Observing the suppression of individual aversive memories from conscious awareness.

When reminded of an unpleasant experience, people often try to exclude the unwanted memory from awareness, a process known as retrieval suppression. Here we used multivariate decoding (MVPA) and representational similarity analyses on EEG data to track how suppression unfolds in time and to reveal its impact on item-specific cortical patterns. We presented reminders to aversive scenes and asked people to either suppress or to retrieve the scene. During suppression, mid-frontal theta power within the first 500 ms distinguished suppression from passive viewing of the reminder, indicating that suppression rapidly recruited control. During retrieval, we could discern EEG cortical patterns relating to individual memories-initially, based on theta-driven visual perception of the reminders (0 to 500 ms) and later, based on alpha-driven reinstatement of the aversive scene (500 to 3000 ms). Critically, suppressing retrieval weakened (during 360 to 600 ms) and eventually abolished item-specific cortical patterns, a robust effect that persisted until the reminder disappeared (780 to 3000 ms). Representational similarity analyses provided converging evidence that retrieval suppression weakened the representation of target scenes during the 500 to 3000 ms reinstatement window. Together, rapid top-down control during retrieval suppression abolished cortical patterns of individual memories, and precipitated later forgetting. These findings reveal a precise chronometry on the voluntary suppression of individual memories.

Distinct SAP102 and PSD-95 Nano-organization Defines Multiple Types of Synaptic Scaffold Protein Domains at Single Synapses.

MAGUK scaffold proteins play a central role in maintaining and modulating synaptic signaling, providing a framework to retain and position receptors, signaling molecules, and other synaptic components. In particular, the MAGUKs SAP102 and PSD-95 are essential for synaptic function at distinct developmental timepoints and perform both overlapping and unique roles. While their similar structures allow for common binding partners, SAP102 is expressed earlier in synapse development and is required for synaptogenesis, whereas PSD-95 expression peaks later and is associated with synapse maturation. PSD-95 and other key synaptic proteins organize into subsynaptic nanodomains that have a significant impact on synaptic transmission, but the nanoscale organization of SAP102 is unknown. How SAP102 is organized within the synapse, and how it relates spatially to PSD-95 on a nanometer scale, could underlie its unique functions and impact how SAP102 scaffolds synaptic proteins. Here we used DNA-PAINT super-resolution microscopy to measure SAP102 nano-organization and its spatial relationship to PSD-95 at individual synapses in mixed-sex rat cultured neurons. We found that like PSD-95, SAP102 accumulates in high-density subsynaptic nanoclusters (NCs). However, SAP102 NCs were smaller and denser than PSD-95 NCs across development. Additionally, only a subset of SAP102 NCs co-organized with PSD-95, revealing MAGUK nanodomains within individual synapses containing either one or both proteins. These MAGUK nanodomain types had distinct NC properties and were differentially enriched with the presynaptic release protein Munc13-1. This organization into both shared and distinct subsynaptic nanodomains may underlie the ability of SAP102 and PSD-95 to perform both common and unique synaptic functions.

Memory control immediately improves unpleasant emotions associated with autobiographical memories of past immoral actions.

The ability to stop unwanted memories from coming to mind is theorised to be essential for maintaining good mental health. People can employ intentional strategies to prevent conscious intrusions of negative memories, and repeated attempts to stop retrieval both reduces the frequency of intrusions and improves subsequent emotions elicited by those memories. However, it is still unknown whether memory control can improve negative emotions immediately, at the time control is attempted. It is also not clear which strategy is most beneficial for emotion regulation; clearing the mind of any thoughts of negative memories via direct suppression, or substituting memory recall with alternative thoughts. Here, we provide novel evidence that memory control immediately regulates negative emotions associated with autobiographical memories of morally wrong actions. Repeated control significantly improved negative emotions over time, regardless of the strategy used to implement control. Thought substitution involving either positive diversionary thinking or counterfactual thinking both induced positive feelings, whereas direct suppression neutralised emotions, regardless of whether memories were positive or negative. These empirical findings have implications for clinical practice as they indicate that memory control strategies could be effective emotion regulation methods for real-world intrusive memories.

Everything you ever wanted to know about the Think/No-Think task, but forgot to ask.

The Think/No-Think (TNT) task has just celebrated 20 years since its inception, and its use has been growing as a tool to investigate the mechanisms underlying memory control and its neural underpinnings. Here, we present a theoretical and practical guide for designing, implementing, and running TNT studies. For this purpose, we provide a step-by-step description of the structure of the TNT task, methodological choices that can be made, parameters that can be chosen, instruments available, aspects to be aware of, systematic information about how to run a study and analyze the data. Importantly, we provide a TNT training package (as Supplementary Material), that is, a series of multimedia materials (e.g., tutorial videos, informative HTML pages, MATLAB code to run experiments, questionnaires, scoring sheets, etc.) to complement this method paper and facilitate a deeper understanding of the TNT task, its rationale, and how to set it up in practice. Given the recent discussion about the replication crisis in the behavioral sciences, we hope that this contribution will increase standardization, reliability, and replicability across laboratories.

Loss of postsynaptic NMDARs drives nanoscale reorganization of Munc13-1 and PSD-95.

Nanoscale protein organization within the active zone (AZ) and post-synaptic density (PSD) influences synaptic transmission. Nanoclusters of presynaptic Munc13-1 are associated with readily releasable pool size and neurotransmitter vesicle priming, while postsynaptic PSD-95 nanoclusters coordinate glutamate receptors across from release sites to control their opening probability. Nanocluster number, size, and protein density vary between synapse types and with development and plasticity, supporting a wide range of functional states at the synapse. Whether or how the receptors themselves control this critical architecture remains unclear. One prominent PSD molecular complex is the NMDA receptor (NMDAR). NMDARs coordinate several modes of signaling within synapses, giving them the potential to influence synaptic organization through direct protein interactions or through signaling. We found that loss of NMDARs results in larger synapses that contain smaller, denser, and more numerous PSD-95 nanoclusters. Intriguingly, NMDAR loss also generates retrograde reorganization of the active zone, resulting in denser, more numerous Munc13-1 nanoclusters, more of which are aligned with PSD-95 nanoclusters. Together, these changes to synaptic nanostructure predict stronger AMPA receptor-mediated transmission in the absence of NMDARs. Notably, while prolonged antagonism of NMDAR activity increases Munc13-1 density within nanoclusters, it does not fully recapitulate these trans-synaptic effects. Thus, our results confirm that NMDARs play an important role in maintaining pre- and postsynaptic nanostructure and suggest that both decreased NMDAR expression and suppressed NMDAR activity may exert distinct effects on synaptic function, yet through unique architectural mechanisms.

Amnesia in healthy people via hippocampal inhibition: A new forgetting mechanism.

Structural damage to the hippocampus gives rise to a severe memory deficit for personal experiences known as organic amnesia. Remarkably, such structural damage may not be the only way of creating amnesia; windows of amnesia can also arise when people deliberately disengage from memory via a process known as retrieval suppression. In this review, we discuss how retrieval suppression induces systemic inhibition of the hippocampus, creating "amnesic shadow" intervals in people's memory for their personal experiences. When new memories are encoded or older memories are reactivated during this amnesic shadow, these memories are disrupted, and such disruption even arises when older memories are subliminally cued. Evidence suggests that the systemic inhibition of the hippocampus during retrieval suppression that gives rise to the amnesic shadow may be mediated by engagement of hippocampal GABAergic inhibitory interneurons. Similar amnesic shadow effects are observed during working memory tasks like the n-back, which also induce notable hippocampal downregulation. We discuss our recent proposal that cognitive operations that require the disengagement of memory retrieval, such as retrieval suppression, are capable of mnemonic process inhibition (the inhibition of mnemonic processes such as encoding, consolidation, and retrieval and not simply individual memories). We suggest that people engage mnemonic process inhibition whenever they shift attention from internal processes to demanding perceptual-motor tasks that may otherwise be disrupted by distraction from our inner world. This hitherto unstudied model of inhibition is a missing step in understanding what happens when attentional shifts occur between internally and externally oriented processes to facilitate goal-directed behaviour. This process constitutes an important novel mechanism underlying the forgetting of life events.

Improving mental health by training the suppression of unwanted thoughts.

Anxiety, posttraumatic stress, and depression markedly increased worldwide during the COVID-19 pandemic. People with these conditions experience distressing intrusive thoughts, yet conventional therapies often urge them to avoid suppressing their thoughts because intrusions might rebound in intensity and frequency, worsening the disorders. In contrast, we hypothesized that training thought suppression would improve mental health. One hundred and twenty adults from 16 countries underwent 3 days of online training to suppress either fearful or neutral thoughts. No paradoxical increases in fears occurred. Instead, suppression reduced memory for suppressed fears and rendered them less vivid and anxiety provoking. After training, participants reported less anxiety, negative affect, and depression with the latter benefit persisting at 3 months. Participants high in trait anxiety and pandemic-related posttraumatic stress gained the largest and most durable mental health benefits. These findings challenge century-old wisdom that suppressing thoughts is maladaptive, offering an accessible approach to improving mental health.

Distinct SAP102 and PSD-95 nano-organization defines multiple types of synaptic scaffold protein domains at single synapses.

The MAGUK family of scaffold proteins plays a central role in maintaining and modulating synaptic signaling, providing a framework to retain and position receptors, signaling molecules, and other synaptic components. Of these scaffold proteins, SAP102 and PSD-95 are essential for synaptic function at distinct developmental timepoints and perform overlapping as well as unique roles. While their similar structures allow for common binding partners, SAP102 is expressed earlier in synapse development and is required for synaptogenesis, whereas PSD-95 expression peaks later in development and is associated with synapse maturation. PSD-95 and other key synaptic proteins organize into subsynaptic nanodomains that have a significant impact on synaptic transmission, but the nanoscale organization of SAP102 is unknown. How SAP102 is organized within the synapse, and how it relates spatially to PSD-95 on a nanometer scale, could impact how SAP102 clusters synaptic proteins and underlie its ability to perform its unique functions. Here we used DNA-PAINT super-resolution microscopy to measure SAP102 nano-organization and its spatial relationship to PSD-95 at individual synapses. We found that like PSD-95, SAP102 accumulates in high-density subsynaptic nanoclusters. However, SAP102 nanoclusters were smaller and denser than PSD-95 nanoclusters across development. Additionally, only a subset of SAP102 nanoclusters co-organized with PSD-95, revealing that within individual synapses there are nanodomains that contain either one or both proteins. This organization into both shared and distinct subsynaptic nanodomains may underlie the ability of SAP102 and PSD-95 to perform both common and unique synaptic functions.

On the role of inhibition in suppression-induced forgetting.

Suppressing retrieval of unwanted memories can cause forgetting, an outcome often attributed to the recruitment of inhibitory control. This suppression-induced forgetting (SIF) generalizes to different cues used to test the suppressed content (cue-independence), a property taken as consistent with inhibition. But does cue-independent forgetting necessarily imply that a memory has been inhibited? Tomlinson et al. (Proc Natl Acad Sci 106:15588-15593, 2009) reported a surprising finding that pressing a button also led to cue-independent forgetting, which was taken as support for an alternative interference account. Here we investigated the role of inhibition in forgetting due to retrieval suppression and pressing buttons. We modified Tomlinson et al.'s procedure to examine an unusual feature they introduced that may have caused memory inhibition effects in their experiment: the omission of explicit task-cues. When tasks were uncued, we replicated the button-press forgetting effect; but when cued, pressing buttons caused no forgetting. Moreover, button-press forgetting partially reflects output-interference effects at test and not a lasting effect of interference. In contrast, SIF occurred regardless of these procedural changes. Collectively, these findings indicate that simply pressing a button does not induce forgetting, on its own, without confounding factors that introduce inhibition into the task and that inhibition likely underlies SIF.

Reduced hippocampal-cortical connectivity during memory suppression predicts the ability to forget unwanted memories.

The ability to suppress unwelcome memories is important for productivity and well-being. Successful memory suppression is associated with hippocampal deactivations and a concomitant disruption of this region's functionality. Much of the previous neuroimaging literature exploring such suppression-related hippocampal modulations has focused on the region's negative coupling with the prefrontal cortex. Task-based changes in functional connectivity between the hippocampus and other brain regions still need further exploration. In the present study, we utilize psychophysiological interactions and seed connectome-based predictive modeling to investigate the relationship between the hippocampus and the rest of the brain as 134 participants attempted to suppress unwanted memories during the Think/No-Think task. The results show that during retrieval suppression, the right hippocampus exhibited decreased functional connectivity with visual cortical areas (lingual and cuneus gyrus), left nucleus accumbens and the brain-stem that predicted superior forgetting of unwanted memories on later memory tests. Validation tests verified that prediction performance was not an artifact of head motion or prediction method and that the negative features remained consistent across different brain parcellations. These findings suggest that systemic memory suppression involves more than the modulation of hippocampal activity-it alters functional connectivity patterns between the hippocampus and visual cortex, leading to successful forgetting.

Suppression-induced forgetting of motor sequences.

Two experiments examined the effects of deliberately suppressing retrieval of motor sequences on their later recall, in the think/no-think paradigm (Anderson & Green, 2001). After several motor sequences had been associated with individual cues through repeated practice cycles, a subset of these sequences was retrieved in response to their respective cues (think trials), whereas other sequences were suppressed. In such no-think trials, cues were shown but participants were instructed to withhold the associated motor response and to suppress its recollection. We found that suppressing retrieval impaired later memory performance for the suppressed sequences in comparison to items that were not cued at all after their initial training (baseline sequences). Suppression impaired later sequence recall and sequence speed although in different ways depending on the training level: with higher initial training of sequences (Experiment 1), suppression impaired reaction time, but not recall accuracy; with lower initial training (Experiment 2), suppression reduced recall accuracy. Reaction time analyses revealed a consistent slowing of movement execution for suppressed sequences. These findings show that inhibitory control processes engaged during retrieval suppression can influence memory representations of motor actions, by not only reducing their accessibility but also by affecting their execution, once retrieved.

Trans-synaptic molecular context of NMDA receptor nanodomains.

Tight coordination of the spatial relationships between protein complexes is required for cellular function. In neuronal synapses, many proteins responsible for neurotransmission organize into subsynaptic nanoclusters whose trans-cellular alignment modulates synaptic signal propagation. However, the spatial relationships between these proteins and NMDA receptors (NMDARs), which are required for learning and memory, remain undefined. Here, we mapped the relationship of key NMDAR subunits to reference proteins in the active zone and postsynaptic density using multiplexed super-resolution DNA-PAINT microscopy. GluN2A and GluN2B subunits formed nanoclusters with diverse configurations that, surprisingly, were not localized near presynaptic vesicle release sites marked by Munc13-1. However, a subset of presynaptic sites was configured to maintain NMDAR activation: these were internally denser, aligned with abundant PSD-95, and associated closely with specific NMDAR nanodomains. This work reveals a new principle regulating NMDAR signaling and suggests that synaptic functional architecture depends on assembly of multiprotein nanodomains whose interior construction is conditional on trans-cellular relationships.

Inducing forgetting of unwanted memories through subliminal reactivation.

Processes that might facilitate the forgetting of unwanted experiences typically require the actual or imagined re-exposure to reminders of the event, which is aversive and carries risks to people. But it is unclear whether awareness of aversive content is necessary for effective voluntary forgetting. Disrupting hippocampal function through retrieval suppression induces an amnesic shadow that impairs the encoding and stabilization of unrelated memories that are activated near in time to people's effort to suppress retrieval. Building on this mechanism, here we successfully disrupt retention of unpleasant memories by subliminally reactivating them within this amnesic shadow. Critically, whereas unconscious forgetting occurs on these affective memories, the amnesic shadow itself is induced by conscious suppression of unrelated and benign neutral memories, avoiding conscious re-exposure of unwelcome content. Combining the amnesic shadow with subliminal reactivation may offer a new approach to voluntary forgetting that bypasses the unpleasantness in conscious exposure to unwanted memories.

EEG evidence that morally relevant autobiographical memories can be suppressed.

Remembering unpleasant events can trigger negative feelings. Fortunately, research indicates that unwanted retrieval can be suppressed to prevent memories from intruding into awareness, improving our mental state. The current scientific understanding of retrieval suppression, however, is based mostly on simpler memories, such as associations between words or pictures, which may not reflect how people control unpleasant memory intrusions in everyday life. Here, we investigated the neural and behavioural dynamics of suppressing personal and emotional autobiographical memories using a modified version of the Think/No-Think task. We asked participants to suppress memories of their own past immoral actions, which were hypothesised to be both highly intrusive and motivating to suppress. We report novel evidence from behavioural, ERP, and EEG oscillation measures that autobiographical memory retrieval can be suppressed and suggest that autobiographical suppression recruits similar neurocognitive mechanisms as suppression of simple laboratory associations. Suppression did fail sometimes, and EEG oscillations indicated that such memory intrusions occurred from lapses in sustained control. Importantly, however, participants improved at limiting intrusions with repeated practice. Furthermore, both behavioural and EEG evidence indicated that intentional suppression may be more difficult for memories of our morally wrong actions than memories of our morally right actions. The findings elucidate the neurocognitive correlates of autobiographical retrieval suppression and have implications for theories of morally motivated memory control.

Dopamine Modulates Adaptive Forgetting in Medial Prefrontal Cortex.

Active forgetting occurs in many species, but how behavioral control mechanisms influence which memories are forgotten remains unknown. We previously found that when rats need to retrieve a memory to guide exploration, it reduces later retention of other competing memories encoded in that environment. As with humans, this retrieval-induced forgetting relies on prefrontal control processes. Dopaminergic input to the prefrontal cortex is important for executive functions and cognitive flexibility. We found that, in a similar way, retrieval-induced forgetting of competing memories in male rats requires prefrontal dopamine signaling through D1 receptors. Blockade of medial prefrontal cortex D1 receptors as animals encountered a familiar object impaired active forgetting of competing object memories as measured on a later long-term memory test. Inactivation of the ventral tegmental area produced the same pattern of behavior, a pattern that could be reversed by concomitant activation of prefrontal D1 receptors. We observed a bidirectional modulation of retrieval-induced forgetting by agonists and antagonists of D1 receptors in the medial prefrontal cortex. These findings establish the essential role of prefrontal dopamine in the active forgetting of competing memories, contributing to the shaping of retention in response to the behavioral goals of an organism.SIGNIFICANCE STATEMENT Forgetting is a ubiquitous phenomenon that is actively promoted in many species. The very act of remembering some experiences can cause forgetting of others, in both humans and rats. This retrieval-induced forgetting process is thought to be driven by inhibitory control signals from the prefrontal cortex that target areas where the memories are stored. Here we started disentangling the neurochemical signals in the prefrontal cortex that are essential to retrieval-induced forgetting. We found that, in rats, the release of dopamine in this area, acting through D1 receptors, was essential to causing active forgetting of competing memories. Inhibition of D1 receptors impaired forgetting, while activation increased forgetting. These findings are important, because the mechanisms of active forgetting and their linkage to goal-directed behavior are only beginning to be understood.

Anterior Cingulate Cortex Signals the Need to Control Intrusive Thoughts during Motivated Forgetting.

How do people limit awareness of unwanted memories? When such memories intrude, a control process engages the right DLPFC (rDLPFC) to inhibit hippocampal activity and stop retrieval. It remains unknown how the need for control is detected, and whether control operates proactively to prevent unwelcome memories from being retrieved, or responds reactively, to counteract intrusions. We hypothesized that dorsal ACC (dACC) detects the emergence of an unwanted trace in awareness and transmits the need for inhibitory control to rDLPFC. During a memory suppression task, we measured in humans (both sexes) trial-by-trial variations in the theta power and N2 amplitude of dACC, two EEG markers that are thought to reflect the need for control. With simultaneous EEG-fMRI recordings, we tracked interactions among dACC, rDLPFC, and hippocampus during suppression. We found a clear role of dACC in detecting the need for memory control and upregulating prefrontal inhibition. Importantly, we identified distinct early (300-450 ms) and late (500-700 ms) dACC contributions, suggesting both proactive control before recollection and reactive control in response to intrusions. Stronger early activity was associated with reduced hippocampal activity and diminished BOLD signal in dACC and rDLPFC, suggesting that preempting retrieval reduced overall control demands. In the later window, dACC activity was larger, and effective connectivity analyses revealed robust communication from dACC to rDLPFC and from rDLPFC to hippocampus, which are tied to successful forgetting. Together, our findings support a model in which dACC detects the emergence of unwanted content, triggering top-down inhibitory control, and in which rDLPFC countermands intruding thoughts that penetrate awareness.SIGNIFICANCE STATEMENT Preventing unwanted memories from coming to mind is an adaptive ability of humans. This ability relies on inhibitory control processes in the prefrontal cortex to modulate hippocampal retrieval processes. How and when reminders to unwelcome memories come to trigger prefrontal control mechanisms remains unknown. Here we acquired neuroimaging data with both high spatial and temporal resolution as participants suppressed specific memories. We found that the anterior cingulate cortex detects the need for memory control, responding both proactively to early warning signals about unwelcome content and reactively to intrusive thoughts themselves. When unwanted traces emerge in awareness, anterior cingulate communicates with prefrontal cortex and triggers top-down inhibitory control over the hippocampus through specific neural oscillatory networks.

Dynamic targeting enables domain-general inhibitory control over action and thought by the prefrontal cortex.

Over the last two decades, inhibitory control has featured prominently in accounts of how humans and other organisms regulate their behaviour and thought. Previous work on how the brain stops actions and thoughts, however, has emphasised distinct prefrontal regions supporting these functions, suggesting domain-specific mechanisms. Here we show that stopping actions and thoughts recruits common regions in the right dorsolateral and ventrolateral prefrontal cortex to suppress diverse content, via dynamic targeting. Within each region, classifiers trained to distinguish action-stopping from action-execution also identify when people are suppressing their thoughts (and vice versa). Effective connectivity analysis reveals that both prefrontal regions contribute to action and thought stopping by targeting the motor cortex or the hippocampus, depending on the goal, to suppress their task-specific activity. These findings support the existence of a domain-general system that underlies inhibitory control and establish Dynamic Targeting as a mechanism enabling this ability.

Prefrontal-hippocampal interactions supporting the extinction of emotional memories: the retrieval stopping model.

Neuroimaging has revealed robust interactions between the prefrontal cortex and the hippocampus when people stop memory retrieval. Efforts to stop retrieval can arise when people encounter reminders to unpleasant thoughts they prefer not to think about. Retrieval stopping suppresses hippocampal and amygdala activity, especially when cues elicit aversive memory intrusions, via a broad inhibitory control capacity enabling prepotent response suppression. Repeated retrieval stopping reduces intrusions of unpleasant memories and diminishes their affective tone, outcomes resembling those achieved by the extinction of conditioned emotional responses. Despite this resemblance, the role of inhibitory fronto-hippocampal interactions and retrieval stopping broadly in extinction has received little attention. Here we integrate human and animal research on extinction and retrieval stopping. We argue that reconceptualising extinction to integrate mnemonic inhibitory control with learning would yield a greater understanding of extinction's relevance to mental health. We hypothesize that fear extinction spontaneously engages retrieval stopping across species, and that controlled suppression of hippocampal and amygdala activity by the prefrontal cortex reduces fearful thoughts. Moreover, we argue that retrieval stopping recruits extinction circuitry to achieve affect regulation, linking extinction to how humans cope with intrusive thoughts. We discuss novel hypotheses derived from this theoretical synthesis.

Task compliance predicts suppression-induced forgetting in a large sample.

Suppression-induced forgetting (SIF) refers to a memory impairment resulting from repeated attempts to stop the retrieval of unwanted memory associates. SIF has become established in the literature through a growing number of reports built upon the Think/No-Think (TNT) paradigm. Not all individuals and not all reported experiments yield reliable forgetting, however. Given the reliance on task instructions to motivate participants to suppress target memories, such inconsistencies in SIF may reasonably owe to differences in compliance or expectations as to whether they will again need to retrieve those items (on, say, a final test). We tested these possibilities on a large (N = 497) sample of TNT participants. In addition to successfully replicating SIF, we found that the magnitude of the effect was significantly and negatively correlated with participants' reported compliance during the No-Think trials. This pattern held true on both same- and independent-probe measures of forgetting, as well as when the analysis was conditionalized on initial learning. In contrast, test expectancy was not associated with SIF. Supporting previous intuition and more limited post-hoc examinations, this study provides robust evidence that a lack of compliance with No-Think instructions significantly compromises SIF. As such, it suggests that diminished effects in some studies may owe, at least in part, to non-compliance-a factor that should be carefully tracked and/or controlled. Motivated forgetting is possible, provided that one is sufficiently motivated and capable of following the task instructions.

Cortical thickness in the right inferior frontal gyrus mediates age-related performance differences on an item-method directed forgetting task.

Evidence suggests that older adults have difficulty relative to younger adults in forgetting irrelevant information. Here we sought to understand the physical basis of this deficit by investigating the relationship between cortical thickness and intentional forgetting, using an item-method directed forgetting task. We tested younger (n = 44) and older (n = 54) adults' memories for words that they were instructed to either remember or to forget, and then extracted cortical thickness values from brain regions previously shown, using functional neuroimaging, to be associated with memory suppression, including the right inferior frontal gyrus, the right postcentral gyrus and the left superior/middle frontal gyrus. Results from a parallel mediation model indicated that variations in cortical thickness in the right inferior frontal gyrus, but not the right postcentral gyrus or left superior/middle frontal gyrus, partially explained age-related differences in directed forgetting: older adults with thinner cortices in this area showed worse forgetting ability. This is the first study to explore how neuromorphological differences affect the ability to intentionally suppress items in memory. The results suggest that age-related differences in directed forgetting may be partly driven by cortical thickness in a brain structure known to be functionally involved in directed forgetting, and inhibitory control more broadly, supporting a contribution of deficient inhibition to this phenomenon.