Building metamemorial knowledge over time: insights from eye tracking about the bases of feeling-of-knowing and confidence judgments

Metamemory processes depend on different factors across the learning and memory time-scale. In the laboratory, subjects are often asked to make prospective feeling-of-knowing (FOK) judgments about target retrievability, or are asked to make retrospective confidence judgments (RCJs) about the retrieved target. We examined distinct and shared contributors to metamemory judgments, and how they were built over time. Eye movements were monitored during a face-scene associative memory task. At test, participants viewed a studied scene, then rated their FOK that they would remember the associated face. This was followed by a forced choice recognition test and RCJs. FOK judgments were less accurate than RCJ judgments, showing that the addition of mnemonic experience can increase metacognitive accuracy over time. However, there was also evidence that the given FOK rating influenced RCJs. Turning to eye movements, initial analyses showed that higher cue fluency was related to both higher FOKs and higher RCJs. However, further analyses revealed that the effects of the scene cue on RCJs were mediated by FOKs. Turning to the target, increased viewing time and faster viewing of the correct associate related to higher FOKs, consistent with the idea that target accessibility is a basis of FOKs. In contrast, the amount of viewing directed to the chosen face, regardless of whether it was correct, predicted higher RCJs, suggesting that choice experience is a significant contributor RCJs. We also examined covariates of the change in RCJ rating from the FOK rating, and showed that increased and faster viewing of the chosen face predicted raising one’s confidence above one’s FOK. Taken together these results suggest that metamemory judgments should not be thought of only as distinct subjective experiences, but complex processes that interact and evolve as new psychological bases for subjective experience become available

Neural Correlates of Metamemory: A Comparison of Feeling-of-Knowing and Retrospective Confidence Judgments

Metamemory refers to knowledge and monitoring of one's own memory. Metamemory monitoring can be done prospectively with respect to subsequent memory retrieval or retrospectively with respect to previous memory retrieval. In this study, we used fMRI to compare neural activity during prospective feeling-of-knowing and retrospective confidence tasks in order to examine common and distinct mechanisms supporting multiple forms of metamemory monitoring. Both metamemory tasks, compared to non-metamemory tasks, were associated with greater activity in medial prefrontal, medial parietal, and lateral parietal regions, which have previously been implicated in internally directed cognition. Furthermore, compared to non-metamemory tasks, metamemory tasks were associated with less activity in occipital regions, and in lateral inferior frontal and dorsal medial prefrontal regions, which have previously shown involvement in visual processing and stimulus-oriented attention, respectively. Thus, neural activity related to metamemory is characterized by both a shift toward internally directed cognition and away from externally directed cognition. Several regions demonstrated differences in neural activity between feeling-of-knowing and confidence tasks, including fusiform, medial temporal lobe, and medial parietal regions; furthermore, these regions also showed interaction effects between task and the subjective metamemory rating, suggesting that they are sensitive to the information monitored in each particular task. These findings demonstrate both common and distinct neural mechanisms supporting metamemory processes and also serve to elucidate the functional roles of previously characterized brain networks.Psycholog

Differential effects of remotely supervised transcranial direct current stimulation on recognition memory depending on task order

BackgroundPrior work has shown positive effects of High Definition transcranial direct current stimulation (HD-tDCS) over the dorsolateral prefrontal cortex (DLPFC) on semantic memory performance and metamemory monitoring accuracy. However, HD-tDCS requires setup by a trained researcher, which is not always feasible. Few studies have used remotely supervised (rs) tDCS in healthy populations, and remote supervision has strong practical benefits.Objective/hypothesisThe goal of the current study was to test if previously shown effects of HD-tDCS over the left DLPFC on semantic memory performance and metamemory monitoring accuracy extended to conventional rs-tDCS, which is less focal than HD-tDCS, and to episodic memory and metamemory tasks.Materials and methodsA total of 36 healthy participants completed 6 weeks of rs-tDCS sessions, with either active left or right anodal DLPFC stimulation, or sham. Participants completed semantic and episodic memory and metamemory tasks, which each lasted for three consecutive sessions, and session order was counterbalanced across participants.ResultsOverall, there were no main effects of rs-tDCS on metamemory monitoring accuracy or memory performance for either the semantic or the episodic tasks. However, there were effects of rs-tDCS that depended on the order of completing the episodic and semantic task sessions. When participants completed the semantic task sessions after the episodic task sessions, semantic recognition was greater in the left anodal DLPFC condition. In a parallel effect, when participants completed the episodic task sessions after the semantic task sessions, episodic recognition was greater in the right anodal DLPFC condition.ConclusionPrior experience with tDCS is a factor for effects of rs-tDCS on cognition. Additionally, the current experiment provides evidence for the feasibility of fully remotely supervised tDCS in healthy participants

Building Metamemorial Knowledge over Time: Insights from Eye Tracking about The Bases of Feeling-of-knowing and Confidence Judgements

Metamemory processes depend on different factors across the learning and memory time-scale. In the laboratory, subjects are often asked to make prospective feeling-of-knowing (FOK) judgments about target retrievability, or are asked to make retrospective confidence judgments (RCJs) about the retrieved target. We examined distinct and shared contributors to metamemory judgments, and how they were built over time. Eye movements were monitored during a face-scene associative memory task. At test, participants viewed a studied scene, then rated their FOK that they would remember the associated face. This was followed by a forced choice recognition test and RCJs. FOK judgments were less accurate than RCJ judgments, showing that the addition of mnemonic experience can increase metacognitive accuracy over time. However, there was also evidence that the given FOK rating influenced RCJs. Turning to eye movements, initial analyses showed that higher cue fluency was related to both higher FOKs and higher RCJs. However, further analyses revealed that the effects of the scene cue on RCJs were mediated by FOKs. Turning to the target, increased viewing time and faster viewing of the correct associate related to higher FOKs, consistent with the idea that target accessibility is a basis of FOKs. In contrast, the amount of viewing directed to the chosen face, regardless of whether it was correct, predicted higher RCJs, suggesting that choice experience is a significant contributor RCJs. We also examined covariates of the change in RCJ rating from the FOK rating, and showed that increased and faster viewing of the chosen face predicted raising one’s confidence above one’s FOK. Taken together these results suggest that metamemory judgments should not be thought of only as distinct subjective experiences, but complex processes that interact and evolve as new psychological bases for subjective experience become available

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3—4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity

Theoretical studies of the historical development of the accounting discipline: a review and evidence

Many existing studies of the development of accounting thought have either been atheoretical or have adopted Kuhn's model of scientific growth. The limitations of this 35-year-old model are discussed. Four different general neo-Kuhnian models of scholarly knowledge development are reviewed and compared with reference to an analytical matrix. The models are found to be mutually consistent, with each focusing on a different aspect of development. A composite model is proposed. Based on a hand-crafted database, author co-citation analysis is used to map empirically the entire literature structure of the accounting discipline during two consecutive time periods, 1972–81 and 1982–90. The changing structure of the accounting literature is interpreted using the proposed composite model of scholarly knowledge development

Endosomal MR1 Trafficking Plays a Key Role in Presentation of Mycobacterium tuberculosis Ligands to MAIT Cells

Mucosal-Associated Invariant T (MAIT) cells, present in high frequency in airway and other mucosal tissues, have Th1 effector capacity positioning them to play a critical role in the early immune response to intracellular pathogens, including Mycobacterium tuberculosis (Mtb). MR1 is a highly conserved Class I-like molecule that presents vitamin B metabolites to MAIT cells. The mechanisms for loading these ubiquitous small molecules are likely to be tightly regulated to prevent inappropriate MAIT cell activation. To define the intracellular localization of MR1, we analyzed the distribution of an MR1-GFP fusion protein in antigen presenting cells. We found that MR1 localized to endosomes and was translocated to the cell surface upon addition of 6-formyl pterin (6-FP). To understand the mechanisms by which MR1 antigens are presented, we used a lentiviral shRNA screen to identify trafficking molecules that are required for the presentation of Mtb antigen to HLA-diverse T cells. We identified Stx18, VAMP4, and Rab6 as trafficking molecules regulating MR1-dependent MAIT cell recognition of Mtb-infected cells. Stx18 but not VAMP4 or Rab6 knockdown also resulted in decreased 6-FP-dependent surface translocation of MR1 suggesting distinct pathways for loading of exogenous ligands and intracellular mycobacterially-derived ligands. We postulate that endosome-mediated trafficking of MR1 allows for selective sampling of the intracellular environment.Career Development Award: (#IK2 CX000538); U.S. Department of Veterans Affairs Clinical Sciences Research and Development Program (MJH); U.S.Department of Veterans Affairs Biomedical Laboratory Research and Development Program (DML) Merit Award: (#I01 BX000533); American Lung Association: (RT-350058)

Assessing dysphagia via telerehabilitation: patient perceptions and satisfaction

To gain insight into factors which may infl uence future acceptance of dysphagia management via telerehabilitation, patients’ perceptions were examined before and after a telerehabilitation assessment session. Forty adult patients with dysphagia(M = 66 years, SD = 16.25) completed pre- and post-session questionnaires which consisted of 14 matched questions worded to suit pre- and post-conditions. Questions explored comfort with the use of telerehabilitation, satisfaction with audio and video quality, benefi ts of telerehabilitation assessments and patients’ preferred assessment modality. Questions were rated on a 5-point scale (1 = strongly disagree, 3 = unsure, 5 = strongly agree). Patients’ comfort with assessment via telerehabilitation was high in over 80% of the group both pre- and post-assessment. Pre-assessment, patients were unsure what to expect with the auditory and visual aspects of the videoconference, however there were signifi cant positive changes reported post-experience. In relation to perceived benefits of telerehabilitation services in general, most patients believed in the value of telerehabilitation and post-assessment this increased to 90 – 100% agreement. Although 92% felt they would be comfortable receiving services via telerehabilitation, 45% of patients indicated ultimate preference for a traditional faceto-face assessment. The data highlight that patients are interested in and willing to receive services via telerehabilitation; however, any concerns should be addressed pre-assessment

Two Novel Point Mutations in Clinical Staphylococcus aureus Reduce Linezolid Susceptibility and Switch on the Stringent Response to Promote Persistent Infection

Staphylococcus aureus frequently invades the human bloodstream, leading to life threatening bacteremia and often secondary foci of infection. Failure of antibiotic therapy to eradicate infection is frequently described; in some cases associated with altered S. aureus antimicrobial resistance or the small colony variant (SCV) phenotype. Newer antimicrobials, such as linezolid, remain the last available therapy for some patients with multi-resistant S. aureus infections. Using comparative and functional genomics we investigated the molecular determinants of resistance and SCV formation in sequential S. aureus isolates from a patient who had a persistent and recurrent S. aureus infection, after failed therapy with multiple antimicrobials, including linezolid. Two point mutations in key staphylococcal genes dramatically affected clinical behaviour of the bacterium, altering virulence and antimicrobial resistance. Most strikingly, a single nucleotide substitution in relA (SACOL1689) reduced RelA hydrolase activity and caused accumulation of the intracellular signalling molecule guanosine 3′, 5′-bis(diphosphate) (ppGpp) and permanent activation of the stringent response, which has not previously been reported in S. aureus. Using the clinical isolate and a defined mutant with an identical relA mutation, we demonstrate for the first time the impact of an active stringent response in S. aureus, which was associated with reduced growth, and attenuated virulence in the Galleria mellonella model. In addition, a mutation in rlmN (SACOL1230), encoding a ribosomal methyltransferase that methylates 23S rRNA at position A2503, caused a reduction in linezolid susceptibility. These results reinforce the exquisite adaptability of S. aureus and show how subtle molecular changes cause major alterations in bacterial behaviour, as well as highlighting potential weaknesses of current antibiotic treatment regimens