Lack of effects of online HD-tDCS over the left or right DLPFC in an associative memory and metamemory monitoring task.

Neuroimaging studies have shown that activity in the prefrontal cortex correlates with two critical aspects of normal memory functioning: retrieval of episodic memories and subjective "feelings-of-knowing" about our memory. Brain stimulation can be used to test the causal role of the prefrontal cortex in these processes, and whether the role differs for the left versus right prefrontal cortex. We compared the effects of online High-Definition transcranial Direct Current Stimulation (HD-tDCS) over the left or right dorsolateral prefrontal cortex (DLPFC) compared to sham during a proverb-name associative memory and feeling-of-knowing task. There were no significant effects of HD-tDCS on either associative recognition or feeling-of-knowing performance, with Bayesian analyses showing moderate support for the null hypotheses. Despite past work showing effects of HD-tDCS on other memory and feeling-of-knowing tasks, and neuroimaging showing effects with similar tasks, these findings add to the literature of non-significant effects with tDCS. This work highlights the need to better understand factors that determine the effectiveness of tDCS, especially if tDCS is to have a successful future as a clinical intervention.

The association between chronic sinonasal inflammation and nasopharyngeal carcinoma - A systematic review and meta-analysis.

PURPOSE: There has been mounting evidence that inflammation is a key risk factor towards the development of certain cancers. Past studies have shown associations between nasopharyngeal carcinoma (NPC) and sinonasal tract inflammation. We aim to conduct a review and meta-analysis on the association between NPC and chronic sinus inflammation. MATERIALS AND METHODS: We conducted a meta-analysis, searching 4 international databases from 1 January 1973 to 28 March 2022 for studies reporting on sinonasal inflammation and NPC in adult patients (>18 years old). We included cohort, case-control or cross-sectional studies. These studies must examine the association between a prior history of sinonasal inflammation and the risk of developing NPC. The outcome is the incidence of NPC in patients who had prior sinonasal inflammation. RESULTS: 8 studies (8245 NPC; 1,036,087 non-NPC) were included. The overall odds ratio (OR) of patients having NPC after reporting sinonasal inflammation was 1.81 (95 % CI 1.73-1.89). Of note, chronic rhinosinusitis (CRS) (OR of 1.78 (95 %-CI: 1.68-1.90)) was more closely associated with an increased risk of NPC, as compared to allergic rhinitis (AR) (OR of 1.60 (95 %-CI: 1.52-1.68)). CONCLUSION: Chronic sinonasal inflammation is significantly associated with NPC in this systemic review and meta-analysis. The true cause-effect relationship and the potential effects of targeted screening need to be explored thoroughly with large scale prospective studies.

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

Background: Prior 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/hypothesis: The 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 methods: A 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. Results: Overall, 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. Conclusion: Prior 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.

HD-tDCS over the left DLPFC increases cued recall and subjective question familiarity rather than other aspects of memory and metamemory.

When retrieving information from memory there is an interplay between memory and metamemory processes, and the prefrontal cortex has been implicated in both memory and metamemory. Previous work shown that High Definition transcranial Direct Current Stimulation (HD-tDCS) over the dorsolateral prefrontal cortex (DLPFC) can lead to improvements in memory and metamemory monitoring, but findings are mixed. Our original design targeted metamemory, but because the prefrontal cortex plays a role in both memory and metamemory, we tested for effects of HD-tDCS on multiple memory tasks (e.g., recall, cued recall, and recognition) and multiple aspects of metamemory (e.g., once-knew-it ratings, feeling-of-knowing ratings, metamemory accuracy, and metamemory control). There were HD-tDCS-related improvements in cued recall performance, but not other memory tasks. For metamemory, there were HD-tDCS-related increases in subjective once-knew-it ratings, but not other aspects of metamemory. These results highlight the need to consider the effects of HD-tDCS on memory and metamemory at different timepoints during retrieval, as well as specific conditions that show benefits from HD-tDCS.

Sex and gender disparity in kidney transplantation: Historical and future perspectives.

Sex and gender disparity exist in various stages of kidney transplantation. Females were found to be less likely to be referred for kidney transplant, complete pre-transplant evaluation, be placed on the waitlist, and receive a kidney transplant compared to their male counterparts. Interestingly, females comprise the majority of living kidney donors. This review explores the biological and psychosocial factors that contribute to sex and gender disparity in kidney transplantation and proposes ways to address the disparity.

Retrospective metamemory monitoring of semantic memory in community-dwelling older adults with subjective cognitive decline and mild cognitive impairment.

In neurodegenerative conditions, better memory/cognitive awareness, indexed by greater "metamemory monitoring accuracy", is linked to stronger cognitive remediation outcomes. Differences in metamemory monitoring accuracy in predementia conditions, which could inform treatment effectiveness, have not been systematically investigated. We utilized a retrospective confidence judgment (RCJ) task for general knowledge recognition in community-dwelling older adults: 106 cognitively healthy (HC), 68 subjective cognitive decline (SCD) despite intact neuropsychological function, 14 amnestic mild cognitive impairment (aMCI), and 31 non-amnestic mild cognitive impairment (naMCI). Participants gave confidence ratings after making recognition responses to general knowledge questions. Recognition accuracy, confidence levels, and absolute and relative RCJ accuracy (i.e., metamemory monitoring accuracy) were analysed. Compared to HC and SCD, absolute RCJ accuracy was significantly poorer in both MCI groups but relative RCJ accuracy was significantly poorer in naMCI, but not aMCI. This novel result may be driven by lower confidence for correct recognition responses in naMCI and suggests that poorer RCJ accuracy in naMCI may be attributable to poorer performance monitoring. We discuss results in relation to the possibility that individuals in distinct preclinical dementia conditions, who have different levels of memory/cognitive awareness, may differentially benefit from cognitive remediation strategies tailored to their levels of memory/cognitive awareness.

Prospective Metamemory Monitoring of Episodic Visual Memory in Community-Dwelling Older Adults with Subjective Cognitive Decline and Mild Cognitive Impairment.

OBJECTIVE: Metamemory tasks have been utilized to investigate anosognosia in older adults with dementia, though previous research has not systematically compared memory self-awareness in prodromal dementia groups. This represents an important oversight given that remedial and interventional efforts may be most beneficial before individuals' transition to clinical dementia. We examine differences in memory self-awareness and memory self-monitoring between cognitively healthy elderly controls and prodromal dementia groups. METHODS: Participants with subjective cognitive decline despite intact objective neuropsychological functioning (SCD; n = 82), amnestic mild cognitive impairment (aMCI; n = 18), nonamnestic mild cognitive impairment (naMCI; n = 38), and normal cognitive functioning (HC; n = 120) were recruited from the Einstein Aging Study for a cross-sectional study. Participants completed an experimental visual memory-based global metamemory prediction task and subjective assessments of memory/cognition and self-awareness. RESULTS: While, relative to HC, memory self-awareness and memory self-monitoring were preserved for delayed memory performance in SCD and aMCI, these processes were impaired in naMCI. Furthermore, results suggest that poor metamemory accuracy captured by our experimental task can be generalized to everyday memory problems. CONCLUSIONS: Within the framework of the Cognitive Awareness Model, our findings provide preliminary evidence that poor memory self-awareness/self-monitoring in naMCI may reflect an executive or primary anosognosia, with implications for tailored rehabilitative interventions.

Hypoglycemia in cystic fibrosis during an extended oral glucose tolerance test.

BACKGROUND: Hypoglycemia in cystic fibrosis (CF), in the absence of glucose-lowering therapies, has long been identified as an important issue in the management of CF. There is currently still no unifying hypothesis for its etiology. AIM: The aims of this study were to perform a 3-h oral glucose tolerance test (OGTT) in participants with CF and (1) document glucose, insulin, glucagon, glucagon-like-peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) release patterns within varying glucose tolerance groups during the OGTT; (2) determine the prevalence of hypoglycemic during the OGTT; and (3) define any association between hypoglycemia and patterns of insulin, glucagon, GLP-1, and GIP release. METHODS: Eligible participants attending an adult CF clinic completed a 3-h OGTT. Hypoglycemia on OGTT was defined as mild (glucose 3.4-3.9 mmol/L), moderate (glucose 3.1-3.3 mmol/L), and severe (glucose ≤ 3 mmol/L). Hormones were measured at fasting, 30, 60, 120, and 180 min. RESULTS: Twenty-four participants completed the study, of which 7 had normal glucose tolerance, 12 had abnormal glucose tolerance, and 5 had cystic fibrosis related diabetes (CFRD). All participants had a delayed insulin response compared with normative data. All glucose tolerance groups showed appropriate and similar suppression of fasting glucagon. Four participants (17%) had mild hypoglycemic, three (13%) had moderate hypoglycemic, and eight (33%) had severe hypoglycemic. No participant with CFRD demonstrated hypoglycemic. Of the 19 participants without CFRD, 15 (79%) experienced hypoglycemic. Participants with hypoglycemic had greater peak glucose and insulin responses than those that did not have hypoglycemic, and this approached significance (p = .0625 for glucose and p = .0862 for insulin). No significant mean differences between GLP-1 and GIP release were found. There was no relationship between hypoglycemic and modulator therapy. CONCLUSION: Postprandial hypoglycemic was unmasked by the extension of an OGTT to 3 h. Delayed and abnormal insulin release, and ineffective counter-regulatory action of glucagon may have a role in its etiology.

Liver enzyme profile and progression in association with thyroid autoimmunity in Graves' disease.

OBJECTIVE: To investigate the associations of Graves' disease (GD) severity, autoimmunity and longitudinal liver enzyme changes with time in a cohort with well-characterized GD. DESIGN: Retrospective cohort study. PATIENTS: Patients diagnosed with Graves' disease, treated at Royal Prince Alfred Hospital Sydney, Adult Thyroid Clinic from 2000 to 2012 inclusive. MEASUREMENTS: Inclusion criteria were patients with a complete set of TSH, FT4, FT3, liver enzymes and TSH receptor antibody (TRAb) results prior to commencement of thionamide therapy. RESULTS: Of the 146 patients who had complete results, 69 (47%) had at least one abnormal liver enzyme. Gamma glutamyltransferase (GGT) was most frequently abnormal (74%), followed by alanine aminotransferase (ALT) (57%), alkaline phosphatase (ALP) (39%) and then aspartate aminotransferase (AST) (29%). Subsequent to thyroid function normalization, 78% of the liver enzymes were normalized, 10% were persistently abnormal and 12% were lost to follow-up. Circulating TRAb, FT3 and FT4 results were categorized into mild, moderate and severe elevations. At univariate regression analyses, TRAb, FT3 and FT4 levels were each significantly associated with abnormal liver enzyme profile. Multivariate regression including TRAB, FT3 and FT4 as independent variables demonstrated FT3 and FT4 were more strongly associated with abnormal liver profile than TRAb. However, the initial FT3 and FT4 levels were not associated with abnormal liver profile in the subgroup with persistently abnormal liver profile. CONCLUSION: Graves' disease is commonly associated with abnormal liver enzymes, and most commonly with abnormal levels of GGT, and that an abnormal liver enzyme profile is more directly linked to the degree of thyrotoxicosis than levels of TRAB.

Transcranial Direct Current Stimulation over the Prefrontal Cortex Alters Encoding and Judgments of Learning Based on Fluency.

Past research has shown that judgments of learning (JOLs), subjective confidence judgments made at study about later memorability, are inferential in nature and based on cues available during encoding. Participants tend to use fluency as a cue and give higher JOLs to more fluently encoded items, despite having better recognition memory for disfluently encoded items, which leads to poor JOL accuracy. Research has implicated the dorsolateral prefrontal cortex (DLPFC) and anterior prefrontal cortex (aPFC) in JOL and encoding processes, but no studies to date have tested how the roles of these regions vary with the information on which JOLs are based. We used high-definition transcranial direct current stimulation to test the causal roles of DLPFC and aPFC in encoding success, JOL ratings, and JOL accuracy. Participants studied and made JOLs about words that varied in fluency (i.e., frequency and orientation). High-definition transcranial direct current stimulation over the DLPFC impaired encoding, as evidenced by an increase in subsequent false alarms. For words that were less fluently encoded, aPFC stimulation improved JOL accuracy, perhaps making participants more aware of encoding failures under conditions of disfluency. Conversely, DLPFC and aPFC stimulation decreased JOL accuracy for high-frequency words, suggesting the roles of these regions in JOLs vary with the cognitive bases of the judgments. These results contribute to our understanding of the causal roles of prefrontal regions in objective and subjective memory processes and how their contributions to metamemory accuracy vary with information on which subjective assessments are based.

Transcranial direct current stimulation over the right and left VLPFC leads to differential effects on working and episodic memory.

Previous research suggests that the left VLPFC is involved in working memory, whereas right VLPFC is involved with subsequent episodic memory. High-Definition Transcranial Direct Current Stimulation (HD-tDCS) was used to test whether excitation of the left or right VLPFC would show differential effects of negative and neutral stimuli on working memory and episodic memory tasks. While receiving HD-tDCS over the left or right VLPFC or sham stimulation, participants completed a working memory task with negative and neutral distractors followed by a surprise recognition test for the distractors. HD-tDCS over the left VLPFC led to improved working memory performance compared to sham for both negative and neutral distractors. However, for trials that were subsequently remembered, a greater proportion of working memory trials were correct for both the right and left VLPFC group compared to the sham group, for both negative and neutral distractors. Whereas the results from the left VLPFC group can be attributed to overall higher working memory performance, findings from the right VLPFC suggest a role of the right VLPFC in coping with distracting stimuli. Taken together, these results indicate causal roles for the left VLPFC in working memory and the right VLPFC in working memory and episodic memory.

The role of the ventrolateral prefrontal cortex in emotional enhancement of memory: A TMS study.

Negative stimuli are often remembered better than neutral stimuli, which is called the emotional enhancement of memory (EEM). We tested whether the role of the ventrolateral prefrontal cortex (VLPFC) in the EEM depended on stimulus valence and/or arousal, and attentional resources. Continuous theta burst stimulation (cTBS) was applied over the left VLPFC, right VLPFC and vertex before encoding 'negative arousing,' 'negative nonarousing,' and 'neutral' words under full and divided attention, followed by a recognition test. The vertex condition showed the EEM effect for 'negative arousing' and 'negative nonarousing' words. However, the right VLPFC condition showed no evidence of the EEM effect for 'negative arousing' or 'negative nonarousing' words, under full attention. In contrast, the left VLPFC condition showed the EEM effect for 'negative arousing' words, but not 'negative nonarousing' words, under full attention. Thus, the left and right VLPFC have different roles in the EEM, depending on valence and arousal.

Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management.

Immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4 antibodies) are a standard of care for advanced melanoma. Novel toxicities comprise immune-related adverse events (irAE). With increasing use, irAE require recognition, practical management strategies, and multidisciplinary care. We retrospectively evaluated the incidence, kinetics, and management of irAE in 41 patients receiving anti-PD-1 antibody therapy (pembrolizumab) for advanced melanoma. 63% received prior anti-CTLA-4 antibody therapy (ipilimumab). IrAE occurred in 54%, most commonly dermatological (24%), rheumatological (22%), and thyroid dysfunction (12%). Thyroiditis was characterised by a brief asymptomatic hyperthyroid phase followed by a symptomatic hypothyroid phase requiring thyroxine replacement. Transplant rejection doses of methylprednisolone were necessary to manage refractory hepatotoxicity. A bullous pemphigoid-like skin reaction with refractory pruritus responded to corticosteroids and neuropathic analgesia. Disabling grade 3-4 oligoarthritis required sulfasalazine therapy in combination with steroids. The median interval between the last dose of anti-CTLA-4 antibody and the first dose of anti-PD-1 therapy was 2.0 months (range: 0.4 to 22.4). Toxicities may occur late; this requires vigilance and multidisciplinary management which may allow effective anticancer therapy to continue. Management algorithms for thyroiditis, hypophysitis, arthralgia/arthritis, colitis, steroid-refractory hepatitis, and skin toxicity are discussed.

Increased contextual cue utilization with tDCS over the prefrontal cortex during a recognition task.

The precise role of the prefrontal and posterior parietal cortices in recognition performance remains controversial, with questions about whether these regions contribute to recognition via the availability of mnemonic evidence or via decision biases and retrieval orientation. Here we used an explicit memory cueing paradigm, whereby external cues probabilistically predict upcoming memoranda as old or new, in our case with 75% validity, and these cues affect recognition decision biases in the direction of the cue. The present study applied bilateral transcranial direct current stimulation (tDCS) over prefrontal or posterior parietal cortex, or sham tDCS, to test the causal role of these regions in recognition accuracy or decision biasing. Participants who received tDCS over prefrontal cortex showed increased cue utilization compared to tDCS over posterior parietal cortex and sham tDCS, suggesting that the prefrontal cortex is involved in processes that contribute to decision biases in memory.

Effects of HD-tDCS on memory and metamemory for general knowledge questions that vary by difficulty.

BACKGROUND: The ability to monitor one's own memory is an important feature of normal memory and is an aspect of 'metamemory'. Lesion studies have shown dissociations between memory and metamemory, but only single dissociations have been shown using transcranial direct current stimulation (tDCS). One potential reason that only single dissociations have been shown is that tDCS effects may be moderated by task difficulty. OBJECTIVE/HYPOTHESIS: We used high definition (HD) tDCS to test for dissociable roles of the dorsolateral prefrontal cortex (DLPFC) and anterior temporal lobe (ATL) in semantic long-term memory and metamemory tasks. We also tested whether general knowledge question difficulty moderated the effects of HD-tDCS. METHODS: Across 3 sessions, participants received active HD-tDCS over the left DLPFC or left ATL, or sham HD-tDCS during general knowledge recall and recognition tests, and a 'feeling-of-knowing' metamemory task. General knowledge questions were blocked by difficulty. Repeated measures ANOVAs were used to examine the effects of HD-tDCS on memory and metamemory tasks by memory question difficulty. RESULTS: HD-tDCS over the ATL led to improved recall compared to DLPFC and sham HD-tDCS, and this occurred only for medium difficulty questions. In contrast, for non-recalled questions, HD-tDCS over the DLPFC led to improved recognition accuracy and improved feeling-of-knowing accuracy compared to ATL and sham HD-tDCS, and this was not moderated by memory question difficulty. CONCLUSION (S): HD-tDCS can be used to dissociate the roles of the ATL and DLPFC in different memory and 'metamemory' tasks. The effects of HD-tDCS on task may be moderated by task difficulty, depending on the nature of the task and site of stimulation.

tDCS over the prefrontal cortex alters objective but not subjective encoding.

Previous research has implicated the prefrontal cortex (PFC) in successful associative encoding and subjective awareness of one's memory performance. We tested the causal role of the PFC in these processes by applying transcranial direct current stimulation (tDCS) during a verbal associative encoding and judgment-of-learning (JOL) task. tDCS over the PFC impaired associative encoding compared to sham and parietal tDCS, as shown by fewer hits on a subsequent associative recognition test. There were no effects of tDCS on the magnitude or accuracy of JOLs. These results suggest the PFC plays a causal role in objective measures of encoding, and that objective and subjective aspects of associative encoding are separable.

Knowing your heart and your mind: The relationships between metamemory and interoception.

Humans experience a unified self that integrates our mental lives and physical bodies, but many studies focus on isolated domains of self-knowledge. We tested the hypothesis that knowledge of one's mind and body are related by examining metamemory and interoception. We evaluated two dimensions of metamemory and interoception: subjective beliefs and the accuracy of those beliefs compared to objective criteria. We first demonstrated, in two studies, that metamemory beliefs were positively correlated with interoceptive beliefs, and this was not due to domain-general confidence. Finally, we showed that individuals with better metamemory accuracy also had better interoceptive accuracy. Taken together, these findings suggest a common mechanism subserving knowledge of our cognitive and bodily states.

Transcranial direct current stimulation over the parietal cortex alters bias in item and source memory tasks.

Neuroimaging data have shown that activity in the lateral posterior parietal cortex (PPC) correlates with item recognition and source recollection, but there is considerable debate about its specific contributions. Performance on both item and source memory tasks were compared between participants who were given bilateral transcranial direct current stimulation (tDCS) over the parietal cortex to those given prefrontal or sham tDCS. The parietal tDCS group, but not the prefrontal group, showed decreased false recognition, and less bias in item and source discrimination tasks compared to sham stimulation. These results are consistent with a causal role of the PPC in item and source memory retrieval, likely based on attentional and decision-making biases.