Sharing voxelwise neuroimaging results from rhesus monkeys and other species with Neurovault.

Animal neuroimaging studies can provide unique insights into brain structure and function, and can be leveraged to bridge the gap between animal and human neuroscience. In part, this power comes from the ability to combine mechanistic interventions with brain-wide neuroimaging. Due to their phylogenetic proximity to humans, nonhuman primate neuroimaging holds particular promise. Because nonhuman primate neuroimaging studies are often underpowered, there is a great need to share data amongst translational researchers. Data sharing efforts have been limited, however, by the lack of standardized tools and repositories through which nonhuman neuroimaging data can easily be archived and accessed. Here, we provide an extension of the Neurovault framework to enable sharing of statistical maps and related voxelwise neuroimaging data from other species and template-spaces. Neurovault, which was previously limited to human neuroimaging data, now allows researchers to easily upload and share nonhuman primate neuroimaging results. This promises to facilitate open, integrative, cross-species science while affording researchers the increased statistical power provided by data aggregation. In addition, the Neurovault code-base now enables the addition of other species and template-spaces. Together, these advances promise to bring neuroimaging data sharing to research in other species, for supplemental data, location-based atlases, and data that would otherwise be relegated to a "file-drawer". As increasing numbers of researchers share their nonhuman neuroimaging data on Neurovault, this resource will enable novel, large-scale, cross-species comparisons that were previously impossible.

Landmarks: A solution for spatial navigation and memory experiments in virtual reality.

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.

Stochasticity and Infectious Disease Dynamics: Density and Weather Effects on a Fungal Insect Pathogen.

In deterministic models of epidemics, there is a host abundance threshold above which the introduction of a few infected individuals leads to a severe epidemic. Studies of weather-driven animal pathogens often assume that abundance thresholds will be overwhelmed by weather-driven stochasticity, but tests of this assumption are lacking. We collected observational and experimental data for a fungal pathogen, Entomophaga maimaiga, that infects the gypsy moth, Lymantria dispar. We used an advanced statistical-computing algorithm to fit mechanistic models to our data, such that different models made different assumptions about the effects of host density and weather on E. maimaiga epizootics (epidemics in animals). We then used Akaike information criterion analysis to choose the best model. In the best model, epizootics are driven by a combination of weather and host density, and the model does an excellent job of explaining the data, whereas models that allow only for weather effects or only for density-dependent effects do a poor job of explaining the data. Density-dependent transmission in our best model produces a host density threshold, but this threshold is strongly blurred by the stochastic effects of weather. Our work shows that host-abundance thresholds may be important even if weather strongly affects transmission, suggesting that epidemiological models that allow for weather have an important role to play in understanding animal pathogens. The success of our model means that it could be useful for managing the gypsy moth, an important pest of hardwood forests in North America.

Cytoarchitectonically-driven MRI atlas of nonhuman primate hippocampus: Preservation of subfield volumes in aging.

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.

Behavioral Impact of Long-Term Chronic Implantation of Neural Recording Devices in the Rhesus Macaque.

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.

A Tale of Two Temporal Coding Strategies: Common and Dissociable Brain Regions Involved in Recency versus Associative Temporal Order Retrieval Strategies.

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.

Complementary roles of human hippocampal subregions during retrieval of spatiotemporal context.

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.

Complementary roles of human hippocampal subfields in differentiation and integration of spatial context.

The unique circuitry of the hippocampus is thought to support the encoding and retrieval of context-rich episodic memories. Given the neuroanatomical differences between the hippocampal subfields, determining their functional roles during representation of contextual features in humans is an important yet unaddressed research goal. Prior studies suggest that, during the acquisition of information from the environment, the dentate gyrus (DG) and CA3 subfields rapidly differentiate competing contextual representations, whereas CA1, situated downstream from CA3/DG, is believed to process input from both CA3 and neocortical areas via the temporoammonic pathway. To further explore the functionality of these roles, we used high-resolution fMRI to investigate multivariate response patterns within CA3/DG and CA1 during the processing of spatial context. While undergoing functional imaging, participants viewed videos of virtual environments and were asked to discriminate between similar yet geometrically distinct cities. We manipulated a single contextual feature by systematically morphing the city configurations from one common geometric shape to another, resulting in four cities--two distinctively shaped cities and two intermediate "morphed" cities. Pattern similarity within CA3/DG scaled with geometric changes to the environment. In contrast, CA1 pattern similarity, as well as interregional pattern similarity between CA1 and parahippocampal cortex, increased for the regularly shaped configurations compared with the morphs. These results highlight different roles for subfields CA3/DG and CA1 in memory and advance our understanding of how subcomponents of the human hippocampal circuit represent contextual features of memories.

Successful retrieval of competing spatial environments in humans involves hippocampal pattern separation mechanisms.

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.

Roles of human hippocampal subfields in retrieval of spatial and temporal context.

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.

A non-randomised experimental feasibility study into the immediate effect of three different spinal manipulative protocols on kicking speed performance in soccer players.

BACKGROUND: The most utilized soccer kicking method is the instep kicking technique. Decreased motion in spinal joint segments results in adverse biomechanical changes within in the kinematic chain. These changes may be linked to a negative impact on soccer performance. This study tested the immediate effect of lumbar spine and sacroiliac manipulation alone and in combination on the kicking speed of uninjured soccer players. METHODS: This 2010 prospective, pre-post experimental, single-blinded (subject) required forty asymptomatic soccer players, from regional premier league teams, who were purposively allocated to one of four groups (based on the evaluation of the players by two blinded motion palpators). Segment dysfunction was either localized to the lumbar spine (Group 1), sacroiliac joint (Group 2), the lumbar spine and sacroiliac joint (Group 3) or not present in the sham laser group (Group 4). All players underwent a standardized warm-up before the pre-measurements. Manipulative intervention followed after which post-measurements were completed. Measurement outcomes included range of motion changes (digital inclinometer); kicking speed (Speed Trac™ Speed Sport Radar) and the subjects' perception of a change in kicking speed. SPSS version 15.0 was used to analyse the data, with repeated measures ANOVA and a p-value <0.05 (CI 95%). RESULTS: Lumbar spine manipulation resulted in significant range of motion increases in left and right rotation. Sacroiliac manipulation resulted in no significant changes in the lumbar range of motion. Combination manipulative interventions resulted in significant range of motion increases in lumbar extension, right rotation and right SI joint flexion. There was a significant increase in kicking speed post intervention for all three manipulative intervention groups (when compared to sham). A significant correlation was seen between Likert based-scale subjects' perception of change in kicking speed post intervention and the objective results obtained. CONCLUSIONS: This pilot study showed that lumbar spine manipulation combined with SI joint manipulation, resulted in an effective intervention for short-term increases in kicking speed/performance. However, the lack of an a priori analysis, a larger sample size and an unblinded outcome measures assessor requires that this study be repeated, addressing these concerns and for these outcomes to be validated.

Count your eggs before they invade: identifying and quantifying egg clutches of two invasive apple snail species (Pomacea).

Winning the war against invasive species requires early detection of invasions. Compared to terrestrial invaders, aquatic species often thrive undetected under water and do not garner notice until too late for early action. However, fortunately for managers, apple snails (Family Ampullariidae, Genus Pomacea) provide their own conspicuous sign of invasion in the form of vibrantly colored egg clutches. Managers can potentially use egg clutches laid in the riparian zone as a means of early detection and species identification. To facilitate such efforts, we quantified differences in characteristics (length, width, depth, mass, egg number) of field-laid clutches for the two most common invasive species of apple snail, P. canaliculata and P. maculata, in native and non-native populations. Pomacea canaliculata native and non-native populations differed noticeably only in width. Native P. maculata clutches possessed significantly greater width, mass and eggs numbers compared with native P. canaliculata. Non-native P. maculata clutches significantly exceeded all other populations in all measured characteristics. Consequently, these traits may successfully distinguish between species. Fecundity data also allowed us to develop models that accurately estimated the number of eggs per clutch for each species based on clutch dimensions. We tested one, two and three dimensional models of clutches, including rendering a clutch as either a complete ellipsoid or an ellipsoid intersected by a cylinder to represent the oviposition site. Model comparisons found the product of length and depth, with a different function for each population, best predicted egg number for both species. Comparisons of egg number to clutch volume and mass implied non-native P. canaliculata may be food limited, while non-native P. maculata appeared to produce such enormous clutches by having access to greater nutrients than the native population. With these new tools, researchers and managers can quickly identify, quantify and begin eradication of new non-native apple snail populations.