Biology subjects

Insausti, R.

Publications and source records attributed to Insausti, R..

5 recordsLinked to original sources

bioRxiv2025

Harmonized Protocol for Subfield Segmentation in the Hippocampal Body on High-Resolution in vivo MRI from the Hippocampal Subfields Group (HSG)

Hippocampal subfields differentially develop and age, and they vary in vulnerability to neurodegenerative diseases. Innovation in high-resolution imaging has accelerated clinical research on human hippocampal subfields, but substantial differences in segmentation protocols impede comparisons of results across laboratories. The Hippocampal Subfields Group (HSG) is an international organization seeking to address this issue by developing a histologically-valid, reliable, and freely available segmentation protocol for high-resolution T2-weighted 3 tesla MRI (http://www.hippocampalsubfields.com). Here, we report the first portion of the protocol focused on subfields in the hippocampal body; protocols for the head and tail are in development. The body protocol includes definitions of the internal boundaries between subiculum, Cornu Ammonis (CA) 1-3 subfields, and dentate gyrus, in addition to the external boundaries of the hippocampus apart from surrounding white matter and cerebrospinal fluid. The segmentation protocol is based on a novel histological reference data set labeled by multiple expert neuroanatomists. With broad participation of the research community, we voted on the segmentation protocol via online survey, which included detailed protocol information, feasibility testing, demonstration videos, example segmentations, and labeled histology. All boundary definitions were rated as having high clarity and reached consensus agreement by Delphi procedure. The harmonized body protocol yielded high inter- and intra-rater reliability. In the present paper we report the procedures to develop and test the protocol, as well as the detailed procedures for manual segmentation using the harmonized protocol. The harmonized protocol will significantly facilitate cross-study comparisons and provide increased insight into the structure and function of hippocampal subfields across the lifespan and in neurodegenerative diseases.

neuroscience↗

bioRxiv2025

Developing an anatomically valid segmentation protocol for anterior regions of the medial temporal lobe for neurodegenerative diseases

BackgroundThe anterior portion of the medial temporal lobe (MTL) is one of the first regions targeted by pathology in sporadic Alzheimers disease (AD) and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) indicating a potential for metrics from this region to serve as imaging biomarkers. Leveraging a unique post-mortem dataset of histology and magnetic resonance imaging (MRI) scans we aimed to 1) develop an anatomically valid segmentation protocol for anterior entorhinal cortex (ERC), Brodmann Area (BA) 35, and BA36 for in vivo 3 tesla (T) MRI and 2) incorporate this protocol in an automated approach. MethodsWe included 20 cases (61-97 years old, 50% females) with and without neurodegenerative diseases (11 vs. 9 cases) to ensure generalizability of the developed protocol. Digitized MTL Nissl-stained coronal histology sections from these cases were annotated and registered to same-subject post-mortem MRI. The protocol was developed by determining the location of histological borders of the MTL cortices in relation to anatomical landmarks. Subsequently the protocol was applied to 15 cases twice, with a 2-week interval, to assess intra-rater reliability with the Dice Similarity Index (DSI). Thereafter it was implemented in our in- house Automatic Segmentation of Hippocampal Subfields (ASHS)-T1 approach and evaluated with DSIs. ResultsThe anterior histological border distances of ERC, BA35 and BA36 were evaluated with respect to various anatomical landmarks and the distance relative to the beginning of the hippocampus was chosen. To formulate segmentation rules, we examined the histological sections for the location of borders in relationship to anatomical landmarks in the coronal sections. The DSI for the anterior MTL cortices for the intra-rater reliability was 0.85-0.88 and for the ASHS-T1 against the manual segmentation was 0.62-0.65. DiscussionWe developed a reliable segmentation protocol and incorporated it in an automated approach. Given the vulnerability of the anterior MTL cortices to tau deposition in AD and LATE, the updated approach is expected to improve imaging biomarkers for these diseases.

neuroscience↗

bioRxiv2024

Anatomy, histology and ultrastructure of the adult human olfactory peduncle: blood vessel and corpora amylacea assessment

The mammalian olfactory system is responsible for processing volatile chemical stimuli and is composed of several structures including the olfactory epithelium, olfactory bulb, olfactory peduncle (OP), and olfactory cortices. Despite the critical role played by the OP in the transport of information it has remained understudied. In this work, optical, confocal, and electron microscopy were employed to examine the anatomy, histology, and ultrastructure of six human OP specimens (ages 37-84 years). Three concentric layers were identified in coronal sections: the external layer (EL), the axonal layer (AL), and the internal layer (IL). Immunohistochemistry revealed the distribution of neurons and glial cells throughout the OP. Two neuronal morphologies were observed: granule cells and larger pyramidal cells, the latter associated with projection neurons of the anterior olfactory nucleus. Astrocytes were uniformly distributed with a more radial morphology in the EL. Oligodendrocytes were mainly located in the AL. Blood vessels (BVs) were evenly distributed along the OP, with a mean luminal area of 82.9 {micro}m{superscript 2} and a density of 1.26 %, with a significant increase in the IL. CA were abundant, with an average size of 49.3 {micro}m{superscript 2} and a density of 3.23 %. CA clustered near BVs, particularly at tissue edges, with both size and density increasing with age. Notably, CA showed strong associations with astrocytes. This study provides the first detailed qualitative and quantitative data on the internal organization of the human OP, which may contribute to a better understanding of the pathophysiology of some neuropathological disorders.

neuroscience↗

bioRxiv2023

Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories

The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimers disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the cortices that make up the parahippocampal gyrus (entorhinal and parahippocampal cortices) and the adjacent Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 {micro}m thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized (20X resolution) slices with 5 mm spacing. Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed more gradually. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed human neuroimaging research on the MTL cortex.

neuroscience↗

bioRxiv2019

Pathological and non-pathological aging, SAMP8 and SAMR1. What do hippocampal neuronal populations tell us?

Alterations of cognitive processes and memory are one of the most important manifestations related to aging. However, not all memory types are affected in the same way. Learning and spatial memory are susceptible to these changes. The hippocampus represents the anatomical substrate of this type of memory, affected by structural and functional alterations along the normal aging and neurological diseases such as Alzheimers disease, Parkinsons, schizophrenia and epilepsy. Some of the alterations related to aging are associated with alterations in the hippocampal interneuron populations and with an increase in excitability in the hippocampal circuit.\n\nIn order to understand better the underlying processes in normal and pathological aging mechanisms, a murine model (Senescence-Accelerated Mouse Prone, SAMP8) and its respective controls (Senescence-Accelerated Mouse Resistant, SAMR1) have been used. While SAMP8 is a naturally occurring mouse line that displays a phenotype of accelerated aging with learning and memory impairment and these changes of learning and memory might be linked to some alterations in neuronal populations of the hippocampus. Thus, we analyzed the distribution and density of PV, CR and STT interneurons in the hippocampus of young and old mice as well as possible morphological and cholinergic changes in hippocampal formation. Comparing SAMR1 and SAMP8 we did not find any neural population that was specifically affected by aging in both groups. Interestingly, CR immunoreactivity and STT immunoreactivity showed changes in SAMP8 mice when they were compared to their controls. In SAMP8 CR+ and STT+ neurons decreased significantly along aging which suggests that CR and STT interneurons play a more important role than PV neurons in the pathological aging of the brain. In the case of SAMP8 mice the neural changes might be related to changes of the cholinergic system that might be affecting the wiring into the hippocampus formation through the perforant pathway. Further studies of this local circuitry will help to comprehend better how different inputs into these neural populations of the hippocampus could be affecting the development of neurodegerative diseases.

neuroscience↗