A hallmark of cognitive control is the ability to rein in impulsive responses. Previously, we used a Bayesian model to describe trial-by-trial likelihood of the stop signal or p(Stop) and related ...regional activations to p(Stop) to response slowing in a stop signal task. Here, we characterized the regional processes of conflict anticipation in association with intersubject variation in impulse control in 114 young adults. We computed the stop signal reaction time (SSRT) and a measure of motor urgency, indexed by the reaction time (RT) difference between go and stop error trials or "GoRT - SERT," where GoRT is the go trial RT and SERT is the stop error RT. Motor urgency and SSRT were positively correlated across subjects. A linear regression identified regional activations to p(Stop), each in correlation with SSRT and motor urgency. We hypothesized that shared neural activities mediate the correlation between motor urgency and SSRT in proactive control of impulsivity. Activation of the ventromedial prefrontal cortex, posterior cingulate cortex and right superior frontal gyrus (SFG) during conflict anticipation correlated negatively with the SSRT. Activation of the right SFG also correlated negatively with GoRT - SERT. Therefore, activation of the right SFG was associated with more efficient response inhibition and less motor urgency. A mediation analysis showed that right SFG activation to conflict anticipation mediates the correlation between SSRT and motor urgency bidirectionally. The current results highlight a specific role of the right SFG in translating conflict anticipation to the control of impulsive response, which is consistent with earlier studies suggesting its function in action restraint.
Individuals vary in impulse control. However, the neural bases underlying individual variation in proactive control of impulsive responses remain unknown. Here, in a large sample of young adults, we showed that activation of the right superior frontal gyrus (SFG) during conflict anticipation is positively correlated with the capacity of inhibitory control and negatively with motor urgency in the stop signal task. Importantly, activity of the right SFG mediates the counteracting processes of inhibitory control and motor urgency across subjects. The results support a unique role of the right SFG in individual variation in cognitive control.
The neural basis of motor response inhibition has drawn considerable attention in recent imaging literature. Many studies have used the go/no-go or stop signal task to examine the neural processes ...underlying motor response inhibition. In particular, showing greater activity during no-go (stop) compared with go trials and during stop success compared with stop error trials, the right inferior prefrontal cortex (IFC) has been suggested by numerous studies as the cortical area mediating response inhibition. Many of these same studies as well as others have also implicated the presupplementary motor area (preSMA) in this process, in accord with a function of the medial prefrontal cortex in goal-directed action. Here we used connectivity analyses to delineate the roles of IFC and preSMA during stop signal inhibition. Specifically, we hypothesized that, as an integral part of the ventral attention system, the IFC responds to a stop signal and expedites the stop process in the preSMA, the primary site of motor response inhibition. This hypothesis predicted that preSMA and primary motor cortex would show functional interconnectivity via the basal ganglia circuitry to mediate response execution or inhibition, whereas the IFC would influence the basal ganglia circuitry via connectivity with preSMA. The results of Granger causality analyses in 57 participants confirmed this hypothesis. Furthermore, psychophysiological interaction showed that, compared with stop errors, stop successes evoked greater effective connectivity between the IFC and preSMA, providing additional support for this hypothesis. These new findings provided evidence critically differentiating the roles of IFC and preSMA during stop signal inhibition and have important implications for our understanding of the component processes of inhibitory control.
The dorsal anterior cingulate cortex (dACC) has been implicated in a variety of cognitive control functions, among them the monitoring of conflict, error, and volatility, error anticipation, reward ...learning, and reward prediction errors. In this work, we used a Bayesian ideal observer model, which predicts trial-by-trial probabilistic expectation of stop trials and response errors in the stop-signal task, to differentiate these proposed functions quantitatively. We found that dACC hemodynamic response, as measured by functional magnetic resonance imaging, encodes both the absolute prediction error between stimulus expectation and outcome, and the signed prediction error related to response outcome. After accounting for these factors, dACC has no residual correlation with conflict or error likelihood in the stop-signal task. Consistent with recent monkey neural recording studies, and in contrast with other neuroimaging studies, our work demonstrates that dACC reports at least two different types of prediction errors, and beyond contexts that are limited to reward processing.
The medial superior frontal cortex (SFC), including the supplementary motor area (SMA) and presupplementary motor area (preSMA), is implicated in movement and cognitive control, among other functions ...central to decision making. Previous studies delineated the anatomical boundaries and functional connectivity of the SMA. However, it is unclear whether the preSMA, which responds to a variety of behavioral tasks, comprises functionally distinct areas. With 24 seed regions systematically demarcated throughout the anterior and posterior medial SFC, we examined here the functional divisions of the medial SFC on the basis of the "correlograms" of resting-state functional magnetic resonance imaging data of 225 adult individuals. In addition to replicating segregation of the SMA and posterior preSMA, the current results elucidated functional connectivities of anterior preSMA-the most anterior part of the medial SFC. In contrast to the caudal medial SFC, the anterior preSMA is connected with most of the prefrontal but not with somatomotor areas. Overall, the SMA is strongly connected to the thalamus and epithalamus, the posterior preSMA to putamen, pallidum, and subthalamic nucleus, and anterior preSMA to the caudate, with the caudate showing significant hemispheric asymmetry. These findings may provide a useful platform for future studies to investigate frontal cortical functions.
Abstract
Previous research has demonstrated reduction in cortical and subcortical, including basal ganglia (BG), gray matter volumes (GMV) in individuals with attention deficit hyperactivity disorder ...(ADHD), a neurodevelopmental condition that is more prevalent in males than in females. However, the volumetric deficits vary across studies. Whether volumetric reductions are more significant in males than females; to what extent these neural markers are heritable and relate to cognitive dysfunction in ADHD remain unclear. To address these questions, we followed published routines and performed voxel-based morphometry analysis of a data set (n = 11,502; 5,464 girls, 9–10 years) curated from the Adolescent Brain Cognition Development project, a population-based study of typically developing children. Of the sample, 634 and 2,826 were identified as monozygotic twins and dizygotic twins/siblings, respectively. In linear regressions, a cluster in the hypothalamus showed larger GMV, and bilateral caudate and putamen, lateral orbitofrontal and occipital cortex showed smaller GMVs, in correlation with higher ADHD scores in girls and boys combined. When examined separately, boys relative to girls showed more widespread (including BG) and stronger associations between GMV deficits and ADHD scores. ADHD traits and the volumetric correlates demonstrated heritability estimates (
a
2
) between 0.59 and 0.79, replicating prior findings of the genetic basis of ADHD. Further, ADHD traits and the volumetric correlates (except for the hypothalamus) were each negatively and positively correlated with N-back performance. Together, these findings confirm volumetric deficits in children with more prominent ADHD traits. Highly heritable in both girls and boys and potentially more significant in boys than in girls, the structural deficits underlie diminished capacity in working memory and potentially other cognitive deficits in ADHD.
Approach and avoidance represent two fundamental behavioral traits that develop early in life. Previous studies have examined the neural correlates of approach and avoidance traits in adults and ...adolescents. Here, using the data set of the Adolescent Brain Cognition Development project, we investigated the structural cerebral bases of behavioral activation system (BAS) and behavioral inhibition system (BIS) in children. We employed voxel-based morphometry to examine how gray matter volumes (GMV) related specifically to BAS and BIS traits in 11,542 children (5491 girls, age 9–10 years) with 648 and 2697 identified as monozygotic twins (MZ) and dizygotic twins/siblings (DZ), respectively. After accounting for the BIS score, higher BAS scores (residuals) were positively correlated with the GMV of the ventral striatum (VS), and the correlation was stronger in MZ than in DZ and unrelated children, with a heritability (h2) of 0.8463. Higher BAS scores were negatively correlated with the GMV of bilateral visual, lateral orbitofrontal, temporal, and inferior frontal cortex, as well as the precuneus. Higher BIS (after accounting for BAS) scores were negatively correlated with the GMVs of the ventral caudate and bilateral putamen/pallidum, hypothalamus, and right anterior insula, and the correlation was stronger in MZ than in DZ and unrelated children, with a heritability of 0.8848. A cluster in the VS showed positive and negative correlation with the BAS and BIS scores, respectively. These findings suggest shared and distinct cerebral volumetric bases of the BAS and BIS traits in children. Whereas both traits have a strong genetic basis, the BAS relative to BIS appears to be more amenable to environmental influences. These findings add to the literature of developmental neuroscience and may help identify genetic risk factors of externalizing and internalizing psychopathology.
•We use VBM to study the volumetric correlates of the BAS and BIS in children.•The VS GMV shows positive and negative correlation each with the BAS and BIS.•Girls and boys do not show distinct regional GMV in association with BAS or BIS.•The volumetric correlates of BAS and BIS are highly heritable.•The BAS relative to BIS appears to be more amenable to environmental influences.
Error detection and behavioral adjustment are core components of cognitive control. Numerous studies have focused on the anterior cingulate cortex (ACC) as a critical locus of this executive ...function. Our previous work showed greater activation in the dorsal ACC and subcortical structures during error detection, and activation in the ventrolateral prefrontal cortex (VLPFC) during post-error slowing (PES) in a stop signal task (SST). However, the extent of error-related cortical or subcortical activation across subjects was not correlated with VLPFC activity during PES. So then, what causes VLPFC activation during PES? To address this question, we employed Granger causality mapping (GCM) and identified regions that Granger caused VLPFC activation in 54 adults performing the SST during fMRI. These brain regions, including the supplementary motor area (SMA), cerebellum, a pontine region, and medial thalamus, represent potential targets responding to errors in a way that could influence VLPFC activation. In confirmation of this hypothesis, the error-related activity of these regions correlated with VLPFC activation during PES, with the cerebellum showing the strongest association. The finding that cerebellar activation Granger causes prefrontal activity during behavioral adjustment supports a cerebellar function in cognitive control. Furthermore, multivariate GCA described the “flow of information” across these brain regions. Through connectivity with the thalamus and SMA, the cerebellum mediates error and post-error processing in accord with known anatomical projections. Taken together, these new findings highlight the role of the cerebello-thalamo-cortical pathway in an executive function that has heretofore largely been ascribed to the anterior cingulate-prefrontal cortical circuit.
►Error-related ACC activation is not associated with post-error prefrontal activation. ►Regions Granger-causing VLPFC activation. ►Cerebello-thalamo-cortical circuit causes prefrontal activation in cognitive control.
Inhibitory control or the ability to refrain from incorrect responses is a critical executive function known to diminish during aging. Imaging studies have elucidated cerebral changes that may ...underlie the age-related deficits. However, it remains unclear whether the structural and functional changes occur in the same brain regions and whether reduced gray matter volumes (GMV) mediate decreased activation during inhibition. Here, in a sample of 149 participants, we addressed the issues using structural and functional magnetic resonance imaging. Individual's response inhibition was evaluated by the stop signal reaction time (SSRT) in a stop signal task. The results showed that age was associated with prolonged SSRT across participants. Many cortical and subcortical regions demonstrated age-related reduction in GMV and activation to response inhibition. Additionally, age-related diminution in inhibitory control, as indexed by the SSRT, was associated with both shared and distinct morphometric and functional changes. Voxel-based morphometry demonstrated age-related reduction in GMV in the right dorsolateral prefrontal cortex and caudate head as well as bilateral insula, in association with prolonged SSRT. In a contrast of stop success versus go success trials, age was associated with lower activation in the medial and inferior frontal cortex and inferior parietal cortex. Further, reduction in GMV mediated age-related differences in activations only of the medial prefrontal cortex, providing limited evidence for structure function association. Thus, the decline in inhibitory control, as evidenced in the stop signal task, manifest with both shared and distinct structural and functional processes during aging.
Genetic factors confer risks for depression. Understanding the neural endophenotypes, including brain morphometrics, of genetic predisposition to depression would help in unraveling the ...pathophysiology of depression. We employed voxel-based morphometry (VBM) to examine how gray matter volumes (GMVs) were correlated with the polygenic risk score (PRS) for depression in 993 young adults of the Human Connectome Project. The phenotype of depression was quantified with a DSM-oriented scale of the Achenbach Adult Self-Report. The PRS for depression was computed for each subject using the Psychiatric Genomics Association Study as the base sample. In multiple regression with age, sex, race, drinking severity, and total intracranial volume as covariates, regional GMVs in positive correlation with the PRS were observed in bilateral hippocampi and right gyrus rectus. Regional GMVs in negative correlation with the PRS were observed in a wide swath of brain regions, including bilateral frontal and temporal lobes, anterior cingulate cortex, thalamus, lingual gyri, cerebellum, and the left postcentral gyrus, cuneus, and parahippocampal gyrus. We also found sex difference in anterior cingulate volumes in manifesting the genetic risk of depression. In addition, the GMV of the right cerebellum crus I partially mediated the link from PRS to depression severity. These findings add to the literature by highlighting 1) a more diverse pattern of the volumetric markers of depression, with most regions showing lower but others higher GMVs in association with the genetic risks of depression, and 2) the cerebellar GMV as a genetically informed neural phenotype of depression, in neurotypical individuals.