The directed forgetting paradigm is frequently used to determine the ability to voluntarily suppress information. However, little is known about brain areas associated with information to forget. The present study used functional magnetic resonance imaging to determine brain activity during the encoding and retrieval phases of an item-method directed forgetting recognition task with neutral verbal material in order to apprehend all processing stages that information to forget and to remember undergoes. We hypothesized that regions supporting few selective processes, namely recollection and familiarity memory processes, working memory, inhibitory and selection processes should be differentially activated during the processing of to-be-remembered and to-be-forgotten items. Successful encoding and retrieval of items to remember engaged the entorhinal cortex, the hippocampus, the anterior medial prefrontal cortex, the left inferior parietal cortex, the posterior cingulate cortex and the precuneus; this set of regions is well known to support deep and associative encoding and retrieval processes in episodic memory. For items to forget, encoding was associated with higher activation in the right middle frontal and posterior parietal cortex, regions known to intervene in attentional control. Items to forget but nevertheless correctly recognized at retrieval yielded activation in the dorsomedial thalamus, associated with familiarity-based memory processes and in the posterior intraparietal sulcus and the anterior cingulate cortex, involved in attentional processes.

Funding: This research was supported by the Belgian National Fund for Scientific Research (FRS-FNRS to SM, EB, PM, FC), by the University of Liège, by the InterUniversity Attraction Pole (IAP P6/29 to CB) and the French Speaking Community Concerted Research Action (ARC-06/11-340 to DF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Introduction

Directed forgetting (DF) refers to a deliberate attempt to limit the future expression of specific memory contents [1]–[4]. This active form of forgetting differs from the simple attenuation of memory contents over time and from proactive or retroactive interference. It is involved in many daily memory activities since it allows one to suppress information that is no longer relevant from one's consciousness or to update outdated information. Consequently, intentional forgetting as assessed by DF effects is a desirable and adaptative outcome that can be distinguished from unintentional forgetting and aims at preventing outdated irrelevant information from interfering with current processing and recollection.

Two methods are classically used to study DF effects: the item and list methods. In the item method, participants are presented with words one by one with, after a short delay, the presentation of a “remember” cue (to-be-remembered “TBR” items) or a “forget” cue (to-be-forgotten “TBF” items). Typically, TBR items are better remembered than TBF items, that is, TBR items are better recalled or recognized when participants are subsequently tested on all presented words, regardless of study instructions. In the list method, the participants are generally warned of the status of the items only after a block of items was presented. Some data suggest that each method depends on partially different processes, such as retrieval inhibition for the list method and selective rehearsal or attentional inhibition for the item method [5]–[7]. Currently, the specific mechanisms of directed forgetting and its neural substrates are still discussed. At the cognitive level, two hypotheses have been proposed to explain the DF effect observed with the item method. The first one, the selective rehearsal hypothesis, emphasizes differential encoding and rehearsal of TBR items [6], [8]. According to this hypothesis, when an item is followed by a “remember” cue, participants typically engage in rehearsal and more elaborated encoding than when items are followed by a “forget” cue, naturally making the TBR items more accessible for later remembering. The second hypothesis, the attentional inhibition hypothesis, argues that the item-method DF effect results from the attentional inhibition of TBF items triggered by the “forget” cue [9], [10]. According to this hypothesis, TBF items and/or the rehearsal of these items are assumed to be inhibited just after they are encoded (when the “forget” cue is displayed).

With regard to neuroimaging, only the item-by-item directed forgetting paradigm has been used to explore the neural substrates of (un)successful encoding [11] and (un)intentional forgetting [12]. Reber et al. [11] observed that the anterior ventral portion of the left inferior prefrontal cortex (BA 9), the anterior cingulate (BA 32) and medial superior frontal gyrus (BA 6) exhibited greater activity for TBR than TBF items at encoding. Additionally, the left parahippocampal gyrus and right superior parietal gyrus (BA 7) exhibited greater activity for subsequently remembered words than for subsequently forgotten words. These data show that activity in the ventral prefrontal and superior frontal regions was associated with encoding effort whereas the medial temporal and superior parietal areas were involved in the success of encoding. Wylie et al. [12] observed that intentional forgetting of TBF items was associated with increased activity in the hippocampus and superior frontal gyrus (BA10/11) when contrasted with unintentional forgetting of TBR items, but with higher activity in the medial frontal gyrus (BA10), middle temporal gyrus (BA21), parahippocampal gyrus (BA34/35) and cingulate gyrus (BA31) when contrasted with intentional remembering of TBR items. As a whole, these findings revealed that different brain regions involved in declarative memory are related to intentional forgetting and intentional remembering. These two studies focused on the encoding phase of the item DF paradigm. Recently, Nowicka et al. [13] explored the neural substrates of forgetting effects at encoding and retrieval of neutral and emotionally negative images. They showed that, at encoding, the intention to forget and the success in forgetting negative images were related to more widespread right-hemisphere activations than for neutral images, suggesting greater forgetting effort for emotional materials. At retrieval, forgotten neutral and negative images yielded no cerebral activation. This may indicate that forgetting resulted mainly from inhibitory processes acting at encoding rather than at retrieval.

Finally, the question of inter-individual variability in the ability to overcome the inhibitory/suppression influence of the forget instruction was recently tackled by Nowicka et al. [14] with voxel-based morphometry. In a group of participants with high recognition rates for TBF items, the rate of recognition was related to increased gray matter volume in the left ventrolateral prefrontal cortex (BA 47) and right hippocampus. Such a relationship was not observed for individuals with a low recognition rate for TBF items. Nowicka et al. concluded that these two regions may be part of a neuroanatomical network supporting efficient and successful retrieval of visual information that was not properly encoded and thus difficult to recollect.

The intervention of distinct processes during the DF paradigm is also supported by psycho-physiological data, which demonstrate that the processing of TBF and TBR items is associated with specific event-related potential (ERP) activity. The differential ERP activity was attributed to inhibitory processes of TBF items during encoding [15]–[18] and retrieval [19], [20], and to the involvement of recollection processes for TBR items only [16], [19], [20].

In that context, the main aim of the present study was to explore the neural substrates associated with remembering and forgetting at both the encoding and retrieval stages of a long-term directed forgetting task. Using fMRI, we examined cerebral activation at both encoding and retrieval in relation to memory instructions and behavioural performance in order to apprehend all processing stages that TBR and TBF information undergoes. Whereas Nowicka et al. [13] explored the influence of emotion on the neural bases of directed forgetting, we selected neutral verbal materials so as to focus on basic processes underlying the directed forgetting effect. This will shed further light on the mechanisms of intentional forgetting as well as on the differential richness of the memory trace created for each type of information. Indeed, behavioural studies have highlighted distinct memory processes to operate during the processing of TBR and TBF items. Specifically, TBR information has been shown to lead to elaborated memory traces that can be recollected, while TBF information is shallowly encoded and recognized without recollection of the encoding context [21], [22]. Working memory/executive processes are also considered to intervene in the directed forgetting effect. More particularly, inhibition is the classical explanation of the effect [9] and should operate during the processing of TBF information at encoding. However, another interpretation of the directed forgetting effect consists in selective rehearsal of TBR information [6]. Moreover, intentional forgetting may rely on suppression of irrelevant information, which can be achieved by selection of relevant information before or after its encoding in working memory. Finally, thought suppression should also be observed after presentation of the TBF cue.

Concretely, behavioural recognition data were used to sort encoding and retrieval fMRI event-related responses into 4 conditions based on the combination of memory instruction (to remember vs. to forget) and behavioural outcome (successful vs. unsuccessful recognition). This approach allowed evidencing that processing of TBR and TBF information recruit a very different set of brain regions, compatible with the idea that specific working memory/executive processes induces intentional forgetting and that TBR and TBF information are encoded and retrieved via recollection and familiarity processes respectively.