Two years later - Revisiting autobiographical memory representations in vmPFC and hippocampus

A long-standing question in memory neuroscience concerns how and where autobiographical memories of personal experiences are represented in the brain. In a previous high resolution multivoxel pattern analysis fMRI study, we examined two week old (recent) and ten year old (remote) autobiographical memories (Bonnici et al., 2012, J. Neurosci. 32:16982-16991). We found that remote memories were particularly well represented in ventromedial prefrontal cortex (vmPFC) compared to recent memories. Moreover, while both types of memory were represented within anterior and posterior hippocampus, remote memories were more easily distinguished in the posterior portion. These findings suggested that a change of some kind had occurred between two weeks and ten years in terms of where autobiographical memories were represented in the brain. In order to examine this further, here participants from the original study returned two years later and recalled the memories again. We found that there was no difference in the detectability of memory representations within vmPFC for the now 2 year old and 12 year old memories, and this was also the case for the posterior hippocampus. Direct comparison of the two week old memories (original study) with themselves two years later (present study) confirmed that their representation within vmPFC had become more evident. Overall, this within-subjects longitudinal fMRI study extends our understanding of autobiographical memory representations by allowing us to narrow the window within which their consolidation is likely to occur. We conclude that after a memory is initially encoded, its representation within vmPFC has stablised by, at most, two years later

Dissociating Landmark Stability from Orienting Value Using Functional Magnetic Resonance Imaging

Retrosplenial cortex (RSC) plays a role in using environmental landmarks to help orientate oneself in space. It has also been consistently implicated in processing landmarks that remain fixed in a permanent location. However, it is not clear whether the RSC represents the permanent landmarks themselves or instead the orienting relevance of these landmarks. In previous functional magnetic resonance imaging (fMRI) studies, these features have been conflated-stable landmarks were always useful for orienting. Here, we dissociated these two key landmark attributes to investigate which one best reflects the function of the RSC. Before scanning, participants learned the features of novel landmarks about which they had no prior knowledge. During fMRI scanning, we found that the RSC was more engaged when people viewed permanent compared with transient landmarks and was not responsive to the orienting relevance of landmarks. Activity in RSC was also related to the amount of landmark permanence information a person had acquired and, as knowledge increased, the more the RSC drove responses in the anterior thalamus while viewing permanent landmarks. In contrast, the angular gyrus and the hippocampus were engaged by the orienting relevance of landmarks, but not their permanence, with the hippocampus also sensitive to the distance between relevant landmarks and target locations. We conclude that the coding of permanent landmarks in RSC may drive processing in regions like anterior thalamus, with possible implications for the efficacy of functions such as navigation

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

Scenes, Spaces, and Memory Traces: What Does the Hippocampus Do?

The hippocampus is one of the most closely scrutinized brain structures in neuroscience. While traditionally associated with memory and spatial cognition, in more recent years it has also been linked with other functions, including aspects of perception and imagining fictitious and future scenes. Efforts continue apace to understand how the hippocampus plays such an apparently wide-ranging role. Here we consider recent developments in the field and in particular studies of patients with bilateral hippocampal damage. We outline some key findings, how they have subsequently been challenged, and consider how to reconcile the disparities that are at the heart of current lively debates in the hippocampal literature

Efficacy of navigation may be influenced by retrosplenial cortex-mediated learning of landmark stability

Human beings differ considerably in their ability to orient and navigate within the environment, but it has been difficult to determine specific causes of these individual differences. Permanent, stable landmarks are thought to be crucial for building a mental representation of an environment. Poor, compared to good, navigators have been shown to have difficulty identifying permanent landmarks, with a concomitant reduction in functional MRI (fMRI) activity in the retrosplenial cortex. However, a clear association between navigation ability and the learning of permanent landmarks has not been established. Here we tested for such a link. We had participants learn a virtual reality environment by repeatedly moving through it during fMRI scanning. The environment contained landmarks of which participants had no prior experience, some of which remained fixed in their locations while others changed position each time they were seen. After the fMRI learning phase, we divided participants into good and poor navigators based on their ability to find their way in the environment. The groups were closely matched on a range of cognitive and structural brain measures. Examination of the learning phase during scanning revealed that, while good and poor navigators learned to recognise the environment's landmarks at a similar rate, poor navigators were impaired at registering whether landmarks were stable or transient, and this was associated with reduced engagement of the retrosplenial cortex. Moreover, a mediation analysis showed that there was a significant effect of landmark permanence learning on navigation performance mediated through retrosplenial cortex activity. We conclude that a diminished ability to process landmark permanence may be a contributory factor to sub-optimal navigation, and could be related to the level of retrosplenial cortex engagement

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

Characterizing Strategy Use During the Performance of Hippocampal-Dependent Tasks

Recalling the past, thinking about the future, and navigating in the world are linked with a brain structure called the hippocampus. Precisely, how the hippocampus enables these critical cognitive functions is still debated. The strategies people use to perform tasks associated with these functions have been under-studied, and yet, such information could augment our understanding of the associated cognitive processes and neural substrates. Here, we devised and deployed an in-depth protocol to examine the explicit strategies used by 217 participants to perform four naturalistic tasks widely acknowledged to be hippocampal-dependent, namely, those assessing scene imagination, autobiographical memory recall, future thinking, and spatial navigation. In addition, we also investigated strategy use for three laboratory-based memory tasks, one of which is held to be hippocampal-dependent – concrete verbal paired associates (VPA) – and two tasks, which are likely hippocampal-independent – abstract VPA and the dead or alive semantic memory test. We found that scene visual imagery was the dominant strategy not only when mentally imagining scenes, but also during autobiographical memory recall, when thinking about the future and during navigation. Moreover, scene visual imagery strategies were used most frequently during the concrete VPA task, whereas verbal strategies were most prevalent for the abstract VPA task and the dead or alive semantic memory task. The ubiquity of specifically scene visual imagery use across a range of tasks may attest to its, perhaps underappreciated, importance in facilitating cognition, while also aligning with perspectives that emphasize a key role for the hippocampus in constructing scene imagery

Scene construction in developmental amnesia: An fMRI study.

Amnesic patients with bilateral hippocampal damage sustained in adulthood are generally unable to construct scenes in their imagination. By contrast, patients with developmental amnesia (DA), where hippocampal damage was acquired early in life, have preserved performance on this task, although the reason for this sparing is unclear. One possibility is that residual function in remnant hippocampal tissue is sufficient to support basic scene construction in DA. Such a situation was found in the one amnesic patient with adult-acquired hippocampal damage (P01) who could also construct scenes. Alternatively, DA patients' scene construction might not depend on the hippocampus, perhaps being instead reliant on non-hippocampal regions and mediated by semantic knowledge. To adjudicate between these two possibilities, we examined scene construction during functional MRI (fMRI) in Jon, a well-characterised patient with DA who has previously been shown to have preserved scene construction. We found that when Jon constructed scenes he activated many of the regions known to be associated with imagining scenes in control participants including ventromedial prefrontal cortex, posterior cingulate, retrosplenial and posterior parietal cortices. Critically, however, activity was not increased in Jon's remnant hippocampal tissue. Direct comparisons with a group of control participants and patient P01, confirmed that they activated their right hippocampus more than Jon. Our results show that a type of non-hippocampal dependent scene construction is possible and occurs in DA, perhaps mediated by semantic memory, which does not appear to involve the vivid visualisation of imagined scenes

Joan Mott Prize Lecture 2013 - Memory consolidation in humans: New evidence and opportunities.

We are endlessly fascinated by memory; we desire to improve it and fear its loss. While it has long been recognised that brain regions such as the hippocampus are vital for supporting memories of our past experiences - autobiographical memories - we still lack fundamental knowledge about the mechanisms involved. This is because the study of specific neural signatures of autobiographical memories in vivo in humans presents a significant challenge. However, recent developments in high-resolution structural and functional magnetic resonance imaging (MRI) coupled with advanced analysis methods now permit access to the neural substrates of memory representations that has hitherto been precluded in humans. Here I describe how the application of 'decoding' techniques to brain imaging data is beginning to disclose how individual autobiographical memory representations evolve over time, deepening our understanding of systems-level consolidation, prompting in particular new questions about the roles of the hippocampus and ventromedial prefrontal cortex, and offering new opportunities to interrogate the elusive memory trace that has for so long confounded neuroscientists