Depression is a leading cause of disability and premature death, affecting more than 300 million people worldwide (Friedrich, 2017). Individuals with subthreshold depression (high-risk status characterized by clinically relevant depressive symptoms that do not meet the standard diagnostic criteria for major depressive disorder) are three to five times more likely to develop MDD in the future than individuals without symptoms (Fogel et al., 2006; Zhang et al., 2023), especially when the onset occurs in young adulthood (Wilcox & Anthony, 2004). Given its strong predictive value for later psychopathology, early intervention and prevention are essential, accordingly to the World Health Organization’s Mental Health Action Plan (2013–2030). This includes addressing cognitive risk factors such as impaired memory suppression, which could contribute to the persistence and escalation of depressive symptoms (WHO, 2021).

Researchers and clinicians have long recognized cognitive deficits as key mechanisms for understanding symptoms of depression (Beck, 2008; Joormann & Tanovic, 2015; LeMoult & Gotlib, 2019), such as memory suppression. Specifically, they exhibit difficulty in exerting control to prevent intrusive memories, particularly those with negative valence, from entering conscious thought (Joormann et al., 2005). Such impairment prevents effective disengagement from negative thoughts, thus contributing to the development of recurrent and uncontrollable negative thinking. This pattern, in turn, further exacerbates and sustains the negative mood (Hertel et al., 2018; Joormann, 2010). Studies examining memory suppression and its associated neural mechanisms in individuals with depression offer valuable insights into the etiology of the disorder and the optimization of cognitive intervention programs (Joormann et al., 2009; Yang et al., 2020; Zhang et al., 2016).

One frequently employed paradigm to examine memory suppression is the Think/No-Think task (Anderson & Green, 2001). In this paradigm, participants first learn a list of cue-target pairs. Then, they enter the Think/No-Think phase in which cues are presented, and are instructed to either suppress retrieval of the paired target (No-Think condition) or repeatedly retrieve the paired target (Think condition). The No-think condition involves memory control through retrieval suppression, requiring efforts to suppress the mental representation of intrusive memories from awareness. Some cue-target pairs from the initial learning session were not displayed during the Think/No-Think phase, thus serving as the baseline condition. In a memory test that followed, retrieval suppression significantly impaired recall, as evidenced by fewer targets remembered in the No-Think condition compared to the baseline condition.

When emotional materials are used in the Think/No-Think task, research in healthy populations has found that the suppression effect is reduced for negative materials compared to neutral materials (Depue et al., 2007; Sacchet et al., 2017), indicating that negative information is more difficult to suppress. This challenge is expected to be even more pronounced in depression. Indeed, individuals with depression exhibit memory suppression deficits with neutral stimuli (Hertel & Gerstle, 2003; Hertel & Mahan, 2008). Subsequent work using emotional stimuli has further demonstrated that this impairment is especially severe for negative content (Joormann et al., 2009; Yang et al., 2020; Zhang et al., 2016). A meta-analysis has confirmed a significantly smaller suppression effect in individuals with depression versus healthy individuals, underscoring the memory suppression deficit in depression (Stramaccia et al., 2021).

Neuroimaging research has elucidated the neural correlates underlying memory suppression. This process relies on top-down control mechanisms, primarily involving the bilateral ventrolateral prefrontal cortex, the right dorsolateral prefrontal cortex (rDLPFC), and the anterior cingulate cortex (Benoit & Anderson, 2012). Concurrently, suppression is associated with reduced neural activity in the hippocampus and parahippocampal cortex—regions critical for memory consolidation, maintenance and reactivation (Anderson & Hanslmayr, 2014; Anderson & Hulbert, 2021; Depue et al., 2007; Meyer & Benoit, 2022). Analyses of effective connectivity—the directed, causal influence of one brain region on another—have revealed that reduced activation in the hippocampus is driven by the inhibitory top-down control from the DLPFC. Notably, this influence correlates with successful memory suppression at the behavioral level (Apšvalka et al., 2022; Benoit & Anderson, 2012). Further evidence comes from an intracranial EEG study in epilepsy patients, which demonstrated that DLPFC activation precedes and likely drives hippocampal suppression in both EEG power and phase, providing evidence for the role of the DLPFC in initiating memory suppression (Oehrn et al., 2018).

A limited number of studies have explored the neural mechanisms underlying impaired memory suppression in depression using the Think/No-Think task. One event-related potential study focused on the frontal N2 component—an electrophysiological marker of motivation and mental effort during retrieval suppression—and found that depressed patients exhibited a reduced N2 amplitude when suppressing negative compared to neutral items (Zhang et al., 2016). Further neuroimaging studies have examined the neural correlates of these deficits in both individuals with MDD (Sacchet et al., 2017) and those with subthreshold depression (Yang et al., 2020). These investigations reported hyperactivation in the DLPFC, particularly the rDLPFC, in individuals with depression relative to healthy controls. This heightened prefrontal activation is consistent with other studies (Harvey et al., 2005; Matsuo et al., 2007; Pizzagalli & Robert, 2022) and is often interpreted as a sign of compensatory effort. According to this view, impaired neural processing efficiency necessitates increased activation to maintain behavioral performance comparable to that of healthy controls.

Previous investigations have emphasized the pivotal role of non-invasive brain stimulation techniques in unraveling the neural mechanisms underlying cognitive function and influencing behavior by modulating cortical excitability (Bestmann et al., 2007; Parkin et al., 2015). Among these techniques, transcranial direct current stimulation (tDCS) is particularly noteworthy; it delivers a weak electric current (1-2 mA) to the scalp, which penetrates the brain and alters membrane resting potentials, thereby influencing cortical excitability (Nitsche et al., 2008). Unlike transcranial magnetic stimulation, which can induce seizures in some participants prone to such issues, tDCS does not increase the risk of such side effects (Bikson et al., 2016; Poreisz et al., 2007). Specifically, anodal stimulation is recognized for enhancing cortical excitability, while cathodal stimulation has the opposite effect. Dysfunction in prefrontal control has been implicated in depression (Pizzagalli & Robert, 2022). Extensive neuromodulation research has therefore applied anodal tDCS over the DLPFC to investigate its role in improving cognitive function (Salehinejad et al., 2016), emotion regulation (He et al., 2020) and symptom severity (Palm et al., 2016) in depression. Nevertheless, it remains unclear whether anodal tDCS can enhance neural efficiency in the DLPFC to facilitate the suppression of intrusive memories in depression.

Although brain stimulation targeting the left DLPFC has demonstrated clinical efficacy in the treatment of depression, converging evidence from memory suppression research highlights a critical role of the right rDLPFC in top-down inhibitory control (Benoit & Anderson, 2012). In healthy populations, facilitating rDLPFC activity promotes forgetting, whereas disrupting rDLPFC function impairs suppression performance (Qi et al., 2025; Stramaccia et al., 2025; Xie et al., 2019). Moreover, the rDLPFC shows altered activity in individuals with depression (Sacchet et al., 2017; Yang et al., 2020). Based on this evidence, the rDLPFC was selected as the neuromodulation target in the present study.

Taken together, the aim of this study was to determine whether increasing activation of the rDLPFC via active tDCS could improve memory suppression in a non-clinical sample of individuals with moderate, subthreshold depressive symptoms. Through anodal stimulation, we sought to enhance the neural efficiency of the rDLPFC, thereby enabling participants to suppress intrusive memories with reduced effort. By focusing on individuals with subthreshold depressive symptoms rather than those diagnosed with MDD, we aimed to avoid the confounding effects of antidepressant medications or other clinical treatments on the outcomes of tDCS. Thus, individuals with subthreshold depression were recruited and randomly assigned to receive a single session of either active or sham tDCS. The active group received 20 minutes of active tDCS, whereas the sham group received a 30-second sham stimulation protocol. In both groups, the anodal electrode was positioned over F4 (corresponding to the rDLPFC), and the cathodal electrode was placed over Fp1. Following this, all participants completed the Think/No-Think task, which incorporated both negative and neutral materials. Our primary outcome was memory accuracy under the different experimental conditions. To quantify memory suppression effects, we derived a suppression-induced forgetting (SIF) index by subtracting No-Think accuracy from baseline accuracy, calculated separately for neutral and negative stimuli. We hypothesized that active tDCS would be associated with greater SIF compared to sham stimulation, indicating enhanced memory suppression. In addition, we examined whether the effect of tDCS on SIF differed between negative and neutral stimuli, given mixed evidence regarding the effects of emotional valence on memory suppression.