Inhibitory Control Mechanisms Research Articles

Medial Prefrontal Cortex Stimulation Reduces Retrieval-Induced Forgetting via Fronto-parietal Beta Desynchronization.

The act of recalling memories can paradoxically lead to the forgetting of other associated memories, a phenomenon known as retrieval-induced forgetting (RIF). Inhibitory control mechanisms, primarily mediated by the prefrontal cortex, are thought to contribute to RIF. In this study, we examined whether stimulating the medial prefrontal cortex (mPFC) with transcranial direct current stimulation modulates RIF and investigated the associated electrophysiological correlates. In a randomized study, 50 participants (27 males and 23 females) received either real or sham stimulation before performing retrieval practice on target memories. After retrieval practice, a final memory test to assess RIF was administered. We found that stimulation selectively increased the retrieval accuracy of competing memories, thereby decreasing RIF, while the retrieval accuracy of target memories remained unchanged. The reduction in RIF was associated with a more pronounced beta desynchronization within the left dorsolateral prefrontal cortex (left-DLPFC), in an early time window (<500 ms) after cue onset during retrieval practice. This led to a stronger beta desynchronization within the parietal cortex in a later time window, an established marker for successful memory retrieval. Together, our results establish the causal involvement of the mPFC in actively suppressing competing memories and demonstrate that while forgetting arises as a consequence of retrieving specific memories, these two processes are functionally independent. Our findings suggest that stimulation potentially disrupted inhibitory control processes, as evidenced by reduced RIF and stronger beta desynchronization in fronto-parietal brain regions during memory retrieval, although further research is needed to elucidate the specific mechanisms underlying this effect.

Neural mechanisms of inhibitory control in preadolescent irritability: Insights from the ABCD study

ObjectiveElevated pediatric irritability is a transdiagnostic symptom that predicts multiple mental health problems in adolescence and adulthood. Altered top-down regulatory networks, such as inhibitory control networks that suppress an impulse in favor of goal-directed behavior, are thought to contribute to high levels of youth irritability. Nevertheless, little work has examined links between youth irritability and neural processes supporting inhibitory control in large diverse samples, nor have they focused on the key period ramping up to adolescence (i.e., preadolescence). MethodFunctional MRI data from 5380 preadolescents (age M=9.97 years, SD=0.62) in the baseline Adolescent Brain and Cognitive Development (ABCD) Study were analyzed. Parents reported on their preadolescent’s irritability. The stop signal task (SST) was leveraged to probe successful and failed inhibitory control. Activation and functional connectivity with amygdala, ventral striatum, and prefrontal seed regions were calculated during the SST and used in whole brain and region of interest (ROI) group-level analyses evaluating irritability effects. ResultsPreadolescents with higher levels of irritability displayed decreases in functional connectivity among amygdala, ventral striatum, and prefrontal cortex regions during both successful and failed inhibitory control conditions. These results remained after adjusting for co-occurring anxiety, depression, and attention-deficit/hyperactivity symptoms. ConclusionsFindings suggest neural aberrations in inhibitory control play a role in the pathophysiology of preadolescent irritability and associations are not merely due to co-occurring symptoms. Neural mechanisms of inhibitory control associated with irritability may provide novel intervention targets.

Impaired inhibitory control when processing real but not cartoon emotional faces in autistic children: Evidence from an event-related potential study.

Impaired socioemotional functioning characterizes autistic children, but does weak inhibition control underlie their socioemotional difficulty? This study addressed this question by examining whether and, if so, how inhibition control is affected by face realism and emotional valence in school-age autistic and neurotypical children. Fifty-two autistic and 52 age-matched neurotypical controls aged 10-12 years completed real and cartoon emotional face Go/Nogo tasks while event-related potentials (ERPs) were recorded. The analyses of inhibition-emotion components (i.e., N2, P3, and LPP) and a face-specific N170 revealed that autistic children elicited greater N2 while inhibiting Nogo trials and greater P3/LPP and late LPP for real but not cartoon emotional faces. Moreover, autistic children exhibited a reduced N170 to real face emotions only. Furthermore, correlation results showed that better behavioral inhibition and emotion recognition in autistic children were associated with a reduced N170. These findings suggest that neural mechanisms of inhibitory control in autistic children are less efficient and more disrupted during real face processing, which may affect their age-appropriate socio-emotional development.

Longitudinal associations between inhibitory control, gratitude, and positive parenting during early childhood.

Children's inhibitory control, which refers to the capability to recognize social and task demands by suppressing inappropriate behavior, is a key element closely related to both external and internal issues in preschoolers. The protective roles of parenting factors and social and moral functions, such as gratitude, remain unknown in the mechanism of inhibitory control. The present study employed a general cross-lagged panel model to explore the relationships between positive parenting, child gratitude, and inhibitory control. The research design involved repeated measurements based on parents' reports on 373 Chinese preschoolers in Hong Kong (179 males, 182 females; Mage = 4.51, SD = 0.60). The cross-lagged panel model revealed that positive parenting at Time 1 (T1) was significantly associated with preschool children's gratitude but not with inhibitory control at Time 2 (T2). Conversely, child gratitude at T1 was positively associated with inhibitory control at T2. These findings underscore the impact of positive parenting on gratitude and the predictive role of gratitude on inhibitory control. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Independent inhibitory control mechanisms for aggressive motivation and action.

Social behaviors often consist of a motivational phase followed by action. Here we show that neurons in the ventromedial hypothalamus ventrolateral area (VMHvl) of mice encode the temporal sequence of aggressive motivation to action. The VMHvl receives local inhibitory input (VMHvl shell) and long-range input from the medial preoptic area (MPO) with functional coupling to neurons with specific temporal profiles. Encoding models reveal that during aggression, VMHvl shellvgat+ activity peaks at the start of an attack, whereas activity from the MPO-VMHvlvgat+ input peaks at specific interaction endpoints. Activation of the MPO-VMHvlvgat+ input promotes and prolongs a low motivation state, whereas activation of VMHvl shellvgat+ results in action-related deficits, acutely terminating attack. Moreover, stimulation of MPO-VMHvlvgat+ input is positively valenced and anxiolytic. Together, these data demonstrate how distinct inhibitory inputs to the hypothalamus can independently gate the motivational and action phases of aggression through a single locus of control.

Attentional modulation of eye blinking is altered by sex, age, and task structure.

Spontaneous eye blinking is gaining popularity as a proxy for higher cognitive functions, as it is readily modulated by both environmental demands and internal processes. Prior studies were impoverished in sample size, sex representation and age distribution, making it difficult to establish a complete picture of the behavior. Here we present eye-tracking data from a large cohort of normative participants (n=604, 393 F, aged 5-93 years) performing two tasks: one with structured, discrete trials (interleaved pro/anti-saccade task; IPAST) and one with a less structured, continuous organization in which participants watch movies (free-viewing; FV). Sex- and age-based analyses revealed that females had higher blink rates between the ages of 22 and 58 years in the IPAST, and 22 and 34 years in FV. We derived a continuous measure of blink probability to reveal behavioral changes driven by stimulus appearance in both paradigms. In the IPAST, blinks were suppressed near stimulus appearance, particularly on correct anti-saccade trials, which we attribute to the stronger inhibitory control required for anti-saccades compared to pro-saccades. In FV, blink suppression occurred immediately after scene changes, and the effect was sustained on scenes where gaze clustered among participants (indicating engagement of attention). Females were more likely than males to blink during appearance of novel stimuli in both tasks, but only within the age bin of 18-44 years. The consistency of blink patterns in each paradigm endorses blinking as a sensitive index for changes in visual processing and attention, while sex and age differences drive interindividual variability.Significance Statement Eye-tracking is becoming useful as a non-invasive tool for detecting preclinical markers of neurological and psychiatric disease. Blinks are understudied despite being an important supplement to saccade and pupil eye-tracking metrics. The present study is a crucial step in developing a healthy baseline for blink behavior to compare to clinical groups. While many prior blink studies suffered from small sample sizes with relatively low age- and sex-diversity (review by Jongkees & Colzato, 2016), our large cohort of healthy participants has permitted a more detailed analysis of sex and age effects in blink behavior. Furthermore, our analysis techniques are robust to temporal changes in blink probability, greatly clarifying the relationship between blinking, visual processing, and inhibitory control mechanisms on visual tasks.

Existential negation modulates inhibitory control processes and impacts recognition memory. Evidence from ERP and source localisation data

ABSTRACT It has recently been proposed that comprehension of negation reuses the inhibitory control mechanisms. However, this Reusing Inhibition for Negation (RIN) hypothesis has mostly been confirmed with imperative sentences. The current study examined whether comprehension of negated existential sentences, which are purely declarative, also shares neural resources with inhibitory control processes. Participants read affirmative or negative existential sentences while performing an embedded Go/NoGo task, followed by a recognition probe to test the impact of negation on words activation. Relative to affirmative sentences, negation increased the P3 amplitude for NoGo trials, with estimated sources in the inhibition-related medial and dorsolateral areas in the prefrontal and parietal cortices. These results indicate that existential negation also shares neural mechanisms with inhibitory control, extending the RIN hypothesis. Furthermore, recognising negated words took longer and decreased the readiness potential of the responses compared to affirmed words, suggesting reduced accessibility of negated words in working memory.

Locus Coeruleus Integrity Is Linked to Response Inhibition Deficits in Parkinson's Disease and Progressive Supranuclear Palsy.

Parkinson's disease (PD) and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals and are linked with worse prognosis, and lack improvement on dopaminergic therapy. Motor and cognitive control are associated with noradrenergic innervation of the cortex, arising from the locus coeruleus (LC) noradrenergic system. Here we test the hypothesis that structural variation of the LC explains response inhibition deficits in PSP and PD. Twenty-four people with idiopathic PD, 14 with PSP-Richardson's syndrome, and 24 age- and sex-matched controls undertook a stop-signal task and ultrahigh field 7T magnetization-transfer-weighted imaging of the LC. Parameters of "race models" of go- versus stop-decisions were estimated using hierarchical Bayesian methods to quantify the cognitive processes of response inhibition. We tested the multivariate relationship between LC integrity and model parameters using partial least squares. Both disorders impaired response inhibition at the group level. PSP caused a distinct pattern of abnormalities in inhibitory control with a paradoxically reduced threshold for go responses, but longer nondecision times, and more lapses of attention. The variation in response inhibition correlated with the variability of LC integrity across participants in both clinical groups. Structural imaging of the LC, coupled with behavioral modeling in parkinsonian disorders, confirms that LC integrity is associated with response inhibition and LC degeneration contributes to neurobehavioral changes. The noradrenergic system is therefore a promising target to treat impulsivity in these conditions. The optimization of noradrenergic treatment is likely to benefit from stratification according to LC integrity.SIGNIFICANCE STATEMENT Response inhibition deficits contribute to clinical symptoms and poor outcomes in people with Parkinson's disease and progressive supranuclear palsy. We used cognitive modeling of performance of a response inhibition task to identify disease-specific mechanisms of abnormal inhibitory control. Response inhibition in both patient groups was associated with the integrity of the noradrenergic locus coeruleus, which we measured in vivo using ultra-high field MRI. We propose that the imaging biomarker of locus coeruleus integrity provides a trans-diagnostic tool to explain individual differences in response inhibition ability beyond the classic nosological borders and diagnostic criteria. Our data suggest a potential new stratified treatment approach for Parkinson's disease and progressive supranuclear palsy.

Spontaneous brain microstates correlate with impaired inhibitory control in internet addiction disorder.

The prevalence of the Internet addiction disorder (IAD) has been on the rise, making it increasingly imperative to explore the neurophysiological markers of it. Using the whole-brain imaging approach of EEG microstate analysis, which treats multichannel EEG recordings as a series of quasi-steady states, similar as the resting-state networks found by fMRI, the present study aimed to investigate the specificity of the IAD in class C of the four canonical microstates. The existing EEG data of 40 participants (N=20 for each group) was used, and correlation between the time parameters of microstate C and the performance of the Go/NoGo task was analyzed. Results suggested that the duration and coverage of class C were significantly reduced in the IAD group as compared to the healthy control (HC) group. Furthermore, the duration of class C had a significant inverse correlation with Go RTs in the IAD group. These results implied that class C might serve as a neurophysiological marker of IAD, helping to understand the underlying neural mechanism of inhibitory control in IAD.

COORDINATING ROLE OF ACTIN CYTOSKELETON IN SHORT-TERM PLASTICITY OF NEURAL ENSEMBLES INVOLVING EXCITATORY AND INHIBITORY SYNAPSES

The problem of frequency coding is closely related to the studies of inhibitory transmission as a factor of neural network plasticity. The rewiew presents basic mechanisms of inhibitory control of spatio-temporal pattern of neural activity during signal processing. Current views are analyzed in respect of dynamic synapses, their instability and variation within the ongoing activity. The results presented here demonstrate that short-term plasticity operates with the combined contribution of excitatory and inhibitory synapses. The role of GABAergic potentials in modulation of intracellular messenger’s activity is discussed, including those implicated in postsynaptic modifications of excitatory and inhibitory transmission. The main topics concerning the molecular mechanisms centered on the lateral diffusion of GABAA receptors. The data of many reports argue for coordinating role of actin cytoskeleton. It is proposed that postsynaptic mechanisms underlying GABAA plasticity may be activated in result of fast adaptation of actin cytoskeleton and associated proteins to disbalance between excitation and inhibition.

Inhibitory control and mood in relation to psychological resilience: an ecological momentary assessment study

Psychological resilience, the ability to adapt to adversity, is theorized to rely on intact inhibitory control (IC) mechanisms, which underlie one’s ability to maintain goal-directed behavior by inhibiting prepotent responses. However, no study to date has explored daily fluctuations of IC performance in relation to resilience. Here, we examined the association between IC and mood measured daily in relation to psychological resilience in young adults in a stressful situation. Baseline resilience was obtained from 144 female and male soldiers during their basic combat training. Then, participants completed an ecological momentary assessment protocol, in which they reported their momentary mood and completed a short IC assessment twice/day for 2 weeks. A hierarchical linear modeling analysis revealed that psychological resilience moderated the relationship between momentary IC and momentary mood, such that better IC was associated with better mood only for those with higher, but not lower, self-reported psychological resilience at baseline. These results show that psychological resilience is manifested in the everyday association between IC and mood. Furthermore, they lend important support to cognitive models of resilience and may have significant contribution to our understanding of resilient behavior in real life.Trial Registration: MOH_2018-0-13_002451.

Altered Inhibitory Control Mechanism of Internet Addiction: An Electroencephalogram Study of Brain Oscillations and Connectivity.

The development of the Internet has changed people's lives and has resulted in a new type of addictive behavior. In the past decade, Internet game addiction has been identified as a mental illness. Considering internet game addiction as the only cause of mental illness is limited in its view, as internet games, social platforms and other internet multimedia are also widely used. Thus, other internet-related behaviors, that maybe addictive, should also be included. Previous neuroimaging studies have reported a role of alteration in brain's inhibitory control mechanism in addiction. However, the results are still diverse with inconsistent findings. In this study, we used an Internet-related stop signal task with EEG signals recorded to study the relationship between internet addiction through brain oscillations and functional connectivity. We also compared the differences in the brain connectivity between addicted and non-addicted participants using phase lag index. We found that the brain connectivity in participants addicted to the internet is significantly greater than that of nonaddicted users.Clinical Relevance- In this study, we assessed brain functional networks of participants with Internet Gaming Disorder and internet addiction.

Neural differences of food-specific inhibitory control in people with healthy vs higher BMI

Consistent with the idea that deficits in inhibition limit resistance to tempting, tasty, high-calorie foods, and might result in a higher BMI, we test whether people with higher BMIs (BMI >25 kg/m2) present inefficient inhibitory control over food-related responses. To unpack this association, we also examine individual differences in the neural mechanisms of food inhibitory control in healthy vs higher BMI individuals. We test these aspects with a sample of 109 participants (49 with higher BMI and 60 with healthy BMI) and the food stop-signal task, which was used to examine individuals’ inhibitory control. Results demonstrated that people with higher BMI had significantly poorer food inhibitory control than healthy BMI individuals. fMRI results showed that, in both Go (Go_food vs Go_nature) and Stop conditions (Stop_food vs Stop_nature), compared to healthy BMI individuals, individuals with higher BMI had lower activation in the superior frontal gyrus, precuneus, precentral gyrus, and supramarginal gyrus in the food stimulus condition. Moreover, ROI analysis results showed that under the Stop_food condition, the activation in the inferior frontal gyrus in the higher BMI group was significantly negatively correlated with inhibitory control abilities. These results suggest that people with a higher BMI have limited ability to inhibit food impulsions, and that the prefrontal regions and parietal cortex may contribute to the progression of inhibitory control limitations in relation to food.

Longitudinal effects of early psychosocial deprivation on macaque executive function: Evidence from computational modelling.

Executive function (EF) describes a group of cognitive processes underlying the organization and control of goal-directed behaviour. Environmental experience appears to play a crucial role in EF development, with early psychosocial deprivation often linked to EF impairment. However, many questions remain concerning the developmental trajectories of EF after exposure to deprivation, especially concerning specific mechanisms. Accordingly, using an 'A-not-B' paradigm and a macaque model of early psychosocial deprivation, we investigated how early deprivation influences EF development longitudinally from adolescence into early adulthood. The contribution of working memory and inhibitory control mechanisms were examined specifically via the fitting of a computational model of decision making to the choice behaviour of each individual. As predicted, peer-reared animals (i.e. those exposed to early psychosocial deprivation) performed worse than mother-reared animals across time, with the fitted model parameters yielding novel insights into the functional decomposition of group-level EF differences underlying task performance. Results indicated differential trajectories of inhibitory control and working memory development in the two groups. Such findings not only extend our knowledge of how early deprivation influences EF longitudinally, but also provide support for the utility of computational modelling to elucidate specific mechanisms linking early psychosocial deprivation to long-term poor outcomes.

M4 muscarinic receptors mediate acetylcholine-induced suppressant effects on the cough reflex in the caudal nucleus tractus solitarii of the rabbit.

It has been shown that muscarinic acetylcholine receptors (mAChRs) located within the caudal nucleus tractus solitarii (cNTS) mediate a cholinergic inhibitory control mechanism of the cough reflex. Thus, identification of the involved mAChR subtypes could be of considerable interest for novel therapeutic strategies. In pentobarbital sodium-anesthetized, spontaneously breathing rabbits we investigated the contribution of different mAChR subtypes in the modulation of mechanically and chemically induced cough reflex. Bilateral microinjections of 1 mM muscarine into the cNTS increased respiratory frequency and decreased expiratory activity even to complete suppression. Interestingly, muscarine induced strong cough-suppressant effects up to the complete abolition of the reflex. Microinjections of specific mAChR subtype antagonists (M1-M5) into the cNTS were performed. Only microinjections of the M4 antagonist tropicamide (1 mM) prevented muscarine-induced changes in both respiratory activity and cough reflex. The results are discussed in light of the notion that cough involves the activation of the nociceptive system. They also suggest that M4 receptor agonists may have an important role in cough downregulation within the cNTS.

Differential Recruitment of Inhibitory Control Processes by Directed Forgetting and Thought Substitution.

Humans have the ability to intentionally forget information via different strategies, included suppression of encoding (directed forgetting) and mental replacement of the item to encode (thought substitution). These strategies may rely on different neural mechanisms; namely, encoding suppression may induce prefrontally mediated inhibition, whereas thought substitution is potentially accomplished through modulating contextual representations. Yet, few studies have directly related inhibitory processing to encoding suppression, or tested its involvement in thought substitution. Here, we directly tested whether encoding suppression recruits inhibitory mechanisms with a cross-task design, relating the behavioral and neural data from male and female participants in a Stop Signal task (a task specifically testing inhibitory processing) to a directed forgetting task with both encoding suppression (Forget) and thought substitution (Imagine) cues. Behaviorally, Stop Signal task performance (stop signal reaction times) was related to the magnitude of encoding suppression, but not thought substitution. Two complementary neural analyses corroborated the behavioral result. Namely, brain-behavior analysis demonstrated that the magnitude of right-frontal beta activity following stop signals was related to stop signal reaction times and successful encoding suppression, but not thought substitution; and classifiers trained to discriminate successful and unsuccessful stopping in the Stop Signal task could also classify successful and unsuccessful forgetting following Forget cues, but not Imagine cues. Importantly, inhibitory neural mechanisms were engaged following Forget cues at a later time than motor stopping. These findings not only support an inhibitory account of directed forgetting, and that thought substitution engages separate mechanisms, but also potentially identify a specific time in which inhibition occurs when suppressing encoding.SIGNIFICANCE STATEMENT Forgetting often seems like an unintended experience, but forgetting can be intentional, and can be accomplished with multiple strategies. These strategies, including encoding suppression and thought substitution, may rely on different neural mechanisms. Here, we test the hypothesis that encoding suppression engages domain-general prefrontally driven inhibitory control mechanisms, while thought substitution does not. Using cross-task analyses, we provide evidence that encoding suppression engages the same inhibitory mechanisms used for stopping motor actions, but these mechanisms are not engaged by thought substitution. These findings not only support the notion that mnemonic encoding processes can be directly inhibited, but also have broad relevance, as certain populations with disrupted inhibitory processing may be more successful accomplishing intentional forgetting through thought substitution strategies.

Investigating the modulation of active preparation and passive dissipation on inhibitory control processes in the language switching paradigm.

Previous language-switching studies have received scholastic attention and the observed switching cost patterns have provided empirical evidence for bilingual language control. However, results are inconsistent as the size of and (a)symmetry in switching costs differ across studies. In addition, there are various methodological differences that go beyond stimulus differences, such as the language proficiency of the participants (the participant-level factor) and the preparation time (a task-related level factor), which might be responsible for these inconsistent results. With a focus on task-related factors, the present study was designed to examine whether and how preparation time modulates the size and (a)symmetry in switching costs by using the language-switching paradigm with cue-to-stimulus and response-to-cue intervals manipulated. Replicating previous literature on language switching and task switching, a clear preparation effect was observed in all trials (stay and switch trials) for both L1 and L2. The switching costs were modulated by the cue-to-stimulus intervals, and specifically, switching costs decreased when the preparation time increased. Another intriguing finding was that even when participants were offered enough time to fully prepare for selecting the target language at the cue window, the switching costs were not completely eliminated. In terms of the passive preparation at the response-to-cue interval, switching costs could be modulated by the response-to-cue interval - the time for passive dissipation of inhibitory control applied in previous trials. The size of switching costs was clearly modulated by manipulating response-to-cue intervals and switching costs decreased as the waiting time after a naming response increased. This study provides empirical evidence for the modulation of preparation effects on switching costs and inhibitory control mechanisms in bilingual language production.

The evaluation of anterior thalamic radiation with diffusion tensor imaging in children with neurofibromatosis type-1

To determine whether there is a difference in the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the anterior thalamic radiation (ATR), which are involved in the inhibitory control mechanism, in Neurofibromatosis type-1 (NF1) patients with or without Neurofibromatosis bright objects (NBOs), in comparison to the healthy control group. Thirty children diagnosed with NF1 and 17 age-matched children were included in the study. 30 children with NF1 had a mean age of 10.47±5.43, compared to 11.35±5.43 of the control group. NF1 patients were divided into two groups as those with and without NBOs. The comparison was made by measuring ADC and FA values of ATR in patients with NF1 and a healthy control group. There was a significant difference in terms of ADC and FA values of ATR between the patients with NF1 and the control group. While a significant decrease was seen in FA values of ATR, ADC values were increased. There was a significant difference in ATR ADC and FA values between NF1 patients with and without NBOs and the healthy control group. On the other hand, no major difference was displayed between NF1 patients with NBOs and without NBOs in terms of ATR ADC and FA values. The results of increased ADC and decreased FA values may denote the demyelination process in ATR. We speculate that the onset of microstructural damage in the ATR may result in executive function impairment, particularly in the inhibitory control mechanism.

On pattern completion, cues and future-oriented cognition.

Barzykowski and Moulin's view on involuntary autobiographical memory focuses on automatic activation of representations and inhibitory control mechanisms. We discuss how and when a known neural mechanism - pattern completion - may result in involuntary autobiographical memories, the types of cues that may elicit this phenomenon and consider interactions with future-oriented cognition.

An event-related potential study of cross-modal translation recognition in Chinese–English bilinguals: the role of cross-linguistic orthography and phonology

AbstractExtensive evidence has demonstrated that bilinguals non-selectively activate lexicons of both languages when reading or hearing words in one language. Here, we further investigated the electrophysiological roles of cross-linguistic orthography and phonology in the processing of L2 spoken words in unbalanced Chinese (L1)–English (L2) bilinguals in a cross-modal situation. Relative to unrelated control, the recognition of auditory L2 words showed behavioral interference effects when paired with orthographic or phonological neighbors of the correct translations of L2 words. Moreover, the lexical effects were also exhibited in the electrophysiological data, as reflected by marginally less positive late positive component (500–800 ms) amplitudes in the frontal region. Importantly, the orthographic rather than phonological translation neighbor condition elicited less negative N400 (300–500 ms) amplitudes in the parietal–occipital regions, suggesting that this orthographic translation neighbor condition facilitated the co-activation of spoken L2 words. Taken together, these findings indicate that cross-linguistic orthographic and phonological activation have different temporal dynamics with both bottom-up parallel cross-linguistic activation and the top-down inhibitory control mechanism governing the two-language lexical organization in L2 spoken word recognition.