What Is a Visual Stream?

The dual stream model of the human and non-human primate visual systems remains Leslie Ungerleider's (1946-2020) most indelible contribution to visual neuroscience. In this model, a dorsal "where" stream specialized for visuospatial representation extends through occipitoparietal cortex, whereas a ventral "what" stream specialized for representing object qualities extends through occipito-temporal cortex. Over time, this model underwent a number of revisions and expansions. In one of her last scientific contributions, Leslie proposed a third visual stream specialized for representing dynamic signals related to social perception. This alteration invites the question: What is a visual stream, and how are different visual streams individuated? In this article, we first consider and reject a simple answer to this question based on a common idealizing visualization of the model, which conflicts with the complexities of the visual system that the model was intended to capture. Next, we propose a taxonomic answer that takes inspiration from the philosophy of science and Leslie's body of work, which distinguishes between neural mechanisms, pathways, and streams. In this taxonomy, visual streams are superordinate to pathways and mechanisms and provide individuation conditions for determining whether collections of cortical connections delineate different visual streams. Given this characterization, we suggest that the proposed third visual stream does not yet meet these conditions, although the tripartite model still suggests important revisions to how we think about the organization of the human and non-human primate visual systems.

Untangling the Animacy Organization of Occipitotemporal Cortex.

Some of the most impressive functional specializations in the human brain are found in the occipitotemporal cortex (OTC), where several areas exhibit selectivity for a small number of visual categories, such as faces and bodies, and spatially cluster based on stimulus animacy. Previous studies suggest this animacy organization reflects the representation of an intuitive taxonomic hierarchy, distinct from the presence of face- and body-selective areas in OTC. Using human functional magnetic resonance imaging, we investigated the independent contribution of these two factors-the face-body division and taxonomic hierarchy-in accounting for the animacy organization of OTC and whether they might also be reflected in the architecture of several deep neural networks that have not been explicitly trained to differentiate taxonomic relations. We found that graded visual selectivity, based on animal resemblance to human faces and bodies, masquerades as an apparent animacy continuum, which suggests that taxonomy is not a separate factor underlying the organization of the ventral visual pathway.SIGNIFICANCE STATEMENT Portions of the visual cortex are specialized to determine whether types of objects are animate in the sense of being capable of self-movement. Two factors have been proposed as accounting for this animacy organization: representations of faces and bodies and an intuitive taxonomic continuum of humans and animals. We performed an experiment to assess the independent contribution of both of these factors. We found that graded visual representations, based on animal resemblance to human faces and bodies, masquerade as an apparent animacy continuum, suggesting that taxonomy is not a separate factor underlying the organization of areas in the visual cortex.

The unreliable influence of multivariate noise normalization on the reliability of neural dissimilarity.

Representational similarity analysis (RSA) is a key element in the multivariate pattern analysis toolkit. The central construct of the method is the representational dissimilarity matrix (RDM), which can be generated for datasets from different modalities (neuroimaging, behavior, and computational models) and directly correlated in order to evaluate their second-order similarity. Given the inherent noisiness of neuroimaging signals it is important to evaluate the reliability of neuroimaging RDMs in order to determine whether these comparisons are meaningful. Recently, multivariate noise normalization (NNM) has been proposed as a widely applicable method for boosting signal estimates for RSA, regardless of choice of dissimilarity metrics, based on evidence that the analysis improves the within-subject reliability of RDMs (Guggenmos et al. 2018; Walther et al. 2016). We revisited this issue with three fMRI datasets and evaluated the impact of NNM on within- and between-subject reliability and RSA effect sizes using multiple dissimilarity metrics. We also assessed its impact across regions of interest from the same dataset, its interaction with spatial smoothing, and compared it to GLMdenoise, which has also been proposed as a method that improves signal estimates for RSA (Charest et al. 2018). We found that across these tests the impact of NNM was highly variable, as also seems to be the case for other analysis choices. Overall, we suggest being conservative before adding steps and complexities to the (pre)processing pipeline for RSA.

The Ventral Visual Pathway Represents Animal Appearance over Animacy, Unlike Human Behavior and Deep Neural Networks.

Recent studies showed agreement between how the human brain and neural networks represent objects, suggesting that we might start to understand the underlying computations. However, we know that the human brain is prone to biases at many perceptual and cognitive levels, often shaped by learning history and evolutionary constraints. Here, we explore one such perceptual phenomenon, perceiving animacy, and use the performance of neural networks as a benchmark. We performed an fMRI study that dissociated object appearance (what an object looks like) from object category (animate or inanimate) by constructing a stimulus set that includes animate objects (e.g., a cow), typical inanimate objects (e.g., a mug), and, crucially, inanimate objects that look like the animate objects (e.g., a cow mug). Behavioral judgments and deep neural networks categorized images mainly by animacy, setting all objects (lookalike and inanimate) apart from the animate ones. In contrast, activity patterns in ventral occipitotemporal cortex (VTC) were better explained by object appearance: animals and lookalikes were similarly represented and separated from the inanimate objects. Furthermore, the appearance of an object interfered with proper object identification, such as failing to signal that a cow mug is a mug. The preference in VTC to represent a lookalike as animate was even present when participants performed a task requiring them to report the lookalikes as inanimate. In conclusion, VTC representations, in contrast to neural networks, fail to represent objects when visual appearance is dissociated from animacy, probably due to a preferred processing of visual features typical of animate objects.SIGNIFICANCE STATEMENT How does the brain represent objects that we perceive around us? Recent advances in artificial intelligence have suggested that object categorization and its neural correlates have now been approximated by neural networks. Here, we show that neural networks can predict animacy according to human behavior but do not explain visual cortex representations. In ventral occipitotemporal cortex, neural activity patterns were strongly biased toward object appearance, to the extent that objects with visual features resembling animals were represented closely to real animals and separated from other objects from the same category. This organization that privileges animals and their features over objects might be the result of learning history and evolutionary constraints.

Laparoscopic ablation or excision with helium thermal coagulator versus electrodiathermy for the treatment of mild-to-moderate endometriosis: randomised controlled trial.

OBJECTIVE: To compare electrodiathermy with helium thermal coagulation in laparoscopic treatment of mild-to-moderate endometriosis. DESIGN: Parallel-group randomised controlled trial. SETTING: A UK endometriosis centre. POPULATION: Non-pregnant women aged 16-50 years with a clinical diagnosis of mild-to-moderate endometriosis. METHODS: If mild or moderate endometriosis was confirmed at laparoscopy, women were randomised to laparoscopic treatment with electrodiathermy or helium thermal coagulator. MAIN OUTCOME MEASURES: Cyclical pain and dyspareunia (rated on a 100-mm visual analogue scale, VAS), quality of life at baseline and at 6, 12 and 36 weeks following surgery, operative blood loss and surgical complications. RESULTS: A total of 192 women were randomised. Of these, 155 (81%) completed the primary outcome point at 12 weeks. In an intention-to-treat analysis, VAS scores for cyclical pain were significantly lower in the electrodiathermy group compared with the helium group at 12 weeks (mean difference, 9.43 mm; 95% CI 0.46, 18.40 mm; P = 0.039) and across all time points (mean difference, 10.13 mm; 95% CI 3.48, 16.78 mm; P = 0.003). A significant difference in dyspareunia also favoured electrodiathermy at 12 weeks (mean difference, 11.66 mm; 95% CI 1.39, 21.93 mm; P = 0.026). These effects were smaller than the proposed minimum important difference of 18.00 mm, however. Differences in some aspects of quality of life favoured electrodiathermy. There was no significant difference in operative blood loss (fold-change with helium as reference, 1.43; 95% CI 0.96, 2.15; P = 0.081). CONCLUSIONS: Although electrodiathermy was statistically superior to helium ablation in reducing cyclical pain and dyspareunia, these effects may be too small to be clinically significant. TWEETABLE ABSTRACT: Helium coagulation is not superior to electrodiathermy in laparoscopic treatment of mild-to-moderate endometriosis.

A Varying Role for Abstraction in Models of Category Learning Constructed from Neural Representations in Early Visual Cortex.

The human capacity for visual categorization is core to how we make sense of the visible world. Although a substantive body of research in cognitive neuroscience has localized this capacity to regions of human visual cortex, relatively few studies have investigated the role of abstraction in how representations for novel object categories are constructed from the neural representation of stimulus dimensions. Using human fMRI coupled with formal modeling of observer behavior, we assess a wide range of categorization models that vary in their level of abstraction from collections of subprototypes to representations of individual exemplars. The category learning tasks range from simple linear and unidimensional category rules to complex crisscross rules that require a nonlinear combination of multiple dimensions. We show that models based on neural responses in primary visual cortex favor a variable, but often limited, extent of abstraction in the construction of representations for novel categories, which differ in degree across tasks and individuals.

Edge-Related Activity Is Not Necessary to Explain Orientation Decoding in Human Visual Cortex.

Multivariate pattern analysis is a powerful technique; however, a significant theoretical limitation in neuroscience is the ambiguity in interpreting the source of decodable information used by classifiers. This is exemplified by the continued controversy over the source of orientation decoding from fMRI responses in human V1. Recently Carlson (2014) identified a potential source of decodable information by modeling voxel responses based on the Hubel and Wiesel (1972) ice-cube model of visual cortex. The model revealed that activity associated with the edges of gratings covaries with orientation and could potentially be used to discriminate orientation. Here we empirically evaluate whether "edge-related activity" underlies orientation decoding from patterns of BOLD response in human V1. First, we systematically mapped classifier performance as a function of stimulus location using population receptive field modeling to isolate each voxel's overlap with a large annular grating stimulus. Orientation was decodable across the stimulus; however, peak decoding performance occurred for voxels with receptive fields closer to the fovea and overlapping with the inner edge. Critically, we did not observe the expected second peak in decoding performance at the outer stimulus edge as predicted by the edge account. Second, we evaluated whether voxels that contribute most to classifier performance have receptive fields that cluster in cortical regions corresponding to the retinotopic location of the stimulus edge. Instead, we find the distribution of highly weighted voxels to be approximately random, with a modest bias toward more foveal voxels. Our results demonstrate that edge-related activity is likely not necessary for orientation decoding. SIGNIFICANCE STATEMENT: A significant theoretical limitation of multivariate pattern analysis in neuroscience is the ambiguity in interpreting the source of decodable information used by classifiers. For example, orientation can be decoded from BOLD activation patterns in human V1, even though orientation columns are at a finer spatial scale than 3T fMRI. Consequently, the source of decodable information remains controversial. Here we test the proposal that information related to the stimulus edges underlies orientation decoding. We map voxel population receptive fields in V1 and evaluate orientation decoding performance as a function of stimulus location in retinotopic cortex. We find orientation is decodable from voxels whose receptive fields do not overlap with the stimulus edges, suggesting edge-related activity does not substantially drive orientation decoding.

Ghosts in machine learning for cognitive neuroscience: Moving from data to theory.

The application of machine learning methods to neuroimaging data has fundamentally altered the field of cognitive neuroscience. Future progress in understanding brain function using these methods will require addressing a number of key methodological and interpretive challenges. Because these challenges often remain unseen and metaphorically "haunt" our efforts to use these methods to understand the brain, we refer to them as "ghosts". In this paper, we describe three such ghosts, situate them within a more general framework from philosophy of science, and then describe steps to address them. The first ghost arises from difficulties in determining what information machine learning classifiers use for decoding. The second ghost arises from the interplay of experimental design and the structure of information in the brain - that is, our methods embody implicit assumptions about information processing in the brain, and it is often difficult to determine if those assumptions are satisfied. The third ghost emerges from our limited ability to distinguish information that is merely decodable from the brain from information that is represented and used by the brain. Each of the three ghosts place limits on the interpretability of decoding research in cognitive neuroscience. There are no easy solutions, but facing these issues squarely will provide a clearer path to understanding the nature of representation and computation in the human brain.

Host-specific differences in the contribution of an ESBL IncI1 plasmid to intestinal colonization by Escherichia coli O104:H4.

Objectives: To assess stability and contribution of a large ESBL-encoding IncI1 plasmid to intestinal colonization by Escherichia coli O104:H4 in two different mammalian hosts. Methods: Specific-pathogen-free 3-4-day-old New Zealand White rabbits and conventionally reared 6-week-old weaned lambs were orally infected with WT E. coli O104:H4 or the ESBL-plasmid-cured derivative, and the recovery of bacteria in intestinal homogenates and faeces monitored over time. Results: Carriage of the ESBL plasmid had differing impacts on E. coli O104:H4 colonization of the two experimental hosts. The plasmid-cured strain was recovered at significantly higher levels than WT during late-stage colonization of rabbits, but at lower levels than WT in sheep. Regardless of the animal host, the ESBL plasmid was stably maintained in virtually all in vivo passaged bacteria that were examined. Conclusions: These findings suggest that carriage of ESBL plasmids has distinct effects on the host bacterium depending upon the animal species it encounters and demonstrates that, as for E. coli O157:H7, ruminants could represent a potential transmission reservoir.

Asymmetric Compression of Representational Space for Object Animacy Categorization under Degraded Viewing Conditions.

Animacy is a robust organizing principle among object category representations in the human brain. Using multivariate pattern analysis methods, it has been shown that distance to the decision boundary of a classifier trained to discriminate neural activation patterns for animate and inanimate objects correlates with observer RTs for the same animacy categorization task [Ritchie, J. B., Tovar, D. A., & Carlson, T. A. Emerging object representations in the visual system predict reaction times for categorization. PLoS Computational Biology, 11, e1004316, 2015; Carlson, T. A., Ritchie, J. B., Kriegeskorte, N., Durvasula, S., & Ma, J. Reaction time for object categorization is predicted by representational distance. Journal of Cognitive Neuroscience, 26, 132-142, 2014]. Using MEG decoding, we tested if the same relationship holds when a stimulus manipulation (degradation) increases task difficulty, which we predicted would systematically decrease the distance of activation patterns from the decision boundary and increase RTs. In addition, we tested whether distance to the classifier boundary correlates with drift rates in the linear ballistic accumulator [Brown, S. D., & Heathcote, A. The simplest complete model of choice response time: Linear ballistic accumulation. Cognitive Psychology, 57, 153-178, 2008]. We found that distance to the classifier boundary correlated with RT, accuracy, and drift rates in an animacy categorization task. Split by animacy, the correlations between brain and behavior were sustained longer over the time course for animate than for inanimate stimuli. Interestingly, when examining the distance to the classifier boundary during the peak correlation between brain and behavior, we found that only degraded versions of animate, but not inanimate, objects had systematically shifted toward the classifier decision boundary as predicted. Our results support an asymmetry in the representation of animate and inanimate object categories in the human brain.

Avoiding illusory effects in representational similarity analysis: What (not) to do with the diagonal.

Representational similarity analysis (RSA) is an important part of the methodological toolkit in neuroimaging research. The focus of the approach is the construction of representational dissimilarity matrices (RDMs), which provide a single format for making comparisons between different neural data types, computational models, and behavior. We highlight two issues for the construction and comparison of RDMs. First, the diagonal values of RDMs, which should reflect within condition reliability of neural patterns, are typically not estimated in RSA. However, without such an estimate, one lacks a measure of the reliability of an RDM as a whole. Thus, when carrying out RSA, one should calculate the diagonal values of RDMs and not take them for granted. Second, although diagonal values of a correlation matrix can be used to estimate the reliability of neural patterns, these values must nonetheless be excluded when comparing RDMs. Via a simple simulation we show that inclusion of these values can generate convincing looking, but entirely illusory, correlations between independent and entirely unrelated data sets. Both of these points are further illustrated by a critical discussion of Coggan et al. (2016), who investigated the extent to which category-selectivity in the ventral temporal cortex can be accounted for by low-level image properties of visual object stimuli. We observe that their results may depend on the improper inclusion of diagonal values in their analysis.

Emerging Object Representations in the Visual System Predict Reaction Times for Categorization.

Recognizing an object takes just a fraction of a second, less than the blink of an eye. Applying multivariate pattern analysis, or "brain decoding", methods to magnetoencephalography (MEG) data has allowed researchers to characterize, in high temporal resolution, the emerging representation of object categories that underlie our capacity for rapid recognition. Shortly after stimulus onset, object exemplars cluster by category in a high-dimensional activation space in the brain. In this emerging activation space, the decodability of exemplar category varies over time, reflecting the brain's transformation of visual inputs into coherent category representations. How do these emerging representations relate to categorization behavior? Recently it has been proposed that the distance of an exemplar representation from a categorical boundary in an activation space is critical for perceptual decision-making, and that reaction times should therefore correlate with distance from the boundary. The predictions of this distance hypothesis have been born out in human inferior temporal cortex (IT), an area of the brain crucial for the representation of object categories. When viewed in the context of a time varying neural signal, the optimal time to "read out" category information is when category representations in the brain are most decodable. Here, we show that the distance from a decision boundary through activation space, as measured using MEG decoding methods, correlates with reaction times for visual categorization during the period of peak decodability. Our results suggest that the brain begins to read out information about exemplar category at the optimal time for use in choice behaviour, and support the hypothesis that the structure of the representation for objects in the visual system is partially constitutive of the decision process in recognition.

A Randomised Assessment of Trainee Doctors' Understanding and Interpretation of Diagnostic Test Results.

INTRODUCTION: Doctors are unfamiliar with diagnostic accuracy parameters despite routine clinical use of diagnostic tests to estimate disease probability. METHODS: Trainee doctors completed a questionnaire exploring their understanding of diagnostic accuracy parameters; ability to calculate post-test probability of a common surgical condition (appendicitis) and their perceptions on training in this area. To determine whether the method of information provision altered interpretation, trainees were randomised to receive diagnostic test information in three ways: positive test only; positive test with specificity and sensitivity; positive test with positive likelihood ratio in layman terms. RESULTS: 326 candidates were recruited across 30 training sessions. Trainees scored a median of three out of seven in questions concerning knowledge of diagnostic accuracy parameters. This was affected neither by training level (P = 0.737) nor by experience in acute general surgery (P = 0.738). 30 (11.8%) candidates correctly estimated post-test probability; with 86.6% overestimating this value. Neither level of training (P = 0.180) nor experience (P = 0.242) influenced the accuracy of the estimate. Provision of the ultrasound scan results in different ways was not associated with likelihood of a correct response (P = 0.857). CONCLUSION: This study highlights the deficiencies in trainee doctors' understanding and application of diagnostic tests results. Most trainees over-estimated disease probability, increasing the risk of unnecessary intervention and treatment.

Targeting the endoplasmic reticulum mediates radiation sensitivity in colorectal cancer.

BACKGROUND: Radiotherapy is an established treatment modality for early and locally advanced rectal cancer as part of short course radiotherapy and long course chemoradiotherapy. The unfolded protein response (UPR) is a cellular stress response pathway often activated in human solid tumours which has been implicated in resistance to both chemotherapy and radiotherapy. This research has investigated whether the UPR pathway is upregulated in ex-vivo samples of human colorectal cancer and characterised the interaction between radiotherapy and UPR activation in two human colorectal cancer cell lines in vitro. METHODS: In vitro UPR expression was determined in response to clinical doses of radiotherapy in both the human colorectal adenocarcinoma (HT-29) cell line and a radio-resistant clone (HT-29R) using western blotting and quantitative polymerase chain reaction. The UPR was induced using a glucose deprivation culture technique before irradiation and radiosensitivity assessed using a clonogenic assay. Ex-vivo human colorectal cancer tissue was immuno-histochemically analysed for expression of the UPR marker glucose regulated protein 78 (GRP-78). RESULTS: The UPR was strongly up regulated in ex-vivo human colorectal tumours with 36 of 50 (72.0%) specimens demonstrating moderate to strong staining for the classic UPR marker GRP-78. In vitro, therapeutic doses of radiotherapy did not induce UPR activation in either radiosensitive or radioresistant cell lines. UPR induction caused significant radiosensitisation of the radioresistant cell line (HT-29R SF2Gy=0.90 S.E.M. +/-0.08; HT-29RLG SF2Gy=0.69 S.E.M. +/-0.050). CONCLUSION: This suggests that UPR induction agents may be potentially useful response modifying agents in patients undergoing therapy for colorectal cancer.

Improving paediatric outreach services for urban Aboriginal children through partnerships: views of community-based service providers.

BACKGROUND: In Australia, Aboriginal children experience significantly poorer health outcomes compared with non-Aboriginal children. Health policies aimed at improving Aboriginal health outcomes include interventions in the early childhood period. There is a need for government health services to work in partnership with Aboriginal people and other services to achieve the highest level of health possible for Aboriginal children, who often require a range of services to meet complex needs. AIM: This paper describes the views of service providers on how paediatric outreach services work in partnership with other services, Aboriginal families and the community and how those partnerships could be improved to maximize health outcomes for children. METHODS: In-depth, semi-structured interviews and focus groups were conducted with managers and service providers over a 6-week period in 2010. The views and suggestions of participants were documented and a thematic analysis was undertaken. RESULTS AND DISCUSSION: Analysis of two focus groups with seven service providers and five individual interviews with service managers resulted in the identification of four themes: (i) using informal and formal ways of working; (ii) cultivating effective relationships; (iii) demonstrating cultural sensitivity; and (iv) forging strong leadership. Use of formal and informal approaches facilitated effective relationships between service providers and Aboriginal families and communities. Partnerships with the community were founded on a culturally appropriate model of care that recognized a holistic approach to health and wellness. Leadership emerged as an essential component of effective partnerships, cultivating the ethos of the workplace and creating an environment where collaboration is supported. CONCLUSION: Culturally appropriate child health services, which utilize effective relationships and employ a range of informal and formal collaboration with other services and community members, are well positioned to implement health policy and improve access to services for Aboriginal children with better health outcomes as a result.

Reaction time for object categorization is predicted by representational distance.

How does the brain translate an internal representation of an object into a decision about the object's category? Recent studies have uncovered the structure of object representations in inferior temporal cortex (IT) using multivariate pattern analysis methods. These studies have shown that representations of individual object exemplars in IT occupy distinct locations in a high-dimensional activation space, with object exemplar representations clustering into distinguishable regions based on category (e.g., animate vs. inanimate objects). In this study, we hypothesized that a representational boundary between category representations in this activation space also constitutes a decision boundary for categorization. We show that behavioral RTs for categorizing objects are well described by our activation space hypothesis. Interpreted in terms of classical and contemporary models of decision-making, our results suggest that the process of settling on an internal representation of a stimulus is itself partially constitutive of decision-making for object categorization.

Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling.

BACKGROUND: Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort. METHOD: We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R. RESULTS: We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD. CONCLUSIONS: These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.

Graspable foods and tools elicit similar responses in visual cortex.

Extrastriatal visual cortex is known to exhibit distinct response profiles to complex stimuli of varying ecological importance (e.g., faces, scenes, and tools). The dominant interpretation of these effects is that they reflect activation of distinct "category-selective" brain regions specialized to represent these and other stimulus categories. We sought to explore an alternative perspective: that the response to these stimuli is determined less by whether they form distinct categories, and more by their relevance to different forms of natural behavior. In this regard, food is an interesting test case, since it is primarily distinguished from other objects by its edibility, not its appearance, and there is evidence of food-selectivity in human visual cortex. Food is also associated with a common behavior, eating, and food consumption typically also involves the manipulation of food, often with the hands. In this context, food items share many properties in common with tools: they are graspable objects that we manipulate in self-directed and stereotyped forms of action. Thus, food items may be preferentially represented in extrastriatal visual cortex in part because of these shared affordance properties, rather than because they reflect a wholly distinct kind of category. We conducted fMRI and behavioral experiments to test this hypothesis. We found that behaviorally graspable food items and tools were judged to be similar in their action-related properties, and that the location, magnitude, and patterns of neural responses for images of graspable food items were similar in profile to the responses for tool stimuli. Our findings suggest that food-selectivity may reflect the behavioral affordances of food items rather than a distinct form of category-selectivity.

Requisite role of dorsal raphé in contextual cocaine-memory reconsolidation.

Memory reconsolidation is a process by which labile drug memories are restabilized in long-term memory stores, permitting their enduring control over drug-seeking behaviors. In the present study, we investigated the involvement of the dorsal raphé nuclei (DRN) in cocaine-memory reconsolidation. Sprague-Dawley rats (male, female) were trained to self-administer cocaine in a distinct environmental context to establish contextual drug memories. They then received extinction training in a different context. Next, the rats were re-exposed to the cocaine-predictive context for 15 min to reactivate their cocaine memories or remained in their home cages (no-reactivation control). Memory reactivation was sufficient to increase c-Fos expression, an index of neuronal activation, in the DRN, but not in the median raphé nuclei, during reconsolidation, compared to no reactivation. To determine whether DRN neuronal activity was necessary for cocaine-memory reconsolidation, rats received intra-DRN baclofen plus muscimol (BM; GABAB/A agonists) or vehicle microinfusions immediately after or 6 h after a memory reactivation session conducted with or without lever access. The effects of DRN functional inactivation on long-term memory strength, as indicated by the magnitude of context-induced cocaine seeking, were assessed 72 h later. Intra-DRN BM treatment immediately after memory reactivation with or without lever access attenuated subsequent context-induced cocaine-seeking behavior, independent of sex. Conversely, BM treatment in the adjacent periaqueductal gray (PAG) immediately after memory reactivation, or BM treatment in the DRN 6 h after memory reactivation, did not alter responding. Together, these findings indicate that the DRN plays a requisite role in maintaining cocaine-memory strength during reconsolidation.

Potential for biomarkers of chronic kidney disease-mineral bone disorder to improve patient care.

Chronic kidney disease (CKD) is a growing public health problem. Cardiovascular disease is common in CKD, but standard risk assessment tools perform poorly in this population. Equally, despite CKD being associated with an increased risk for death and dialysis, standard biochemical measurements have limited prognostic value. Novel serum biomarkers may aid risk assessment; however, studies have shown varying clinical utility in relation to progression of CKD, incident cardiovascular disease and death. This inconsistency may relate to limitations in our understanding of the biological actions and interactions of these biomarkers. This review discusses a range of biomarkers in relation to these clinical endpoints in CKD-mineral bone disorder. We consider where biomarkers may enhance risk stratification and improve clinical management, but also highlight where they fall short of achieving this objective.