Automated protocols for delineating human hippocampal subfields from 3 Tesla and 7 Tesla magnetic resonance imaging data.

Researchers who study the human hippocampus are naturally interested in how its subfields function. However, many researchers are precluded from examining subfields because their manual delineation from magnetic resonance imaging (MRI) scans (still the gold standard approach) is time consuming and requires significant expertise. To help ameliorate this issue, we present here two protocols, one for 3T MRI and the other for 7T MRI, that permit automated hippocampus segmentation into six subregions, namely dentate gyrus/cornu ammonis (CA)4, CA2/3, CA1, subiculum, pre/parasubiculum, and uncus along the entire length of the hippocampus. These protocols are particularly notable relative to existing resources in that they were trained and tested using large numbers of healthy young adults (n = 140 at 3T, n = 40 at 7T) whose hippocampi were manually segmented by experts from MRI scans. Using inter-rater reliability analyses, we showed that the quality of automated segmentations produced by these protocols was high and comparable to expert manual segmenters. We provide full open access to the automated protocols, and anticipate they will save hippocampus researchers a significant amount of time. They could also help to catalyze subfield research, which is essential for gaining a full understanding of how the hippocampus functions.

Release of cognitive and multimodal MRI data including real-world tasks and hippocampal subfield segmentations.

We share data from N = 217 healthy adults (mean age 29 years, range 20-41; 109 females, 108 males) who underwent extensive cognitive assessment and neuroimaging to examine the neural basis of individual differences, with a particular focus on a brain structure called the hippocampus. Cognitive data were collected using a wide array of questionnaires, naturalistic tests that examined imagination, autobiographical memory recall and spatial navigation, traditional laboratory-based tests such as recalling word pairs, and comprehensive characterisation of the strategies used to perform the cognitive tests. 3 Tesla MRI data were also acquired and include multi-parameter mapping to examine tissue microstructure, diffusion-weighted MRI, T2-weighted high-resolution partial volume structural MRI scans (with the masks of hippocampal subfields manually segmented from these scans), whole brain resting state functional MRI scans and partial volume high resolution resting state functional MRI scans. This rich dataset will be of value to cognitive and clinical neuroscientists researching individual differences, real-world cognition, brain-behaviour associations, hippocampal subfields and more. All data are freely available on Dryad.

Mitigating susceptibility-induced distortions in high-resolution 3DEPI fMRI at 7T.

Geometric distortion is a major limiting factor for spatial specificity in high-resolution fMRI using EPI readouts and is exacerbated at higher field strengths due to increased B0 field inhomogeneity. Prominent correction schemes are based on B0 field-mapping or acquiring reverse phase-encoded (reversed-PE) data. However, to date, comparisons of these techniques in the context of fMRI have only been performed on 2DEPI data, either at lower field or lower resolution. In this study, we investigate distortion compensation in the context of sub-millimetre 3DEPI data at 7T. B0 field-mapping and reversed-PE distortion correction techniques were applied to both partial coverage BOLD-weighted and whole brain MT-weighted 3DEPI data with matched distortion. Qualitative assessment showed overall improvement in cortical alignment for both correction techniques in both 3DEPI fMRI and whole-brain MT-3DEPI datasets. The distortion-corrected MT-3DEPI images were quantitatively evaluated by comparing cortical alignment with an anatomical reference using dice coefficient (DC) and correlation ratio (CR) measures. These showed that B0 field-mapping and reversed-PE methods both improved correspondence between the MT-3DEPI and anatomical data, with more substantial improvements consistently obtained using the reversed-PE approach. Regional analyses demonstrated that the largest benefit of distortion correction, and in particular of the reversed-PE approach, occurred in frontal and temporal regions where susceptibility-induced distortions are known to be greatest, but had not led to complete signal dropout. In conclusion, distortion correction based on reversed-PE data has shown the greater capacity for achieving faithful alignment with anatomical data in the context of high-resolution fMRI at 7T using 3DEPI.

Posterior hippocampal CA2/3 volume is associated with autobiographical memory recall ability in lower performing individuals.

People vary substantially in their capacity to recall past experiences, known as autobiographical memories. Here we investigated whether the volumes of specific hippocampal subfields were associated with autobiographical memory retrieval ability. We manually segmented the full length of the two hippocampi in 201 healthy young adults into DG/CA4, CA2/3, CA1, subiculum, pre/parasubiculum and uncus, in the largest such manually segmented subfield sample yet reported. Across the group we found no evidence for an association between any subfield volume and autobiographical memory recall ability. However, when participants were assigned to lower and higher performing groups based on their memory recall scores, we found that bilateral CA2/3 volume was significantly and positively associated with autobiographical memory recall performance specifically in the lower performing group. We further observed that this effect was attributable to posterior CA2/3. By contrast, semantic details from autobiographical memories, and performance on a range of laboratory-based memory tests, did not correlate with CA2/3 volume. Overall, our findings highlight that posterior CA2/3 may be particularly pertinent for autobiographical memory recall. They also reveal that there may not be direct one-to-one mapping of posterior CA2/3 volume with autobiographical memory ability, with size mattering perhaps only in those with poorer memory recall.

Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice.

Background: Gastrointestinal symptoms are commonly associated with acute Plasmodium spp infection. Malaria-associated enteritis may provide an opportunity for enteric pathogens to breach the intestinal mucosa, resulting in life-threatening systemic infections. Methods: To investigate whether intestinal pathology also occurs during infection with a murine model of mild and resolving malaria, C57BL/6J mice were inoculated with recently mosquito-transmitted Plasmodium chabaudi AS. At schizogony, intestinal tissues were collected for quantification and localisation of immune mediators and malaria parasites, by PCR and immunohistochemistry. Inflammatory proteins were measured in plasma and faeces and intestinal permeability was assessed by FITC-dextran translocation after oral administration. Results: Parasitaemia peaked at approx. 1.5% at day 9 and resolved by day 14, with mice experiencing significant and transient anaemia but no weight loss. Plasma IFN-γ, TNF-α and IL10 were significantly elevated during peak infection and quantitative RT-PCR of the intestine revealed a significant increase in transcripts for ifng and cxcl10. Histological analysis revealed parasites within blood vessels of both the submucosa and intestinal villi and evidence of mild crypt hyperplasia. In faeces, concentrations of the inflammatory marker lactoferrin were significantly raised on days 9 and 11 and FITC-dextran was detected in plasma on days 7 to 14. At day 11, plasma FITC-dextran concentration was significantly positively correlated with peripheral parasitemia and faecal lactoferrin concentration. Conclusions: In summary, using a relevant, attenuated model of malaria, we have found that acute infection is associated with intestinal inflammation and increased intestinal permeability. This model can now be used to explore the mechanisms of parasite-induced intestinal inflammation and to assess the impact of increased intestinal permeability on translocation of enteropathogens.

Does memory research have a realistic future?

How do we remember our past experiences? This question remains stubbornly resistant to resolution. The next 25 years may see significant traction on this and other outstanding issues if memory researchers capitalise on exciting technological developments that allow embodied cognition to be studied in ways that closely approximate real life.

Robust estimation of 1/f activity improves oscillatory burst detection.

Neural oscillations often occur as transient bursts with variable amplitude and frequency dynamics. Quantifying these effects is important for understanding brain-behaviour relationships, especially in continuous datasets. To robustly measure bursts, rhythmical periods of oscillatory activity must be separated from arrhythmical background 1/f activity, which is ubiquitous in electrophysiological recordings. The Better OSCillation (BOSC) framework achieves this by defining a power threshold above the estimated background 1/f activity, combined with a duration threshold. Here we introduce a modification to this approach called fBOSC, which uses a spectral parametrisation tool to accurately model background 1/f activity in neural data. fBOSC (which is openly available as a MATLAB toolbox) is robust to power spectra with oscillatory peaks and can also model non-linear spectra. Through a series of simulations, we show that fBOSC more accurately models the 1/f power spectrum compared with existing methods. fBOSC was especially beneficial where power spectra contained a 'knee' below ~.5-10 Hz, which is typical in neural data. We also found that, unlike other methods, fBOSC was unaffected by oscillatory peaks in the neural power spectrum. Moreover, by robustly modelling background 1/f activity, the sensitivity for detecting oscillatory bursts was standardised across frequencies (e.g., theta- and alpha-bands). Finally, using openly available resting state magnetoencephalography and intracranial electrophysiology datasets, we demonstrate the application of fBOSC for oscillatory burst detection in the theta-band. These simulations and empirical analyses highlight the value of fBOSC in detecting oscillatory bursts, including in datasets that are long and continuous with no distinct experimental trials.

Conduction velocity along a key white matter tract is associated with autobiographical memory recall ability.

Conduction velocity is the speed at which electrical signals travel along axons and is a crucial determinant of neural communication. Inferences about conduction velocity can now be made in vivo in humans using a measure called the magnetic resonance (MR) g-ratio. This is the ratio of the inner axon diameter relative to that of the axon plus the myelin sheath that encases it. Here, in the first application to cognition, we found that variations in MR g-ratio, and by inference conduction velocity, of the parahippocampal cingulum bundle were associated with autobiographical memory recall ability in 217 healthy adults. This tract connects the hippocampus with a range of other brain areas. We further observed that the association seemed to be with inner axon diameter rather than myelin content. The extent to which neurites were coherently organised within the parahippocampal cingulum bundle was also linked with autobiographical memory recall ability. Moreover, these findings were specific to autobiographical memory recall and were not apparent for laboratory-based memory tests. Our results offer a new perspective on individual differences in autobiographical memory recall ability, highlighting the possible influence of specific white matter microstructure features on conduction velocity when recalling detailed memories of real-life past experiences.

Universal pulses for homogeneous excitation using single channel coils.

PURPOSE: Universal Pulses (UPs) are excitation pulses that reduce the flip angle inhomogeneity in high field MRI systems without subject-specific optimization, originally developed for parallel transmit (PTX) systems at 7 T. We investigated the potential benefits of UPs for single channel (SC) transmit systems at 3 T, which are widely used for clinical and research imaging, and for which flip angle inhomogeneity can still be problematic. METHODS: SC-UPs were designed using a spiral nonselective k-space trajectory for brain imaging at 3 T using transmit field maps (B1+) and off-resonance maps (B0) acquired on two different scanner types: a 'standard' single channel transmit system and a system with a PTX body coil. The effect of training group size was investigated using data (200 subjects) from the standard system. The PTX system was used to compare SC-UPs to PTX-UPs (15 subjects). In two additional subjects, prospective imaging using SC-UP was studied. RESULTS: Average flip angle homogeneity error fell from 9.5 ± 0.5 % for 'default' excitation to 3.0 ± 0.6 % using SC-UPs trained over 50 subjects. Performance of the UPs was found to steadily improve as training group size increased, but stabilized after ~15 subjects. On the PTX-enabled system, SC-UPs again outperformed default excitation in simulations (4.8 ± 0.6 % error versus 10.6 ± 0.8 % respectively) though greater homogenization could be achieved with PTX-UPs (3.9 ± 0.6 %) and personalized pulses (SC-PP 3.6 ± 1.0 %, PTX-PP 2.9 ± 0.6 %). MP-RAGE imaging using SC-UP resulted in greater separation between grey and white matter signal intensities than default excitation. CONCLUSIONS: SC-UPs can improve excitation homogeneity in standard 3 T systems without further calibration and could be used instead of a default excitation pulse for nonselective neuroimaging at 3 T.

Magnetic Field Mapping and Correction for Moving OP-MEG.

BACKGROUND: Optically pumped magnetometers (OPMs) have made moving, wearable magnetoencephalography (MEG) possible. The OPMs typically used for MEG require a low background magnetic field to operate, which is achieved using both passive and active magnetic shielding. However, the background magnetic field is never truly zero Tesla, and so the field at each of the OPMs changes as the participant moves. This leads to position and orientation dependent changes in the measurements, which manifest as low frequency artefacts in MEG data. OBJECTIVE: We model the spatial variation in the magnetic field and use the model to predict the movement artefact found in a dataset. METHODS: We demonstrate a method for modelling this field with a triaxial magnetometer, then show that we can use the same technique to predict the movement artefact in a real OPM-based MEG (OP-MEG) dataset. RESULTS: Using an 86-channel OP-MEG system, we found that this modelling method maximally reduced the power spectral density of the data by 27.8 ± 0.6 dB at 0 Hz, when applied over 5 s non-overlapping windows. CONCLUSION: The magnetic field inside our state-of-the art magnetically shielded room can be well described by low-order spherical harmonic functions. We achieved a large reduction in movement noise when we applied this model to OP-MEG data. SIGNIFICANCE: Real-time implementation of this method could reduce passive shielding requirements for OP-MEG recording and allow the measurement of low-frequency brain activity during natural participant movement.

Interference suppression techniques for OPM-based MEG: Opportunities and challenges.

One of the primary technical challenges facing magnetoencephalography (MEG) is that the magnitude of neuromagnetic fields is several orders of magnitude lower than interfering signals. Recently, a new type of sensor has been developed - the optically pumped magnetometer (OPM). These sensors can be placed directly on the scalp and move with the head during participant movement, making them wearable. This opens up a range of exciting experimental and clinical opportunities for OPM-based MEG experiments, including paediatric studies, and the incorporation of naturalistic movements into neuroimaging paradigms. However, OPMs face some unique challenges in terms of interference suppression, especially in situations involving mobile participants, and when OPMs are integrated with electrical equipment required for naturalistic paradigms, such as motion capture systems. Here we briefly review various hardware solutions for OPM interference suppression. We then outline several signal processing strategies aimed at increasing the signal from neuromagnetic sources. These include regression-based strategies, temporal filtering and spatial filtering approaches. The focus is on the practical application of these signal processing algorithms to OPM data. In a similar vein, we include two worked-through experiments using OPM data collected from a whole-head sensor array. These tutorial-style examples illustrate how the steps for suppressing external interference can be implemented, including the associated data and code so that researchers can try the pipelines for themselves. With the popularity of OPM-based MEG rising, there will be an increasing need to deal with interference suppression. We hope this practical paper provides a resource for OPM-based MEG researchers to build upon.

Using OPMs to measure neural activity in standing, mobile participants.

Optically pumped magnetometer-based magnetoencephalography (OP-MEG) can be used to measure neuromagnetic fields while participants move in a magnetically shielded room. Head movements in previous OP-MEG studies have been up to 20 cm translation and ∼30° rotation in a sitting position. While this represents a step-change over stationary MEG systems, naturalistic head movement is likely to exceed these limits, particularly when participants are standing up. In this proof-of-concept study, we sought to push the movement limits of OP-MEG even further. Using a 90 channel (45-sensor) whole-head OP-MEG system and concurrent motion capture, we recorded auditory evoked fields while participants were: (i) sitting still, (ii) standing up and still, and (iii) standing up and making large natural head movements continuously throughout the recording - maximum translation 120 cm, maximum rotation 198°. Following pre-processing, movement artefacts were substantially reduced but not eliminated. However, upon utilisation of a beamformer, the M100 event-related field localised to primary auditory regions. Furthermore, the event-related fields from auditory cortex were remarkably consistent across the three conditions. These results suggest that a wide range of movement is possible with current OP-MEG systems. This in turn underscores the exciting potential of OP-MEG for recording neural activity during naturalistic paradigms that involve movement (e.g. navigation), and for scanning populations who are difficult to study with stationary MEG (e.g. young children).

Testing covariance models for MEG source reconstruction of hippocampal activity.

Beamforming is one of the most commonly used source reconstruction methods for magneto- and electroencephalography (M/EEG). One underlying assumption, however, is that distant sources are uncorrelated and here we tested whether this is an appropriate model for the human hippocampal data. We revised the Empirical Bayesian Beamfomer (EBB) to accommodate specific a-priori correlated source models. We showed in simulation that we could use model evidence (as approximated by Free Energy) to distinguish between different correlated and uncorrelated source scenarios. Using group MEG data in which the participants performed a hippocampal-dependent task, we explored the possibility that the hippocampus or the cortex or both were correlated in their activity across hemispheres. We found that incorporating a correlated hippocampal source model significantly improved model evidence. Our findings help to explain why, up until now, the majority of MEG-reported hippocampal activity (typically making use of beamformers) has been estimated as unilateral.

Reducing Susceptibility Distortion Related Image Blurring in Diffusion MRI EPI Data.

Diffusion magnetic resonance imaging (MRI) is an increasingly popular technique in basic and clinical neuroscience. One promising application is to combine diffusion MRI with myelin maps from complementary MRI techniques such as multi-parameter mapping (MPM) to produce g-ratio maps that represent the relative myelination of axons and predict their conduction velocity. Statistical Parametric Mapping (SPM) can process both diffusion data and MPMs, making SPM the only widely accessible software that contains all the processing steps required to perform group analyses of g-ratio data in a common space. However, limitations have been identified in its method for reducing susceptibility-related distortion in diffusion data. More generally, susceptibility-related image distortion is often corrected by combining reverse phase-encoded images (blip-up and blip-down) using the arithmetic mean (AM), however, this can lead to blurred images. In this study we sought to (1) improve the susceptibility-related distortion correction for diffusion MRI data in SPM; (2) deploy an alternative approach to the AM to reduce image blurring in diffusion MRI data when combining blip-up and blip-down EPI data after susceptibility-related distortion correction; and (3) assess the benefits of these changes for g-ratio mapping. We found that the new processing pipeline, called consecutive Hyperelastic Susceptibility Artefact Correction (HySCO) improved distortion correction when compared to the standard approach in the ACID toolbox for SPM. Moreover, using a weighted average (WA) method to combine the distortion corrected data from each phase-encoding polarity achieved greater overlap of diffusion and more anatomically faithful structural white matter probability maps derived from minimally distorted multi-parameter maps as compared to the AM. Third, we showed that the consecutive HySCO WA performed better than the AM method when combined with multi-parameter maps to perform g-ratio mapping. These improvements mean that researchers can conveniently access a wide range of diffusion-related analysis methods within one framework because they are now available within the open-source ACID toolbox as part of SPM, which can be easily combined with other SPM toolboxes, such as the hMRI toolbox, to facilitate computation of myelin biomarkers that are necessary for g-ratio mapping.

Modelling optically pumped magnetometer interference in MEG as a spatially homogeneous magnetic field.

Here we propose that much of the magnetic interference observed when using optically pumped magnetometers for MEG experiments can be modeled as a spatially homogeneous magnetic field. We show that this approximation reduces sensor level variance and substantially improves statistical power. This model does not require knowledge of the underlying neuroanatomy nor the sensor positions. It only needs information about the sensor orientation. Due to the model's low rank there is little risk of removing substantial neural signal. However, we provide a framework to assess this risk for any sensor number, design or subject neuroanatomy. We find that the risk of unintentionally removing neural signal is reduced when multi-axis recordings are performed. We validated the method using a binaural auditory evoked response paradigm and demonstrated that removing the homogeneous magnetic field increases sensor level SNR by a factor of 3. Considering the model's simplicity and efficacy, we suggest that this homogeneous field correction can be a powerful preprocessing step for arrays of optically pumped magnetometers.

Watching Movies Unfold, a Frame-by-Frame Analysis of the Associated Neural Dynamics.

Our lives unfold as sequences of events. We experience these events as seamless, although they are composed of individual images captured in between the interruptions imposed by eye blinks and saccades. Events typically involve visual imagery from the real world (scenes), and the hippocampus is frequently engaged in this context. It is unclear, however, whether the hippocampus would be similarly responsive to unfolding events that involve abstract imagery. Addressing this issue could provide insights into the nature of its contribution to event processing, with relevance for theories of hippocampal function. Consequently, during magnetoencephalography (MEG), we had female and male humans watch highly matched unfolding movie events composed of either scene image frames that reflected the real world, or frames depicting abstract patterns. We examined the evoked neuronal responses to each image frame along the time course of the movie events. Only one difference between the two conditions was evident, and that was during the viewing of the first image frame of events, detectable across frontotemporal sensors. Further probing of this difference using source reconstruction revealed greater engagement of a set of brain regions across parietal, frontal, premotor, and cerebellar cortices, with the largest change in broadband (1-30 Hz) power in the hippocampus during scene-based movie events. Hippocampal engagement during the first image frame of scene-based events could reflect its role in registering a recognizable context perhaps based on templates or schemas. The hippocampus, therefore, may help to set the scene for events very early on.

The distinct and overlapping brain networks supporting semantic and spatial constructive scene processing.

Scene imagery features prominently when we recall autobiographical memories, imagine the future and navigate around in the world. Consequently, in this study we sought to better understand how scene representations are supported by the brain. Processing scenes involves a variety of cognitive processes that in the real world are highly interactive. Here, however, our goal was to separate semantic and spatial constructive scene processes in order to identify the brain areas that were distinct to each process, those they had in common, and the connectivity between regions. To this end, participants searched for either semantic or spatial constructive impossibilities in scenes during functional MRI. We focussed our analyses on only those scenes that were possible, thus removing any error detection that would evoke reactions such as surprise or novelty. Importantly, we also counterbalanced possible scenes across participants, enabling us to examine brain activity and connectivity for the same possible scene images under two different conditions. We found that participants adopted different cognitive strategies, which were reflected in distinct oculomotor behaviour, for each condition. These were in turn associated with increased engagement of lateral temporal and parietal cortices for semantic scene processing, the hippocampus for spatial constructive scene processing, and increased activation of the ventromedial prefrontal cortex (vmPFC) that was common to both. Connectivity analyses showed that the vmPFC switched between semantic and spatial constructive brain networks depending on the task at hand. These findings further highlight the well-known semantic functions of lateral temporal areas, while providing additional support for the previously-asserted contribution of the hippocampus to scene construction, and recent suggestions that the vmPFC may play a key role in orchestrating scene processing.

The relationship between hippocampal-dependent task performance and hippocampal grey matter myelination and iron content.

Individual differences in scene imagination, autobiographical memory recall, future thinking and spatial navigation have long been linked with hippocampal structure in healthy people, although evidence for such relationships is, in fact, mixed. Extant studies have predominantly concentrated on hippocampal volume. However, it is now possible to use quantitative neuroimaging techniques to model different properties of tissue microstructure in vivo such as myelination and iron. Previous work has linked such measures with cognitive task performance, particularly in older adults. Here we investigated whether performance on scene imagination, autobiographical memory, future thinking and spatial navigation tasks was associated with hippocampal grey matter myelination or iron content in young, healthy adult participants. Magnetic resonance imaging data were collected using a multi-parameter mapping protocol (0.8 mm isotropic voxels) from a large sample of 217 people with widely-varying cognitive task scores. We found little evidence that hippocampal grey matter myelination or iron content were related to task performance. This was the case using different analysis methods (voxel-based quantification, partial correlations), when whole brain, hippocampal regions of interest, and posterior:anterior hippocampal ratios were examined, and across different participant sub-groups (divided by gender and task performance). Variations in hippocampal grey matter myelin and iron levels may not, therefore, help to explain individual differences in performance on hippocampal-dependent tasks, at least in young, healthy individuals.

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.

The relationship between hippocampal subfield volumes and autobiographical memory persistence.

Structural integrity of the human hippocampus is widely acknowledged to be necessary for the successful encoding and retrieval of autobiographical memories. However, evidence for an association between hippocampal volume and the ability to recall such memories in healthy individuals is mixed. Here we examined this issue further by combining two approaches. First, we focused on the anatomically distinct subregions of the hippocampus where more nuanced associations may be expressed compared to considering the whole hippocampal volume. A manual segmentation protocol of hippocampal subregions allowed us to separately calculate the volumes of the dentate gyrus/CA4, CA3/2, CA1, subiculum, pre/parasubiculum and uncus. Second, a critical feature of autobiographical memories is that they can span long time periods, and so we sought to consider how memory details persist over time by conducting a longitudinal study whereby participants had to recall the same autobiographical memories on two visits spaced 8 months apart. Overall, we found that there was no difference in the total number of internal (episodic) details produced at Visits 1 and 2. However, further probing of detail subcategories revealed that specifically the amount of subjective thoughts and emotions included during recall had declined significantly by the second visit. We also observed a strong correlation between left pre/parasubiculum volume and the amount of autobiographical memory internal details produced over time. This positive relationship was evident for particular facets of the memories, with remembered events, perceptual observations and thoughts and emotions benefitting from greater volume of the left pre/parasubiculum. These preliminary findings expand upon existing functional neuroimaging evidence by highlighting a potential link between left pre/parasubiculum volume and autobiographical memory. A larger pre/parasubiculum appears not only to protect against memory decay, but may possibly enhance memory persistence, inviting further scrutiny of the role of this brain region in remote autobiographical memory retrieval.