Transitivity performance,relational hierarchy knowledge and awareness: Results of an instructional framing manipulation

The transitive inference (TI) paradigm has been widely used to examine the role of the hippocampus in generalization. Here we consider a surprising feature of experimental findings in this task: the relatively poor transitivity performance and levels of hierarchy knowledge achieved by adult human subjects. We focused on the influence of the task instructions on participants' subsequent performance—a single‐word framing manipulation which either specified the relation between items as transitive (i.e., OLD‐FRAME: choose which item is “older”) or left it ambiguous (i.e., NO‐FRAME: choose which item is “correct”). We show a marked but highly specific effect of manipulating prior knowledge through instruction: transitivity performance and levels of relational hierarchy knowledge were enhanced, but premise performance unchanged. Further, we show that hierarchy recall accuracy, but not conventional awareness scores, was a significant predictor of inferential performance across the entire group of participants. The current study has four main implications: first, our findings establish the importance of the task instructions, and prior knowledge, in the TI paradigm—suggesting that they influence the size of the overall hypothesis space (e.g., to favor a linear hierarchical structure over other possibilities in the OLD‐FRAME). Second, the dissociable effects of the instructional frame on premise and inference performance provide evidence for the operation of distinct underlying mechanisms (i.e., an associative mechanism vs. relational hierarchy knowledge). Third, our findings suggest that a detailed measurement of hierarchy recall accuracy may be a more sensitive index of relational hierarchy knowledge, than conventional awareness score—and should be used in future studies investigating links between awareness and inferential performance. Finally, our study motivates an experimental setting that ensures robust hierarchy learning across participants—therefore facilitating study of the neural mechanisms underlying the learning and representation of linear hierarchies. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

Multicenter evaluation of parametric response mapping as an indicator of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

Parametric response mapping (PRM) is a novel computed tomography (CT) technology that has shown potential for assessment of bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HCT). The primary aim of this study was to evaluate whether variations in image acquisition under real‐world conditions affect the PRM measurements of clinically diagnosed BOS. CT scans were obtained retrospectively from 72 HCT recipients with BOS and graft‐versus‐host disease from Fred Hutchinson Cancer Research Center, Karolinska Institute, and the University of Michigan. Whole lung volumetric scans were performed at inspiration and expiration using site‐specific acquisition and reconstruction protocols. PRM and pulmonary function measurements were assessed. Patients with moderately severe BOS at diagnosis (median forced expiratory volume at 1 second [FEV1] 53.5% predicted) had similar characteristics between sites. Variations in site‐specific CT acquisition protocols had a negligible effect on the PRM‐derived small airways disease (SAD), that is, BOS measurements. PRM‐derived SAD was found to correlate with FEV1% predicted and FEV1/ forced vital capacity (R = ?0.236, P = .046; and R = ?0.689, P < .0001, respectively), which suggests that elevated levels in the PRM measurements are primarily affected by BOS airflow obstruction and not CT scan acquisition parameters. Based on these results, PRM may be applied broadly for post‐HCT diagnosis and monitoring of BOS.     

Distinct Roles for Signals Relayed through the Common Cytokine Receptor γ Chain and Interleukin 7 Receptor α Chain in Natural T Cell Development

The commitment, differentiation, and expansion of mainstream α/β T cells during ontogeny depend on the highly controlled interplay of signals relayed by cytokines through their receptors on progenitor cells. The role of cytokines in the development of natural killer (NK)1⁺ natural T cells is less clearly understood. In an approach to define the role of cytokines in the commitment, differentiation, and expansion of NK1⁺ T cells, their development was studied in common cytokine receptor γ chain (γc) and interleukin (IL)-7 receptor α (IL-7Rα)–deficient mice. These mutations block mainstream α/β T cell ontogeny at an early prethymocyte stage. Natural T cells do not develop in γc-deficient mice; they are absent in the thymus and peripheral lymphoid organs such as the liver and the spleen. In contrast, NK1⁺ T cells develop in IL-7Rα–deficient mice in the thymus, and they are present in the liver and in the spleen. However, the absolute number of NK1⁺ T cells in the thymus of IL-7Rα–deficient mice is reduced to ~10%, compared to natural T cell number in the wild-type thymus. Additional data revealed that NK1⁺ T cell ontogeny is not impaired in IL-2– or IL-4–deficient mice, suggesting that neither IL-2, IL-4, nor IL-7 are required for their development. From these data, we conclude that commitment and/or differentiation to the NK1⁺ natural T cell lineage requires signal transduction through the γc, and once committed, their expansion requires signals relayed through the IL-7Rα.     

Impaired spatial and non-spatial configural learning in patients with hippocampal pathology

The hippocampus has been proposed to play a critical role in memory through its unique ability to bind together the disparate elements of an experience. This hypothesis has been widely examined in rodents using a class of tasks known as "configural" or "non-linear", where outcomes are determined by specific combinations of elements, rather than any single element alone. On the basis of equivocal evidence that hippocampal lesions impair performance on non-spatial configural tasks, it has been proposed that the hippocampus may only be critical for spatial configural learning. Surprisingly few studies in humans have examined the role of the hippocampus in solving configural problems. In particular, no previous study has directly assessed the human hippocampal contribution to non-spatial and spatial configural learning, the focus of the current study. Our results show that patients with primary damage to the hippocampus bilaterally were similarly impaired at configural learning within both spatial and non-spatial domains. Our data also provide evidence that residual configural learning can occur in the presence of significant hippocampal dysfunction. Moreover, evidence obtained from a post-experimental debriefing session suggested that patients acquired declarative knowledge of the underlying task contingencies that corresponded to the best-fit strategy identified by our strategy analysis. In summary, our findings support the notion that the hippocampus plays an important role in both spatial and non-spatial configural learning, and provide insights into the role of the medial temporal lobe (MTL) more generally in incremental reinforcement-driven learning.     

Evaluation of ELISA-Based Multiplex Peptides for the Detection of Human Serum Antibodies Induced by Zika Virus Infection across Various Countries

Zika virus (ZIKV) is a mosquito-borne Flavivirus with a positive-sense RNA genome, which are generally transmitted through the bite of an infected Aedes mosquito. ZIKV infections could be associated with neurological sequelae that, and otherwise produces similar clinical symptoms as other co-circulating pathogens. Past infection with one member of the Flavivirus genus often induces cross-reactive antibodies against other flaviruses. These attributes complicate the ability to differentially diagnose ZIKV infection from other endemic mosquito-borne viruses, making it both a public health issue as well as a diagnostic challenge. We report the results from serological analyses using arbovirus-specific peptides on 339 samples that were previously collected from 6 countries. Overall, we found that our multiplexed peptide-based ELISA was highly efficient for identifying ZIKV antibodies as early as 2 weeks post infection, and that it correlates with microneutralization, plaque reduction neutralization tests (PRNTs) and commercial tests for ZIKV in previously characterized samples. We observed that seropositivity varied by patient cohort, reflecting the sampling period in relation to the 2015–2016 ZIKV outbreak. This work evaluates the accuracy, specificity, and sensitivity of our peptide-based ELISA method for detecting ZIKV antibodies from geographically diverse regions. These findings can contribute to ongoing serological methods development and can be adapted for use in future studies.