Crossbow Injuries: Predictors of Mortality.

INTRODUCTION: Crossbow injuries are rare but carry significant morbidity and mortality, and there is limited evidence in the medical literature to guide care. This paper reviews the case reports and case series of crossbow injuries and looks for trends regarding morbidity and mortality based on the type of arrow, anatomic location of injury, and intent of injury. METHODS: Multiple databases were searched for cases of crossbow injuries and data were abstracted into a spreadsheet. Statistics were done in SPSS. RESULTS: 358 manuscripts were returned in the search. After deduplication and removal of nonclinical articles, 101 manuscripts remained. Seventy-one articles describing 90 incidents met the inclusion criteria. The mean age was 36.5 years. There were 10 female and 79 male victims. Fatality was 36% for injuries by field tip arrows and 71% for broadhead arrows, p = .024. Assaults were fatal in 84% of cases, suicides in 29%, and accidental injuries in 17%, p < .001. Mortality was similar for wounds to the head and neck (41%), chest (42%), abdomen (33%), extremities (50%), and multiple regions, p = .618. CONCLUSIONS: Crossbows are potentially lethal weapons sold with fewer restrictions than firearms. Injuries caused by broadhead arrows are more likely to be fatal than injuries from field tip arrows. The anatomic location of injury does not correlate with fatality. More than half of crossbow injuries are due to attempted suicide, with a high case-fatality rate.

Navigable Space and Traversable Edges Differentially Influence Reorientation in Sighted and Blind Mice.

Reorientation enables navigators to regain their bearings after becoming lost. Disoriented individuals primarily reorient themselves using the geometry of a layout, even when other informative cues, such as landmarks, are present. Yet the specific strategies that animals use to determine geometry are unclear. Moreover, because vision allows subjects to rapidly form precise representations of objects and background, it is unknown whether it has a deterministic role in the use of geometry. In this study, we tested sighted and congenitally blind mice (Ns = 8-11) in various settings in which global shape parameters were manipulated. Results indicated that the navigational affordances of the context-the traversable space-promote sampling of boundaries, which determines the effective use of geometric strategies in both sighted and blind mice. However, blind animals can also effectively reorient themselves using 3D edges by extensively patrolling the borders, even when the traversable space is not limited by these boundaries.

Dissociable spatial memory systems revealed by typical and atypical human development.

Rodent lesion studies have revealed the existence of two causally dissociable spatial memory systems, localized to the hippocampus and striatum that are preferentially sensitive to environmental boundaries and landmark objects, respectively. Here we test whether these two memory systems are causally dissociable in humans by examining boundary- and landmark-based memory in typical and atypical development. Adults with Williams syndrome (WS)-a developmental disorder with known hippocampal abnormalities-and typical children and adults, performed a navigation task that involved learning locations relative to a boundary or a landmark object. We found that boundary-based memory was severely impaired in WS compared to typically-developing mental-age matched (MA) children and chronological-age matched (CA) adults, whereas landmark-based memory was similar in all groups. Furthermore, landmark-based memory matured earlier in typical development than boundary-based memory, consistent with the idea that the WS cognitive phenotype arises from developmental arrest of late maturing cognitive systems. Together, these findings provide causal and developmental evidence for dissociable spatial memory systems in humans.

Coding of Object Size and Object Category in Human Visual Cortex.

A salient aspect of objects is their real-world size. Large objects tend to be fixed in the world and can act as navigational barriers and landmarks, whereas small objects tend to be moveable and manipulable. Previous work has identified regions of visual cortex that respond differentially to large versus small objects, but the role of size in organizing representations of object categories has not been fully explored. To address this issue, we scanned subjects while they viewed large and small objects drawn from 20 categories, with retinotopic extent equated across size classes. Univariate analyses replicated previous results showing a greater response to large than small objects in scene-responsive regions and the converse effect in the left occipitotemporal sulcus. Critically, multivariate analyses revealed organization-by-size both within and across functional regions, as evidenced by activation patterns that were more similar for object categories of the same size than for object categories of different size. This effect was observed in both scene- and object-responsive regions and across high-level visual cortex as a whole, but not in early visual cortex. We hypothesize that real-world size is an important dimension for object category organization because of the many ecologically significant differences between large and small objects.

Place recognition and heading retrieval are mediated by dissociable cognitive systems in mice.

A lost navigator must identify its current location and recover its facing direction to restore its bearings. We tested the idea that these two tasks--place recognition and heading retrieval--might be mediated by distinct cognitive systems in mice. Previous work has shown that numerous species, including young children and rodents, use the geometric shape of local space to regain their sense of direction after disorientation, often ignoring nongeometric cues even when they are informative. Notably, these experiments have almost always been performed in single-chamber environments in which there is no ambiguity about place identity. We examined the navigational behavior of mice in a two-chamber paradigm in which animals had to both recognize the chamber in which they were located (place recognition) and recover their facing direction within that chamber (heading retrieval). In two experiments, we found that mice used nongeometric features for place recognition, but simultaneously failed to use these same features for heading retrieval, instead relying exclusively on spatial geometry. These results suggest the existence of separate systems for place recognition and heading retrieval in mice that are differentially sensitive to geometric and nongeometric cues. We speculate that a similar cognitive architecture may underlie human navigational behavior.

Differences in the right inferior longitudinal fasciculus but no general disruption of white matter tracts in children with autism spectrum disorder.

One of the most widely cited features of the neural phenotype of autism is reduced "integrity" of long-range white matter tracts, a claim based primarily on diffusion imaging studies. However, many prior studies have small sample sizes and/or fail to address differences in data quality between those with autism spectrum disorder (ASD) and typical participants, and there is little consensus on which tracts are affected. To overcome these problems, we scanned a large sample of children with autism (n = 52) and typically developing children (n = 73). Data quality was variable, and worse in the ASD group, with some scans unusable because of head motion artifacts. When we follow standard data analysis practices (i.e., without matching head motion between groups), we replicate the finding of lower fractional anisotropy (FA) in multiple white matter tracts. However, when we carefully match data quality between groups, all these effects disappear except in one tract, the right inferior longitudinal fasciculus (ILF). Additional analyses showed the expected developmental increases in the FA of fiber tracts within ASD and typical groups individually, demonstrating that we had sufficient statistical power to detect known group differences. Our data challenge the widely claimed general disruption of white matter tracts in autism, instead implicating only one tract, the right ILF, in the ASD phenotype.

The occipital place area represents the local elements of scenes.

Neuroimaging studies have identified three scene-selective regions in human cortex: parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA). However, precisely what scene information each region represents is not clear, especially for the least studied, more posterior OPA. Here we hypothesized that OPA represents local elements of scenes within two independent, yet complementary scene descriptors: spatial boundary (i.e., the layout of external surfaces) and scene content (e.g., internal objects). If OPA processes the local elements of spatial boundary information, then it should respond to these local elements (e.g., walls) themselves, regardless of their spatial arrangement. Indeed, we found that OPA, but not PPA or RSC, responded similarly to images of intact rooms and these same rooms in which the surfaces were fractured and rearranged, disrupting the spatial boundary. Next, if OPA represents the local elements of scene content information, then it should respond more when more such local elements (e.g., furniture) are present. Indeed, we found that OPA, but not PPA or RSC, responded more to multiple than single pieces of furniture. Taken together, these findings reveal that OPA analyzes local scene elements - both in spatial boundary and scene content representation - while PPA and RSC represent global scene properties.

The occipital place area is causally and selectively involved in scene perception.

Functional magnetic resonance imaging has revealed a set of regions selectively engaged in visual scene processing: the parahippocampal place area (PPA), the retrosplenial complex (RSC), and a region around the transverse occipital sulcus (previously known as "TOS"), here renamed the "occipital place area" (OPA). Are these regions not only preferentially activated by, but also causally involved in scene perception? Although past neuropsychological data imply a causal role in scene processing for PPA and RSC, no such evidence exists for OPA. Thus, to test the causal role of OPA in human adults, we delivered transcranial magnetic stimulation (TMS) to the right OPA (rOPA) or the nearby face-selective right occipital face area (rOFA) while participants performed fine-grained perceptual discrimination tasks on scenes or faces. TMS over rOPA impaired discrimination of scenes but not faces, while TMS over rOFA impaired discrimination of faces but not scenes. In a second experiment, we delivered TMS to rOPA, or the object-selective right lateral occipital complex (rLOC), while participants performed categorization tasks involving scenes and objects. TMS over rOPA impaired categorization accuracy of scenes but not objects, while TMS over rLOC impaired categorization accuracy of objects but not scenes. These findings provide the first evidence that OPA is causally involved in scene processing, and further show that this causal role is selective for scene perception. Our findings illuminate the functional architecture of the scene perception system, and also argue against the "distributed coding" view in which each category-selective region participates in the representation of all objects.

Reorganization of visual processing in age-related macular degeneration depends on foveal loss.

PURPOSE: When individuals with central vision loss due to macular degeneration (MD) view stimuli in the periphery, most of them activate the region of retinotopic cortex normally activated only by foveal stimuli-a process often referred to as reorganization. Why do some show this reorganization of visual processing whereas others do not? We reported previously that six individuals with complete bilateral loss of central vision showed such reorganization, whereas two with bilateral central vision loss but with foveal sparing did not, and we hypothesized that the effect occurs only after complete bilateral loss of foveal vision. Here, we conduct a stronger test of the dependence of reorganization of visual processing in MD on complete loss of foveal function, by bringing back one (called MD6) of the two participants who previously did not show reorganization and who showed foveal sparing. MD6 has now lost all foveal function, and we predicted that if large-scale reorganization of visual processing in MD individuals depends on complete loss of foveal input, then we will now see such reorganization in this individual. METHODS: MD6 and two normally sighted control subjects were scanned. Stimuli were gray-scale photographs of objects presented at either the fovea or a peripheral retinal location (i.e., the MD participant's preferred retinal locus or the control participants' matched peripheral location). RESULTS: In MD6, visual stimulation at the preferred retinal locus significantly activated not only the expected "peripheral" retinotopic cortex but also the deprived "foveal" cortex. Crucially, MD6 exhibited no such large-scale reorganization 5 years earlier when she had some foveal sparing. By contrast, in the control participants, stimulation at the matched peripheral location produced significant activation in peripheral retinotopic cortex only. CONCLUSIONS: We conclude that complete loss of foveal function may be a necessary condition for large-scale reorganization of visual processing in individuals with MD.

Neural compass in the human brain during naturalistic virtual navigation.

Humans and animals maintain a consistent representation of their facing direction during spatial navigation. In rodents, head direction cells are believed to support this "neural compass", but identifying a similar mechanism in humans during dynamic naturalistic navigation has been challenging. To address this issue, we acquired fMRI data while participants freely navigated through a virtual reality city. Encoding model analyses revealed voxel clusters in retrosplenial complex and superior parietal lobule that exhibited reliable tuning as a function of facing direction. Crucially, these directional tunings were consistent across perceptually different versions of the city, spatially separated locations within the city, and motivationally distinct phases of the behavioral task. Analysis of the model weights indicated that these regions may represent facing direction relative to the principal axis of the environment. These findings reveal specific mechanisms in the human brain that allow us to maintain a sense of direction during naturalistic, dynamic navigation.

Distinct neural mechanisms for heading retrieval and context recognition in the hippocampus during spatial reorientation.

Reorientation, the process of regaining one's bearings after becoming lost, requires identification of a spatial context (context recognition) and recovery of heading direction within that context (heading retrieval). We previously showed that these processes rely on the use of features and geometry, respectively. Here, we examine reorientation behavior in a task that creates contextual ambiguity over a long timescale to demonstrate that mice learn to combine both featural and geometric cues to recover heading with experience. At the neural level, most CA1 neurons persistently align to geometry, and this alignment predicts heading behavior. However, a small subset of cells shows feature-sensitive place field remapping, which serves to predict context. Efficient heading retrieval and context recognition require integration of featural and geometric information in the active network through rate changes. These data illustrate how context recognition and heading retrieval are coded in CA1 and how these processes change with experience.

Mirror-image sensitivity and invariance in object and scene processing pathways.

Electrophysiological and behavioral studies in many species have demonstrated mirror-image confusion for objects, perhaps because many objects are vertically symmetric (e.g., a cup is the same cup when seen in left or right profile). In contrast, the navigability of a scene changes when it is mirror reversed, and behavioral studies reveal high sensitivity to this change. Thus, we predicted that representations in object-selective cortex will be unaffected by mirror reversals, whereas representations in scene-selective cortex will be sensitive to such reversals. To test this hypothesis, we ran an event-related functional magnetic resonance imaging adaptation experiment in human adults. Consistent with our prediction, we found tolerance to mirror reversals in one object-selective region, the posterior fusiform sulcus, and a strong sensitivity to these reversals in two scene-selective regions, the transverse occipital sulcus and the retrosplenial complex. However, a more posterior object-selective region, the lateral occipital sulcus, showed sensitivity to mirror reversals, suggesting that the sense information that distinguishes mirror images is represented at earlier stages in the object-processing hierarchy. Moreover, one scene-selective region (the parahippocampal place area or PPA) was tolerant to mirror reversals. This last finding challenges the hypothesis that the PPA is involved in navigation and reorientation and suggests instead that scenes, like objects, are processed by distinct pathways guiding recognition and action.

Combined targeting of pathways regulating synaptic formation and autophagy attenuates Alzheimer's disease pathology in mice.

All drug trials completed to date have fallen short of meeting the clinical endpoint of significantly slowing cognitive decline in Alzheimer's disease (AD) patients. In this study, we repurposed two FDA-approved drugs, Fasudil and Lonafarnib, targeting synaptic formation (i.e., Wnt signaling) and cellular clearance (i.e., autophagic) pathways respectively, to test their therapeutic potential for attenuating AD-related pathology. We characterized our 3xTg AD mouse colony to select timepoints for separate and combinatorial treatment of both drugs while collecting cerebrospinal fluid (CSF) using an optimized microdialysis method. We found that treatment with Fasudil reduced Aß at early and later stages of AD, whereas administration of Lonafarnib had no effect on Aß, but did reduce tau, at early stages of the disease. Induction of autophagy led to increased size of amyloid plaques when administered at late phases of the disease. We show that combinatorial treatment with both drugs was effective at reducing intraneuronal Aß and led to improved cognitive performance in mice. These findings lend support to regulating Wnt and autophagic pathways in order to attenuate AD-related pathology.

Remapping and realignment in the human hippocampal formation predict context-dependent spatial behavior.

To guide spatial behavior, the brain must retrieve memories that are appropriately associated with different navigational contexts. Contextual memory might be mediated by cell ensembles in the hippocampal formation that alter their responses to changes in context, processes known as remapping and realignment in the hippocampus and entorhinal cortex, respectively. However, whether remapping and realignment guide context-dependent spatial behavior is unclear. To address this issue, human participants learned object-location associations within two distinct virtual reality environments and subsequently had their memory tested during functional MRI (fMRI) scanning. Entorhinal grid-like representations showed realignment between the two contexts, and coincident changes in fMRI activity patterns consistent with remapping were observed in the hippocampus. Critically, in a third ambiguous context, trial-by-trial remapping and realignment in the hippocampal-entorhinal network predicted context-dependent behavior. These results reveal the hippocampal-entorhinal mechanisms mediating human contextual memory and suggest that the hippocampal formation plays a key role in spatial behavior under uncertainty.

How the Brain's Navigation System Shapes Our Visual Experience.

We explore the environment not only by navigating, but also by viewing our surroundings with our eyes. Here we review growing evidence that the mammalian hippocampal formation, extensively studied in the context of navigation and memory, mediates a representation of visual space that is stably anchored to the external world. This visual representation puts the hippocampal formation in a central position to guide viewing behavior and to modulate visual processing beyond the medial temporal lobe (MTL). We suggest that vision and navigation share several key computational challenges that are solved by overlapping and potentially common neural systems, making vision an optimal domain to explore whether and how the MTL supports cognitive operations beyond navigation.

The Neurocognitive Basis of Spatial Reorientation.

The ability to recover one's bearings when lost is a skill that is fundamental for spatial navigation. We review the cognitive and neural mechanisms that underlie this ability, with the aim of linking together previously disparate findings from animal behavior, human psychology, electrophysiology, and cognitive neuroscience. Behavioral work suggests that reorientation involves two key abilities: first, the recovery of a spatial reference frame (a cognitive map) that is appropriate to the current environment; and second, the determination of one's heading and location relative to that reference frame. Electrophysiological recording studies, primarily in rodents, have revealed potential correlates of these operations in place, grid, border/boundary, and head-direction cells in the hippocampal formation. Cognitive neuroscience studies, primarily in humans, suggest that the perceptual inputs necessary for these operations are processed by neocortical regions such as the retrosplenial complex, occipital place area and parahippocampal place area, with the retrosplenial complex mediating spatial transformations between the local environment and the recovered spatial reference frame, the occipital place area supporting perception of local boundaries, and the parahippocampal place area processing visual information that is essential for identification of the local spatial context. By combining results across these various literatures, we converge on a unified account of reorientation that bridges the cognitive and neural domains.

Human entorhinal cortex represents visual space using a boundary-anchored grid.

When participants performed a visual search task, functional MRI responses in entorhinal cortex exhibited a sixfold periodic modulation by gaze-movement direction. The orientation of this modulation was determined by the shape and orientation of the bounded search space. These results indicate that human entorhinal cortex represents visual space using a boundary-anchored grid, analogous to that used by rodents to represent navigable space.

The cognitive map in humans: spatial navigation and beyond.

The 'cognitive map' hypothesis proposes that brain builds a unified representation of the spatial environment to support memory and guide future action. Forty years of electrophysiological research in rodents suggest that cognitive maps are neurally instantiated by place, grid, border and head direction cells in the hippocampal formation and related structures. Here we review recent work that suggests a similar functional organization in the human brain and yields insights into how cognitive maps are used during spatial navigation. Specifically, these studies indicate that (i) the human hippocampus and entorhinal cortex support map-like spatial codes, (ii) posterior brain regions such as parahippocampal and retrosplenial cortices provide critical inputs that allow cognitive maps to be anchored to fixed environmental landmarks, and (iii) hippocampal and entorhinal spatial codes are used in conjunction with frontal lobe mechanisms to plan routes during navigation. We also discuss how these three basic elements of cognitive map based navigation-spatial coding, landmark anchoring and route planning-might be applied to nonspatial domains to provide the building blocks for many core elements of human thought.

Environmental Geometry Aligns the Hippocampal Map during Spatial Reorientation.

When a navigator's internal sense of direction is disrupted, she must rely on external cues to regain her bearings, a process termed spatial reorientation. Extensive research has demonstrated that the geometric shape of the environment exerts powerful control over reorientation behavior, but the neural and cognitive mechanisms underlying this phenomenon are not well understood. Whereas some theories claim that geometry controls behavior through an allocentric mechanism potentially tied to the hippocampus, others postulate that disoriented navigators reach their goals by using an egocentric view-matching strategy. To resolve this debate, we characterized hippocampal representations during reorientation. We first recorded from CA1 cells as disoriented mice foraged in chambers of various shapes. We found that the alignment of the recovered hippocampal map was determined by the geometry of the chamber, but not by nongeometric cues, even when these cues could be used to disambiguate geometric ambiguities. We then recorded hippocampal activity as disoriented mice performed a classical goal-directed spatial memory task in a rectangular chamber. Again, we found that the recovered hippocampal map aligned solely to the chamber geometry. Critically, we also found a strong correspondence between the hippocampal map alignment and the animal's behavior, making it possible to predict the search location of the animal from neural responses on a trial-by-trial basis. Together, these results demonstrate that spatial reorientation involves the alignment of the hippocampal map to local geometry. We hypothesize that geometry may be an especially salient cue for reorientation because it is an inherently stable aspect of the environment.

Dissociating intuitive physics from intuitive psychology: Evidence from Williams syndrome.

Prior work suggests that our understanding of how things work ("intuitive physics") and how people work ("intuitive psychology") are distinct domains of human cognition. Here we directly test the dissociability of these two domains by investigating knowledge of intuitive physics and intuitive psychology in adults with Williams syndrome (WS) - a genetic developmental disorder characterized by severely impaired spatial cognition, but relatively spared social cognition. WS adults and mental-age matched (MA) controls completed an intuitive physics task and an intuitive psychology task. If intuitive physics is a distinct domain (from intuitive psychology), then we should observe differential impairment on the physics task for individuals with WS compared to MA controls. Indeed, adults with WS performed significantly worse on the intuitive physics than the intuitive psychology task, relative to controls. These results support the hypothesis that knowledge of the physical world can be disrupted independently from knowledge of the social world.