT effects in patients with smaller perihippocampal CSF spaces. Analyses of ablation dynamics from intraoperative TDE videos showed variable patterns of lesion progression after laser activation. Ablations tended to be slower for targets with increased preoperative T2 MRI signal and in close proximity to large, surrounding CSF spaces. In addition, greater laser energy was required to ablate mesial versus lateral mesiotemporal structures, an effect associated with laser trajectory and target contrast-enhanced T1 MRI signal.ConclusionsPatient-specific variations in mesiotemporal anatomy and pathology may influence the thermal coagulation of these tissues. We speculate that by incorporating demographic and imaging data into predictive models we may eventually enhance the accuracy and precision with which LITT is delivered, improving outcomes and accelerating adoption of this novel tool.

Functional connectivity of hippocampal subregions in PTSD: relations with symptoms

BackgroundPosttraumatic stress disorder (PTSD) is associated with abnormal hippocampal activity; however, the functional connectivity (FC) of the hippocampus with other brain regions in PTSD and its relations with symptoms warrants further attention. We investigated subregional hippocampal FC in PTSD during a resting state compared with a trauma-exposed control (TEC) group. Based on extant research, we targeted the FCs of the anterior and posterior hippocampal subregions with the amygdala, medial prefrontal cortex (mPFC), and the posterior cingulate (PCC).MethodsResting-state functional magnetic resonance images were acquired from 11 individuals with PTSD and 13 trauma-exposed controls. Anterior and posterior hippocampal FC was compared between groups. Within the PTSD and TEC groups, subregional hippocampal FC was correlated with scores on the Clinician-Administered PTSD Scale (CAPS) at time of scan and 4 months post-scan.ResultsThose with PTSD had significantly greater FC compared with the TEC group between the left posterior hippocampus and the bilateral PCC (g’s > .96). Direct contrasts of the Fisher z-transformed coefficients indicated that the correlations between CAPS scores 4 months post scan and the FC between the left hippocampal head and the right PCC (z = − 2.07, p = .039) as well as the FC between the right hippocampal tail and the right mPFC (z = − 2.19, p = .029) were significantly greater in the PTSD group compared to the TEC group.ConclusionsThese results support between-group differences in posterior hippocampal FC and different relations with PTSD future symptoms, underscoring associations with the anterior and posterior hippocampus. These findings enrich our understanding of PTSD pathophysiology and provide support for future investigations of imaging biomarkers predictive of disease progression.

Results of the radiation dose of head, body and tail of hippocampus in nasopharyngeal carcinoma patients treated with intensity modulated radiotherapy

This study is to analyze the radiation dose of head, body and tail of hippocampus (HC) of nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT). Evaluate cognitive function of patients with Wechsler adult intelligence scale-Chinese revised (WAIS-CR). HC were segmented into HC head (HH), HC body (HB) and HC tail (HT) and the indexes were then analyzed. WAIS-CR was tested before and 3months after radiotherapy. The mean radiation dose of left and right HC was (1147 ± 976)cGy, (1011 ± 602)cGy respectively. The radiation dose and the volume exposed in different dose of HH, HB and HT decreased in turn. For 5 patients, before and after radiotherapy, the regular-order score was 8.60 ± 1.34, 8.0 ± 1.00 (P = 0.43), while the reverse-order score was 5.80 ± 0.84, 5.20 ± 0.84 (P = 0.07). The radiation dose of HH, HB and HT was different, and the radiation dose of HH was the highest, which should be emphasized especially.

Automated trajectory planning for laser interstitial thermal therapy in mesial temporal lobe epilepsy

SummaryObjectiveSurgical resection of the mesial temporal structures brings seizure remission in 65% of individuals with drug‐resistant mesial temporal lobe epilepsy (MTLE). Laser interstitial thermal therapy (LiTT) is a novel therapy that may provide a minimally invasive means of ablating the mesial temporal structures with similar outcomes, while minimizing damage to the neocortex. Systematic trajectory planning helps ensure safety and optimal seizure freedom through adequate ablation of the amygdalohippocampal complex (AHC). Previous studies have highlighted the relationship between the residual unablated mesial hippocampal head and failure to achieve seizure freedom. We aim to implement computer‐assisted planning (CAP) to improve the ablation volume and safety of LiTT trajectories.MethodsTwenty‐five patients who had previously undergone LiTT for MTLE were studied retrospectively. The EpiNav platform was used to automatically generate an optimal ablation trajectory, which was compared with the previous manually planned and implemented trajectory. Expected ablation volumes and safety profiles of each trajectory were modeled. The implemented laser trajectory and achieved ablation of mesial temporal lobe structures were quantified and correlated with seizure outcome.Results CAP automatically generated feasible trajectories with reduced overall risk metrics (P < .001) and intracerebral length (P = .007). There was a significant correlation between the actual and retrospective CAP‐anticipated ablation volumes, supporting a 15 mm diameter ablation zone model (P < .001). CAP trajectories would have provided significantly greater ablation of the amygdala (P = .0004) and AHC (P = .008), resulting in less residual unablated mesial hippocampal head (P = .001), and reduced ablation of the parahippocampal gyrus (P = .02).SignificanceCompared to manually planned trajectories CAP provides a better safety profile, with potentially improved seizure‐free outcome and reduced neuropsychological deficits, following LiTT for MTLE.

Protracted hippocampal development is associated with age-related improvements in memory during early childhood

The hippocampus is a structure that is critical for memory. Previous studies have shown that age-related differences in specialization along the longitudinal axis of this structure (i.e., subregions) and within its internal circuitry (i.e., subfields) relate to age-related improvements in memory in school-age children and adults. However, the influence of age on hippocampal development and its relations with memory ability earlier in life remains under-investigated. This study examined effects of age and sex on hippocampal subregion (i.e., head, body, tail) and subfield (i.e., subiculum, CA1, CA2-4/DG) volumes, and their relations with memory, using a large sample of 4- to 8-year-old children. Results examining hippocampal subregions suggest influences of both age and sex on the hippocampal head during early childhood. Results examining subfields within hippocampal head suggest these age effects may arise from CA1, whereas sex differences may arise from subiculum and CA2-4/DG. Memory ability was not associated with hippocampal subregion volume but was associated with subfield volume. Specifically, within the hippocampal head, relations between memory and CA1 were moderated by age; in younger children bigger was better, whereas in older children smaller was superior. Within the hippocampal body, smaller CA1 and larger CA2-4/DG contributed to better memory performance across all ages. Together, these results shed light on hippocampal development during early childhood and support claims that the prolonged developmental trajectory of the hippocampus contributes to memory development early in life.

Conscious control of breathing: A key to prevention of sudden unexpected death in epilepsy?

Conscious control of breathing: A key to prevention of sudden unexpected death in epilepsy?

Hippocampal shape alterations in healthy young women with familial risk for unipolar depression

BackgroundAlthough reduced hippocampal volume (HCV) is a common finding in depression, it is unclear whether the structural alterations leading to reduction of HCV are pre-existing risk factors before the onset of clinical symptoms or a cumulative process that begins with the onset of clinical symptoms. The aim of the present study was to understand the anatomical status of the hippocampus prior to the clinical symptoms in subjects with high familial risk for depression. MethodsTwenty-seven young women (mean age: 22.3 ± 2.1 years) who were at high risk for familial unipolar depression and 26 age- and gender-matched healthy controls (mean age: 22.1 ± 2.1 years) with low familial risk for depression were included in the study. Total hippocampal volumes were measured by manual tracing. For 3D shape differences, the spherical harmonic basis functions (SPHARM) software was used. The segmented images were parameterized, and the point-to-point based group difference was compared by the Hotelling's T-squared test with total brain volume and Beck Depression Scale as covariates. ResultsAlthough there was no difference in overall HCVs, shape analyses revealed a contracted area on the Cornu Ammonis (CA) 1 region of the right hippocampus head in the high-risk group compared to the low-risk group. Cross-sectional design and small sample size, including only females, were the main limitations of this study. ConclusionThis study with shape analyses provided data suggesting that local structural hippocampal alterations in the CA1 region might be associated with depression vulnerability in women at high risk.

External cortical landmarks for localization of the hippocampus: Application for temporal lobectomy and amygdalohippocampectomy.

Background:Accessing the hippocampus for amygdalohippocampectomy and minimally invasive procedures, such as depth electrode placement, require an accurate knowledge regarding the location of the hippocampus.Methods:The authors removed 10 human cadaveric brains from the cranium and observed the relationships between the lateral temporal neocortex and the underlying hippocampus. They then measured the distance between the hippocampus and superficial landmarks. The authors also validated their study using magnetic resonance imaging (MRI) scans of 10 patients suffering from medial temporal lobe sclerosis where the distance from the hippocampal head to the anterior temporal tip was measured.Results:In general, the length of the hippocampus was along the inferior temporal sulcus and inferior aspect of the middle temporal gyrus. Although the hippocampus tended to be more superiorly located in female specimens and on the left side, this did not reach statistical significance. The length of the hippocampus tended to be shorter in females, but this too failed to reach statistical significance. The mean distance from the anterior temporal tip to the hippocampal head was identical in the cadavers and MRIs of patients with medial temporal lobe sclerosis.Conclusions:Additional landmarks for localizing the underlying hippocampus may be helpful in temporal lobe surgery. Based on this study, there are relatively constant anatomical landmarks between the hippocampus and overlying temporal cortex. Such landmarks may be used in localizing the hippocampus during amygdalohippocampectomy and depth electrode implantation in verifying the accuracy of image-guided methods and as adjuvant methodologies when these latter technologies are not used or are unavailable.

Sex-specific hippocampus volume changes in obstructive sleep apnea.

IntroductionObstructive sleep apnea (OSA) patients show hippocampal-related autonomic and neurological symptoms, including impaired memory and depression, which differ by sex, and are mediated in distinct hippocampal subfields. Determining sites and extent of hippocampal sub-regional injury in OSA could reveal localized structural damage linked with OSA symptoms.MethodsHigh-resolution T1-weighted images were collected from 66 newly-diagnosed, untreated OSA (mean age ± SD: 46.3 ± 8.8 years; mean AHI ± SD: 34.1 ± 21.5 events/h;50 male) and 59 healthy age-matched control (46.8 ± 9.0 years;38 male) participants. We added age-matched controls with T1-weighted scans from two datasets (IXI, OASIS-MRI), for 979 controls total (426 male/46.5 ± 9.9 years). We segmented the hippocampus and analyzed surface structure with “FSL FIRST” software, scaling volumes for brain size, and evaluated group differences with ANCOVA (covariates: total-intracranial-volume, sex; P < .05, corrected).ResultsIn OSA relative to controls, the hippocampus showed small areas larger volume bilaterally in CA1 (surface displacement ≤0.56 mm), subiculum, and uncus, and smaller volume in right posterior CA3/dentate (≥ − 0.23 mm). OSA vs. control males showed higher bilateral volume (≤0.61 mm) throughout CA1 and subiculum, extending to head and tail, with greater right-sided increases; lower bilateral volumes (≥ − 0.45 mm) appeared in mid- and posterior-CA3/dentate. OSA vs control females showed only right-sided effects, with increased CA1 and subiculum/uncus volumes (≤0.67 mm), and decreased posterior CA3/dentate volumes (≥ − 0.52 mm). Unlike males, OSA females showed volume decreases in the right hippocampus head and tail.ConclusionsThe hippocampus shows lateralized and sex-specific, OSA-related regional volume differences, which may contribute to sex-related expression of symptoms in the sleep disorder. Volume increases suggest inflammation and glial activation, whereas volume decreases suggest long-lasting neuronal injury; both processes may contribute to dysfunction in OSA.

Unfolding the hippocampus: An intrinsic coordinate system for subfield segmentations and quantitative mapping

The hippocampus, like the neocortex, has a morphological structure that is complex and variable in its folding pattern, especially in the hippocampal head. The current study presents a computational method to unfold hippocampal grey matter, with a particular focus on the hippocampal head where complexity is highest due to medial curving of the structure and the variable presence of digitations. This unfolding was performed on segmentations from high-resolution, T2-weighted 7T MRI data from 12 healthy participants and one surgical patient with epilepsy whose resected hippocampal tissue was used for histological validation. We traced a critical image feature composed of the hippocampal sulcus and stratum radiatum lacunosum-moleculare, (SRLM) in these images, then employed user-guided semi-automated techniques to detect and subsequently unfold the surrounding hippocampal grey matter. This unfolding was performed by solving Laplace's equation in three dimensions of interest (long-axis, proximal-distal, and laminar). The resulting ‘unfolded coordinate space’ provides an intuitive way of mapping the hippocampal subfields in 2D space (long-axis and proximal-distal), such that similar borders can be applied in the head, body, and tail of the hippocampus independently of variability in folding. This unfolded coordinate space was employed to map intracortical myelin and thickness in relation to subfield borders, which revealed intracortical myelin differences that closely follow the subfield borders used here. Examination of a histological resected tissue sample from a patient with epilepsy reveals that our unfolded coordinate system has biological validity, and that subfield segmentations applied in this space are able to capture features not seen in manual tracing protocols.

Higher Anxiety Symptoms Predict Progressive Hippocampal Atrophy in the Chronic Stages of Moderate to Severe Traumatic Brain Injury

Background. In the chronic stages of moderate-severe traumatic brain injury (TBI), progressive hippocampal volume loss—continuing well after acute neurological insults have resolved—has now been well documented. Previous research in other populations suggests that elevated anxiety symptoms are associated with compromise to the medial temporal lobes. Objective. To examine whether higher anxiety symptoms predict greater hippocampal volume loss in moderate-severe TBI. Methods. We conducted an analysis of prospectively collected, longitudinal behavioral and magnetic resonance imaging (MRI) data from 5 to 12 to 30 months post-injury. Eighty participants were included in the study, with anxiety symptom and MRI data collected at a minimum of 2 time points. Correlational and bivariate latent difference score (with imputation) analyses were used to examine the relationship of Beck Anxiety Inventory scores with hippocampal volume loss, while controlling for depressive symptoms and total brain volume. Results. Analyses revealed that higher anxiety symptoms at 5 and at 12 months following moderate-severe TBI predicted significant later volume loss in the right hippocampal complex and the right hippocampal head. Right hippocampal volume and volume change did not predict subsequent anxiety scores or anxiety change scores. Conclusions. These novel findings implicate anxiety symptoms as a possible predictor of progressive hippocampal volume loss in the chronic stages of moderate-severe TBI.

Memory and the hippocampal formation following pediatric traumatic brain injury.

IntroductionPrevious research indicates disruption of learning and memory in children who have experienced traumatic brain injury (TBI).ObjectiveThis research evaluates the impact of pediatric TBI on volumetric differences along the long axis of the hippocampus, a region of the brain that is critical for explicit memory.MethodsStructural brain data and behavioral measures were collected 6 weeks following TBI or extracranial injury (EI), in children aged 8–15 years and from a group of age matched typically developing controls (TDC). Total hippocampal volume and hippocampal subregion volumes corresponding to hippocampal head, body, and tail were compared across groups and were examined in relation to verbal and visual memory.ResultsGroup differences were evident such that hippocampal body volume was found to be smaller for TBI and EI groups compared to the TDC group. Analysis restricted to the TBI group indicated that hippocampal head volume was associated with severity of injury. The relation between severity of injury and hippocampal head volume is particularly important considering results from our investigation of hippocampal volume‐to‐memory performance relations indicating positive correlations between hippocampal head volume and performance on memory measures for both the TBI group and the TDC group. Significant negative correlations between hippocampal body volume and memory were evident for the TBI group but not EI or TDC groups. Correlations between memory performance and hippocampal tail volume were not significant for the TBI or TDC groups, although for the EI group, a positive correlation was found between hippocampal tail volume and memory.ConclusionTogether these results underscore an important relation between hippocampal structure and memory function during the subacute stage of recovery from pediatric TBI.

Atrophy of the Posterior Subiculum Is Associated with Memory Impairment, Tau- and Aβ Pathology in Non-demented Individuals

Alzheimer’s disease (AD) is associated with atrophy of the cornu ammonis (CA) 1 and the subiculum subfield of the hippocampus (HC), and with deficits in episodic memory and spatial orientation. These deficits are mainly associated with the functionality of the posterior HC. We therefore hypothesized that key AD pathologies, i.e., β-amyloid and tau pathology would be particularly associated with the volume of the posterior subiculum in non-demented individuals. In our study we included 302 cognitively normal elderly participants (CN), 183 patients with subjective cognitive decline (SCD) and 171 patients with amnestic mild cognitive impairment (MCI), all of whom underwent 3T magnetic resonance images (MRI). The subicular subfield was segmented using Freesurfer 5.3 and divided into 10 volumetric segments moving from the most posterior (segment 1) to the most anterior part along the axis of the hippocampal head and body (segment 10). Cerebrospinal fluid (CSF) Aβ42 and phosphorylated tau (P-tau) were quantified using ELISA and were used as biomarkers for β-amyloid and tau pathology, respectively. In the total sample, tau-pathology and Aβ-pathology and (measured by elevated P-tau and low Aβ42 levels in CSF) and mild memory dysfunction were mostly associated with the volume changes of the posterior subiculum. Both SCD and MCI patients with elevated P-tau or low Aβ42 levels displayed predominantly posterior subicular atrophy in comparisons to control subjects with normal CSF biomarker levels. Finally, there was no main effect of Aβ42 or P-tau when comparing SCD with abnormal P-tau or Aβ42 with SCD with normal levels of these CSF-biomarkers. However, in the left subiculum there was a significant interaction revealing atrophy in the left posterior but not the anterior subiculum in participants with low Aβ42 levels. The same pattern was observed on the contralateral side in participants with elevated P-tau levels. In conclusion, AD pathologies and mild memory dysfunction are mainly associated with atrophy of the posterior parts of the subicular subfields of the HC in non-demented individuals. In light of these findings we suggest that segmentation of the HC subfields may benefit from considering the volume of the different anterior-posterior subsections of each subfield.