Biology subjects

Hodgetts, C. J.

Publications and source records attributed to Hodgetts, C. J..

16 recordsLinked to original sources

bioRxiv2026

Eye movement markers of relational encoding predict scene memory precision

Recalling scenes and events depends on how information is relationally organised in memory, but it is unclear whether the organisation of eye movements during encoding, rather than simply how much is explored, shapes what is remembered. Using a scene-viewing paradigm and drawing-based free recall task to capture the content and structure of remembered scenes, we examined whether scene memory was better explained by 'lower-order' measures reflecting the magnitude and spatial extent of sampling, or 'higher-order' measures capturing gaze organisation and temporal dynamics. Relative to lower-order measures (number of fixations and scanpath length), memory precision was better predicted by repeated sampling of viewed regions (refixations) and gaze distributions (stationary gaze entropy) during encoding. Thus, the organisation of visual attention, rather than sampling quantity, contributed to scene representations that preserved relationships between elements. These findings highlight a role for spatial gaze dynamics in optimally encoding organised, relational scene representations for episodic memory.

animal behavior and cognition↗

bioRxiv2026

Myelin-weighted Core Network Connectivity Supports Trait-Level Future Thinking

Why are some individuals able to recollect past events and imagine future events more richly than others? Here we examine how structural connectivity within a 'core network' supporting mnemonic cognition, substantially overlapping with the canonical default network, underpins inter-individual variation in autobiographical thought. We analysed state-of-the-art magnetic resonance imaging data from 109 adults collected on a high-gradient 3T Connectom scanner, in relation to their Survey of Autobiographical Memory (SAM) scores - a psychometric measure of self-reported episodic autobiographical, semantic, spatial, and future thinking abilities. We anatomically defined a core network, employed streamline tractography to derive participant-specific structural brain networks, and weighted their connections with the myelin water fraction derived from quantitative multicomponent relaxometry. We investigated associations between graph theoretical metrics of the core network and self-reported mnemonic abilities. We found a negative association between future thinking abilities and characteristic path length, and a positive association between future thinking abilities and mean clustering coefficient. Further analysis showed that the node-specific clustering coefficient of most core network nodes was positively correlated with future thinking scores, with frontotemporal nodes showing the strongest associations. Our findings indicate that both efficient integration and local segregation of the core network are important for trait-level future thinking.

neuroscience↗

bioRxiv2025

Fornix subdivisions and spatial learning: a diffusion MRI study

The fornix is the major white matter tract linking the hippocampal formation with distal brain sites. Human and animal lesion studies show that the connections comprising the fornix are vital for specific attributes of episodic and spatial memory. The fornix, however, interconnects the hippocampal formation with an array of subcortical and cortical sites and it is not known which specific connections support spatial-mnemonic function. To address this, making use of a partly previously published dataset (Hodgetts et al., 2020), we applied a novel deterministic tractography protocol to diffusion-weighted magnetic resonance imaging (dMRI) data from a group of healthy young adult humans who separately completed a desktop-based virtual reality analogue of the Morris water maze task. The tractography protocol enabled the two main parts of the fornix, delineated previously in axonal tracing studies in rodents and primates, to be reconstructed in vivo, namely the pre-commissural fornix (connecting the hippocampus to the medial prefrontal cortex and the basal forebrain) and the post-commissural fornix (connecting the hippocampus to the medial diencephalon). We found that inter-individual differences in pre-commissural - but not, surprisingly, post-commissural - fornix microstructure (indexed by free water corrected fractional anisotropy, FA) were significantly correlated with individual differences in spatial learning, indexed by reduction in search error as individuals learned to navigate to a hidden target location from multiple starting points. This study provides novel evidence that flexible and/or precise spatial learning involves a hippocampal-basal forebrain/prefrontal network underpinned in part by the pre-commissural fornix.

neuroscience↗

bioRxiv2024

Mapping hippocampal-cerebellar functional connectivity across the adult lifespan

Although the hippocampus and cerebellum are traditionally considered to support distinct memory systems, evidence from nonhuman species indicates a close bidirectional relationship during learning and navigational behaviour, with the hippocampus projecting to - and receiving input from - several cerebellar regions. However, little is known about the nature and topography of hippocampal-cerebellar connectivity in the human brain. To address this gap, we applied seed-based functional connectivity analyses to resting-state fMRI data from 479 cognitively normal participants, aged 18-88 years. We identified significant functional correlations between the hippocampus and widespread areas of cerebellar cortex, particularly lobules HIV, HV, HVI, HVIIA (Crus I and II), HIX, and HX. Contrasting the left and right hippocampus, we found significant correlations with the contralateral Crus II. We also compared longitudinal subdivisions of the hippocampus, revealing that anterior hippocampus demonstrated stronger connectivity with right Crus II, whereas posterior hippocampus was strongly connected to vermal parts of lobule V. Finally, we found that functional correlations between several hippocampal seeds (left, right, and anterior) and lobules HVI and HV decreased significantly with age. These results provide novel insights into hippocampal-cerebellar functional organisation and the influence of ageing on this system. Further studies are required to establish the role of this connection in learning and memory, as well as its potential vulnerability to neurodegeneration.

neuroscience↗

bioRxiv2024

Human BNST volume is not simply sexually dimorphic

The bed nucleus of the stria terminalis (BNST) is a sexually dimorphic basal forebrain region is a claim prevalent across rodent and human neuroscience research, arising from the observation that it is substantially larger in male versus female brains. Despite the pervasiveness of this claim, which may have implications for understanding sex differences in anxiety and substance use disorders, inspection of prior literature reveals a complex and nuanced picture. Research on volumetric human BNST sex differences comes from a handful of mostly small-scale post-mortem studies and two MRI studies, between them reporting no, moderate, or very large differences. This indicates the need for a more detailed systematic investigation. Addressing this, we developed a novel 3T T1-weighted (T1w) manual segmentation protocol for the BNST, which was applied to sub-millimetre resolution T1w structural MRI data in 170 young human adults. Using a Bayesian modelling approach, taking into account existing data and accounting for total brain volume, age, and sibship, we find substantial evidence favouring no sex difference in total BNST volume. We recommend that researchers exercise caution when reporting evidence of BNST sexual dimorphism, particularly when translating findings from rodent models in which the BNST may play a different, olfaction-focused, role.

neuroscience↗

bioRxiv2024

Multimodal MEG and microstructure-MRI investigations of the human hippocampal scene network

Although several studies have demonstrated that perceptual discrimination of complex scenes relies on an extended hippocampal network, distinct from an anterotemporal network supporting the perceptual discrimination of faces, we currently have limited insight into the specific functional and structural properties of these networks. Here, combining electrophysiological (magnetoencephalography, MEG) and microstructural (multi-shell diffusion MRI, dMRI) imaging in healthy human adults (30 female/10 male), we show that both hippocampal theta power modulation and fibre restriction of the fornix (a major input/output pathway of the hippocampus) independently related to accuracy during scene, but not face, perceptual discrimination. Conversely, microstructural features of the inferior longitudinal fasciculus (a long-range occipito- anterotemporal tract) correlated with face, but not scene, perceptual discrimination accuracy. Our results provide new mechanistic insight into the neurocognitive systems underpinning complex scene and face perception, providing support for multiple-system representation-based accounts of the medial temporal lobe. Significance StatementIn contrast to theories positing segregated cortical areas for perception and memory, the specialized representations of the hippocampus may support both the perception and memory of visual scenes. To investigate, we utilised the unique window into hippocampal electrophysiological activity offered by Magnetoencephalography (MEG). We found hippocampal theta activity modulations in the hippocampus and posteromedial cortex during scene, versus face and shape-size, perceptual oddity discrimination, the magnitude of which correlated with scene, but not face or shape- size, discrimination accuracy. Moreover, multimodal white matter imaging revealed that tissue restriction of the fornix - the major hippocampal output tract - independently predicted scene discrimination performance. Our multimodal MEG-microstructure study provides novel evidence that the hippocampus and connected structures conjointly support online scene processing.

neuroscience↗

bioRxiv2023

Scene-selectivity in CA1/subicular complex: Multivoxel pattern analysis at 7T

Prior univariate functional magnetic resonance imaging (fMRI) studies in humans suggest that the anteromedial subicular complex of the hippocampus is a hub for scene-based cognition. However, it is possible that univariate approaches were not sufficiently sensitive to detect scene-related activity in other subfields that have been implicated in spatial processing (e.g., CA1). Further, as connectivity-based functional gradients in the hippocampus do not respect classical subfield boundary definitions, category sensitivity may be distributed across anatomical subfields. Region-of-interest approaches, therefore, may limit our ability to observe category selectivity across discrete subfield boundaries. To address these issues, we applied searchlight multivariate pattern analysis to 7T fMRI data of healthy adults who undertook a simultaneous visual odd-one-out discrimination task for scene and non-scene (including face) visual stimuli, hypothesising that scene classification would be possible in multiple hippocampal regions within, but not constrained to, anteromedial subicular complex and CA1. Indeed, we found that the scene-selective searchlight map overlapped not only with anteromedial subicular complex (distal subiculum, pre/para subiculum), but also inferior CA1, alongside retrosplenial and parahippocampal cortices. Probabilistic overlap maps revealed gradients of scene category selectivity, with the strongest overlap located in the medial hippocampus, converging with searchlight findings. This was contrasted with gradients of face category selectivity, which had stronger overlap in more lateral hippocampus, supporting ideas of parallel processing streams for these two categories. Our work helps to map the scene, in contrast to, face processing networks within, and connected to, the human hippocampus.

neuroscience↗

bioRxiv2023

Does ipsilateral remapping following hand loss impact motor control of the intact hand?

What happens once a cortical territory becomes functionally redundant? We addressed brain and behavioural adaptations for the intact hand in individuals with a missing hand. Previous studies reported increased ipsilateral activity in the somatosensory territory of the missing hand (i.e., remapping) in acquired amputees, but not in individuals with a congenitally missing hand (one-handers). It is unclear whether remapping in amputees involves recruiting more neural resources to support the intact hand, and whether such activity is increased in tasks that demand greater motor control. We investigated sensorimotor learning and neural representation of the intact hand in one-handers and amputees using a multi-finger configuration task, as well as univariate and multivariate fMRI. We found that ipsilateral activity increased with motor demand - but only in the amputees group. However, these changes did not reflect behavioural differences. The representation of the finger configurations, as revealed by multivariate analysis, was stronger in amputees and closer to the typical representation found in controls contralateral hand territory, compared to one-handers. This collaborative contra-ipsilateral activity may reflect the intact hands efference copy. One-handers struggled to learn difficult finger configurations, but this did not translate to differences in univariate or multivariate activity relative to controls. Together with a supplementary structural white matter analysis, our results suggest that enhanced activity in the missing hand territory may not reflect intact hand function. Instead, we suggest that plasticity is more restricted than generally assumed and may depend on the availability of homologous pathways acquired early in life. Significant StatementWe studied whether brain resources in the missing-hand territory support demanding intact hand motor control in people who were born with one hand or lost a hand later in life. We found that amputees had increased activity in the brain area used for the missing hand, but no improvement in the performance of their intact hand. This collaborative contra-ipsilateral activity may reflect the intact hands efference copy. One-handers showed slight deficits while learning to perform complex motor movements, but no brain activity differences in the missing hand territory, compared to controls. Our results suggest that brain plasticity is limited and may depend on early life experiences.

neuroscience↗

bioRxiv2022

The association between real-world experiential diversity and event cognition

Parsing experience into meaningful events or units, known as event segmentation, may be critical for structuring episodic memory, planning, and navigating the spatial and social world. However, little is known about what factors shape inter-individual differences in event segmentation. Here, we show that individuals with greater variation in their daily social and spatial lives (experiential diversity) displayed more fine-grained event segmentation during a movie-viewing task. Further analyses revealed that this relationship held after considering potential confounds, such as anxiety and loneliness, and was primarily driven by variation in social experiential diversity. These results support the view that event segmentation can occur proactively based on social and spatial environmental dynamics learned in the wild and provide a potential cognitive pathway through which isolation impacts cognitive health.

animal behavior and cognition↗

bioRxiv2022

The limited place in cognitive space

The idea that objects can be represented within multi-dimensional cognitive spaces remains popular within psychology and neuroscience, and yet the restrictive topology of such spaces is seldom considered. Here, we show that it is possible, even within a simple set of items, to break such models by imposing neighbourhood relations that are incompatible with a purely spatial representation. These results highlight the fundamental limits of cognitive space as a representational format for complex cognition.

neuroscience↗

bioRxiv2022

Tract-specific white matter microstructure alterations among young adult APOE ε4 carriers: A replication and extension study

The parahippocampal cingulum bundle (PHCB) connects regions known to be vulnerable to early Alzheimers disease (AD) pathology, such as posteromedial cortex and medial temporal lobe. While AD-related pathology has been robustly associated with alterations in PHCB microstructure, specifically lower fractional anisotropy (FA) and higher mean diffusivity (MD), emerging evidence indicates that the reverse pattern is evident in younger adults at-risk of AD. In one such study, Hodgetts et al. (2019) reported that healthy young adult carriers of the apolipoprotein-E (APOE) {varepsilon}4 allele - the strongest common genetic risk factor for AD - showed higher FA and lower MD in the PHCB but not the inferior longitudinal fasciculus (ILF). These results are consistent with proposals claiming that heightened neural activity and connectivity have a significant role in posteromedial cortex vulnerability to amyloid-{beta} and tau spread beyond the medial temporal lobe. Given the implications for understanding AD risk, here we sought to replicate Hodgetts et al.s finding in a larger sample (N = 128; 40 APOE {varepsilon}4 carriers, 88 APOE {varepsilon}4 non-carriers) of young adults (age range: 19-33). Extending this work further, we also conducted exploratory analyses using a more advanced measure of microstructure: hindrance modulated orientational anisotropy (HMOA). These analyses included an investigation of hemispheric asymmetry in PHCB and ILF HMOA. Contrary to the original study, we observed no difference in PHCB microstructure between APOE {varepsilon}4 carriers and non-carriers. Bayes factors (BFs) further revealed moderate-to-strong evidence in support of these null findings. APOE {varepsilon}4-related differences in ILF HMOA asymmetry were evident, however, with carriers demonstrating lower leftward asymmetry. Our findings indicate that young adult APOE {varepsilon}4 carriers do not show alterations in PHCB microstructure, as observed by Hodgetts et al., but may show altered asymmetry in ILF microstructure.

neuroscience↗

bioRxiv2019

The role of the pre-commissural fornix in episodic autobiographical memory and simulation

Neuropsychological and functional magnetic resonance imaging (MRI) evidence suggests that the ability to vividly remember our personal past, and imagine future scenarios, involves two closely connected regions: the hippocampus and ventromedial prefrontal cortex (vmPFC). Despite evidence of a direct anatomical connection from hippocampus to vmPFC, it is unknown whether hippocampal-vmPFC structural connectivity supports both past and future-oriented episodic thinking. To address this, we applied diffusion-weighted magnetic resonance imaging (dMRI) and a novel deterministic tractography protocol to reconstruct distinct subdivisions of the fornix previously detected in axonal tracer studies, namely pre-commissural (connecting the hippocampus to vmPFC) and post-commissural (linking the hippocampus and medial diencephalon) fornix, in a group of healthy young adult humans who undertook an adapted past-future autobiographical interview. As predicted, we found that inter-individual differences in pre-commissural - but not post-commissural - fornix microstructure (fractional anisotropy) was significantly correlated with the episodic richness of both past and future autobiographical narratives. Notably, these results remained significant when controlling for both non-episodic narrative content and grey matter volumes of the hippocampus and vmPFC. This study provides novel evidence that reconstructing events from ones personal past, and constructing possible future events, involves a distinct, structurally-instantiated hippocampal-vmPFC pathway. Significance StatementA novel anatomically-guided protocol that allows the pre-commissural and post-commissural fornix fibers to be separately reconstructed in vivo (Christiansen et al., 2016) was applied to reconstruct the pre-commissural subdivision of the white matter fornix tract (anatomically linking the hippocampal formation to the vmPFC) and investigate its contribution to episodic memory and future simulation. We demonstrated that the amount of episodic details contained in past and future narratives, collected via an adapted autobiographical interview, was positively correlated with pre-, but not post-, commissural fornix microstructure. These findings highlight how inter-individual variation in the pre-commissural subdivision of the fornix underpins the construction of self-reflective, contextual events - for both the past and future.

neuroscience↗

bioRxiv2019

Curious connections: white matter pathways supporting individual differences in epistemic and perceptual curiosity

Across the lifespan, curiosity motivates us to learn, yet curiosity varies strikingly between individuals. Such individual differences have been shown for two distinct dimensions of curiosity: epistemic curiosity (EC), the desire to acquire conceptual knowledge, and perceptual curiosity (PC), the desire for sensory information. It is not known, however, whether both dimensions of curiosity depend on different brain networks and whether inter-individual differences in curiosity depend on variation in anatomical connectivity within these networks. Here, we investigated the neuroanatomical connections underpinning individual variation in trait curiosity. Fifty-one female participants underwent a two-shell diffusion MRI sequence and completed questionnaires measuring EC and PC. Using deterministic spherical deconvolution tractography we extracted microstructural metrics (fractional anisotropy (FA) and mean diffusivity (MD)) from two key white matter tracts: the fornix (implicated in novelty processing, exploration, information seeking and episodic memory) and the inferior longitudinal fasciculus (ILF) (implicated in semantic learning and memory). In line with our predictions, we found that EC - but not PC - correlated with ILF microstructure. Fornix microstructure, in contrast, correlated with both EC and PC, with posterior hippocampal fornix fibres - associated with posterior hippocampal network connectivity - linked to PC specifically. These findings suggest that differences in distinct dimensions of curiosity map systematically onto specific white matter tracts underlying well characterized brain networks. Furthermore, the results pave the way to study the anatomical substrates of inter-individual differences in dimensions of trait curiosity that motivate the learning of distinct forms of knowledge and skills.

neuroscience↗

bioRxiv2018

Neurochemical correlates of scene processing in the precuneus/posterior cingulate cortex: a multimodal fMRI and 1H-MRS study

Precuneus/posterior cingulate cortex (PCu/PCC) are key components of a midline network, activated during rest but also in tasks that involve construction of scene or situation models. Despite growing interest in PCu/PCC functional alterations in disease, the underlying neurochemical modulators of PCu/PCCs task-induced activity are largely unstudied. Here, a multimodal imaging approach was applied to investigate whether inter-individual differences in PCu/PCC fMRI activity, elicited during perceptual discrimination of scene stimuli, were correlated with local brain metabolite levels, measured during resting-state 1H-MRS. Forty healthy young adult participants (12 male) completed an fMRI perceptual odd-one-out task for scenes, objects and faces. 1H-MRS metabolites N-acetyl-aspartate (tNAA), glutamate (Glx) and {gamma}-amino-butyric acid (GABA+) were quantified via PRESS and MEGA-PRESS scans in a PCu/PCC voxel and an occipital (OCC) control voxel. Whole brain fMRI revealed a cluster in right dorsal PCu/PCC that showed a greater BOLD response to scenes versus faces and objects. When extracted from an independently defined PCu/PCC region of interest, scene activity (versus faces and objects and also versus baseline) was positively correlated with PCu/PCC, but not OCC, tNAA. A complementary fMRI analysis restricted to the PCu/PCC MRS voxel area identified a significant PCu/PCC cluster, confirming the positive correlation between scene-related BOLD activity and PCu/PCC tNAA. There were no correlations between PCu/PCC fMRI activity and Glx or GABA+ levels. These results demonstrate, for the first time, that scene activity in PCu/PCC is linked to local tNAA levels, identifying a neurochemical influence on inter-individual differences in the task-driven activity of a key brain hub.

neuroscience↗

bioRxiv2018

The role of the fornix in human navigational learning

Studies in rodents have demonstrated that transecting the white matter pathway linking the hippocampus and anterior thalamic nuclei - the fornix - impairs flexible navigational learning in the Morris Water Maze (MWM), as well as similar spatial learning tasks. While diffusion MRI studies in humans have linked fornix microstructure to scene discrimination and memory, its role in human navigation is currently unknown. We used high-angular resolution diffusion MRI to ask whether inter-individual differences in fornix microstructure would be associated with spatial learning in a virtual MWM task. To increase sensitivity to individual learning across trials, we adopted a novel curve fitting approach to estimate a single index of learning rate. We found a significant correlation between learning rate and the microstructure (mean diffusivity) of the fornix, but not that of a control tract linking occipital and anterior temporal cortices (the inferior longitudinal fasciculus, ILF). Further, this correlation remained significant when controlling for hippocampal volume. These findings extend previous animal studies by demonstrating the functional relevance of the fornix for human navigational learning, and highlight the importance of a distributed neuroanatomical network, underpinned by key white matter pathways, such as the fornix, in complex spatial behaviour.

neuroscience↗

bioRxiv2018

Increased posterior default mode network activity and structural connectivity in young adult APOE-ε4 carriers: a multi-modal imaging investigation

Young adult APOE-{varepsilon}4 carriers show increased activity in posterior regions of the default mode network (pDMN), but how this is related to structural connectivity is unknown. Thirty young adults (half APOE-{varepsilon}4 carriers, the other half APOE-{varepsilon}3{varepsilon}3/{varepsilon}2{varepsilon}3; mean age 20 years) were scanned using both diffusion and functional magnetic resonance imaging. Diffusion tractography was used to quantify the microstructure (mean diffusivity, MD; fractional anisotropy, FA) of the parahippocampal cingulum bundle (PHCB), which links pDMN and the medial temporal lobe. APOE-{varepsilon}4 carriers had lower MD and higher FA relative to non-carriers in PHCB. Further, PHCB microstructure was selectively associated with pDMN activity during a scene discrimination task known to be sensitive to Alzheimers disease (AD). These findings are consistent with a lifespan view of AD risk, where early-life structural and functional brain changes in specific, vulnerable networks leads to increased neural activity that may ultimately trigger amyloid-{beta} deposition.

neuroscience↗