Peter Zeidman

Anterior hippocampus: the anatomy of perception, imagination and episodic memory

The brain creates a model of the world around us. We can use this representation to perceive and comprehend what we see at any given moment, but also to vividly re-experience scenes from our past and imagine future (or even fanciful) scenarios. Recent work has shown that these cognitive functions — perception, imagination and recall of scenes and events — all engage the anterior hippocampus. In this Opinion article, we capitalize on new findings from functional neuroimaging to propose a model that links high-level cognitive functions to specific structures within the anterior hippocampus.

Bayesian model reduction and empirical Bayes for group (DCM) studies.

This technical note describes some Bayesian procedures for the analysis of group studies that use nonlinear models at the first (within-subject) level – e.g., dynamic causal models – and linear models at subsequent (between-subject) levels. Its focus is on using Bayesian model reduction to finesse the inversion of multiple models of a single dataset or a single (hierarchical or empirical Bayes) model of multiple datasets. These applications of Bayesian model reduction allow one to consider parametric random effects and make inferences about group effects very efficiently (in a few seconds). We provide the relatively straightforward theoretical background to these procedures and illustrate their application using a worked example. This example uses a simulated mismatch negativity study of schizophrenia. We illustrate the robustness of Bayesian model reduction to violations of the (commonly used) Laplace assumption in dynamic causal modelling and show how its recursive application can facilitate both classical and Bayesian inference about group differences. Finally, we consider the application of these empirical Bayesian procedures to classification and prediction.

Constructing, Perceiving, and Maintaining Scenes: Hippocampal Activity and Connectivity

In recent years, evidence has accumulated to suggest the hippocampus plays a role beyond memory. A strong hippocampal response to scenes has been noted, and patients with bilateral hippocampal damage cannot vividly recall scenes from their past or construct scenes in their imagination. There is debate about whether the hippocampus is involved in the online processing of scenes independent of memory. Here, we investigated the hippocampal response to visually perceiving scenes, constructing scenes in the imagination, and maintaining scenes in working memory. We found extensive hippocampal activation for perceiving scenes, and a circumscribed area of anterior medial hippocampus common to perception and construction. There was significantly less hippocampal activity for maintaining scenes in working memory. We also explored the functional connectivity of the anterior medial hippocampus and found significantly stronger connectivity with a distributed set of brain areas during scene construction compared with scene perception. These results increase our knowledge of the hippocampus by identifying a subregion commonly engaged by scenes, whether perceived or constructed, by separating scene construction from working memory, and by revealing the functional network underlying scene construction, offering new insights into why patients with hippocampal lesions cannot construct scenes.

Crowdsourcing for cognitive science--the utility of smartphones.

By 2015, there will be an estimated two billion smartphone users worldwide. This technology presents exciting opportunities for cognitive science as a medium for rapid, large-scale experimentation and data collection. At present, cost and logistics limit most study populations to small samples, restricting the experimental questions that can be addressed. In this study we investigated whether the mass collection of experimental data using smartphone technology is valid, given the variability of data collection outside of a laboratory setting. We presented four classic experimental paradigms as short games, available as a free app and over the first month 20,800 users submitted data. We found that the large sample size vastly outweighed the noise inherent in collecting data outside a controlled laboratory setting, and show that for all four games canonical results were reproduced. For the first time, we provide experimental validation for the use of smartphones for data collection in cognitive science, which can lead to the collection of richer data sets and a significant cost reduction as well as provide an opportunity for efficient phenotypic screening of large populations.

Reading without the left ventral occipito-temporal cortex

The left ventral occipito-temporal cortex (LvOT) is thought to be essential for the rapid parallel letter processing that is required for skilled reading. Here we investigate whether rapid written word identification in skilled readers can be supported by neural pathways that do not involve LvOT. Hypotheses were derived from a stroke patient who acquired dyslexia following extensive LvOT damage. The patient followed a reading trajectory typical of that associated with pure alexia, re-gaining the ability to read aloud many words with declining performance as the length of words increased. Using functional MRI and dynamic causal modelling (DCM), we found that, when short (three to five letter) familiar words were read successfully, visual inputs to the patient’s occipital cortex were connected to left motor and premotor regions via activity in a central part of the left superior temporal sulcus (STS). The patient analysis therefore implied a left hemisphere “reading-without-LvOT” pathway that involved STS. We then investigated whether the same reading-without-LvOT pathway could be identified in 29 skilled readers and whether there was inter-subject variability in the degree to which skilled reading engaged LvOT. We found that functional connectivity in the reading-without-LvOT pathway was strongest in individuals who had the weakest functional connectivity in the LvOT pathway. This observation validates the findings of our patient’s case study. Our findings highlight the contribution of a left hemisphere reading pathway that is activated during the rapid identification of short familiar written words, particularly when LvOT is not involved. Preservation and use of this pathway may explain how patients are still able to read short words accurately when LvOT has been damaged.

Forward and backward inference in spatial cognition

This paper shows that the various computations underlying spatial cognition can be implemented using statistical inference in a single probabilistic model. Inference is implemented using a common set of ‘lower-level’ computations involving forward and backward inference over time. For example, to estimate where you are in a known environment, forward inference is used to optimally combine location estimates from path integration with those from sensory input. To decide which way to turn to reach a goal, forward inference is used to compute the likelihood of reaching that goal under each option. To work out which environment you are in, forward inference is used to compute the likelihood of sensory observations under the different hypotheses. For reaching sensory goals that require a chaining together of decisions, forward inference can be used to compute a state trajectory that will lead to that goal, and backward inference to refine the route and estimate control signals that produce the required trajectory. We propose that these computations are reflected in recent findings of pattern replay in the mammalian brain. Specifically, that theta sequences reflect decision making, theta flickering reflects model selection, and remote replay reflects route and motor planning. We also propose a mapping of the above computational processes onto lateral and medial entorhinal cortex and hippocampus.

Exploring the parahippocampal cortex response to high and low spatial frequency spaces

The posterior parahippocampal cortex (PHC) supports a range of cognitive functions, in particular scene processing. However, it has recently been suggested that PHC engagement during functional MRI simply reflects the representation of three-dimensional local space. If so, PHC should respond to space in the absence of scenes, geometric layout, objects or contextual associations. It has also been reported that PHC activation may be influenced by low-level visual properties of stimuli such as spatial frequency. Here, we tested whether PHC was responsive to the mere sense of space in highly simplified stimuli, and whether this was affected by their spatial frequency distribution. Participants were scanned using functional MRI while viewing depictions of simple three-dimensional space, and matched control stimuli that did not depict a space. Half the stimuli were low-pass filtered to ascertain the impact of spatial frequency. We observed a significant interaction between space and spatial frequency in bilateral PHC. Specifically, stimuli depicting space (more than nonspatial stimuli) engaged the right PHC when they featured high spatial frequencies. In contrast, the interaction in the left PHC did not show a preferential response to space. We conclude that a simple depiction of three-dimensional space that is devoid of objects, scene layouts or contextual associations is sufficient to robustly engage the right PHC, at least when high spatial frequencies are present. We suggest that coding for the presence of space may be a core function of PHC, and could explain its engagement in a range of tasks, including scene processing, where space is always present.

Investigating the functions of subregions within anterior hippocampus

Previous functional MRI (fMRI) studies have associated anterior hippocampus with imagining and recalling scenes, imagining the future, recalling autobiographical memories and visual scene perception. We have observed that this typically involves the medial rather than the lateral portion of the anterior hippocampus. Here, we investigated which specific structures of the hippocampus underpin this observation. We had participants imagine novel scenes during fMRI scanning, as well as recall previously learned scenes from two different time periods (one week and 30 min prior to scanning), with analogous single object conditions as baselines. Using an extended segmentation protocol focussing on anterior hippocampus, we first investigated which substructures of the hippocampus respond to scenes, and found both imagination and recall of scenes to be associated with activity in presubiculum/parasubiculum, a region associated with spatial representation in rodents. Next, we compared imagining novel scenes to recall from one week or 30 min before scanning. We expected a strong response to imagining novel scenes and 1-week recall, as both involve constructing scene representations from elements stored across cortex. By contrast, we expected a weaker response to 30-min recall, as representations of these scenes had already been constructed but not yet consolidated. Both imagination and 1-week recall of scenes engaged anterior hippocampal structures (anterior subiculum and uncus respectively), indicating possible roles in scene construction. By contrast, 30-min recall of scenes elicited significantly less activation of anterior hippocampus but did engage posterior CA3. Together, these results elucidate the functions of different parts of the anterior hippocampus, a key brain area about which little is definitely known.

Age-related changes in working memory and the ability to ignore distraction

Significance We reveal a novel and highly significant change in how items are held in mind in healthy aging. Using smartphones, data were collected from 29,631 participants, between the ages of 18–69 y. We compare the ability to exclude distractors when items are entered into working memory (WM) (encoding distraction, ED) and when items are held in mind (delay distraction, DD). In older adults, WM in the absence of distraction was more similar to ED exclusion than DD exclusion. A greater reliance on focused attention during encoding may reflect compensation for the more pronounced deterioration we observed in DD exclusion in older age. This can inform other areas of cognition and strategies to ameliorate or manage debilitating age-related cognitive decline. A weakened ability to effectively resist distraction is a potential basis for reduced working memory capacity (WMC) associated with healthy aging. Exploiting data from 29,631 users of a smartphone game, we show that, as age increases, working memory (WM) performance is compromised more by distractors presented during WM maintenance than distractors presented during encoding. However, with increasing age, the ability to exclude distraction at encoding is a better predictor of WMC in the absence of distraction. A significantly greater contribution of distractor filtering at encoding represents a potential compensation for reduced WMC in older age.

A central role for the retrosplenial cortex in de novo environmental learning

With experience we become accustomed to the types of environments that we normally encounter as we navigate in the world. But how does this fundamental knowledge develop in the first place and what brain regions are involved? To examine de novo environmental learning, we created an ‘alien’ virtual reality world populated with landmarks of which participants had no prior experience. They learned about this environment by moving within it during functional MRI (fMRI) scanning while we tracked their evolving knowledge. Retrosplenial cortex (RSC) played a central and highly selective role by representing only the most stable, permanent features in this world. Subsequently, increased coupling was noted between RSC and hippocampus, with hippocampus then expressing knowledge of permanent landmark locations and overall environmental layout. Studying how environmental representations emerge from scratch provided a new window into the information processing underpinning the brains navigation system, highlighting the key influence of the RSC. DOI: http://dx.doi.org/10.7554/eLife.09031.001