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.

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.

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.

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.

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.

Electrical stimulation of the dorsolateral prefrontal cortex improves memory monitoring.

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.

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.

Transcranial direct current stimulation (tDCS) of the parietal cortex leads to increased false recognition.

A robust finding is that brain activity in the lateral posterior parietal cortex (PPC) correlates with successful recognition. Here we test whether the PPC has a causal role in memory retrieval using transcranial direct current stimulation (tDCS). Participants were given a modified version of the Deese-Roediger-McDermott (DRM) paradigm, a well-established method for producing false recognition with high confidence. In Experiment 1, false recognition was significantly greater for active compared to sham tDCS when the anode was placed over left parietal cortex (CP3) and the cathode over right parietal cortex (CP4). These findings were replicated in Experiment 2, with both anode CP3/cathode CP4 and anode CP4/cathode CP3 active stimulation leading to greater false recognition. Differences also emerged, with anode CP4/cathode CP3 active stimulation leading to greater hits. Our findings support the proposal that the lateral PPC plays a causal role in episodic memory retrieval and can lead to enhanced subjective aspects of memory.

Distinguishing highly confident accurate and inaccurate memory: insights about relevant and irrelevant influences on memory confidence.

It is generally believed that accuracy and confidence in one's memory are related, but there are many instances when they diverge. Accordingly it is important to disentangle the factors that contribute to memory accuracy and confidence, especially those factors that contribute to confidence, but not accuracy. We used eye movements to separately measure fluent cue processing, the target recognition experience, and relative evidence assessment on recognition confidence and accuracy. Eye movements were monitored during a face-scene associative recognition task, in which participants first saw a scene cue, followed by a forced-choice recognition test for the associated face, with confidence ratings. Eye movement indices of the target recognition experience were largely indicative of accuracy, and showed a relationship to confidence for accurate decisions. In contrast, eye movements during the scene cue raised the possibility that more fluent cue processing was related to higher confidence for both accurate and inaccurate recognition decisions. In a second experiment we manipulated cue familiarity, and therefore cue fluency. Participants showed higher confidence for cue-target associations for when the cue was more familiar, especially for incorrect responses. These results suggest that over-reliance on cue familiarity and under-reliance on the target recognition experience may lead to erroneous confidence.

Neural basis for recognition confidence in younger and older adults.

Although several studies have examined the neural basis for age-related changes in objective memory performance, less is known about how the process of memory monitoring changes with aging. The authors used functional magnetic resonance imaging to examine retrospective confidence in memory performance in aging. During low confidence, both younger and older adults showed behavioral evidence that they were guessing during recognition and that they were aware they were guessing when making confidence judgments. Similarly, both younger and older adults showed increased neural activity during low- compared to high-confidence responses in the lateral prefrontal cortex, anterior cingulate cortex, and left intraparietal sulcus. In contrast, older adults showed more high-confidence errors than younger adults. Younger adults showed greater activity for high compared to low confidence in medial temporal lobe structures, but older adults did not show this pattern. Taken together, these findings may suggest that impairments in the confidence-accuracy relationship for memory in older adults, which are often driven by high-confidence errors, may be primarily related to altered neural signals associated with greater activity for high-confidence responses.

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.

Evidence for a specific role of the anterior hippocampal region in successful associative encoding.

It has been well established that the hippocampal formation plays a critical role in the formation of memories. However, functional specialization within the hippocampus remains controversial. Using functional magnetic resonance imaging (fMRI) during a face-name associative encoding task, followed by a postscan recognition test for face memory and face-name pair memory, we investigated the roles of anterior and posterior hippocampal regions in successful encoding of associations and items. Whole-brain and region of interest (ROI) analyses revealed that the anterior hippocampal formation showed increased activation for subsequently remembered face-name associations compared with pairs that were forgotten. In contrast, the posterior hippocampal formation showed activation above baseline during attempted encoding of face-name pairs, but no evidence of differential activation based on subsequent memory. Furthermore, exploratory whole-brain analyses revealed that a parahippocampal region, most likely corresponding to perirhinal cortex, showed subsequent memory effects for faces. These data provide evidence for functional specialization within the hippocampal formation based on the associative nature of the stimuli and subsequent memory.