From fossils to mind.

Fossil endocasts record features of brains from the past: size, shape, vasculature, and gyrification. These data, alongside experimental and comparative evidence, are needed to resolve questions about brain energetics, cognitive specializations, and developmental plasticity. Through the application of interdisciplinary techniques to the fossil record, paleoneurology has been leading major innovations. Neuroimaging is shedding light on fossil brain organization and behaviors. Inferences about the development and physiology of the brains of extinct species can be experimentally investigated through brain organoids and transgenic models based on ancient DNA. Phylogenetic comparative methods integrate data across species and associate genotypes to phenotypes, and brains to behaviors. Meanwhile, fossil and archeological discoveries continuously contribute new knowledge. Through cooperation, the scientific community can accelerate knowledge acquisition. Sharing digitized museum collections improves the availability of rare fossils and artifacts. Comparative neuroanatomical data are available through online databases, along with tools for their measurement and analysis. In the context of these advances, the paleoneurological record provides ample opportunity for future research. Biomedical and ecological sciences can benefit from paleoneurology's approach to understanding the mind as well as its novel research pipelines that establish connections between neuroanatomy, genes and behavior.

Evolutionary history of hominin brain size and phylogenetic comparative methods.

An absolutely and relatively large brain has traditionally been viewed as a distinctive characteristic of the Homo genus, with anatomically modern humans presented at the apex of a long line of progressive increases in encephalization. Many studies continue to focus attention on increasing brain size in the Homo genus, while excluding measures of absolute and relative brain size of more geologically recent, smaller brained, hominins such as Homo floresiensis, and Homo naledi and smaller brained Homo erectus specimens. This review discusses the benefits of using phylogenetic comparative methods to trace the diverse changes in hominin brain evolution and the drawbacks of not doing so.

A natural history of vision loss: Insight from evolution for human visual function.

Research on the origin of vision and vision loss in naturally "blind" animal species can reveal the tasks that vision fulfills and the brain's role in visual experience. Models that incorporate evolutionary history, natural variation in visual ability, and experimental manipulations can help disentangle visual ability at a superficial level from behaviors linked to vision but not solely reliant upon it, and could assist the translation of ophthalmological research in animal models to human treatments. To unravel the similarities between blind individuals and blind species, we review concepts of "blindness" and its behavioral correlates across a range of species. We explore the ancestral emergence of vision in vertebrates, and the loss of vision in blind species with reference to an evolution-based classification scheme. We applied phylogenetic comparative methods to a mammalian tree to explore the evolution of visual acuity using ancestral state estimations. Future research into the natural history of vision loss could help elucidate the function of vision and inspire innovations in how to address vision loss in humans.

Testing hypotheses of marsupial brain size variation using phylogenetic multiple imputations and a Bayesian comparative framework.

Considerable controversy exists about which hypotheses and variables best explain mammalian brain size variation. We use a new, high-coverage dataset of marsupial brain and body sizes, and the first phylogenetically imputed full datasets of 16 predictor variables, to model the prevalent hypotheses explaining brain size evolution using phylogenetically corrected Bayesian generalized linear mixed-effects modelling. Despite this comprehensive analysis, litter size emerges as the only significant predictor. Marsupials differ from the more frequently studied placentals in displaying a much lower diversity of reproductive traits, which are known to interact extensively with many behavioural and ecological predictors of brain size. Our results therefore suggest that studies of relative brain size evolution in placental mammals may require targeted co-analysis or adjustment of reproductive parameters like litter size, weaning age or gestation length. This supports suggestions that significant associations between behavioural or ecological variables with relative brain size may be due to a confounding influence of the extensive reproductive diversity of placental mammals.

Visual-to-auditory sensory substitution alters language asymmetry in both sighted novices and experienced visually impaired users.

Visual-to-auditory sensory substitution devices (SSDs) provide improved access to the visual environment for the visually impaired by converting images into auditory information. Research is lacking on the mechanisms involved in processing data that is perceived through one sensory modality, but directly associated with a source in a different sensory modality. This is important because SSDs that use auditory displays could involve binaural presentation requiring both ear canals, or monaural presentation requiring only one - but which ear would be ideal? SSDs may be similar to reading, as an image (printed word) is converted into sound (when read aloud). Reading, and language more generally, are typically lateralised to the left cerebral hemisphere. Yet, unlike symbolic written language, SSDs convert images to sound based on visuospatial properties, with the right cerebral hemisphere potentially having a role in processing such visuospatial data. Here we investigated whether there is a hemispheric bias in the processing of visual-to-auditory sensory substitution information and whether that varies as a function of experience and visual ability. We assessed the lateralization of auditory processing with two tests: a standard dichotic listening test and a novel dichotic listening test created using the auditory information produced by an SSD, The vOICe. Participants were tested either in the lab or online with the same stimuli. We did not find a hemispheric bias in the processing of visual-to-auditory information in visually impaired, experienced vOICe users. Further, we did not find any difference between visually impaired, experienced vOICe users and sighted novices in the hemispheric lateralization of visual-to-auditory information processing. Although standard dichotic listening is lateralised to the left hemisphere, the auditory processing of images in SSDs is bilateral, possibly due to the increased influence of right hemisphere processing. Auditory SSDs might therefore be equally effective with presentation to either ear if a monaural, rather than binaural, presentation were necessary.

Primate hippocampus size and organization are predicted by sociality but not diet.

The hippocampus is well known for its roles in spatial navigation and memory, but it is organized into regions that have different connections and functional specializations. Notably, the region CA2 has a role in social and not spatial cognition, as is the case for the regions CA1 and CA3 that surround it. Here, we investigated the evolution of the hippocampus in terms of its size and organization in relation to the evolution of social and ecological variables in primates, namely home range, diet and different measures of group size. We found that the volumes within the whole cornu ammonis coevolve with group size, while only the volume of CA1 and subiculum can also be predicted by home range. On the other hand, diet, expressed as a shift from folivory towards frugivory, was shown to not be related to hippocampal volume. Interestingly, CA2 was shown to exhibit phylogenetic signal only against certain measures of group size, but not with ecological factors. We also found that sex differences in the hippocampus are related to body size sex dimorphism. This is in line with reports of sex differences in hippocampal volume in non-primates that are related to social structure and sex differences in behaviour. Our findings support the notion that in primates, the hippocampus is a mosaic structure evolving in line with social pressures, where certain subsections evolve in line with spatial ability too.

Primate Brain Anatomy: New Volumetric MRI Measurements for Neuroanatomical Studies.

Since the publication of the primate brain volumetric dataset of Stephan and colleagues in the early 1980s, no major new comparative datasets covering multiple brain regions and a large number of primate species have become available. However, technological and other advances in the last two decades, particularly magnetic resonance imaging (MRI) and the creation of institutions devoted to the collection and preservation of rare brain specimens, provide opportunities to rectify this situation. Here, we present a new dataset including brain region volumetric measurements of 39 species, including 20 species not previously available in the literature, with measurements of 16 brain areas. These volumes were extracted from MRI of 46 brains of 38 species from the Netherlands Institute of Neuroscience Primate Brain Bank, scanned at high resolution with a 9.4-T scanner, plus a further 7 donated MRI of 4 primate species. Partial measurements were made on an additional 8 brains of 5 species. We make the dataset and MRI scans available online in the hope that they will be of value to researchers conducting comparative studies of primate evolution.

Corrigendum: Where am I? Who am I? The Relation Between Spatial Cognition, Social Cognition, and Individual Differences in the Built Environment.

[This corrects the article on p. 64 in vol. 7, PMID: 26903893.].

Where am I? Who am I? The Relation Between Spatial Cognition, Social Cognition and Individual Differences in the Built Environment.

Knowing who we are, and where we are, are two fundamental aspects of our physical and mental experience. Although the domains of spatial and social cognition are often studied independently, a few recent areas of scholarship have explored the interactions of place and self. This fits in with increasing evidence for embodied theories of cognition, where mental processes are grounded in action and perception. Who we are might be integrated with where we are, and impact how we move through space. Individuals vary in personality, navigational strategies, and numerous cognitive and social competencies. Here we review the relation between social and spatial spheres of existence in the realms of philosophical considerations, neural and psychological representations, and evolutionary context, and how we might use the built environment to suit who we are, or how it creates who we are. In particular we investigate how two spatial reference frames, egocentric and allocentric, might transcend into the social realm. We then speculate on how environments may interact with spatial cognition. Finally, we suggest how a framework encompassing spatial and social cognition might be taken in consideration by architects and urban planners.

Corneal melt as the initial presentation of primary Sjögren's syndrome.

Corneal melting is a rare complication of S ogren's syndrome (SS). Previously reported cases of corneal ulceration occurred in patients with established SS, usually secondary to RA. We describe the first case of corneal ulceration with stromal melting as the initial presentation of primary SS. A 79-year-old man without prior sicca symptoms developed a large sterile corneal ulcer that required extensive treatment over several months with ocular lubricants, systemic immunosuppressives, and surgical repair. Evaluation for an underlying connective tissue disease revealed positive antinuclear antibodies (1:640 speckled) and anti-SSA antibody. A lip biopsy established the diagnosis of SS. Ulceration later occurred in the contralateral eye. Two years after the last corneal ulcer and no longer taking prednisone, the patient's ocular disease remained quiescent taking azathioprine 175 mg and hydroxychloroquine 400 mg daily. This case highlights the potential for primary SS to present with serious ocular complications despite lack of a priori sicca symptoms, as well as the importance of immunosuppressive therapy in the treatment of this complication.

Postexposure effectiveness of varicella vaccine.

OBJECTIVE: 1) To describe the postexposure effectiveness of varicella vaccine in a homeless shelter; and 2) to demonstrate an effective public health intervention and its implications. DESIGN: A prospective observational study. SETTING: A women and children's shelter in Philadelphia with 2 cases of varicella before intervention. OUTCOME MEASURES: Varicella in vaccinated and unvaccinated shelter residents; vaccine effectiveness for prevention of varicella when administered after exposure among children <13 years of age. RESULTS: Sixty-seven shelter residents received varicella vaccine after exposure, including 42 children <13 years of age. One child who was unvaccinated developed varicella, but no vaccinated child developed typical disease. Vaccine effectiveness was 95.2% (95% CI, 81.6%-98.8%) for prevention of any disease and 100% for prevention of moderate or severe disease among the children <13 years of age. CONCLUSION: When used within 36 hours after exposure to varicella in a setting where close contact occurred, varicella vaccine was highly effective in preventing further disease. This study provides support for the recent recommendation by the Advisory Committee on Immunization Practices to administer varicella vaccine after exposure: this practice should minimize the number of moderate or severe cases of disease and prevent prolonged outbreaks.

Plasminogen activator inhibitor type 2 in human corneal epithelium.

PURPOSE: To examine normal human corneal epithelium in vivo and in vitro for expression and status of plasniinogcn activ:ltor inhibitor type 2 (PAI-2). METHODS: Normal hiuman corneas were prepared for frozen sections and for culture of corneal keratinocytes. PAI-2 was analyzed by immunohistochemistry and western blot analysis uising antibodies that recognize all forms of PAI-2. RESULTS: In vivo and in vitro, PAI-2 was immunohistochemically localized to the superficial corneal keratinocytes. Immunostaining also revealed the presence of PAI-2 in its relaxed (i.e., cleaved) conformation. In vivo, the staining pattern of the relaxed form was identical with that of total PAI-2, but in vitro the relaxed form was detected in a smaller subpopulation of superficial cells. In vitro, the staining pattern indicated a cytoplasmic localization for PAI-2. Western blot analysis revealed that most of the PAI-2 was cell associated and functionally active. CONCLUSIONS: The present results are the first to show that PAI-2 is found in normal human corneal epithelium in vivo and in vitro, where it can be considered as a differentiation product. At least in vitro, all detectable PAI-2 is cell associated, with a cytoplasmic distribution. A subpopulation of keratinocytes also contains PAI-2 in its relaxed (i.e., cleaved) conformation. Cleavage by an as yet unidentified cytoplasmic proteinase may constitute a crucial aspect of the function of corneal epithelial PAI-2, which may be relevant to terminal differentiation and death of the corneal keratinocyte.

Efficacy of media enriched with nonlactate-generating substrate for organ preservation: in vitro and clinical studies using the cornea model.

BACKGROUND: Using a rabbit cornea model, our recent study demonstrated that Chen Medium (CM), an isotonic media enriched with nonlactate-generating high-energy substrates, is very effective for organ preservation. In the present study, the efficacy of CM is further evaluated with human corneas METHODS: The effectiveness of CM and Optisol for preserving the endothelial integrity of human corneas in vitro was evaluated by scanning electron microscopy. Clinical efficacy was evaluated in a total of 83 patients: 10 patients with keratoconus grafted randomly with either CM- or Optisol-stored cornea of the same donor, and 73 patients with various conditions grafted with CM-stored corneas. After surgery, visual acuity and quality of the graft were monitored for up to 4.6 years. RESULTS: The scanning electron microscopic study revealed that after 11-day storage at 4 degrees C, the CM-stored cornea had only marginal disruptive changes, 9.4+/-1.1%, in endothelial cells, as opposed to 42.4+/-4.6% of the Optisol-stored cornea. All 78 CM-stored corneas, including 67 with 12.2- to 17.7-hr death-to-storage time, 3-7.6 days of storage time, and initial marginal quality before storage, were successfully transplanted. These grafts were thin and clear, with an excellent epithelial integrity and without significant changes in endothelial cell density. Five Optisol-stored corneas were also successfully grafted; one of them, however, was edematous for about 4 weeks, and all the grafts were slightly thicker with substantial endothelial cell loss. CONCLUSION: Using a cornea model, present and recent studies show that CM is very effective for preserving tissue viability and endothelial integrity. Previous study revealed that CM-stored tissues maintained high levels of ATP and metabolic function, with suppression of lactate formation and accumulation. Thus, these findings support the concept that preservation of tissue viability is closely associated with the ability of the tissues to retain metabolic activity, to generate ATP efficiently, and to prevent acidosis effectively during storage.

Spontaneous corneal perforation in pellucid marginal degeneration.

PURPOSE: We present a report of a spontaneous corneal perforation in a patient with pellucid marginal corneal degeneration. METHODS: We describe the presentation and management of a 74 year old male with spontaneous corneal perforation related to pellucid marginal corneal degeneration. RESULTS: The corneal perforation was repaired with a 3 mm penetrating patch graft. The cornea has remained stable for 7 years with no further progression of corneal ectasia in either eye. CONCLUSIONS: Although rare, spontaneous corneal perforations in patients with pellucid marginal corneal degeneration can occur, and patients should be cautioned about this possibility.

Delayed-onset fungal keratitis after endophthalmitis.

PURPOSE: This study aimed to present two patients with delayed-onset, endogenous fungal keratitis after treatment for fungal endophthalmitis after cataract surgery. METHODS: The authors retrospectively reviewed the clinical course of two patients in whom deep stromal fungal keratitis developed 2 weeks and 3 months, respectively, after apparent successful aggressive therapy for fungal endophthalmitis. Before the onset of the keratitis, both patients underwent vitrectomies with intraocular injection of 7.5 to 10.0 mcg amphotericin B, as well as treatment with systemic fluconazole and topical antifungal therapy. In case 1, a pre-existing prosthetic intraocular lens and lens capsular bag were removed at the time of vitrectomy, whereas in case 2, the intraocular lens was left in place and a posterior capsulectomy was performed. RESULTS: The keratitis worsened in both patients, despite intensive systemic and topical antifungal therapy. Both patients underwent therapeutic penetrating keratoplasties. In case 1, this resulted in successful resolution of the infection and no recurrences 3 months after the transplant. The corneal transplant was complicated by an expulsive choroidal hemorrhage in the other patient. Fusarium solani was cultured from the initial vitrectomy specimen in patient 1, and although it was not cultured from the keratitis, septate hyphal elements were present on histopathologic examination. The causative organism in case 2 was Acremonium kiliense, which was cultured from both the original vitrectomy specimen and the deep corneal stromal infiltrate. CONCLUSIONS: Fungal organisms may not be eradicated completely from eyes with endophthalmitis despite aggressive therapy and apparent initial successful treatment. These patients need to be monitored for prolonged periods, and treatment should be reinitiated at the earliest sign of recrudescence of infection.

Successful visual rehabilitation after neonatal penetrating keratoplasty.

BACKGROUND: Penetrating keratoplasty in infancy and childhood has traditionally met with limited visual success due to a combination of unique physiology and technical problems in this patient population. With the advances in microsurgical instrumentation, corneal preservation, and visual developmental physiology ophthalmologists are finding increasing indications for penetrating keratoplasty in the childhood population. The long term results of neonatal penetrating keratoplasty in two patients with unilateral congenital corneal opacification are reported. METHODS: Penetrating keratoplasty was performed on one eye in each of two infants within the first 3 weeks of life. Amblyopia treatment and optical therapy have been continued since surgery. RESULTS: After 6 years both grafts have remained clear. One patient developed the infantile esotropia syndrome. Visual development using Snellen optotypes is age normal for both transplanted eyes. CONCLUSIONS: Penetrating keratoplasty when combined with optical correction and amblyopia therapy may restore and preserve vision in selected patients with congenital corneal opacification if performed in the neonatal period.