Biology subjects

Dalton, M. A.

Publications and source records attributed to Dalton, M. A..

11 recordsLinked to original sources

bioRxiv2025

Reorganisation of Cortico-Hippocampal White Matter Pathways in Healthy Ageing: Evidence for Paradoxical Shifts in Structural Connectivity.

The hippocampus plays a central role in episodic memory and has been the focus of extensive research over past decades. A substantial body of work has demonstrated that age-related memory decline is linked to changes in how the hippocampus functionally interacts with distributed brain networks. While functional connectivity changes in ageing are well documented, relatively little is known about alterations in the structural connectivity (SC) of the hippocampus, despite its foundational role in supporting communication across neural systems. In this study, we combined high-quality data from the Human Connectome Project and advanced diffusion-weighted imaging (DWI) methods to investigate age-related changes in hippocampal SC. Using a recently developed tractography pipeline that allows greater anatomical specificity than conventional approaches, we systematically compared connectivity patterns between younger (26-30 years) and older (56-60 years) adults. Results revealed reduced hippocampal SC with the entorhinal cortex and medial parietal cortices in older participants, alongside increased SC with anterior temporal areas. This paradoxical pattern suggests that ageing is associated with both vulnerability and reorganisation of hippocampal networks, with increased hippocampal-temporal connectivity potentially reflecting compensatory plasticity in response to reduced posterior medial connection. These findings provide in vivo evidence of cortico-hippocampal structural reorganisation in late middle age, a critical period when pathological processes such as tau deposition are already detectable in cognitively healthy individuals. More broadly, they demonstrate the power of our anatomically refined tractography pipeline as a proof of concept for detecting subtle, regionally specific changes in hippocampal pathway density. This approach holds promise for charting normative ageing trajectories and identifying early biomarkers of vulnerability and compensation in memory-related networks.

neuroscience↗

bioRxiv2025

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

The hippocampus is a heterogeneous structure with cytoarchitectonically distinct subfields that exhibit heterogeneous lifespan trajectories and are differentially susceptible to diseases. Advances in high-resolution imaging have accelerated research on these structures, yet variability in segmentation protocols limits cross-study comparability. The Hippocampal Subfields Group (HSG) is an international consortium addressing this challenge by developing a reliable, accessible, and freely available segmentation protocol for high-resolution T2-weighted 3 tesla MRI scans (http://www.hippocampalsubfields.com). Here, we present the harmonized protocol for the posterior portion of the hippocampus (the "tail"), complementing the previously established "body" protocol, and with an anterior "head" protocol under development. The tail protocol provides standardized definitions of the external boundaries for the posterior-most extent of the hippocampus, facilitating consistent segmentation from surrounding tissues. The research community was extensively involved through an online survey that incorporated comprehensive protocol details, feasibility assessments, tutorial videos, and illustrative segmentations. Through this collaborative process, consensus emerged to exclude subfield labeling in the hippocampal tail due to limited visibility of internal landmarks and substantial anatomical variability in this region. All proposed boundary guidelines were deemed clear and agreed upon via a Delphi procedure. The harmonized tail protocol has high intra-(Averaged ICC(2,1) > 0.98; Averaged Dice Similarity Coefficient = 0.92) and inter-rater reliability (Averaged ICC(2,k) > 0.98; Averaged Dice Similarity Coefficient = 0.86) and offers a practical framework for replicable segmentation. By establishing standardized guidelines, this protocol enhances comparability of findings across developmental, aging, and clinical research and is compatible with ongoing technological advances.

neuroscience↗

bioRxiv2025

Disentangling structure-function relationships between the human hippocampus and the whole brain using track-weighted dynamic functional connectivity.

Understanding how structural and functional connectivity shape hippocampal interactions with the rest of the brain is critical for elucidating its role in cognition. Here, we combine high-resolution diffusion MRI, a novel fibre-tracking pipeline designed to specifically probe anatomical connectivity of the in vivo human hippocampus, and track-weighted dynamic functional connectivity (TW-dFC) to investigate how direct anatomical connections between the hippocampus and the rest of the brain relate to time-varying functional interactions. In Study 1, TW-dFC maps were computed for 10 participants from the Human Connectome Project and subjected to ICA and k-means clustering to derive a data-driven parcellation of the hippocampus based on its structure-function relationships. This revealed circumscribed clusters distributed along anterior-posterior and medial-lateral axes, which broadly aligned with hippocampal subfields. In Study 2, we examined the resting-state functional connectivity profiles of each TW-dFC derived cluster in an independent sample of 100 participants. Each hippocampal cluster displayed distinct patterns of functional connectivity with specific substructures within medial temporal, parietal, frontal and occipital cortices as well as subcortical and cerebellar regions. Our findings demonstrate that TW-dFC provides a powerful framework for anatomically informed functional parcellation of the hippocampus and offers new insights into the structural-functional organisation underlying hippocampal-(sub)cortical interactions. Our approach opens new avenues for probing memory systems in health and their disruption in aging and disease.

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

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↗

bioRxiv2022

Hippocampal subfields and their neocortical interactions during autobiographical memory using submillimeter whole-brain fMRI at 7 Tesla

Advances in ultra-high field 7 Tesla functional magnetic resonance imaging (7T fMRI) have provided unprecedented opportunities to gain insights into the neural underpinnings supporting human memory. The hippocampus, a heterogeneous brain structure comprising several subfields plays a central role during vivid re-experiencing of autobiographical memories (AM). However, due to technical limitations, how hippocampal subfields differentially support AM, whether this contribution is specific to one portion along the hippocampal long-axis, and how subfields are functionally connected with other brain regions typically associated with AM retrieval remains elusive. Here, we leveraged technical advances of parallel imaging and employed a submillimeter Echo Planar Imaging sequence over the whole brain while participants re-experienced vivid, detail-rich AM. We found that all hippocampal subfields along the long-axis were engaged during AM retrieval. Nonetheless, only the pre/parasubiculum within the anterior body of the hippocampus, contributed over and above to AM retrieval. Moreover, whole-brain functional connectivity analyses of the same data revealed that this part of the hippocampus was the only one that was strongly connected to other brain regions typically associated with AM, such as the ventromedial prefrontal cortex (vmPFC) and medial/lateral parietal regions. In the context of the broader literature, our results support recent proposals that the anterior body of the pre/parasubiculum may play an essential role in scene-based cognition, such as the re-experience of personal past events. HighlightsO_LIAll hippocampal subfields differentiate AM retrieval from mental arithmetic problem solving C_LIO_LIThe anterior body of the pre/parasubiculum engages in AM more than other subfields C_LIO_LIThe anterior body of the pre/parasubiculum is strongly connected to the AM network C_LIO_LIThe pre/parasubiculum may be preferentially involved in scene-based cognition C_LI

neuroscience↗

bioRxiv2021

Anatomical connectivity along the anterior-posterior axis of the human hippocampus: new insights using quantitative fibre-tracking.

The hippocampus supports multiple cognitive functions including episodic memory. Recent work has highlighted functional differences along the anterior-posterior axis of the human hippocampus but the neuroanatomical underpinnings of these differences remain unclear. We leveraged track-density imaging to systematically examine anatomical connectivity between the cortical mantle and the anterior-posterior axis of the in-vivo human hippocampus. We first identified the most highly connected cortical areas and detailed the degree to which they preferentially connect along the anterior-posterior axis of the hippocampus. Then, using a tractography pipeline specifically tailored to measure the location and density of streamline endpoints within the hippocampus, we characterised where, within the hippocampus, these cortical areas preferentially connect. Our results were striking in showing that different parts of the hippocampus preferentially connect with distinct cortical areas. Furthermore, we provide evidence that both gradients and circumscribed areas of dense extrinsic anatomical connectivity exist within the human hippocampus. These findings inform conceptual debates in the field by unveiling how specific regions along the anterior-posterior axis of the hippocampus are associated with different cortical inputs/outputs. Overall, our results represent a major advance in our ability to map the anatomical connectivity of the human hippocampus in-vivo and inform our understanding of the neural architecture of hippocampal dependent memory systems in the human brain. This detailed characterization of how specific portions of the hippocampus anatomically connect with cortical brain regions may promote a better understanding of its role in cognition and we emphasize the importance of considering the hippocampus as a heterogeneous structure.

neuroscience↗

bioRxiv2020

Characterising the hippocampal response to perception, construction and complexity

The precise role played by the hippocampus in supporting cognitive functions such as episodic memory and future thinking is debated, but there is general agreement that it involves constructing representations comprised of numerous elements. Visual scenes have been deployed extensively in cognitive neuroscience because they are paradigmatic multi-element stimuli. However, questions remain about the specificity and nature of the hippocampal response to scenes. Here, we devised a paradigm in which we had participants search pairs of images for either colour or layout differences, thought to be associated with perceptual or spatial constructive processes respectively. Importantly, images depicted either naturalistic scenes or phase-scrambled versions of the same scenes, and were either simple or complex. Using this paradigm during functional MRI scanning, we addressed three questions: 1. Is the hippocampus recruited specifically during scene processing? 2. If the hippocampus is more active in response to scenes, does searching for colour or layout differences influence its activation? 3. Does the complexity of the scenes affect its response? We found that, compared to phase-scrambled versions of the scenes, the hippocampus was more responsive to scene stimuli. Moreover, a clear anatomical distinction was evident, with colour detection in scenes engaging the posterior hippocampus whereas layout detection in scenes recruited the anterior hippocampus. The complexity of the scenes did not influence hippocampal activity. These findings seem to align with perspectives that propose the hippocampus is especially attuned to scenes, and its involvement occurs irrespective of the cognitive process or the complexity of the scenes.

neuroscience↗

bioRxiv2020

The role of hippocampal-vmPFC neural dynamics in building mental representations

The hippocampus and ventromedial prefrontal cortex (vmPFC) play key roles in numerous cognitive domains including mind-wandering, episodic memory and imagining the future. Perspectives differ on precisely how they support these diverse functions, but there is general agreement that it involves constructing representations comprised of numerous elements. Visual scenes have been deployed extensively in cognitive neuroscience because they are paradigmatic multi-element stimuli. However, it remains unclear whether scenes, rather than other types of multi-feature stimuli, preferentially engage hippocampus and vmPFC. Here we leveraged the high temporal resolution of magnetoencephalography to test participants as they gradually built scene imagery from three successive auditorily-presented object descriptions and an imagined 3D space. This was contrasted with constructing mental images of non-scene arrays that were composed of three objects and an imagined 2D space. The scene and array stimuli were, therefore, highly matched, and this paradigm permitted a closer examination of step-by-step mental construction than has been undertaken previously. We observed modulation of theta power in our two regions of interest - anterior hippocampus during the initial stage, and in vmPFC during the first two stages, of scene relative to array construction. Moreover, the scene-specific anterior hippocampal activity during the first construction stage was driven by the vmPFC, with mutual entrainment between the two brain regions thereafter. These findings suggest that hippocampal and vmPFC neural activity is especially tuned to scene representations during the earliest stage of their formation, with implications for theories of how these brain areas enable cognitive functions such as episodic memory.

neuroscience↗

bioRxiv2018

Differences in functional connectivity along the anterior-posterior axis of human hippocampal subfields

There is a paucity of information about how human hippocampal subfields are functionally connected to each other and to neighbouring extra-hippocampal cortices. In particular, little is known about whether patterns of functional connectivity (FC) differ down the anterior-posterior axis of each subfield. Here, using high resolution structural MRI we delineated the hippocampal subfields in healthy young adults. This included the CA fields, separating DG/CA4 from CA3, separating the pre/parasubiculum from the subiculum, and also segmenting the uncus. We then used high resolution resting state functional MRI to interrogate FC. We first analysed the FC of each hippocampal subfield in its entirety, in terms of FC with other subfields and with the neighbouring regions, namely entorhinal, perirhinal, posterior parahippocampal and retrosplenial cortices. Next, we analysed FC for different portions of each hippocampal subfield along its anterior-posterior axis, in terms of FC between different parts of a subfield, FC with other subfield portions, and FC of each subfield portion with the neighbouring cortical regions of interest. We found that intrinsic functional connectivity between the subfields aligned generally with the tri-synaptic circuit but also extended beyond it. Our findings also revealed that patterns of functional connectivity between the subfields and neighbouring cortical areas differed markedly along the anterior-posterior axis of each hippocampal subfield. Overall, these results contribute to ongoing efforts to characterise human hippocampal subfield connectivity, with implications for understanding hippocampal function. HighlightsO_LIHigh resolution resting state functional MRI scans were collected C_LIO_LIWe investigated functional connectivity (FC) of human hippocampal subfields C_LIO_LIWe specifically examined FC along the anterior-posterior axis of subfields C_LIO_LIFC between subfields extended beyond the canonical tri-synaptic circuit C_LIO_LIDifferent portions of subfields showed different patterns of FC with neocortex C_LI

neuroscience↗

bioRxiv2017

Differentiable processing of objects, associations and scenes within the hippocampus

The hippocampus is known to be important for a range of cognitive functions including episodic memory, spatial navigation and future-thinking. Wide agreement on the exact nature of its contribution has proved elusive, with some theories emphasising associative processes and another proposing that scene construction is its primary role. To directly compare these accounts of hippocampal function, we devised a novel mental imagery paradigm where different tasks were closely matched for associative processing and mental construction, but either did or did not evoke scene representations, and we combined this with high resolution functional MRI. The results were striking in showing that differentiable parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or non-scene-evoking associative processing. The contrasting patterns of neural engagement could not be accounted for by differences in eye movements, mnemonic processing or the phenomenology of mental imagery. These results inform conceptual debates in the field by showing that the hippocampus does not seem to favour one type of process over another; it is not a story of exclusivity. Rather, there may be different circuits within the hippocampus, each associated with different cortical inputs, which become engaged depending on the nature of the stimuli and the task at hand. Overall, our findings emphasise the importance of considering the hippocampus as a heterogeneous structure, and that a focus on characterising how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.\n\nSignificance statementThe hippocampus is known to be important for a range of cognitive functions including episodic memory, spatial navigation and future-thinking. Wide agreement on the exact nature of its contribution has proved elusive. Here we used a novel mental imagery paradigm and high resolution fMRI to compare accounts of hippocampal function that emphasise associative processes with a theory that proposes scene construction as a primary role. The results were striking in showing that differentiable parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or non-scene-evoking associative processing. We conclude that a greater emphasis on characterising how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.\n\nAbbreviations

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