The case for a relationship between human memory, hippocampus and corpus callosum

Unilateral brain damage which includes the hippocampus leads to memory impairments consistent with hemispheric specialization on the same side. Damage to the corpus callosum, the major connecting pathway between the left and right hemispheres, also leads to memory impairments. This suggests both hemispheric specialization on the hippocampal level and a critical role for the corpus callosum in memory functions. A complete hippocampal formation is present on either side of the brain but traditionally only one is studied. However, a comparison between the neuronal populations in the hippocampus on both sides revealed asymmetry in connectivity among hippocampal subfields. The profile of memory impairments of commissurotomy (‘split-brain’) patients is described. The results are discussed in terms of a relationship between hippocampus and corpus callosum in humans. As hemispheric specialization evolved, inter-hippocampal connections became less important and the corpus callosum became prominent in memory functions

Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia

Context: Classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain. Objective: To characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH, compared to controls. Design: A cross-sectional study of 27 CAH youth (16 female; 12.6 ± 3.4 year) and 35 typically developing, healthy controls (20 female; 13.0 ± 2.8 year) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex, and nine amygdala and six hippocampal subregions. Between-subject effects of group (CAH vs control) and sex, and their interaction (group-by-sex) on brain volumes were studied, while controlling for intracranial volume (ICV) and group differences in body mass index and bone age. Results: CAH youth had smaller ICV and increased cerebrospinal fluid volume compared to controls. In fully-adjusted models, CAH youth had smaller bilateral, superior and caudal middle frontal volumes, and smaller left lateral orbito-frontal volumes compared to controls. Medial temporal lobe analyses revealed the left hippocampus was smaller in fully-adjusted models. CAH youth also had significantly smaller lateral nucleus of the amygdala and hippocampal subiculum and CA1 subregions. Conclusions: This study replicates previous findings of smaller medial temporal lobe volumes in CAH patients, and suggests that lateral nucleus of the amygdala, as well as subiculum and subfield CA1 of the hippocampus are particularly affected within the medial temporal lobes in CAH youth

Regional differentiation of neuron morphology in human left and right hippocampus: Comparing normal to schizophrenia

Regional differentiation based on size, form, and orientation angle of the soma of individual neurons in human post-mortem hippocampus was determined through correlations between pairs of hippocampal subfields in each side separately. The neurons were previously measured on a computer. In the normal cases, a left-right asymmetrical pattern of regional differentiation based on soma size emerged, while for form and orientation angle, the patterns appeared symmetrical. In schizophrenia, regional soma size, form, and orientation variability were expressed largely symmetrically. Regional correlations based on neuronal density revealed an asymmetrical hemispheric pattern in the normal cases versus a nearly symmetrical pattern in schizophrenia. Taken together, the inter-regional correlations favor a hippocampal landscape that deviates in each side from connectivity based on the canonical trisynaptic hippocampal circuitry. It is proposed that during morphogenesis, rudimentary inter-regional networks are formed through specific interactions between regional neurons; these networks are present in the adult hippocampus and may be vulnerable in brain diseases

Hippocampal subregion abnormalities in schizophrenia: A systematic review of structural and physiological imaging studies.

AimThe hippocampus is considered a key region in schizophrenia pathophysiology, but the nature of hippocampal subregion abnormalities and how they contribute to disease expression remain to be fully determined. This study reviews findings from schizophrenia hippocampal subregion volumetric and physiological imaging studies published within the last decade.MethodsThe PubMed database was searched for publications on hippocampal subregion volume and physiology abnormalities in schizophrenia and their findings were reviewed.ResultsThe main replicated findings include smaller CA1 volumes and CA1 hyperactivation in schizophrenia, which may be predictive of conversion in individuals at clinical high risk of psychosis, smaller CA1 and CA4/DG volumes in first-episode schizophrenia, and more widespread smaller hippocampal subregion volumes with longer duration of illness. Several studies have reported relationships between hippocampal subregion volumes and declarative memory or symptom severity.ConclusionsTogether these studies provide support for hippocampal formation circuitry models of schizophrenia. These initial findings must be taken with caution as the scientific community is actively working on hippocampal subregion method improvement and validation. Further improvements in our understanding of the nature of hippocampal formation subregion involvement in schizophrenia will require the collection of structural and physiological imaging data at submillimeter voxel resolution, standardization and agreement of atlases, adequate control for possible confounding factors, and multi-method validation of findings. Despite the need for cautionary interpretation of the initial findings, we believe that improved localization of hippocampal subregion abnormalities in schizophrenia holds promise for the identification of disease contributing mechanisms

Successful retrieval of competing spatial environments in humans involves hippocampal pattern separation mechanisms.

The rodent hippocampus represents different spatial environments distinctly via changes in the pattern of "place cell" firing. It remains unclear, though, how spatial remapping in rodents relates more generally to human memory. Here participants retrieved four virtual reality environments with repeating or novel landmarks and configurations during high-resolution functional magnetic resonance imaging (fMRI). Both neural decoding performance and neural pattern similarity measures revealed environment-specific hippocampal neural codes. Conversely, an interfering spatial environment did not elicit neural codes specific to that environment, with neural activity patterns instead resembling those of competing environments, an effect linked to lower retrieval performance. We find that orthogonalized neural patterns accompany successful disambiguation of spatial environments while erroneous reinstatement of competing patterns characterized interference errors. These results provide the first evidence for environment-specific neural codes in the human hippocampus, suggesting that pattern separation/completion mechanisms play an important role in how we successfully retrieve memories

Working memory learning method and astrocytes number in different subfields of rat's Hippocampus

The aim of this study was evaluation of the astrocytes number in different subfields of rat's Hippocampus after spatial learning with usage of Morris Water Maze technique and working memory method. In this study, between 2005-2006 years in Pasteur institute of Iran-Tehran and histological department of Gorgan University with usage of Morris Water Maze and working memory technique, we used 14 male albino wistar rats. Seventh rats were in control group and 7 rats in working memory group. After histological preparation, the slides were stained with PTAH staining for showing the Astrocytes. Present results showed significant difference in astrocytes number in CA1, CA2 and CA3 areas of hippocampus between control and reference memory group. The number of astrocytes is increased in working memory group. Then we divided the hippocampus to three parts: Anterior, middle and posterior and with compare of different area (CA1, CA2 and CA3) of hippocampus, we found that the differences between Anterior-middle and Middle-Posterior of CA1 and CA2 area of hippocampus were significant, whereas the difference between Anterior-Posterior parts was not significant in CA1 and CA2 areas. In CA3 area, the difference between Anterior-Middle and Anterior-Posterior parts was significant, whereas the difference between middle and posterior parts was not significant. We concluded that the number of astrocytes increased due to spatial learning and working memory technique. © 2008 Science Publications

Hippocampal subfields and limbic white matter jointly predict learning rate in older adults

First published online: 04 December 2019Age-related memory impairments have been linked to differences in structural brain parameters, including cerebral white matter (WM) microstructure and hippocampal (HC) volume, but their combined influences are rarely investigated. In a population-based sample of 337 older participants aged 61-82 years (Mage = 69.66, SDage = 3.92 years), we modeled the independent and joint effects of limbic WM microstructure and HC subfield volumes on verbal learning. Participants completed a verbal learning task of recall over five repeated trials and underwent magnetic resonance imaging (MRI), including structural and diffusion scans. We segmented three HC subregions on high-resolution MRI data and sampled mean fractional anisotropy (FA) from bilateral limbic WM tracts identified via deterministic fiber tractography. Using structural equation modeling, we evaluated the associations between learning rate and latent factors representing FA sampled from limbic WM tracts, and HC subfield volumes, and their latent interaction. Results showed limbic WM and the interaction of HC and WM-but not HC volume alone-predicted verbal learning rates. Model decomposition revealed HC volume is only positively associated with learning rate in individuals with higher WM anisotropy. We conclude that the structural characteristics of limbic WM regions and HC volume jointly contribute to verbal learning in older adults

Building a surface atlas of hippocampal subfields from high resolution T2-weighted MRI scans using landmark-free surface registration

The hippocampus is widely studied in neuroimaging field as it plays important roles in memory and learning. However, the critical subfield information is often not explored in most hippocampal studies. We previously proposed a method for hippocampal subfield morphometry by integrating FreeSurfer, FSL, and SPHARM tools. But this method had some limitations, including the analysis of T1-weighted MRI scans without detailed subfield information and hippocampal registration without using important subfield information. To bridge these gaps, in this work, we propose a new framework for building a surface atlas of hippocampal subfields from high resolution T2-weighted MRI scans by integrating state-of-the-art methods for automated segmentation of hippocampal subfields and landmark-free, subfield-aware registration of hippocampal surfaces. Our experimental results have shown the promise of the new framework

The preventive and treatment effect of Urtica dioica on astrocyte density in the CA1 and CA3 subfields of hippocampus in STZ induced diabetic rats

Several animal model studies have shown that Diabetes mellitus can affect on the activity of hippocampus astrocytes, but these studies reported controversial findings. This study was done to evaluate the preventive and treatment effect of Urtica dioica (U. dioica) on astrocytes density in the CA1 and CA3 subfields of hippocampus of streptozotocin (STZ) induced diabetic rats. Twenty-eight male albino Wistar rats were randomly allocated equally into control, diabetic, U. dioica treatment and U. dioica preventive groups. Hyperglycemia was induced by STZ (80 mg/kg/BW). One week after injection of the streptozotocin, animals in treatment group were received hydroalcoholic extract of U. dioica (100 mg/kg/BW /day) for 4 weeks by intraperitoneally. In preventive group, diabetic rats were received 100 mg/kg/BW/ daily hydroalcoholic extract of U. dioica for 5 days before STZ injection. Then, animals were sacrificed and coronal sections were taken from the right dorsal hippocampus, stained with PTAH. The area densities of the astrocytes were measured. The number of astrocytes in CA1 of controls, diabetic treatment and preventive groups was 19.00±5.5, 17.14±6.4, 21±8.1 and 16.48±3.2, respectively. The densities of astrocytes in CA3 of controls, diabetic, treatment and preventive groups were 25.45±7.60, 21.54±7.5, 23.75±5.6 and 19.89±3.8, respectively. The density of astrocytes in diabetic rats reduced in comparison with controls (P<0.05). In CA1 and CA3, in spite of preventive administration, treatment of diabetic rats with U. dioica significantly increased the astrocytes. This study showed that treatment with U. dioica extract can help compensate for the CA1 and CA3 subfields of hippocampus astrocytes in diabetic rats

Microstructural Alterations in Hippocampal Subfields Mediate Age-Related Memory Decline in Humans.

Aging, even in the absence of clear pathology of dementia, is associated with cognitive decline. Neuroimaging, especially diffusion-weighted imaging, has been highly valuable in understanding some of these changes in live humans, non-invasively. Traditional tensor techniques have revealed that the integrity of the fornix and other white matter tracts significantly deteriorates with age, and that this deterioration is highly correlated with worsening cognitive performance. However, traditional tensor techniques are still not specific enough to indict explicit microstructural features that may be responsible for age-related cognitive decline and cannot be used to effectively study gray matter properties. Here, we sought to determine whether recent advances in diffusion-weighted imaging, including Neurite Orientation Dispersion and Density Imaging (NODDI) and Constrained Spherical Deconvolution, would provide more sensitive measures of age-related changes in the microstructure of the medial temporal lobe. We evaluated these measures in a group of young (ages 20-38 years old) and older (ages 59-84 years old) adults and assessed their relationships with performance on tests of cognition. We found that the fiber density (FD) of the fornix and the neurite density index (NDI) of the fornix, hippocampal subfields (DG/CA3, CA1, and subiculum), and parahippocampal cortex, varied as a function of age in a cross-sectional cohort. Moreover, in the fornix, DG/CA3, and CA1, these changes correlated with memory performance on the Rey Auditory Verbal Learning Test (RAVLT), even after regressing out the effect of age, suggesting that they were capturing neurobiological properties directly related to performance in this task. These measures provide more details regarding age-related neurobiological properties. For example, a change in fiber density could mean a reduction in axonal packing density or myelination, and the increase in NDI observed might be explained by changes in dendritic complexity or even sprouting. These results provide a far more comprehensive view than previously determined on the possible system-wide processes that may be occurring because of healthy aging and demonstrate that advanced diffusion-weighted imaging is evolving into a powerful tool to study more than just white matter properties