Children (4–12 Years Old)
Similar findings were obtained in studies evaluating the biobehavioral expression of inhibitory control in two groups of participants aged 4 and 4.5 years old. Children who performed better on inhibitory control tasks (such as the day/night task and the yes/no Stroop task) had changes in EEG activities in the medial frontal cortex, indicating prefrontal cortex activation in both hemispheres. Preschoolers who performed poorly on the task, on the other hand, showed no task-related increases in EEG activity (Wolfe and Bell, 2004, 2007).
Bunge et al. (2002) examined the inhibitory control ability in children aged 8–12 years old with go/no-go tasks. They found that the performance depends on the recruitment of a subset of the network that was recruited during adult response inhibition. More specifically, effective performances in children recruited posterior regions in both hemispheres, but not frontal regions as activated in adults. This suggested that the functional network of adults for response inhibition is partially recruited in children, and this develops with age (Bunge et al., 2002). Bunge et al. (2002) also included a condition where they could study cognitive control ability (interference suppression) in these participants.
Bunge et al. (2002) found that increases in inhibitory control capacity in children aged 8–12 were linked to activations in a subset of posterior brain areas that were consistently active in adulthood. Brain activities in the bilateral precuneus, left angular gyrus, right middle temporal gyrus, and right middle frontal gyrus were linked to children’s performance. Furthermore, children’s activities in posterior association areas were a better predictor of performance than prefrontal regions. In other words, poor performance was linked to activation of the left ventrolateral and bilateral dorsolateral prefrontal cortex (DLPFC), whereas good performance was linked to bilateral inferior parietal activation. It’s possible that the prefrontal actions in children who performed poorly were related to the tactics they utilized, rather than being important to their capacity to suppress during the task. Moreover, they discovered one commonality between the two activities studied: adults activated the right ventrolateral prefrontal cortex (VLPFC), particularly the rIFG, but children did not. In contrast to the modular hypothesis of inhibitory regulation, they discovered that the PFC areas (especially the rIFG) do not have a distinct inhibition area.
A subsequent study using the go/no-go paradigm found that successful behavioral inhibition was related with stronger activations in the prefrontal and parietal areas for children, compared with adults. To manipulate the difficulties of the task demands, Durston et al. (2002) varied the number of go trials that preceded no-go trials. This type of manipulation allowed for a comparison of children’s and adults’ performance on trials of similar difficulty. More importantly, researchers might change the prominence of the interfering information to see how much immature inhibitory control capacity is defined by vulnerability to interference. In adults with increased interference from go trials, successful inhibitory control was linked to increased activities in the VLPFC, right parietal lobe, and right DLPFC regions. When blocking a behavioral response in children, however, the networks showed the maximum level of activation, regardless of the number of previous responses (Durston et al., 2002). In addition, activations in the ventral-striatal areas were linked to age and performance. The findings show that children are more vulnerable to interference than adults, which may be due to variations in underlying frontal-striatal circuits.
Another recent study employed functional magnetic resonance imaging (fMRI) to ask children (years 10–12) and adults (ages 18–26) while they performing the marble challenge, in which they had to choose between acting on and blocking a prepotent reaction while fMRI data was recorded (Schel et al., 2014). The right hemisphere’s purposeful inhibition was linked to the activation of the fronto-basal ganglia network. The STN and the right dorsal fronto-medial cortex, which had previously been associated to intentional inhibition and purposeful behavior, had similar levels of activation. Despite the fact that both children and adults actively restrained their behavior to the same degree, children showed higher activation in the right fronto-basal ganglia network, but not in the STN or the dorsal fronto-medial cortex, during intentional inhibition.
Furthermore, there was a link between self-reported impulsivity and deliberate inhibition. The neurological underpinnings of early childhood response inhibition were explored by Rahman et al. (2017). Five-year-old youngsters did a go/no-go task with or without time pressure while scalp EEG was recorded (fast vs. slow condition). In comparison to go trials, when inhibition was required on no-go trials, the left frontal N2 and posterior P3 were elevated. Time pressure affected the early-occurring P1 variable, which was detrimental to behavioral performance. Similar to the N2, the topography of the heightened no-go P3 identified in their sample differed significantly from that documented in adult studies. In their early study on children, the heightened no-go P3 was detected at posterior midline electrode sites, whereas in adults, it is frequently shown at frontal midline electrode sites, a phenomenon known as “no-go anteriorization” (Fallgatter and Strik, 1999).
At posterior electrode sites, adults display a more significant go P3 than no-go P3, indicating that they are paying attention to targets (Bruin et al., 2001). Adults show a posterior P3 in the oddball task, indicating that they are processing infrequent targets (Friedman et al., 2001; Gaeta et al., 2003). Although it is possible that the P3 impact observed in this study is an outlier, we feel it is unlikely to be the result of rare target probability because individual go and no-go stimuli were delivered at the same frequency. The change in the topography of the no-go P3 identified in Rahman et al. (2017) study could represent children’s reliance on additional posterior brain regions in the right hemisphere to facilitate response inhibition. Similar results have been reported in middle childhood when it comes to N2 (Jonkman et al., 2007). Jonkman et al. (2007) discovered that in adults, right medial frontal sources were enough to explain the brain activity underpinning response inhibition, but that in children, additional right posterior sources were required. The neural networks governing inhibitory processes evolve from a more posterior, dispersed structure to a more frontal, concentrated pattern as children get older, according to studies utilizing brain imaging technologies (Bunge et al., 2002; Durston et al., 2006).
Lo et al. (2013) used EEG indices to study age-related changes in response inhibition in preschool children. They suggested that N2 amplitude and beta and gamma power are important indicators of inhibitory control ability. In preschoolers aged 5–6 they showed a positive correlation between electrophysiological components and behavioral improvement in inhibitory control. In particular, they observed a significant improvement in response inhibition in 6-year-olds over 5-year-olds. Moreover, they discovered an increase in the right frontal beta power during successful stop trails. This shows that age-related variations in response inhibition may reflect preschool children’s comparatively undeveloped frontal brain development.
Moreover, neurological and psychiatric diseases were analyzed in other studies with health controls (Tremblay et al., 2020). For example, Tremblay et al. (2020) elucidated the brain mechanisms of an important cognitive deficit in ADHD, identifying potential white matter tracts related to deficient inhibitory control. Twelve adolescents with ADHD and twelve age-matched healthy controls (age range 9–18) were scanned while performing the stop signal task (SST). Reactive inhibition activated the right inferior frontal gyrus (IFG) in both groups. ADHD participants recruited the IFG bilaterally. Prospective inhibition preactivated the same area of the right IFG that was activated during reactive inhibition in controls. In ADHD participants, prospective inhibition was associated with deactivation in this region. Controls also deactivated the right medial prefrontal cortex (rMPFC) during prospective inhibition, whereas ADHD participants activated the same area (Bhaijiwala et al., 2014; Tremblay et al., 2020).
Moreover, children with deficits in behavioral inhibition face increased risk for social anxiety (Thai et al., 2016). However, not all children with behavioral inhibition develop anxiety symptoms. Inhibitory control has been suggested as a moderator of the pathway between behavioral inhibition and social anxiety. In fact, Troller-Renfree et al. (2019) suggested that inhibitory control development in childhood occurs independent of behavioral inhibition levels. However, rapid increases in inhibitory control performance moderate risk for social anxiety symptoms in children with behavioral inhibition (BI) deficit. Notwithstanding, Triplett et al. (2014) found that children with epilepsy demonstrated impaired AS performance compared to controls during both neutral (no reward) and reward trials but exhibited significant task improvements during reward trials. Post-hoc analysis revealed that younger patients made more errors than older patients and all controls. fMRI results showed preserved activation in task-relevant regions such as bilateral frontal and supplementary eye fields, putamen, and precuneus in patient and controls, with the exception of increased activation in the left posterior cingulate gyrus in patients, specifically with generalized epilepsy across neutral and reward trials.
Teenagers
Inhibitory control ability is especially important in teenagers, as adolescence is a period of time that coincides with responsibility, peer interactions, and social awareness (Vara et al., 2014). Moreover, inhibitory control plays a central role in these evolving social executive functions in adolescents (Ellis et al., 2004; Crone et al., 2008; Pharo et al., 2011; Vetter et al., 2013). Poor inhibitory control development may have negative impacts on adolescent socialization processes (Vara et al., 2014). For example, Gligorović and Buha Ðurović (2014) suggested that inhibitory control represents a significant developmental factor of different adaptive behavior domains in children with mild intellectual disability.
There are a bulk of literature suggesting the developments in the frontal lobe maturation and white matter over the adolescence (e.g., Gogtay et al., 2004; Sowell et al., 2004; Paus, 2005; Shaw et al., 2006). Some of the earlier studies found the recruitment of the unilateral prefrontal cortex (Tamm et al., 2002, 2004), and others found a bilateral activation pattern of the prefrontal cortex (Durston et al., 2006; Smith et al., 2006; Carrion et al., 2008). Moreover, it seems that cross-network integration, predominantly of the cingulo-opercular/salience network, increased with age. Importantly, this augmented integration of the cingulo-opercular/salience network significantly moderated the robust effect of age on the latency to initiate a correct inhibitory control response (Marek et al., 2015). Furthermore, Tamm et al. (2002) used the go/no-go task on participants aged from 8 to 20 years old they detected a positive correlation between age and activities in the left IFG, insula, and orbitofrontal gyrus. However, there was a negative relationship between age and activations in the middle and superior frontal gyri. Similarly, in a later fMRI study using SST, Rubia et al. (2007) found a positive correlation between age and activities in bilateral inferior frontal cortex. Moreover, there were enhanced activities in the right inferior prefrontal cortex in adults compared to adolescents. Thus, right frontal regions were found to be reliably involved during inhibitory control. Velanova et al. (2008) scanned 77 people aged between 8 and 27 years old with fMRI while asking them to perform an oculomotor task that requires inhibitory control ability. They found that age-related increases in performance are attributed to functional changes in the dorsal anterior cingulate cortex (dACC) linked with error management and error-feedback use, as well as changes in the recruitment of attentional networks. In adults, dACC showed higher and prolonged modulation for mistake vs. correct trials, but drastically reduced in children. Activities in posterior attentional areas were low in younger age groups. This could be expected because of on higher level of activations of prefrontal cortical regions.
One longitudinal fMRI study using the AS found that the prefrontal engagement was at the max during childhood, but by adolescence, the right DLPFC engages at adult levels. The activities in the right dACC showed increased engagement throughout adolescence, which mediate behavioral developments in AS performance (Ordaz et al., 2013). Age-related development in anterior cingulate functions has also been used to describe SST using fMRI and EEG (Segalowitz et al., 2010; Ferdinand and Kray, 2014). The dACC was also found in performance monitoring tasks, and works as an altering system to engage cognitive control systems (Cavanagh and Frank, 2014). Thus, immaturities in error processing during adolescence may also impact the limitations in inhibitory control tasks. Another longitudinal neuroimaging study revealed that higher externalizing scores were associated with developmentally stable hypo-activation in the left middle frontal gyrus, but divergent developmental pattern of left posterior parietal cortex activation, suggesting that early adolescence may be a unique period of substance use vulnerability via cognitive and phenotypic disinhibition (Kim-Spoon et al., 2016; Quach et al., 2020). Studies about eating disorders in adolescents suggested that failed inhibitory control is an early marker of those disorders (Bartholdy et al., 2019; Cope et al., 2020). In particular, Bartholdy et al. (2019) found greater recruitment of the medial prefrontal and anterior cingulate regions during failed inhibition accords with abnormal evaluation of errors contributing to disordered eating behavior development.
Similarly, another fMRI study on 290 participants used a go/no-go task, with 88 patients undertaking repeated scanning at 1- to 2-year intervals (Cope et al., 2020). One group (N = 117) were scanned when they were 7–13 years old, while the other were scanned when they were 18–23 years old (N = 173). There were two patients with a substance use disorder (SUD) in 33.1% of the study, one patient with a SUD in 43.8%, and no patients with a SUD in 23.1%. There were 1,162 scans performed, ranging in age from 7 to 28, with longitudinal data from the cohorts overlapping between the ages of 16 and 21. To describe voxel-by-voxel shifts in hemodynamic response associated with efficient inhibitory control, Cope et al. (2020) used a marginal model with sandwich estimator standard errors. Cope et al. (2020) discovered that age was correlated with strong positive linear activation in the frontal, temporal, parietal, and occipital cortices in the left hemisphere. Negative linear, positive or negative quadratic, or positive or negative cubic comparisons resulted in no clusters survived thresholding.
A recent study found that inhibition and intrinsic functional brain architecture could be influenced in their relationship by age and emotional function (Petrican and Grady, 2019). Using fMRI dataset from Human Connectome Project (N = 359 participants) and Nathan Kline Institute-Rockland lifespan sample (N = 247), they found that between subjects with superior affective functioning, adolescence and old early adulthood with better inhibitory control correlated to brain pattern that typified processing of motivationally salient information, with a stronger resting state expression. On the contrary, after the age of 49, the reverse impact developed. Moreover, a substantial relationship between inhibition and brain architecture occurred just before the age of 28 in people with lower emotional functioning. Superior inhibition was related to the neural pattern of effortful cognitive processing in this group, also with higher resting state expression. Therefore, their findings suggest that motivational relevance contributes significantly to excellent cognitive functioning during the early stages of development.
Banich et al. (2019) investigated how cognitive control affects the processing of both task-relevant and task-irrelevant information. During adolescence, cognitive control areas in the prefrontal cortex can block sensory cortex, influencing processing of task-irrelevant information. The processing of task-relevant information could potentially impact performance, although no evidence of such processing was found to be controlled by cognitive control areas (Banich et al., 2019). The purpose of their study was to see if stimulation of the dorsolateral prefrontal cortex (DLPFC) changes in reaction time by modifying processing of task-relevant/task-irrelevant information in posterior brain areas (Banich et al., 2019). The amygdala, a brain area involved in the processing of salient task-irrelevant emotional input, was subjected to the same procedure. They discovered that greater DLPFC activity on a given trial was linked with decreased perceptual processing of the task-irrelevant face, supporting the hypothesis that top-down cognitive control might modify processing of task-irrelevant information (Banich et al., 2019).
Wang et al. (2021) used a large-scale longitudinal dataset, which consist of adolescents aged from 14 to 19, to track their inhibitory control development. During fMRI sessions, individuals in their research performed a SST. They attempted to identify brain traits that predict development by building prediction models inside a network or between two networks (Wang et al., 2021). In particular, they found that interconnections between ventral attention (VAN) and subcortical networks might predict individual inhibitory control development and construct a prediction model that extended to previously undiscovered people. Individual disparities in inhibitory control development are shown by their research. Additionally, within 5 years, they discovered that connection between these two networks was associated to drug misuse difficulties (Wang et al., 2021). Therefore, they hypothesized that early neural predictors of development might offer a neural foundation for early customized therapies to prevent inhibitory control impairments in adolescents. According to these results, functional connection of network analyzed (VAN and subcortical networks) could predict future drug misuse, revealing a feasible therapeutic translation pathway for this neurological predictor (Wang et al., 2021).
On the other hand, magnetoencephalography (MEG) offers a temporal resolution and the millisecond level, which allows characterization of electrophysiological activities generated by neuronal dynamics during different phases of cognitive processing. One MEG study on inhibitory control development focused on the differences in the preparatory period between adolescents and adults and found that there were significant differences in oscillatory activities in adolescents compared with adults, which also corresponds with performance (Everling and Munoz, 2000; Hwang et al., 2016). Specifically, adolescents demonstrated adult level beta-band power, but lower alpha-band power and beta in the frontal eye field (FEF). Moreover, there were beta/alpha DLPFC/FEF cross-frequency couplings. Previous research has found that beta rhythms are related to cortical glutamatergic functions in deep layers (Roopun et al., 2010) via top-down inputs activating pyramids neurons (Constantinidis and Luna, 2019). Moreover, Alpha rhythms are linked to dampening of neuronal activities through inhibitory processes (Jensen and Mazaheri, 2010), which support inhibition in the AS task (Belyusar et al., 2013).
A subsequent study used MEG to investigate the spatial temporal neural characteristics for behavioral inhibition during a go/no-go task in both teenagers and adults. Vidal et al. (2012) focused on the spatial temporal activities of neural responses during a go/no-go task in 14 teenaged and 14 adults. They controlled the task complexity of both groups. Results demonstrated bilateral prefrontal activities during inhibitory control in both groups. However, they had different temporal spatial patterns. There was an increased activity in the middle frontal gyri in teenagers at around 300 ms after stimulus onset, but at around 260 ms in the IFG in adults. Furthermore, the inhibition of a prepotent response demonstrated a stronger involvement of the left hemisphere in teenagers compared with adults.
A more recent study used MEG and co-registered magnetic resonance imaging (MRI) to investigate the neural basis underlying the inhibitory control abilities in teenagers with that of adults (Vara et al., 2014). Specifically, Vara et al. (2014) recruited 15 adolescents and 15 adults to do the go/no-go task. There were two conditions in the experiment: control condition (go: no-go trials = 2:1), and an experimental condition (go/no-go trials = 1:2). Vara et al. (2014) compared acquired images of brain activations between both the teenager group and the adult group. The results revealed the recruitment of the rIFG in adults, but delayed recruitment of the left inferior frontal gyrus (lIFG) in adolescents. In addition, adolescents recruited the right middle and superior temporal gyri, nonetheless adults activated the right temporal gyrus for a much brief duration. Together, these results suggest that adolescents are able to demonstrate adult-level inhibitory control behaviorally. However, the prefrontal systems in adolescents do not reach full maturity, so do not engage readily in inhibitory control, thus undermine optimal inhibitory control.