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Summary: Common executive functioning (cEF) is a domain-general factor that captures shared variance in performance across diverse executive function tasks. To investigate the neural mechanisms of individual differences in cEF (e.g., goal maintenance, biasing), we conducted the largest fMRI study of multiple executive tasks to date (N = 546). Group average activation during response inhibition (antisaccade task), working memory updating (keep track task), and mental set shifting (number–letter switch task) overlapped in classic cognitive control regions. However, there were no areas across tasks that were consistently correlated with individual differences in cEF ability. Although similar brain areas are recruited when completing different executive function tasks, activation levels of those areas are not consistently associated with better performance. This pattern is inconsistent with a simple model in which higher cEF is associated with greater or less activation of a set of control regions across different task contexts; however, it is potentially consistent with a model in which individual differences in cEF primarily depend on activation of domain-specific targets of executive function. Brain features that explain commonalities in executive function performance across tasks remain to be discovered.

Extracellular free water (FW) increases are suggested to better provide pathophysiological information in brain aging than conventional biomarkers such as fractional anisotropy. The aim of the present study was to determine the relationship between conventional biomarkers, FW in white matter hyperintensities (WMH), FW in normal appearing white matter (NAWM) and in white matter tracts and executive functions (EF) with a speed component in elderly persons. We examined 226 healthy elderly participants (median age 69.83 years, IQR: 56.99-74.42) who underwent brain MRI and neuropsychological examination. FW in WMH and in NAWM as well as FW corrected diffusion metrics and measures derived from conventional MRI (white matter hyperintensities, brain volume, lacunes) were used in partial correlation (adjusted for age) to assess their correlation with EF with a speed component. Random forest analysis was used to assess the relative importance of these variables as determinants. Lastly, linear regression analyses of FW in white matter tracts corrected for risk factors of cognitive and white matter deterioration, were used to examine the role of specific tracts on EF with a speed component, which were then ranked with random forest regression. Partial correlation analyses revealed that almost all imaging metrics showed a significant association with EF with a speed component (r = -0.213 - 0.266). Random forest regression highlighted FW in WMH and in NAWM as most important among all diffusion and structural MRI metrics. The fornix (R

Executive function (EF) performance in older adults has been linked with functional and structural profiles within the executive control network (ECN) and default mode network (DMN), white matter hyperintensities (WMH) burden and levels of Alzheimer’s disease (AD) pathology. Here, we simultaneously explored the unique contributions of these factors to baseline and longitudinal EF performance in older adults. Thirty-two cognitively normal (CN) older adults underwent neuropsychological testing at baseline and annually for three years. Neuroimaging and AD pathology measures were collected at baseline. Separate linear regression models were used to determine which of these variables predicted composite EF scores at baseline and/or average annual change in composite ΔEF scores over the three-year follow-up period. Results demonstrated that low DMN deactivation, high ECN activation and WMH burden were the main predictors of EF scores at baseline. In contrast, poor DMN and ECN WM microstructure and higher AD pathology predicted greater annual decline in EF scores. Subsequent mediation analysis demonstrated that DMN WM microstructure uniquely mediated the relationship between AD pathology and ΔEF. These results suggest that functional activation patterns within the DMN and ECN and WMHs contribute to baseline EF while structural connectivity within these networks impact longitudinal EF performance in older adults.

Paediatric traumatic brain injury (pTBI) results in inconsistent changes to regional morphometry of the brain across studies. Structural-covariance networks represent the degree to which the morphology (typically cortical-thickness) of cortical-regions co-varies with other regions, driven by both biological and developmental factors. Understanding how heterogeneous regional changes may influence wider cortical network organization may more appropriately capture prognostic information in terms of long term outcome following a pTBI. The current study aimed to investigate the relationships between cortical organisation as measured by structural-covariance, and long-term cognitive impairment following pTBI. T1-weighted magnetic resonance imaging (MRI) from n = 83 pTBI patients and 33 typically developing controls underwent 3D-tissue segmentation using Freesurfer to estimate cortical-thickness across 68 cortical ROIs. Structural-covariance between regions was estimated using Pearson's correlations between cortical-thickness measures across 68 regions-of-interest (ROIs), generating a group-level 68 × 68 adjacency matrix for patients and controls. We grouped a subset of patients who underwent executive function testing at 2-years post-injury using a neuropsychological impairment (NPI) rule, defining impaired- and non-impaired subgroups. Despite finding no significant reductions in regional cortical-thickness between the control and pTBI groups, we found specific reductions in graph-level strength of the structural covariance graph only between controls and the pTBI group with executive function (EF) impairment. Node-level differences in strength for this group were primarily found in frontal regions. We also investigated whether the top n nodes in terms of effect-size of cortical-thickness reductions were nodes that had significantly greater strength in the typically developing brain than n randomly selected regions. We found that acute cortical-thickness reductions post-pTBI are loaded onto regions typically high in structural covariance. This association was found in those patients with persistent EF impairment at 2-years post-injury, but not in those for whom these abilities were spared. This study posits that the topography of post-injury cortical-thickness reductions in regions that are central to the typical structural-covariance topology of the brain, can explain which patients have poor EF at follow-up.

Executive function (EF) refers as to a set of high-level cognitive abilities that are critical to many aspects of daily life. Despite its importance in human daily life, the neural networks responsible for the development of EF in childhood are not well understood. The present study thus aimed to examine the development of task-dependent brain network organization and its relationship to age-related improvements in EF. To address this issue, we recruited eighty-eight Chinese children ranging in age from 7 to 12 years old, and collected their functional magnetic resonance imaging (fMRI) data when they performed an EF task. By utilizing graph theory, we found that the task-dependent brain network modules became increasingly segregated with age. Specifically, the intra-module connections within the default-mode network (DMN), frontal-parietal network (FPN) and sensorimotor network (SMN) increased significantly with age. In contrast, the inter-module connections of the visual network to both the FPN/SMN decreased significantly with age. Most importantly, modular segregation of the FPN significantly mediated the relationship between age and EF performance. These findings add to our growing understanding of how development changes in task-dependent brain network organization support vast behavioral improvements in EF observed during childhood.

Despite extensive research into executive function (EF), the precise relationship between brain dynamics and flexible cognition remains unknown. Using a large, publicly available dataset (189 participants), we find that functional connections measured throughout 56 minutes of resting state fMRI data comprise five distinct connectivity states. Elevated EF performance as measured outside of the scanner was associated with greater episodes of more frequently occurring connectivity states, and fewer episodes of less frequently occurring connectivity states. Frequently occurring states displayed metastable properties, where cognitive flexibility may be facilitated by attenuated correlations and greater functional connection variability. Less frequently occurring states displayed properties consistent with low arousal and low vigilance. These findings suggest that elevated EF performance may be associated with the propensity to occupy more frequently occurring brain configurations that enable cognitive flexibility, while avoiding less frequently occurring brain configurations related to low arousal/vigilance states. The current findings offer a novel framework for identifying neural processes related to individual differences in executive function.

On a daily basis, we constantly deal with changing environmental cues and perceptual conflicts and as such, our brains must flexibly adapt to current demands in order to act appropriately. Brains become more efficient and are able to switch states more readily by increasing the complexity of their neural networks. However, it is unclear how brain signal complexity relates to behavior in young adults performing cognitively demanding executive function tasks. Here we used multiscale entropy analysis and multivariate statistics on EEG data while participants performed a bivalency effect task-switching paradigm to show that brain signal complexity in young adults increases as task demands increase, that increases in brain signal complexity are associated with both speed gains and losses depending on scalp location, and that more difficult tasks are associated with more circumscribed complexity across the scalp. Overall, these findings highlight a critical role for brain signal complexity in predicting behavior on an executive function task among young adults.

Executive function is a quintessential human capacity that emerges late in development and displays different developmental trends in males and females. Sex differences in executive function in youth have been linked to vulnerability to psychopathology as well as to behaviors that impinge on health, wellbeing, and longevity. Yet, the neurobiological basis of these differences is not well understood, in part due to the spatiotemporal complexity inherent in patterns of brain network maturation supporting executive function. Here we test the hypothesis that sex differences in impulsivity in youth stem from sex differences in the controllability of structural brain networks as they rewire over development. Combining methods from network neuroscience and network control theory, we characterize the network control properties of structural brain networks estimated from diffusion imaging data acquired in males and females in a sample of 879 youth aged 8-22 years. We summarize the control properties of these networks by estimating average and modal controllability, two statistics that probe the ease with which brain areas can drive the network towards easy versus difficult-to-reach states. We find that females have higher modal controllability in frontal, parietal, and subcortical regions while males have higher average controllability in frontal and subcortical regions. Furthermore, controllability profiles in males are negatively related to the false positive rate on a continuous performance task, a common measure of impulsivity. Finally, we find associations between average controllability and individual differences in activation during an n-back working memory task. Taken together, our findings support the notion that sex differences in the controllability of structural brain networks can partially explain sex differences in executive function. Controllability of structural brain networks also predicts features of task-relevant activation, suggesting the potential for controllability to represent context-specific constraints on network state more generally.

The goal of the present study was to examine relationships between individual differences in resting state functional connectivity as ascertained by fMRI (rs-fcMRI) and performance on tasks of executive function (EF), broadly defined as the ability to regulate thoughts and actions. Unlike most previous research that focused on the relationship between rs-fcMRI and a single behavioral measure of EF, in the current study we examined the relationship of rs-fcMRI with individual differences in subcomponents of EF. Ninety-one adults completed a resting state fMRI scan and three separate EF tasks outside the magnet: inhibition of prepotent responses, task set shifting, and working memory updating. From these three measures, we derived estimates of common aspects of EF, as well as abilities specific to working memory updating and task shifting. Using Independent Components Analysis (ICA), we identified across the group of participants several networks of regions (Resting State Networks, RSNs) with temporally correlated time courses. We then used dual regression to explore how these RSNs covaried with individual differences in EF. Dual regression revealed that increased higher common EF was associated with connectivity of a) frontal pole with an attentional RSN, and b) Crus I and II of the cerebellum with the right frontoparietal RSN. Moreover, higher shifting-specific abilities were associated with increased connectivity of angular gyrus with a ventral attention RSN. The results of the current study suggest that the organization of the brain at rest may have important implications for individual differences in EF, and that individuals higher in EF may have expanded resting state networks as compared to individuals with lower EF.

Diffusion magnetic resonance imaging is increasingly used as a non-invasive method to investigate white matter structure in neurological and neuropsychiatric disease. However, many options are available for the acquisition sequence and analysis method. Here we used Parkinson's disease as a model neurodegenerative disorder to compare imaging protocols and analysis options. We investigated fractional anisotropy and mean diffusivity of white matter in patients and age-matched controls, comparing two datasets acquired with different imaging protocols. One protocol prioritised the number of b value acquisitions, whilst the other prioritised the number of gradient directions. The dataset with more gradient directions was more sensitive to reductions in fractional anisotropy in Parkinson's disease, whilst the dataset with more b values was more sensitive to increases in mean diffusivity. Moreover, the areas of reduced fractional anisotropy were highly similar to areas of increased mean diffusivity in PD patients. Next, we compared two widely used analysis methods: tract-based spatial statistics identified reduced fractional anisotropy and increased mean diffusivity in Parkinson's disease in many of the major white matter tracts in the frontal and parietal lobes. Voxel-based analyses were less sensitive, with similar patterns of white matter pathology observed only at liberal statistical thresholds. We also used tract-based spatial statistics to identify correlations between a test of executive function (phonemic fluency), fractional anisotropy and mean diffusivity in prefrontal white matter in both Parkinson's disease patients and controls. These findings suggest that in Parkinson's disease there is widespread pathology of cerebral white matter, and furthermore, pathological white matter in the frontal lobe may be associated with executive dysfunction. Diffusion imaging protocols that prioritised the number of directions versus the number of b values were differentially sensitive to alternative markers of white matter pathology, such as fractional anisotropy and mean diffusivity., Highlights ► DTI shows abnormal frontal white matter in Parkinson's disease. ► FA and MD in the frontal lobe correlate with executive function in PD. ► The number of directions and b values affects sensitivity to FA/MD changes in PD. ► TBSS is more sensitive than VBM to white matter change in Parkinson's disease.

Motivation and executive function are both necessary for the completion of goal-directed behavior. Research investigating the manner in which these processes interact is beginning to emerge and has implicated middle frontal gyrus (MFG) as a site of interaction for relevant neural mechanisms. However, this research has focused on state motivation, and it has not examined functional lateralization. The present study examined the impact of trait levels of approach and avoidance motivation on neural processes associated with executive function. Functional magnetic resonance imaging was conducted while participants performed a color-word Stroop task. Analyses identified brain regions in which trait approach and avoidance motivation (measured by questionnaires) moderated activation associated with executive control. Approach was hypothesized to be associated with left-lateralized MFG activation, whereas avoidance was hypothesized to be associated with right-lateralized MFG activation. Results supported both hypotheses. Present findings implicate areas of middle frontal gyrus in top-down control to guide behavior in accordance with motivational goals.

Research on the processing of objects at different hierarchical levels has suggested that understanding superordinate concepts (e.g. fruit), relative to basic level concepts (e.g. apple), requires greater semantic control demands. Yet, it is unclear which factors underlie this difference in executive processing. We built on previous research showing that superordinate concepts have less shared features among their members and therefore may involve higher semantic control requirements. To test this hypothesis, we developed an fMRI study in which we orthogonally manipulated feature sharedness (more shared vs. less shared) and concept level (superordinate vs. basic) in a sentence verification task. Sentences involving less shared features, relative to more shared features, significantly engaged the L lateral PFC. Importantly, sentences that included superordinate concepts, relative to those with basic level concepts, also revealed a stronger response in L lateral PFC, along with posterior temporal gyrus activation. There was also a significant interaction between feature sharedness and concept level in several PFC regions and L posterior temporal areas. The results suggest that relative to basic level concepts, processing superordinate concepts requires extra semantic control in L lateral PFC to coordinate information that is less shared by other members of the category level. These findings demonstrate that feature sharedness impacts the neural basis of semantic knowledge, and is a critical dimension in the processing of superordinate concepts.

Despite the practical implication of mild exercise, little is known about its influence on executive function and its neural substrates. To address these issues, the present study examined the effect of an acute bout of mild exercise on executive function and attempted to identify potential neural substrates using non-invasive functional near-infrared spectroscopy (fNIRS). Twenty-five young individuals performed a color-word matching Stroop task (CWST) and a two-dimensional scale to measure changes of psychological mood states both before and after a 10-minute exercise session on a cycle ergometer at light intensity (30% v(·)o2peak) and, for the control session, without exercise. Cortical hemodynamic changes in the prefrontal area were monitored with fNIRS during the CWST in both sessions. The acute bout of mild exercise led to improved Stroop performance, which was positively correlated with increased arousal levels. It also evoked cortical activations regarding Stroop interference on the left dorsolateral prefrontal cortex and frontopolar area. These activations significantly corresponded with both improved cognitive performance and increased arousal levels. Concurrently, this study provides empirical evidence that an acute bout of mild exercise improves executive function mediated by the exercise-induced arousal system, which intensifies cortical activation in task-related prefrontal sub-regions.

Dynamic networking of brain regions is suggested to be one of the key factors involved in various brain computations. Central executive function typically requires instantaneous coordination among the medial prefrontal regions and other distant regions, depending on the on-going task situation. In human scalp-recorded electroencephalography (EEG), the medial prefrontal area is estimated to be the current source of the theta rhythm, while there is no direct evidence that the theta rhythm is involved in the dynamic networking of central executive circuits. Here we hypothesize that the central executive circuit over the prefrontal and task-related cortices is dynamically linked by theta synchronization. By using simultaneous functional magnetic resonance imaging (fMRI) and EEG, we elucidated cortical circuits emerging with theta phase synchronization during free pacing repeated subtraction. Theta phase synchronization in the scalp EEG was found to emerge at two major clusters of electrode pairs, between the right frontal and left parietal sites and between the frontal and right parietal sites. The phase synchronization of two clusters is accompanied by fMRI responses in the cortical regions responsible for central executive function, working memory, visual imagery and cognitive action sequence. Here we report the first evidence that theta phase synchronization dynamically coordinates the central executive circuits, including the medial prefrontal cortex and relevant cortical regions.

Using fMRI, neural substrates of the executive system were investigated with respect to differences in working memory capacity. To explore the executive control processes, reading span test (RST) and read conditions were performed. Two subject groups were selected: those with large working memory capacities, labeled high-span subjects (HSS) according to the reading span test, and those with small working memory capacities, labeled low-span subjects (LSS). Significant activation was found mainly in three regions in comparison with the control: anterior cingulate cortex (ACC), left inferior frontal gyrus (IFG), visual association cortex (VAC) and superior parietal lobule (SPL). For both groups, the fMRI signal intensity increased in ACC and IFG during the RST condition compared to that under the read condition. A group difference was also found in the ACC and IFG region, specifically a significant increase in signal intensity was observed only for the HSS group but not for the LSS group. Behavioral data also showed that the performance was better in HSS than in LSS. Moreover, the cross correlation of signal change between ACC and IFG was higher in HSS than in LSS, indicating that the network system between ACC and IFG was more activated in HSS compared to that of LSS. These results suggest that executive function, that is, working attention controlling system is more active in HSS than in LSS. Moreover, the results confirmed our hypothesis that there is a general neural basis for the central executive function in both RST and previous LST (listening span test) tasks despite differences in modality-specific buffers.

Executive functions, such as working memory, must intersect with functions that determine value for the organism. Functional imaging work in humans and single-unit recordings in non-human primates provide evidence that PFC might integrate motivational context with working memory. With functional magnetic resonance imaging (fMRI), we addressed the question of motivation and working memory, using a trial-related design in an object-working memory task. The design permitted the analysis of BOLD signal at separate stages, corresponding to encoding, maintenance, and retrieval. Subjects were motivated by a financial incentive during the task, such that they could gain a high or a low reward. The two different levels of reward also entailed greater or lesser risk of losing money for incorrect responses. In the high, relative to the low, reward condition, subjects shifted response bias, and showed a trend to greater sensitivity. We found main effects in fMRI BOLD signal for reward, which overlapped with BOLD effects for maintenance of information, in the right superior frontal sulcus and bilateral intraparietal sulcus. We also found an interaction between reward and retrieval from working memory in the right dorsolateral prefrontal cortex. Main effects of load and reward occurred in adjacent regions of the ventrolateral PFC during retrieval. The data demonstrate that when subjects perform a simple working memory task, financial incentives motivate performance and interact with some of the same neural networks that process various stages of working memory. Areas of overlap and interaction may integrate information about value, or they may represent a general effect of motivation increasing neural effort.

Executive functions are complex both in the cognitive operations involved and in the neural structures and functions that support those operations. This complexity makes executive function highly vulnerable to the detrimental effects of aging, brain injury, and disease, but may also open paths to compensation. Neural compensation is often used to explain findings of additional or altered patterns of brain activations by older adults or patient populations compared to young adults or healthy controls, especially when associated with relatively preserved performance. Here we test the hypothesis of an alternative form of compensation, between different neuromodulator systems. 135 patients with Parkinson's Disease (PD) completed vesicular monoamine transporter type2 (VMAT2) and acetylcholinesterase PET scanning to assess the integrity of nigrostriatal dopaminergic, thalamic cholinergic, and cortical cholinergic pathways, and a behavioral test (Stroop + task-switching) that puts high demands on conflict processing, an important aspect of executive control. Supporting the compensatory hypothesis, regression models controlling for age and other covariates revealed an interaction between caudate dopamine and cortical cholinergic integrity: Cortical cholinergic integrity was a stronger predictor of conflict processing in patients with relatively low caudate dopaminergic function. These results suggest that although frontostriatal dopaminergic function plays a central role in executive control, cholinergic systems may also make an important contribution. The present results suggest potential pathways for remediation, and that the appropriate interventions for each patient may depend on their particular profile of decline. Furthermore, they help to elucidate the brain systems that underlie executive control, which may be important for understanding other disorders as well as executive function in healthy adults.

The cognitive effects of pharmacologically enhancing cortical dopamine (DA) tone are variable across healthy human adults. It has been postulated that individual differences in drug responses are linked to baseline cortical DA activity according to an inverted-U-shaped function. To better understand the effect of divergent starting points along this curve on DA drug responses, researchers have leveraged a common polymorphism (rs4680) in the gene encoding the enzyme catechol-O-methyltransferase (COMT) that gives rise to greater (Met allele) or lesser (Val allele) extracellular levels of cortical DA. Here we examined the extent to which changes in resting cortical perfusion following the administration of two mechanistically-distinct dopaminergic drugs vary by COMT genotype, and thereby track predictions of the inverted-U model. Using arterial spin labeling (ASL) and a double-blind, within-subject design, perfusion was measured in 75 healthy, genotyped participants once each after administration of tolcapone (a COMT inhibitor), bromocriptine (a DA D2/3 agonist), and placebo. COMT genotype and drug interacted such that COMT Val homozygotes exhibited increased prefusion in response to both drugs, whereas Met homozygotes did not. Additionally, tolcapone-related perfusion changes in the right inferior frontal gyrus correlated with altered performance on a task of executive function. No comparable effects were found for a genetic polymorphism (rs1800497) affecting striatal DA system function. Together, these results indicate that both the directionality and magnitude of drug-induced perfusion change provide meaningful information about individual differences in response to enhanced cortical DA tone.

Aging is associated with declines in a host of cognitive functions, including attentional control, inhibitory control, episodic memory, processing speed, and executive functioning. Theoretical models attribute the age-related decline in cognitive functioning to deficits in goal maintenance and attentional inhibition. Despite these well-documented declines in executive control resources, older adults endorse fewer episodes of mind-wandering when assessed using task-embedded thought probes. Furthermore, previous work on the neural basis of mind-wandering has mostly focused on young adults with studies predominantly focusing on the activity and connectivity of a select few canonical networks. However, whole-brain functional networks associated with mind-wandering in aging have not yet been characterized. In this study, using response time variability-the trial-to-trial fluctuations in behavioral responses-as an indirect marker of mind-wandering or an "out-of-the-zone" attentional state representing suboptimal behavioral performance, we show that brain-based predictive models of response time variability can be derived from whole-brain task functional connectivity. In contrast, models derived from resting-state functional connectivity alone did not predict individual response time variability. Finally, we show that despite successful within-sample prediction of response time variability, our models did not generalize to predict response time variability in independent cohorts of older adults with resting-state connectivity. Overall, our findings provide evidence for the utility of task-based functional connectivity in predicting individual response time variability in aging. Future research is needed to derive more robust and generalizable models.

While accumulating evidence suggests positive effects of exercise on executive function, such effects vary with environment. In particular, exercise in a hypoxic environment (hypobaric or normobaric hypoxia), leading to decreased oxygen supply, may dampen or cancel such effects. Thus, we further explore the relation between the effects of hypoxic exercise on executive function and their underlying neural mechanisms by monitoring changes of cortical activation patterns using functional near-infrared spectroscopy (fNIRS). Fifteen healthy participants performed color-word Stroop tasks (CWST) before and after a 10 min bout of moderate-intensity exercise (50%VO2peak) under normoxic and hypoxic conditions (fraction of inspired oxygen (FIO2) = 0.135). During the CWST, we monitored prefrontal activation using fNIRS. CWST performance under hypoxic conditions decreased compared with normoxic conditions. In addition, CWST-related activation in the left dorsolateral prefrontal cortex (DLPFC) was reduced after a bout of hypoxic exercise. There was statistically significant association between decreased CWST performance and activation in the left DLPFC. These results suggest that moderate exercise under normobaric hypoxic conditions has negative effects on executive function by reducing task-related activations in the DLPFC.

Although growing attention has been drawn to attainable, high-intensity intermittent exercise (HIE)-based intervention, which can improve cardiovascular and metabolic health, for sedentary individuals, there is limited information on the impact and potential benefit of an easily attainable HIE intervention for cognitive health. We aimed to reveal how acute HIE affects executive function focusing on underlying neural substrates. To address this issue, we examined the effects of acute HIE on executive function using the color-word matching Stroop task (CWST), which produces a cognitive conflict in the decision-making process, and its neural substrate using functional near infrared spectroscopy (fNIRS). Twenty-five sedentary young adults (mean age: 21.0 ± 1.6 years; 9 females) participated in two counter-balanced sessions: HIE and resting control. The HIE session consisted of two minutes of warm-up exercise (50 W load at 60 rpm) and eight sets of 30 s of cycling exercise at 60% of maximal aerobic power (mean: 127 W ± 29.5 load at 100 rpm) followed by 30 s of rest on a recumbent-ergometer. Participants performed a CWST before and after the 10-minute exercise session, during both of which cortical hemodynamic changes in the prefrontal cortex were monitored using fNIRS. Acute HIE led to improved Stroop performance reflected by a shortening of the response time related to Stroop interference. It also evoked cortical activation related to Stroop interference on the left-dorsal-lateral prefrontal cortex (DLPFC), which corresponded significantly with improved executive performance. These results provide the first empirical evidence using a neuroimaging method, to our knowledge, that acute HIE improves executive function, probably mediated by increased activation of the task-related area of the prefrontal cortex including the left-DLPFC.

A growing body of evidence indicates a pivotal role of cognition and in particular executive function in gait control and fall prevention. In a recent gait study using electroencephalographic (EEG) imaging, we provided direct proof for cortical top-down inhibitory control in step adaptation. A crucial part of motor inhibition is recognizing stimuli that signal the need to inhibit or adjust motor actions such as steps during walking. One of the EEG signatures of performance monitoring in response to events signaling the need to adjust motor responses, are error-related potential (error-ERP) features. To examine whether error-ERP features may index executive control during gait adaptation, we analyzed high-density (108-channel) EEG data from an auditory gait pacing study. Participants (N = 18) walking on a steadily moving treadmill were asked to step in time to an auditory cue tone sequence, and then to quickly adapt their step length and rate, to regain step-cue synchrony following occasional unexpected shifts in the pacing cue train to a faster or slower cue tempo. Decomposition of the continuous EEG data by independent component analysis revealed a negative deflection in the source-resolved event-related potential (ERP) time locked to ‘late’ cue tones marking a shift to a slower cue tempo. This vertex-negative ERP feature, localized primarily to posterior medial frontal cortex (pMFC) and peaking 250 ms after the onset of the tempo-shift cue, we here refer to as the step-cue delay negativity (SDN). SDN source, timing, and polarity resemble other error-related ERP features, e.g., the Error-Related Negativity (ERN) and Feedback-Related Negativity (FRN) in (seated) button press response tasks. In single trials, SDN amplitude varied with the magnitude of the cue latency deviation (the time interval between the expected and actual cue onsets). Regression analysis also identified linear coupling between SDN amplitude and the subsequent speed of gait tempo adaptation (as measured by the increase in length of the ensuing adaptation step). The SDN in this paradigm thus seems both to index the perceived need for and the subsequent magnitude of the immediate gait adjustment, consistent with performance-monitoring models. Future research might investigate relationships of these control processes to the impairment of gait adjustment in motor disorders and cognitive decline, for example to develop a biomarker for fall risk prediction in early-stage Parkinson's.

Aberrant patterns of brain functional connectivity in the default mode network (DMN) have been observed across different classes of substance use disorder (SUD) and are associated with craving and relapse. In addicted individuals resting functional connectivity (RSFC) of the anterior DMN, which participates in attribution of personal value and emotional regulation, tends to be decreased, whereas RSFC of the posterior DMN, which directs attention to the internal world, tends to be increased. Aberrant RSFC within the DMN is believed to contribute to impaired self-awareness, negative emotions and to ruminations in addiction. Additionally, the disrupted connectivity between DMN and cortical regions involved with executive function, memory and emotion could be critical to drug-taking regardless of negative consequences and to stress-triggered relapse. At the system level, the dynamics of DMN interactions with the executive control and the salience networks are also disturbed in addiction. The DMN is prominently engaged during the withdrawal and preoccupation phases of the addiction cycle at the expense of the executive control network and with an enhanced participation of the salience network. In contrast, DMN prominence appears to be transitorily decreased during the intoxication phases. There is also growing evidence that disruption of the DMN in addiction reflects in part changes in dopaminergic, glutamatergic, and GABAergic signaling associated with acute and chronic drug use. Findings are starting to reveal DMN RSFC as a potential biomarker for predicting clinical outcomes in SUD and identify the DMN as a promising target for the treatment of addiction.

Social relationships change across the lifespan as social networks narrow and motivational priorities shift to the present. Interestingly, aging is also associated with changes in executive function, including decision-making abilities, but it remains unclear how age-related changes in both domains interact to impact financial decisions involving other people. To study this problem, we recruited 50 human participants (Nyounger = 26, ages 18-34; Nolder = 24, ages 63-80) to play an economic trust game as the investor with three partners (friend, stranger, and computer) who played the role of investee. Investors underwent functional magnetic resonance imaging (fMRI) during the trust game while investees were seated outside of the scanner. Building on our previous work with younger adults showing both enhanced striatal responses and altered default-mode network (DMN) connectivity as a function of social closeness during reciprocated trust, we predicted that these relations would exhibit age-related differences. We found that striatal responses to reciprocated trust from friends relative to strangers and computers were blunted in older adults relative to younger adults, thus supporting our primary pre-registered hypothesis regarding social closeness. We also found that older adults exhibited enhanced DMN connectivity with the temporoparietal junction (TPJ) during reciprocated trust from friends compared to computers while younger adults exhibited the opposite pattern. Taken together, these results advance our understanding of age-related differences in sensitivity to social closeness in the context of trusting others.

Control processes allow us to constrain the retrieval of semantic information from long-term memory so that it is appropriate for the task or context. Control demands are influenced by the strength of the target information itself and by the circumstances in which it is retrieved, with more control needed when relatively weak aspects of knowledge are required and after the sustained retrieval of related concepts. To investigate the neurocognitive basis of individual differences in these aspects of semantic control, we used resting-state fMRI to characterise the intrinsic connectivity of left ventrolateral prefrontal cortex (VLPFC), implicated in controlled retrieval, and examined associations on a paced serial semantic task, in which participants were asked to detect category members amongst distractors. This task manipulated both the strength of target associations and the requirement to sustain retrieval within a narrow semantic category over time. We found that individuals with stronger connectivity between VLPFC and medial prefrontal cortex within the default mode network (DMN) showed better retrieval of strong associations (which are thought to be recalled more automatically). Stronger connectivity between the same VLPFC seed and another DMN region in medial parietal cortex was associated with larger declines in retrieval over the course of the category. In contrast, participants with stronger connectivity between VLPFC and cognitive control regions within the ventral attention network (VAN) had better controlled retrieval of weak associations and were better able to sustain their comprehension throughout the category. These effects overlapped in left insular cortex within the VAN, indicating that a common pattern of connectivity is associated with different aspects of controlled semantic retrieval induced by both the structure of long-term knowledge and the sustained retrieval of related information.

White matter deterioration is associated with cognitive impairment in healthy aging and Alzheimer's disease. It is critical to identify interventions that can slow down white matter deterioration. So far, clinical trials have failed to demonstrate the benefits of aerobic exercise on the adult white matter using diffusion Magnetic Resonance Imaging. Here, we report the effects of a 6-month aerobic walking and dance interventions (clinical trial NCT01472744) on white matter integrity in healthy older adults (n = 180, 60–79 years) measured by changes in the ratio of calibrated T1- to T2-weighted images (T1w/T2w). Specifically, the aerobic walking and social dance interventions resulted in positive changes in the T1w/T2w signal in late-myelinating regions, as compared to widespread decreases in the T1w/T2w signal in the active control. Notably, in the aerobic walking group, positive change in the T1w/T2w signal correlated with improved episodic memory performance. Lastly, intervention-induced increases in cardiorespiratory fitness did not correlate with change in the T1w/T2w signal. Together, our findings suggest that white matter regions that are vulnerable to aging retain some degree of plasticity that can be induced by aerobic exercise training. In addition, we provided evidence that the T1w/T2w signal may be a useful and broadly accessible measure for studying short-term within-person plasticity and deterioration in the adult human white matter.

We report the first neuroimaging experiment to investigate the impact of explicitly activating aging stereotypes (i.e., stereotype threat) on brain activity during cognitive tasks. Cognitively normal older adults read about aging stereotypes or a control passage prior to taking episodic memory, working memory, and a non-demanding control task during fMRI. At the group level, stereotype activation did not impact cognitive performance or measures sensitive to stress and anxiety (physiological or self-report), but like prior work, highly educated and retired adults exhibited greater stereotype effects on episodic memory. At the neural level, stereotype activation did not impact brain activity in executive control or emotional regulation regions previously linked to stereotype threat effects in younger adults, suggesting that stereotype threat operates differently in older adults. Instead, on each task, the stereotype group showed more brain activity than the control group in parietal midline regions (e.g., precuneus, posterior cingulate). Although activity in these regions can arise from many processes, they have previously been associated with self-referential thinking and error-prevention focus, and in our study, brain activity in these regions was associated with slower responses and lower false alarm errors on the episodic memory task. Collectively, these findings are more consistent with the regulatory fit hypothesis than an executive control interference hypothesis of stereotype threat effects in older adults, whereby older adults adopt an error-prevention mindset in response to explicit stereotype threat.

Non-heme iron accumulation contributes to age-related decline in brain structure and cognition via a cascade of oxidative stress and inflammation, although its effect on brain function is largely unexplored. Thus, we examine the impact of striatal iron on dynamic range of BOLD modulation to working memory load. N=166 healthy adults (age 20-94) underwent cognitive testing and an imaging session including n-back (0-, 2-, 3-, and 4-back fMRI), R2*-weighted imaging, and pcASL to measure cerebral blood flow. A statistical model was constructed to predict voxelwise BOLD modulation by age, striatal iron content and an age × iron interaction, controlling for cerebral blood flow, sex, and task response time. A significant interaction between age and striatal iron content on BOLD modulation was found selectively in the putamen, caudate, and inferior frontal gyrus. Greater iron was associated with reduced modulation to difficulty, particularly in middle-aged and younger adults with greater iron content. Further, iron-related decreases in modulation were associated with poorer executive function in an age-dependent manner. These results suggest that iron may contribute to differences in functional brain activation prior to older adulthood, highlighting the potential role of iron as an early factor contributing to trajectories of functional brain aging.

Inhibitory control is an important executive function that is necessary to suppress premature actions and to block interference from irrelevant stimuli. Current experimental studies and models highlight proactive and reactive mechanisms and claim several cortical and subcortical structures to be involved in response inhibition. However, the involved structures, network mechanisms and the behavioral relevance of the underlying neural activity remain debated. We report cortical EEG and invasive subthalamic local field potential recordings from a fully implanted sensing neurostimulator in Parkinson's patients during a stimulus- and response conflict task with and without deep brain stimulation (DBS). DBS made reaction times faster overall while leaving the effects of conflict intact: this lack of any effect on conflict may have been inherent to our task encouraging a high level of proactive inhibition. Drift diffusion modelling hints that DBS influences decision thresholds and drift rates are modulated by stimulus conflict. Both cortical EEG and subthalamic (STN) LFP oscillations reflected reaction times (RT). With these results, we provide a different interpretation of previously conflict-related oscillations in the STN and suggest that the STN implements a general task-specific decision threshold. The timecourse and topography of subthalamic-cortical oscillatory connectivity suggest the involvement of motor, frontal midline and posterior regions in a larger network with complementary functionality, oscillatory mechanisms and structures. While beta oscillations are functionally associated with motor cortical-subthalamic connectivity, low frequency oscillations reveal a subthalamic-frontal-posterior network. With our results, we suggest that proactive as well as reactive mechanisms and structures are involved in implementing a task-related dynamic inhibitory signal. We propose that motor and executive control networks with complementary oscillatory mechanisms are tonically active, react to stimuli and release inhibition at the response when uncertainty is resolved and return to their default state afterwards.

Growing evidence suggests that both the medial prefrontal cortex (mPFC) and the subthalamic nucleus (STN) play crucial roles in conflict processing, but how these two structures coordinate their activities remains poorly understood. We simultaneously recorded electroencephalogram from the mPFC and local field potentials from the STN using deep brain stimulation electrodes in 13 Parkinson's disease patients while they performed a Stroop task. Both mPFC and STN showed significant increases in theta activities (2-8 Hz) in incongruent trials compared to the congruent trials. The theta activity in incongruent trials also demonstrated significantly increased phase synchronization between mPFC and STN. Furthermore, the amplitude of gamma oscillation was modulated by the phase of theta activity at the STN in incongruent trials. Such theta-gamma phase-amplitude coupling (PAC) was much stronger for incongruent trials with faster reaction times than those with slower reaction times. Elevated theta-gamma PAC in the STN provides a novel mechanism by which the STN may operationalize its proposed “hold-your-horses” role. The co-occurrence of mPFC-STN theta phase synchronization and STN theta-gamma PAC reflects a neural substrate for fronto-subthalamic communication during conflict processing. More broadly, it may be a general mechanism for neuronal interactions in the cortico-basal ganglia circuits via a combination of long-range, within-frequency phase synchronization and local cross-frequency PAC.

Background Total hippocampal volume has been consistently linked to cognitive function and dementia. Yet, given its complex and parcellated internal structure, the role of subregions of the hippocampus in cognition and risk of dementia remains relatively underexplored. We studied subregions of the hippocampus in a large population-based cohort to further understand their role in cognitive impairment and dementia risk. Methods We studied 5035 dementia- and stroke-free persons from the Rotterdam Study, aged over 45 years. All participants underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Automatic segmentation of the hippocampus and 12 of its subregions was performed using the FreeSurfer software (version 6.0). A cognitive test battery was performed, and participants were followed up for the development of dementia until 2015. Associations of hippocampal subregion volumes with cognition and incident dementia were examined using linear and Cox regression models, respectively. All analyses were adjusted for age, sex, education, and total hippocampal volume. Results Mean age was 64.3 years (SD 10.6) with 56% women. Smaller volumes of the hippocampal fimbria, presubiculum and subiculum showed the strongest associations with poor performance on several cognitive domains, including executive function but not memory. During a mean follow-up of 5.5 years, 76 persons developed dementia. Smaller subiculum volume was associated with risk of dementia adjusted for total volume (hazard ratio per SD decrease in volume: 1.75, 95% confidence interval 1.35; 2.26). Conclusions In a community-dwelling non-demented population, we describe patterns of association between hippocampal subregions with cognition and risk of dementia. Specifically, the subiculum was associated with both poorer cognition and higher risk of dementia.

White matter hyperintensities (WMH) are a prominent feature of cerebral small vessel disease and are associated with cognitive impairment. These deficits in cognition may be caused by the disruption of large-scale functional networks due to the presence of WMHs. However, knowledge regarding the relevance of these lesions on functional networks remains inconclusive. These inconsistencies may derive from issues with interpreting functional imaging data from clinical populations. Lesion network mapping is a technique that allows the overlaying of lesions from a patient population to the functional connectivity of a human connectome derived from healthy adults. This allows researchers to identify functional networks that would be disrupted in a healthy population should the WMHs seen in cerebral small vessel disease be present. We hypothesized that the extent to which these functional networks are disrupted by WMHs is associated with cognitive performance in older adults with cerebral small vessel disease. This cross-sectional study combined baseline data from four studies to create a total sample of 164 older adults (aged ≥55) from metropolitan Vancouver with cerebral small vessel disease. Using lesion network mapping, we assessed the percentage overlap between voxels functionally connected with both the WMHs (lesion network) and five common functional networks: (1) visual; (2) dorsal attention; (3) ventral attention; (4) sensorimotor; and (5) frontoparietal. Cognition was assessed using: (1) Montreal Cognitive Assessment (MoCA); (2) Stroop Colour Word Test (3-2); (3) Trail Making Tests (Part B-A); and (4) Digit Symbol Substitution Test. A One-Way ANOVA and Tukey post-hoc tests were performed to identify the functional networks with greatest percentage overlap with the lesion network. Partial correlations controlling for age were used to analyse whether the extent of the overlap between the lesion and functional networks was associated with poorer cognition. The visual, ventral attention, and frontoparietal networks had significantly greater overlap with the lesion network. After controlling for multiple comparisons, level of lesion network overlap with both the sensorimotor network (p

Studies of occipital cortex plasticity in blindness provide insight into how intrinsic constraints interact with experience to determine cortical specialization. We tested the cognitive nature and anatomical origins of occipital responses during non-verbal, non-spatial auditory tasks. In a go/no-go task, congenitally blind (N=23) and sighted (N=24) individuals heard rapidly occurring (

Sequence processing is critical for complex behavior, and counting sequences hold a unique place underlying human numerical development. Despite this, the neural bases of counting sequences remain unstudied. We hypothesized that counting sequences in adults would involve representations in sensory, order, magnitude, and linguistic codes that implicate regions in auditory, supplementary motor, posterior parietal, and inferior frontal areas, respectively. In an fMRI scanner, participants heard four-number sequences in a 2 × 2 × 2 design. The sequences were adjacent or not (e.g., 5, 6, 7, 8 vs. 5, 6, 7, 9), ordered or not (e.g., 5, 6, 7, 8 vs. 8, 5, 7, 6), and were spoken by a voice of consistent or variable identity. Then, neural substrates of counting sequences were identified by testing for the effect of consecutiveness (ordered nonadjacent versus ordered adjacent, e.g., 5, 6, 7, 9 > 5, 6, 7, 8) in the hypothesized brain regions. Violations to consecutiveness elicited brain activity in the right inferior frontal gyrus (IFG) and the supplementary motor area (SMA). In contrast, no such activation was observed in the auditory cortex, despite violations in voice identity recruiting strong activity in that region. Also, no activation was observed in the inferior parietal lobule, despite a robust effect of orderedness observed in that brain region. These findings indicate that listening to counting sequences do not automatically elicit sensory or magnitude codes but suggest that the precise increments in the sequence are tracked by the mechanism for processing ordered associations in the SMA and by the mechanism for binding individual lexical items into a cohesive whole in the IFG.

Cognitive trajectories vary greatly across older individuals, and the neural mechanisms underlying these differences remain poorly understood. Here, we investigate the cognitive variability in older adults by linking the influence of white matter microstructure on the task-related organization of fast and effective communications between brain regions. Using diffusion tensor imaging and electroencephalography, we show that individual differences in white matter network organization are associated with network clustering and efficiency in the alpha and high-gamma bands, and that functional network dynamics partly explain individual differences in cognitive control performance in older adults. We show that older individuals with high versus low structural network clustering differ in task-related network dynamics and cognitive performance. These findings were corroborated by investigating magnetoencephalography networks in an independent dataset. This multimodal (fMRI and biological markers) brain connectivity framework of individual differences provides a holistic account of how differences in white matter microstructure underlie age-related variability in dynamic network organization and cognitive performance.

The human mediodorsal thalamic nucleus (MD) is crucial for higher cognitive functions, while the fine anatomical organization of the MD and the function of each subregion remain elusive. In this study, using high-resolution data provided by the Human Connectome Project, an anatomical connectivity-based method was adopted to unveil the topographic organization of the MD. Four fine-grained subregions were identified in each hemisphere, including the medial (MDm), central (MDc), dorsal (MDd), and lateral (MDl), which recapitulated previous cytoarchitectonic boundaries from histological studies. The subsequent connectivity analysis of the subregions also demonstrated distinct anatomical and functional connectivity patterns, especially with the prefrontal cortex. To further evaluate the function of MD subregions, partial least squares analysis was performed to examine the relationship between different prefrontal-subregion connectivity and behavioral measures in 1012 subjects. The results showed subregion-specific involvement in a range of cognitive functions. Specifically, the MDm predominantly subserved emotional-cognition domains, while the MDl was involved in multiple cognitive functions especially cognitive flexibility and inhibition. The MDc and MDd were correlated with fluid intelligence, processing speed, and emotional cognition. In conclusion, our work provides new insights into the anatomical and functional organization of the MD and highlights the various roles of the prefrontal-thalamic circuitry in human cognition.

Available online 30 April 2019. Behavioral adaptations during performance rely on predicting and evaluating the consequences of our actions through action monitoring. Previous studies revealed that proprioceptive and exteroceptive signals contribute to error-monitoring processes, which are implemented in the posterior medial frontal cortex. Interestingly, errors also trigger changes in autonomic nervous system activity such as pupil dilation or heartbeat deceleration. Yet, the contribution of implicit interoceptive signals of bodily states to error-monitoring during ongoing performance has been overlooked. This study investigated whether cardiovascular interoceptive signals influence the neural correlates of error processing during performance, with an emphasis on the early stages of error processing. We recorded musicians’ electroencephalography and electrocardiogram signals during the performance of highly-trained music pieces. Previous event-related potential (ERP) studies revealed that pitch errors during skilled musical performance are preceded by an error detection signal, the pre-error-negativity (preERN), and followed by a later error positivity (PE). In this study, by combining ERP, source localization and multivariate pattern classification analysis, we found that the error-minus-correct ERP waveform had an enhanced amplitude within 40–100 ms following errors in the systolic period of the cardiac cycle. This component could be decoded from single-trials, was dissociated from the preERN and PE, and stemmed from the inferior parietal cortex, which is a region implicated in cardiac autonomic regulation. In addition, the phase of the cardiac cycle influenced behavioral alterations resulting from errors, with a smaller post-error slowing and less perturbed velocity in keystrokes following pitch errors in the systole relative to the diastole phase of the cardiac cycle. Lastly, changes in the heart rate anticipated the upcoming occurrence of errors. This study provides the first evidence of preconscious visceral information modulating neural and behavioral responses related to early error monitoring during skilled performance. The study was supported by Goldsmiths University of London, the British Academy, through grant SG161006, and the German Research Foundation, through project HE 6013/1-2 to MHR.

Warning stimuli in sensorimotor tasks induce a state of preparedness characterized by increased alertness, focused attention and immobility. This state of attentive anticipation is associated with heart rate deceleration. Ageing affects the amplitude of the anticipatory cardiac deceleration responses; yet, the impact of this physiological change on cognitive performance is still to be elucidated. In fact, how cardiac deceleration relates to brain function and cognitive performance in the context of perceptual decision-making and different levels of decision complexity remains unknown. Here, we aimed to investigate the relationship between cardiac deceleration, brain function, and performance in perceptual decision tasks and how these associate with age-related changes. We measured simultaneously the electrocardiogram, the pupilogram, and the electroencephalogram in 36 young and 39 older adults, while they were engaged in two auditory cued reaction time tasks: a detection task and a go/no-go task requiring inhibitory control. We observed robust cardiac deceleration responses that increased with increasing task complexity. Notably, stronger modulation of the cardiac response across tasks was associated with the ability to maintain response speed as decision complexity increased suggesting a link between cardiac deceleration and facilitation of perceptual decisions. Additionally, cardiac deceleration appears to have a cortical origin as it correlated with frontocentral event-related potentials. In contrast, beta oscillations at baseline and task-related beta suppression were not predictive of cardiac deceleration suggesting a dissociation between sensorimotor oscillatory activity and this cardiac response. Importantly, we found age-related changes in anticipatory cardiac deceleration associated with deficits in perceptual decision-making.

For bilinguals, language control is needed for selecting the target language during language production. Numerous studies have examined the neural correlates of language control and shown a close relationship between language control and domain-general cognitive control. However, it remains unknown how these brain regions coordinate with each other when bilinguals exert cognitive control over linguistic and nonlinguistic representations. We addressed this gap using an extended unified structural equation modeling (euSEM) approach. Sixty-five Chinese-English bilinguals performed language switching and nonverbal switching tasks during functional magnetic resonance imaging (fMRI) scanning. The results showed that language control was served by a cooperative brain network, including the frontal lobe, the parietal cortex, subcortical areas, and the cerebellum. More importantly, we found that language control recruited more subcortical areas and connections from frontal to subcortical areas compared with domain-general cognitive control, demonstrating a reconfigurable brain network. In addition, the reconfiguration efficiency of the brain network was mainly determined by general cognitive ability but was also mediated by second language (L2) proficiency. These findings provide the first data-driven connectivity model that specifies the brain network for language control in bilinguals and also shed light on the relationship between language control and domain-general cognitive control.

Structural and functional analyses of the human claustrum, a poorly understood telencephalic gray matter structure, are hampered by its sheet-like anatomical arrangement. Here, we first describe a functional magnetic resonance imaging (fMRI) method to reveal claustrum signal with no linear relationship with adjacent regions in human subjects. We applied this approach to resting state functional connectivity (RSFC) analysis of the claustrum at high resolution (1.5 mm isotropic voxels) using a 7T dataset (n = 20) and a separate 3T dataset for replication (n = 35). We then assessed claustrum activation during performance of a cognitive task, the multi-source interference task, at 3T (n = 33). Extensive functional connectivity was observed between claustrum and cortical regions associated with cognitive control, including anterior cingulate, prefrontal and parietal cortices. Cognitive task performance was associated with widespread activation and deactivation that overlapped with the cortical areas showing functional connectivity to the claustrum. Furthermore, during high cognitive conflict conditions of the task, the claustrum was significantly activated at the onset of the task, but not during the remainder of the difficult condition. Both of these findings suggest that the human claustrum can be functionally isolated with fMRI, and that it may play a role in cognitive control, and specifically task switching, independent of sensorimotor processing.

The ability to perform at a high level, even when the task at hand is interrupted by an unrelated secondary task, is central to human information processing. Executive control processes, in particular the reallocation of attentional resources, are crucial for coping with interruptions. Although the age-related decline in cognitive control functions is well described, the consequences of such changes for the ability to deal with interruptions are as of yet unclear. In the present study, we examined behavioral performance as well as electrophysiological parameters associated with executive control processes in older and younger participants using a nested task design: In one third of all trials, an ongoing working memory task was interrupted by a math task. We found that the impact of interruptions on primary task performance was more severe in the older age group. In the EEG, older adults showed stronger frontal midline theta activation and fronto-parietal connectivity in the theta range in response to the cue indicating the relevant attentional set. Younger participants, on the other hand, showed distinct and specific increases in cognitive control as indexed by frontal midline theta in response to the stimulus signaling an upcoming interruption. Overall, the results reveal strategic differences between the age groups, as older participants seem to prioritize the primary task more strongly. The data furthermore indicate that the combination of a rapid succession of events and the decreased ability to shift executive resources renders older adults’ performance particularly vulnerable to the occurrence of interruptions.

Reward learning has the ability to bias both attention and behaviour. The current study presents behavioural and neural evidence that irrelevant responses evoked by previously reward-associated stimuli are more robustly represented in the motor system using a combined go/no-go and flankers task. Following a colour-reward association training, participants were instructed to respond to a central target only in a response-relevant context, while ignoring flankers that appeared either in a high-value or low-value colour. The motor cortex and cerebellum exhibited reduced activation to low-value flankers in a response-irrelevant context, consistent with goal-directed response suppression. However, these same regions exhibited similar activation to high-value flankers regardless of their response relevance, indicating less effective suppression, and the resulting interaction in motor cortex activation was strongly predicted by the influence of the flankers on behaviour. These findings suggest that associative reward learning produces a general approach bias, which is particularly evident when it conflicts with task goals, extending the principle of value-driven attention to stimulus-evoked responses in the motor system.

Background The term executive functions (EF) describes a set of higher cognitive abilities/skills needed for goal-oriented and flexible behavior. In contrast to a multitude of functional neuroimaging studies of EF performance, only limited and partially inconclusive data is available for the structural-neuroanatomical underpinnings of EFs, particularly in healthy adults. Methods Here, we applied voxel-based morphometry (VBM) and additional analyses of cortical thickness (CTH; via surface-based morphometry) to a large sample of healthy young adults from the Human Connectome Project (N = 1110; Age 28.8 ± 3.7 years) with structural MRI data and test data reflective of three core EFs [i.e. cognitive flexibility (CF), inhibitory control (IC) and working memory (WM)]. Results For CF and IC, VBM analyses yielded a distinct and largely overlapping pattern of exclusively negative associations (CF>IC), most prominently within the medial prefrontal cortex, the insular cortex, central/precentral regions, subcortical and mesotemporal structures. A similar, yet less pronounced pattern of negative associations was found in analyses of CTH. In contrast, both VBM and CTH analyses yielded no significant associations with WM performance. Conclusions Brain regions we found negatively associated with measures of CF and IC have been repeatedly highlighted by functional imaging studies of EF performance. The here observed inverse relationship with brain structural parameters may be related to the young age of our study population and well established neurobiological mechanisms of cortical maturation (i.e. cortical thinning via synaptic pruning and cortical myelination).

Investigations into the neurophysiological underpinnings of control suggest that frontal theta activity is increased with the need for control. However, these studies typically show this link by reporting associations between increased theta and RT slowing – a process that is contemporaneous with cognitive control but does not strictly reflect the specific use of control. In this study, we assessed frontal theta responses that underpinned the switch cost in task switching – a specific index of cognitive control that does not rely exclusively on RT slowing. Here, we utilised a single-trial regression approach to assess 1) how cognitive control demands beyond simple RT slowing were linked to midfrontal theta and 2) whether midfrontal theta effects remained stable over time. In a large cohort that included a longitudinal subsample, we found that midfrontal theta was modulated by switch costs, with enhanced theta power when preparing to switch vs. repeating a task. These effects were reliable after a two-year interval (Cronbach's α.39-0.74). In contrast, we found that trial-by-trial modulations of midfrontal theta power predicted the size of the switch cost – so that switch trials with increased theta produced smaller switch costs. Interestingly, these relationships between theta and behaviour were less stable over time (Cronbach's α 0-0.61), with participants first using both delta and theta bands to influence behaviour whereas after two years only theta associations with behaviour remained. Together, these findings suggest midfrontal theta supports the need for control beyond simple RT slowing and reveal that midfrontal theta effects remain relatively stable over time.

Cognitive flexibility is often examined using task-switch paradigms, whereby individuals either switch between tasks or repeat the same task on successive trials. The behavioral costs of switching in terms of accuracy and reaction time are well-known, but the oscillatory dynamics underlying such costs are poorly understood. Herein, we examined 25 healthy adults who performed a task-switching paradigm during magnetoencephalography (MEG). All MEG data were transformed into the time-frequency domain and significant oscillatory responses were imaged separately per condition (i.e., switch, repeat) using a beamformer. To determine the impact of task-switching on the neural dynamics, the resulting images were examined using paired-samples t-tests. Whole-brain correlations were also computed using the switch-related difference images (switch – repeat) and the switch-related behavioral data (i.e., switch costs). Our key results indicated stronger decreases in alpha and beta activity, and greater increases in gamma activity in nodes of the cingulo-opercular and fronto-parietal networks during switch relative to repeat trials. In addition, behavioral switch costs were positively correlated with switch-related differences in right frontal and inferior parietal alpha activity, and negatively correlated with switch effects in anterior cingulate and right temporoparietal gamma activity. In other words, participants who had a greater decrease in alpha or increase in gamma in these respective regions had smaller behavioral switch costs, which suggests that these oscillations are critical to supporting cognitive flexibility. In sum, we provide novel data linking switch effects and gamma oscillations, and employed a whole-brain approach to directly link switch-related oscillatory differences with switch-related performance differences.

A mental set generally refers to the human brain's tendency to persist with a familiar solution and stubbornly ignore alternatives. However, if a familiar solution is unable to solve a problem similar to a previous problem, does it continue to hinder alternative solutions, and if so, how and why? To answer these questions, a Chinese character decomposition task was adopted in this study. Participants were asked to perform a practice problem that could be solved by a familiar loose chunk decomposition (LCD) solution followed by a test problem that was similar to the practice problem but could only be solved by an unfamiliar tight chunk decomposition (TCD) solution or were asked to repeatedly perform 3-5 practice problems followed by a test problem; the former is the base-set condition, and the latter is the enhanced-set condition. The results showed that the test problem recruited more activation of the inferior frontal gyrus (IFG), middle occipital cortex (MOG), superior parietal lobule (SPL) and dorsal anterior cingulate cortex (dACC) than the practice problem in the latter operation and verification stage, but almost equal activation of the dACC occurred in the early exploration stage. This likely implied that people did not think that the familiar but currently invalid LCD solution could not be used to solve the test problem; thus, it continuously competed for attention with the unfamiliar TCD solution, which required more executive control to suppress. Moreover, compared with the base-set condition, the test problem in the enhanced-set condition recruited greater activations of the IFG, SPL and dACC in the latter verification stage but less activations of regions in the left IFG and MOG in the early exploration stage. These results revealed that people less actively explored and had to work harder to operate the unfamiliar TCD solution, particularly to resolve competition from the familiar but currently invalid LCD solution. In conclusion, people lost the ability to identify errors in the familiar but currently invalid solution, which in turn decreased the exploration efforts and increased the processing demands associated with alternative solutions in the form of attentional bias and competition. This finding broadly explains the dilemma of creative problem solving.

Cognitive flexibility is critical for humans living in complex societies with ever-growing multitasking demands. Yet the low-frequency neural dynamics of distinct task-specific and domain-general mechanisms sub-serving mental flexibility are still ill-defined. Here we estimated phase electroencephalogram synchronization by using inter-trial phase coherence (ITPC) at the source space while twenty six young participants were intermittently cued to switch or repeat their perceptual categorization rule of Gabor gratings varying in color and thickness (switch task). Therefore, the aim of this study was to examine whether a proactive control is associated with connectivity only in the frontoparietal theta network, or also involves distinct neural connectivity within the delta band, as distinct neural signatures while preparing to switch or repeat a task set, respectively. To this end, we focused the analysis on late-latencies (from 500 to 800 msec post-cue onset), since they are known to be associated with top-down cognitive control processes. We confirmed that proactive control during a task switch was associated with frontoparietal theta connectivity. But importantly, we also found a distinct role of delta band oscillatory synchronization in proactive control, engaging more posterior frontotemporal regions as opposed to frontoparietal theta connectivity. Additionally, we built a regression model by using the ITPC results in delta and theta bands as predictors, and the behavioral accuracy in the switch task as the criterion, obtaining significant results for both frequency bands. All these findings support the existence of distinct proactive cognitive control processes related to functionally distinct though highly complementary theta and delta frontoparietal and temporoparietal oscillatory networks at late-latency temporal scales.

Deactivation of the default mode network (DMN) is one of the most reliable observations from neuroimaging and has significant implications in development, aging, and various neuropsychiatric disorders. However, the neural mechanism underlying DMN deactivation remains elusive. As the coordination of regional neurochemical substrates and interregional neural interactions are both essential in support of brain functions, a quantitative description of how they impact DMN deactivation may provide new insights into the mechanism. Using an n-back working memory task fMRI and magnetic resonance spectroscopy, we probed the pairwise relationship between task-induced deactivation, interregional functional connectivity and regional excitation-inhibition balance (evaluated by glutamate/GABA ratio) in the posterior cingulate cortex/precuneus (PCC/PCu). Task-induced PCC/PCu deactivation correlated with its excitation-inhibition balance and interregional functional connectivity, where participants with lower glutamate/GABA ratio, stronger intra-DMN connections and stronger antagonistic DMN-SN (salience network)/ECN (executive control network) inter-network connections had greater PCC/PCu deactivation. Mediation analyses revealed that the DMN-SN functional interactions partially mediated the relationship between task-induced deactivation and the excitation-inhibition balance at the PCC/PCu. The triple-relationship discovered in the present study has the potential to bridge DMN-deactivation related findings from various neuroimaging modalities and may provide new insights into the neural mechanism of DMN deactivation. Moreover, this finding may have significant implications for neuropsychiatric disorders related to the DMN dysfunction and suggests an integrated application of pharmacological and neuromodulation-based strategies for rescuing DMN deactivation deficits.