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Research into the behavioral and neural correlates of spatial cognition and navigation has benefited greatly from recent advances in virtual reality (VR) technology. Devices such as head-mounted displays (HMDs) and omnidirectional treadmills provide research participants with access to a more complete range of body-based cues, which facilitate the naturalistic study of learning and memory in three-dimensional (3D) spaces. One limitation to using these technologies for research applications is that they almost ubiquitously require integration with video game development platforms, also known as game engines. While powerful, game engines do not provide an intrinsic framework for experimental design and require at least a working proficiency with the software and any associated programming languages or integrated development environments (IDEs). Here, we present a new asset package, called Landmarks, for designing and building 3D navigation experiments in the Unity game engine. Landmarks combines the ease of building drag-and-drop experiments using no code, with the flexibility of allowing users to modify existing aspects, create new content, and even contribute their work to the open-source repository via GitHub, if they so choose. Landmarks is actively maintained and is supplemented by a wiki with resources for users including links, tutorials, videos, and more. We compare several alternatives to Landmarks for building navigation experiments and 3D experiments more generally, provide an overview of the package and its structure in the context of the Unity game engine, and discuss benefits relating to the ongoing and future development of Landmarks.

Background: Ensemble recording methods are pervasive in basic and clinical neuroscience research. Invasive neural implants are used in patients with drug resistant epilepsy to localize seizure origin, in neuropsychiatric or Parkinson's patients to alleviate symptoms via deep brain stimulation, and with animal models to conduct basic research. Studies addressing the brain's physiological response to chronic electrode implants demonstrate that the mechanical trauma of insertion is followed by an acute inflammatory response as well as a chronic foreign body response. Despite use of invasive recording methods with animal models and humans, little is known of their effect on behavior in healthy populations., Objective: To quantify the effect of chronic electrode implantation targeting the hippocampus on recognition memory performance., Methods: Four healthy female rhesus macaques were tested in a delayed nonmatching-to-sample (DNMS) recognition memory task before and after hippocampal implantation with a tetrode array device., Results: Trials to criterion and recognition memory performance were not significantly different before vs. after chronic electrode implantation., Conclusion: Our results suggest that chronic implants did not produce significant impairments on DNMS performance., (© 2018 International Neuromodulation Society.)

Identification of primate hippocampal subfields in vivo using structural MRI imaging relies on variable anatomical guidelines, signal intensity differences, and heuristics to differentiate between regions (Yushkevich et al., 2015a). Thus, a clear anatomically-driven basis for subfield demarcation is lacking. Recent work, however, has begun to develop methods to use ex vivo histology or ex vivo MRI (Adler et al., 2014; Iglesias et al., 2015) that have the potential to inform subfield demarcations of in vivo images. For optimal results, however, ex vivo and in vivo images should ideally be matched within the same healthy brains, with the goal to develop a neuroanatomically-driven basis for in vivo structural MRI images. Here, we address this issue in young and aging rhesus macaques (young n = 5 and old n = 5) using ex vivo Nissl-stained sections in which we identified the dentate gyrus, CA3, CA2, CA1, subiculum, presubiculum, and parasubiculum guided by morphological cell properties (30 μm thick sections spaced at 240 μm intervals and imaged at 161 nm/pixel). The histologically identified boundaries were merged with in vivo structural MRIs (0.625 × 0.625 × 1 mm) from the same subjects via iterative rigid and diffeomorphic registration resulting in probabilistic atlases of young and old rhesus macaques. Our results indicate stability in hippocampal subfield volumes over an age range of 13 to 32 years, consistent with previous results showing preserved whole hippocampal volume in aged macaques (Shamy et al., 2006). Together, our methods provide a novel approach for identifying hippocampal subfields in non-human primates and a potential 'ground truth' for more accurate identification of hippocampal subfield boundaries on in vivo MRIs. This could, in turn, have applications in humans where accurately identifying hippocampal subfields in vivo is a critical research goal., (© 2017 Wiley Periodicals, Inc.)

Numerous studies indicate the importance of the hippocampus to temporal order retrieval. However, behavioral studies suggest that there are different ways to retrieve temporal order information from encoded sequences, one involving an associative strategy (retrieving associations using neighboring items in a list) and another involving a recency strategy (determining which of two items came first). It remains unresolved, however, whether both strategies recruit the hippocampus or only associative strategies, consistent with the hippocampus's role in relational processing. To address this, we developed a paradigm in which we dissociated associative versus recency-based retrieval, involving the same stimulus presentation during retrieval. Associative retrieval involved an increase in RT (and decrease in performance) with greater distances between intervals, consistent with the need to retrieve intervening associations. Recency-based retrieval involved an increase in RT (and decrease in performance) with shorter distances between intervals, suggesting the use of a strength-based coding mechanism to retrieve information. We employed fMRI to determine the neural basis of the different strategies. Both strategies showed significant levels of hippocampal activation and connectivity that did not differ between tasks. In contrast, both univariate and connectivity pattern analyses revealed differences in extrahippocampal areas such as parietal and frontal cortices. A covariate analysis suggested that differences could not be explained by task difficulty alone. Together, these findings suggest that the hippocampus plays a role in both forms of temporal order retrieval, with neocortical networks mediating the different cognitive demands for associative versus recency-based temporal order retrieval.

The rodent hippocampus represents different spatial environments distinctly via changes in the pattern of "place cell" firing. It remains unclear, though, how spatial remapping in rodents relates more generally to human memory. Here participants retrieved four virtual reality environments with repeating or novel landmarks and configurations during high-resolution functional magnetic resonance imaging (fMRI). Both neural decoding performance and neural pattern similarity measures revealed environment-specific hippocampal neural codes. Conversely, an interfering spatial environment did not elicit neural codes specific to that environment, with neural activity patterns instead resembling those of competing environments, an effect linked to lower retrieval performance. We find that orthogonalized neural patterns accompany successful disambiguation of spatial environments while erroneous reinstatement of competing patterns characterized interference errors. These results provide the first evidence for environment-specific neural codes in the human hippocampus, suggesting that pattern separation/completion mechanisms play an important role in how we successfully retrieve memories.

While numerous studies indicate the involvement of the hippocampus in encoding and retrieval of spatial and temporal context, the neural basis of spatial and temporal processing within the hippocampal circuit remains unclear. We employed a novel paradigm in which participants encoded stores within a spatial layout by visiting them in a specific temporal order. Participants then underwent high-resolution functional magnetic resonance imaging (fMRI) targeting the hippocampus while retrieving details of the spatial or temporal context in alternating blocks. During retrieval, participants made judgments about either near or far intervals within the spatial layout or temporal sequence. Across both near and far intervals, we found that retrieving spatial layout and temporal order information resulted in comparable levels of activation in the hippocampus that was not preferentially localized to a specific subfield. Furthermore, using a multivariate approach called multivariate pattern similarity analysis (MPSA), we found that correct near judgments vs. correct far judgments differed in their patterns of activity for spatial vs. temporal order judgments. Despite these differences in MPSA patterns, we did not find any specific subfields differentially recruited for spatial vs. temporal order retrieval. We discuss our results in terms of their relation to computational models of hippocampal subfield function and suggest mechanisms by which the hippocampus could process space and temporal order without the need for specific contributions from hippocampal subfields., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Current evidence strongly supports the central involvement of the human medial temporal lobes (MTL) in storing and retrieving memories for recently experienced events. However, a critical remaining question regards exactly how the hippocampus and surrounding cortex represents spatiotemporal context defining an event in memory. Competing accounts suggest that this process may be accomplished by the following: (1) an overall increase in neural similarity of representations underlying spatial and temporal context, (2) a differentiation of competing spatiotemporal representations, or (3) a combination of the two processes, with different subregions performing these two functions within the MTL. To address these competing proposals, we used high-resolution functional magnetic resonance imaging targeting the MTL along with a multivariate pattern similarity approach with 19 participants. While undergoing imaging, participants performed a task in which they retrieved spatial and temporal contextual representations from a recently learned experience. Results showed that successfully retrieving spatiotemporal context defining an episode involved a decrease in pattern similarity between putative spatial and temporal contextual representations in hippocampal subfields CA2/CA3/DG, whereas the parahippocampal cortex (PHC) showed the opposite pattern. These findings could not be accounted for by differences in univariate activations for complete versus partial retrieval nor differences in correlations for correct or incorrect retrieval. Together, these data suggest that the CA2/CA3/DG serves to differentiate competing contextual representations, whereas the PHC stores a comparatively integrated trace of scene-specific context, both of which likely play important roles in successful episodic memory retrieval., (Copyright © 2014 the authors 0270-6474/14/346834-09$15.00/0.)

Endocytotic transport may provide a mechanism for myocyte uptake of agents which ameliorate the effects of myocardial ischaemia. Examination of the inner capillary surface by transmission electron microscopy (TEM) is tedious and slow, while use of scanning electron microscopy permits the examination of greater areas in less time. Methods to obtain oblique exposures of capillaries and provide sufficient resolution to observe endocytotic pits were explored. Partial success was achieved using glutaraldehyde fixed tissue, treated with 30% glycerol, frozen-fractured under hexane at -85 degrees C, then dehydrated with acetone at -25 degrees C, critical-point dried and lightly coated with gold. Ultrastructural detail comparable with TEM images of heart tissue was obtained, but the resolution appeared limited by the coating process. It was not possible to verify stimulation of endocytosis by AMP in coronary capillary endothelia with scanning electron microscopy, due to this limitation.