Biology subjects

Keresztes, A.

Publications and source records attributed to Keresztes, A..

10 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↗

bioRxiv2024

Neocortical differentiation and hippocampal integration of non-meaningful items and their spatial location

Computational theories of memory posit that the dentate gyrus and CA3 (CA3DG) hippocampal subfields reduce mnemonic interference via a process called pattern separation. While the CA3DG is viewed as a domain-general pattern separator, the parahippocampal and perirhinal cortices may play a role in content-specific (e.g., spatial or object-related) interference reduction. Recent work highlighted the role of frontal and parietal control areas in allocating resources during mnemonic discrimination, but the interactions between the medial temporal lobe and frontoparietal regions have been rarely studied. Moreover, mnemonic discrimination tasks designed for humans almost exclusively use everyday items as stimuli, confounding retrieval processes with pattern separation. To address these challenges we acquired high-resolution structural images of the medial temporal lobe, and full-brain high-resolution functional MRI data of 39 participants while they studied non-meaningful fractals with varying degrees of interference in either their spatial or object features. We found that the parahippocampal cortex contributes to interference reduction in the spatial domain, while the perirhinal cortex contributes to interference reduction in the object domain. The dorsolateral frontal and parietal regions were recruited during the encoding of interfering stimuli in both object and location domains, and displayed strengthened within- and cross-network connectivity in response to interference. Contrary to our expectations, we did not find significantly increased activation in the CA3DG to similar trials relative to repeats, indicating a lack of sensitivity to small differences in interfering stimuli. Altogether, these results are in line with content-specific interference reduction in the medial temporal lobe, possibly orchestrated by frontoparietal regions, but challenge the view of the CA3DG as the universal pattern separator of the human brain.

neuroscience↗

bioRxiv2023

A (Sub)field Guide to Quality Control in Hippocampal Subfield Segmentation on High-resolution T2-weighted MRI

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements. Despite its importance, there is little guidance on best QC practices and reporting procedures. The study of hippocampal subfields in vivo is a critical case for QC because of their small size, inter-dependent boundary definitions, and common artifacts in the MRI data used for subfield measurements. We addressed this gap by surveying the broader scientific community studying hippocampal subfields on their views and approaches to QC. We received responses from 37 investigators spanning 10 countries, covering different career stages, and studying both healthy and pathological development and aging. In this sample, 81% of researchers considered QC to be very important or important, and 19% viewed it as fairly important. Despite this, only 46% of researchers reported on their QC processes in prior publications. In many instances, lack of reporting appeared due to ambiguous guidance on relevant details and guidance for reporting, rather than absence of QC. Here, we provide recommendations for correcting errors to maximize reliability and minimize bias. We also summarize threats to segmentation accuracy, review common QC methods, and make recommendations for best practices and reporting in publications. Implementing the recommended QC practices will collectively improve inferences to the larger population, as well as have implications for clinical practice and public health.

neuroscience↗

bioRxiv2023

Multi-night EEG reveals positive association between sleep efficiency and hippocampal subfield volumes in healthy aging

Age-related atrophy of the human hippocampus and the enthorinal cortex starts accelerating at around age 60. Due to the contributions of these regions to many cognitive functions seamlessly used in everyday life, this can heavily impact the lives of elderly people. The hippocampus is not a unitary structure and mechanisms of its age-related decline appear to differentially affect its subfields. Human and animal studies have suggested that altered sleep is associated with hippocampal atrophy. Yet, we know little about subfield specific effects of altered sleep in healthy aging and their effect on cognition. Here, in a sample of 118 older adults (Mage = 63.25 years), we examined the association between highly reliable hippocampal subfield volumetry, sleep measures derived from multi-night recordings of portable electroencephalography and episodic memory. Objective sleep efficiency - but not self-report measures of sleep - was associated with entorhinal cortex volume when controlling for age. Age-related differences in subfield volumes were associated with objective sleep efficiency, but not with self-report measures of sleep. Moreover, older adults characterized by a common multivariate pattern of subfield volumes that contributed to positive sleep- subfield volume associations, showed lower rates of forgetting. Our results showcase the benefit of objective sleep measures in identifying potential contributors of age-related differences in brain-behavior couplings.

neuroscience↗

bioRxiv2023

Terpenes from Cannabis sativa Induce Antinociception in Mouse Chronic Neuropathic Pain via Activation of Spinal Cord Adenosine A2A Receptors

Terpenes are small hydrocarbon compounds that impart aroma and taste to many plants, including Cannabis sativa. A number of studies have shown that terpenes can produce pain relief in various pain states in both humans and animals. However, these studies were methodologically limited and few established mechanisms of action. In our previous work, we showed that the terpenes geraniol, linalool, {beta}-pinene, - humulene, and {beta}-caryophyllene produced cannabimimetic behavioral effects via multiple receptor targets. We thus expanded this work to explore the efficacy and mechanism of these Cannabis terpenes in relieving chronic pain. We first tested for antinociceptive efficacy by injecting terpenes (200 mg/kg, IP) into male and female CD- 1 mice with chemotherapy-induced peripheral neuropathy (CIPN) or lipopolysaccharide-induced inflammatory pain, finding that the terpenes produced roughly equal efficacy to 10 mg/kg morphine or 3.2 mg/kg WIN55,212. We further found that none of the terpenes produced reward as measured by conditioned place preference, while low doses of terpene (100 mg/kg) combined with morphine (3.2 mg/kg) produced enhanced antinociception vs. either alone. We then used the adenosine A2A receptor (A2AR) selective antagonist istradefylline (3.2 mg/kg, IP) and spinal cord-specific CRISPR knockdown of the A2AR to identify this receptor as the mechanism for terpene antinociception in CIPN. In vitro cAMP and binding studies and in silico modeling studies further suggested that the terpenes act as A2AR agonists. Together these studies identify Cannabis terpenes as potential therapeutics for chronic neuropathic pain, and identify a receptor mechanism in the spinal cord for this activity.

neuroscience↗

bioRxiv2021

Longitudinal developmental trajectories do not follow cross-sectional age associations in hippocampal subfield and memory development

Many cross-sectional findings suggest that volumes of specific hippocampal subfields increase in middle childhood and early adolescence. In contrast, a small number of available longitudinal studies observed decreased volumes in most subfields over this age range. Further, it remains unknown whether structural changes in development are associated with corresponding gains in childrens memory. Here we report cross-sectional age differences in childrens hippocampal subfield volumes together with longitudinal developmental trajectories and their relationships with memory performance. In two waves, 109 healthy participants aged 6 to 10 years (wave 1: MAge=7.25, wave 2: MAge=9.27) underwent high-resolution magnetic resonance imaging to assess hippocampal subfield volumes, and completed cognitive tasks assessing hippocampus dependent memory processes. We found that cross-sectional age-associations and longitudinal developmental trends in hippocampal subfield volumes were highly discrepant, both by subfields and in direction. Further, volumetric changes were largely unrelated to changes in memory, with the exception that increase in subiculum volume was associated with gains in spatial memory. Importantly, the observed longitudinal patterns of brain-cognition coupling could not be inferred from cross-sectional findings. We discuss potential sources of these discrepancies. This study underscores that childrens structural brain development and its relationship to cognition cannot be inferred from cross-sectional age comparisons. HighlightsO_LIThe subiculum undergoes volumetric increase between 6-10 years of age C_LIO_LIChange across two years in CA1-2 and DG-CA3 was not observed in this age window C_LIO_LIChange across two years did not reflect age differences spanning two years C_LIO_LICross-sectional and longitudinal slopes in stark contrast for hippocampal subfields C_LIO_LILongitudinal brain-cognition coupling cannot be inferred from cross-sectional data C_LI

neuroscience↗

bioRxiv2021

Age-related declines in neural selectivity manifest differentially during encoding and recognition

The authors have withdrawn the preprint due to two errors in the analyses: The first error was a failure to account for three dummy volumes (TR = 2s) collected at the beginning of each experimental run. The second error was a coding error related to the definition of the category-selective clusters. Since correcting for these errors drastically altered the results and conclusions of this paper, the authors have withdrawn the preprint and retracted the published paper (https://doi.org/10.1016/j.neurobiolaging.2021.12.001). A report comparing original and corrected results can be found on https://osf.io/7n3mz/. If you have any questions please contact the corresponding author (sander@mpib-berlin.mpg.de).

neuroscience↗

bioRxiv2020

Cannabis sativa Terpenes are Cannabimimetic and Provide Support for the Entourage Effect Hypothesis

Limited evidence has suggested that terpenes found in Cannabis sativa are analgesic, and could produce an "entourage effect" whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence. We thus investigated Cannabis sativa terpenes alone and with the cannabinoid agonist WIN55,212 using in vitro and in vivo approaches. We found that the terpenes -humulene, geraniol, linalool, and {beta}-pinene produced cannabinoid tetrad behaviors in mice, suggesting cannabimimetic activity. Some behaviors could be blocked by cannabinoid or adenosine receptor antagonists, suggesting a mixed mechanism of action. These behavioral effects were additive with WIN55,212, providing support for a terpene "entourage effect." In vitro experiments showed that all terpenes activated the CB1R, while some activated other targets. Our findings suggest that these Cannabis terpenes are multifunctional cannabimimetic ligands that provide support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids.

pharmacology and toxicology↗

bioRxiv2020

Tracking age differences in neural distinctiveness across representational levels

The authors have withdrawn the preprint due to two errors in the analyses: The first error was a failure to account for three dummy volumes (TR = 2s) collected at the beginning of each experimental run. The second error was a coding error related to the definition of the category-selective clusters. Since correcting for these errors drastically altered the results and conclusions of this paper, the authors have withdrawn the preprint and retracted the published paper. More information as well as a report comparing original and corrected results can be found on https://osf.io/t8dpv/. If you have any questions please contact the corresponding author (sander@mpib-berlin.mpg.de).

neuroscience↗

bioRxiv2019

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

Age-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 61-82 years of age (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 over five learning 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, as well as 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 levels of WM anisotropy. We conclude that structural characteristics of limbic WM regions and HC volume jointly contribute to verbal learning in older adults.

neuroscience↗