Biology subjects

Maguire, E. A.

Publications and source records attributed to Maguire, E. A..

9 recordsLinked to original sources

bioRxiv2018

The neural dynamics of novel scene imagery

Retrieval of long-term episodic memories is characterised by synchronised neural activity between hippocampus and ventromedial prefrontal cortex (vmPFC), with additional evidence that vmPFC activity leads that of the hippocampus. It has been proposed that the mental generation of scene imagery is a crucial component of episodic memory processing. If this is the case, then a comparable interaction between the two brain regions should exist during the construction of novel scene imagery. To address this question, we leveraged the high temporal resolution of magnetoencephalography (MEG) to investigate the construction of novel mental imagery. We tasked male and female humans with imagining scenes and single isolated objects in response to one-word cues. We performed source level power, coherence and causality analyses to characterise the underlying inter-regional interactions. Both scene and object imagination resulted in theta power changes in the anterior hippocampus. However, higher theta coherence was observed between the hippocampus and vmPFC in the scene compared to the object condition. This inter-regional theta coherence also predicted whether or not imagined scenes were subsequently remembered. Dynamic causal modelling of this interaction revealed that vmPFC drove activity in hippocampus during novel scene construction. Additionally, theta power changes in the vmPFC preceded those observed in the hippocampus. These results constitute the first evidence in humans that episodic memory retrieval and scene imagination rely on similar vmPFC-hippocampus neural dynamics. Furthermore, they provide support for theories emphasising similarities between both cognitive processes, and perspectives that propose the vmPFC guides the construction of context-relevant representations in the hippocampus. Significance statementEpisodic memory retrieval is characterised by a dialogue between hippocampus and ventromedial prefrontal cortex (vmPFC). It has been proposed that the mental generation of scene imagery is a crucial component of episodic memory processing. An ensuing prediction would be of a comparable interaction between the two brain regions during the construction of novel scene imagery. Here, we leveraged the high temporal resolution of magnetoencephalography (MEG), and combined it with a scene imagination task. We found that a hippocampal-vmPFC dialogue existed, and that it took the form of vmPFC driving the hippocampus. We conclude that episodic memory and scene imagination share fundamental neural dynamics, and the process of constructing vivid, spatially coherent, contextually appropriate scene imagery is strongly modulated by vmPFC.

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

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bioRxiv2018

Identifying the cognitive processes underpinning hippocampal-dependent tasks

Autobiographical memory, future thinking and spatial navigation are critical cognitive functions that are thought to be related, and are known to depend upon a brain structure called the hippocampus. Surprisingly, direct evidence for their interrelatedness is lacking, as is an understanding of why they might be related. There is debate about whether they are linked by an underlying memory-related process or, as has more recently been suggested, because they each require the endogenous construction of scene imagery. Here, using a large sample of participants and multiple cognitive tests with a wide spread of individual differences in performance, we found that these functions are indeed related. Mediation analyses further showed that scene construction, and not memory, mediated (explained) the relationships between the functions. These findings offer a fresh perspective on autobiographical memory, future thinking, navigation, and also on the hippocampus, where scene imagery appears to play an influential role.

neuroscience↗

bioRxiv2018

Thalamus, subiculum and retrosplenial cortex encode 3D head direction information in volumetric space

Head direction cells are critical for navigation because they convey information about which direction an animal is facing within an environment. To date, most studies on head direction encoding have been conducted on a horizontal two-dimensional (2D) plane, and little is known about how three-dimensional (3D) direction information is encoded in the brain despite humans and other animals living in a 3D world. Here, we investigated head direction encoding in the human brain while participants moved within a virtual 3D \"spaceship\" environment. Movement was not constrained to planes and instead participants could move along all three axes in volumetric space as if in zero gravity. Using functional MRI multivoxel pattern similarity analysis, we found evidence that the thalamus, particularly the anterior portion, and the subiculum encoded the horizontal component of 3D head direction (azimuth). In contrast, the retrosplenial cortex was significantly more sensitive to the vertical direction (pitch) than to the azimuth. Our results also indicated that vertical direction information in the retrosplenial cortex was significantly correlated with behavioural performance during a direction judgment task. Our findings represent the first evidence showing that the classic head direction system that has been identified on a horizontal 2D plane also seems to encode vertical and horizontal heading in 3D space in the human brain.

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bioRxiv2018

3D grid cells in human entorhinal cortex: Theoretical and methodological considerations and fMRI findings

Recent human functional magnetic resonance imaging (fMRI) and animal electrophysiology studies suggest that grid cells in entorhinal cortex are an efficient neural mechanism for encoding knowledge about the world, not only for spatial location but also for more abstract cognitive information. The world, be it physical or abstract, is often high-dimensional, but grid cells have been mainly studied on a simple two-dimensional (2D) plane. Recent theoretical studies have proposed how grid cells encode three-dimensional (3D) physical space, but it is unknown whether grid codes can be examined non-invasively in humans. Here, we investigated whether it was feasible to test different 3D grid models using fMRI based on the direction-modulated property of grid signals. In doing so, we developed interactive software to help researchers visualize 3D grid fields and predict grid activity in 3D as a function of movement directions. We found that a direction-modulated grid analysis was sensitive to one type of 3D grid model - a face-centred cubic (FCC) lattice model. As a proof of concept, we searched for 3D grid-like signals in human entorhinal cortex using a novel 3D virtual reality paradigm and a new fMRI analysis method. We found that signals in the left entorhinal cortex were explained by the FCC model. This is preliminary evidence for 3D grid codes in the human brain, notwithstanding the inherent methodological limitations of fMRI. We believe that our findings and software serve as a useful initial stepping-stone for studying grid cells in realistic 3D worlds and also, potentially, for interrogating abstract high-dimensional cognitive processes.\n\nHighlightsWe present software and an analysis method to probe 3D grid codes using human fMRI Based on an alignment score between 3D movement direction and grid orientation We then tested this using a 3D virtual environment and fMRI\n\nSignals in entorhinal cortex were explained by a face-centred cubic lattice model

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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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bioRxiv2017

Confronting the elephant in the room - verbal paired associates and the hippocampus

It is widely agreed that patients with bilateral hippocampal damage are impaired at binding pairs of words together. Consequently, the verbal paired associates (VPA) task has become emblematic of hippocampal function. This VPA deficit is not well understood, and is particularly difficult for hippocampal theories with a visuospatial bias to explain (e.g., cognitive map and scene construction theories). Resolving the tension among hippocampal theories concerning the VPA could be important for leveraging a fuller understanding of hippocampal function. Notably, VPA tasks typically use high imagery concrete words and so conflate imagery and binding. To determine why VPA engages the hippocampus, we devised an fMRI encoding task involving closely matched pairs of scene words, pairs of object words and pairs of very low imagery abstract words. We found that the anterior hippocampus was engaged during processing of both scene and object word pairs in comparison to abstract word pairs, despite binding occurring in all conditions. This was also the case when just subsequently remembered stimuli were considered. Moreover, for object word pairs, fMRI activity patterns in anterior hippocampus were more similar to those for scene imagery than object imagery. This was especially evident in participants who were high imagery users, and not in mid and low imagery users. Overall, our results show that hippocampal engagement during VPA, even when object word pairs are involved, seems to be evoked by scene imagery rather than binding. This may help to resolve the issue that visuospatial hippocampal theories have in accounting for verbal memory.

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bioRxiv2017

Temporally discontinuous engagement of the vmPFC in remote memory retrieval

Systems-level consolidation refers to the time-dependent reorganisation of memory traces in the neocortex, a process in which the ventromedial prefrontal cortex (vmPFC) has been implicated. Capturing the precise temporal evolution of this crucial process in humans has long proved elusive. Here, we used multivariate methods and a longitudinal functional MRI design to detect, with high granularity, the extent to which autobiographical memories of different ages were represented in vmPFC and how this changed over time. We observed an unexpected time-course of vmPFC recruitment during retrieval, rising and falling around an initial peak of 8-12 months, before re-engaging for older two and five year old memories. This pattern was replicated in two independent sets of memories. Moreover, it was further replicated in a follow-up study eight months later with the same participants and memories, where the individual memory representations had undergone their hypothesised strengthening or weakening over time. We conclude that the temporal engagement of vmPFC in memory retrieval seems to be non-monotonic, revealing a complex relationship between systems-level consolidation and prefrontal cortex recruitment that is unaccounted for by current theories.\n\nAuthor SummaryOur past experiences are captured in autobiographical memories which allow us to recollect events from our lives long after they originally occurred. A part of the brains frontal lobe, called the ventromedial prefrontal cortex or vmPFC, is known to be important for supporting autobiographical memories especially as memories become more remote. The precise temporal profile of the vmPFCs involvement is unclear, yet this information is vital if we are to understand how memories change over time and the mechanisms involved. In this study we sought to establish the time-course of vmPFC engagement in the recollection of autobiographical memories while participants recalled memories of different ages during functional magnetic resonance imaging (fMRI). Using a method that detects brain activity patterns associated with individual memories, we found that memory-specific neural patterns in vmPFC became more distinct over the first few months after a memory was formed, but then this initial involvement of vmPFC subsided after one year. However, more remote memories (two years and older), appeared to re-engage vmPFC once again. This temporal profile is difficult to accommodate within any single existing theory. Consequently, our results provoke a re-think about how memories evolve over time and the role played by the vmPFC.

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bioRxiv2017

Hippocampus, retrosplenial and parahippocampal cortices encode multi-compartment 3D space in a hierarchical manner

Humans commonly operate within 3D environments such as multi-floor buildings and yet there is a surprising dearth of studies that have examined how these spaces are represented in the brain. Here we had participants learn the locations of paintings within a virtual multi-level gallery building and then used behavioural tests and fMRI repetition suppression analyses to investigate how this 3D multi-compartment space was represented, and whether there was a bias in encoding vertical and horizontal information. We found faster response times for within-room egocentric spatial judgments and behavioural priming effects of visiting the same room, providing evidence for a compartmentalised representation of space. At the neural level, we observed a hierarchical encoding of 3D spatial information, with left anterior hippocampus representing local information within a room, while retrosplenial cortex, parahippocampal cortex and posterior hippocampus represented room information within the wider building. Of note, both our behavioural and neural findings showed that vertical and horizontal location information was similarly encoded, suggesting an isotropic representation of 3D space even in the context of a multi-compartment environment. These findings provide much-needed information about how the human brain supports spatial memory and navigation in buildings with numerous levels and rooms.

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