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.

05 2023 10.59390/JVIC5712 https://www.funjournal.org/volume-21-issue-2-spring-2023/chagas-et-al-june-212-e2-7 Monica M. Gaudier-Diaz Shveta V. Parekh Rachel E. Penton Sabrina D Robertson Aeisha Thomas Case studies are a valuable teaching tool to engage students in course content using real-world scenarios. As part of the High-throughput Discovery Science & Inquiry-based Case Studies for Today’s Students (HITS) Research Coordination Network (RCN), our team has created the Sleepy Mice Case Study for students to engage with RStudio and the Allen Institute for Brain Science’s open access high-throughput sleep dataset on mice. Sleep is important for health, a familiar concern to college students, and was a basis for this case study. In this case, students completed an initial homework assignment, in-class work, and a final take-home application assignment. The case study was implemented in synchronous and asynchronous Introductory Neuroscience courses, a Biopsychology course, and a Human Anatomy and Physiology course, reflecting its versatility. The case can be used to teach course-specific learning objectives such as sleep-related content and/or science data processing skills. The case study was successful as shown by gains in student scores and confidence in achieving learning objectives. Most students reported enjoying learning about sleep deprivation course content using the case study. Best practices based on instructor experiences in implementation are also included to facilitate future use so that the Sleepy Mice Case Study can be used to teach content and/or research-related skills in various courses and modalities.

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.

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.

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 bemost 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 EinsteinAging 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.

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.

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.

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.

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.

Transcranial direct current stimulation (tDCS) can causally manipulate cortical excitability, making it useful to understand cognitive functions supported by the brain. Neuroimaging studies have shown that activity in the posterior parietal cortex (PPC) correlates with memory performance, but the nature of the PPC's role in episodic memory is controversial. Here we use tDCS to clarify the nature of the causal role of the PPC in recognition memory. In Experiment 1, participants received parietal (2 mA; n = 18), prefrontal (2 mA; n = 18), or sham (n = 18) tDCS during a recognition test. The Kruskal-Wallis test showed that the mean ranks for false recognition differed between groups (p < 0.05; parietal = 21.17, prefrontal = 26.06, and sham = 35.28). Post-hoc tests revealed this to be driven by lower false recognition for parietal compared to sham participants, p < .05. Reduced false recognition may result from how experimental cues were used to attend to relevant memories. To examine this, in Experiment 2 we randomly presented external cues at test that predicted upcoming memoranda as “likely old” or “likely new” with 75% validity. Participants received parietal (2 mA; n = 24), prefrontal (2 mA; n = 24), or sham (n = 24) tDCS during test. A significant interaction emerged, (p < .01), where parietal participants incorporated cues for items predicted as new, whereas frontal stimulation incorporated cues for items predicted new or old. This means parietal cortex selectively incorporates external cues into recognition judgments when they direct attention away from the memory trace, and is dissociable from frontal cortex, which relies on explicit cues for all recognition judgments.

Sometimes when individuals don’t know the answer to a question, they may nevertheless have a “feeling of knowing” (FOK) that the answer is in their memory. FOK reflects ‘metamemory’, or knowledge of one’s own memory. Previous work showed that high definition transcranial direct current stimulation (HD-tDCS) over the dorsal lateral prefrontal cortex (DLPFC) enhanced FOK accuracy, whereas HD-tDCS over the anterior temporal lobes (ATL) showed no effect on memory or metamemory. However, other studies show that the effects of tDCS on cognition vary based on task difficulty. We hypothesized that difficulty moderates the effects of HD-tDCS on memory and metamemory. Thirty-six adults completed 3 sessions with DLPFC, ATL, and sham stimulation during 3 tasks: recall, recognition, and an FOK task using 100 general knowledge questions of varying difficulty (easy, medium, and hard). Recall tests showed effects of difficulty. During the medium block, there was greater recall with ATL stimulation compared to sham (p<0.005) and DLPFC stimulation (p<0.02), but no effects of HD-tDCS during easy and hard blocks. In contrast, during recognition, DLPFC stimulation led to better recognition compared to sham (p<0.05) and ATL stimulation (p<0.005), but there was no interaction with difficulty. A similar pattern was seen for metamemory accuracy; DLPFC stimulation led to more accurate FOK judgments compared to sham (p<0.00005) and ATL stimulation (p<0.0003), and no interaction with difficulty. These results indicate that HD-tDCS can dissociate the roles of the ATL and DLPFC, and that the effects of HD-tDCS on behavior can be moderated by task difficulty.

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.

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.

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.

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.

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.

The ability to accurately monitor one's own memory is an important feature of normal memory function. Converging evidence from neuroimaging and lesion studies have implicated the dorsolateral prefrontal cortex (DLPFC) in memory monitoring. Here we used high definition transcranial direct stimulation (HD-tDCS), a non-invasive form of brain stimulation, to test whether the DLPFC has a causal role in memory monitoring, and the nature of that role. We used a metamemory monitoring task, in which participants first attempted to recall the answer to a general knowledge question, then gave a feeling-of-knowing (FOK) judgment, followed by a forced choice recognition task. When participants received DLPFC stimulation, their feeling-of-knowing judgments were better predictors of memory performance, i.e., they had better memory monitoring accuracy, compared to stimulation of a control site, the anterior temporal lobe (ATL). Effects of DLPFC stimulation were specific to monitoring accuracy, as there was no significant increase in memory performance, and if anything, there was poorer memory performance with DLPFC stimulation. Thus we have demonstrated a causal role for the DLPFC in memory monitoring, and showed that electrically stimulating the left DLPFC led people to more accurately monitor and judge their own memory.

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.