Neural Systems Underlying the Implementation of Working Memory Removal Operations.

Recently, multi-voxel pattern analysis has verified that information can be removed from working memory (WM) via three distinct operations replacement, suppression, or clearing compared to information being maintained ( Kim et al., 2020). While univariate analyses and classifier importance maps in Kim et al. (2020) identified brain regions that contribute to these operations, they did not elucidate whether these regions represent the operations similarly or uniquely. Using Leiden-community-detection on a sample of 55 humans (17 male), we identified four brain networks, each of which has a unique configuration of multi-voxel activity patterns by which it represents these WM operations. The visual network (VN) shows similar multi-voxel patterns for maintain and replace, which are highly dissimilar from suppress and clear, suggesting this network differentiates whether an item is held in WM or not. The somatomotor network (SMN) shows a distinct multi-voxel pattern for clear relative to the other operations, indicating the uniqueness of this operation. The default mode network (DMN) has distinct patterns for suppress and clear, but these two operations are more similar to each other than to maintain and replace, a pattern intermediate to that of the VN and SMN. The frontoparietal control network (FPCN) displays distinct multi-voxel patterns for each of the four operations, suggesting that this network likely plays an important role in implementing these WM operations. These results indicate that the operations involved in removing information from WM can be performed in parallel by distinct brain networks, each of which has a particular configuration by which they represent these operations.

Suppressing the Maintenance of Information in Working Memory Alters Long-term Memory Traces.

The sensory recruitment hypothesis conceptualizes information in working memory as being activated representations of information in long-term memory. Accordingly, changes made to an item in working memory would be expected to influence its subsequent retention. Here, we tested the hypothesis that suppressing information from working memory, which can reduce short-term access to that information, may also alter its long-term neural representation. We obtained fMRI data (n = 25; 13 female / 12 male participants) while participants completed a working memory removal task with scene images as stimuli, followed by a final surprise recognition test of the examined items. We applied a multivariate pattern analysis to the data to quantify the engagement of suppression on each trial, to track the contents of working memory during suppression, and to assess representational changes afterward. Our analysis confirms previous reports that suppression of information in working memory involves focused attention to target and remove unwanted information. Furthermore, our findings provide new evidence that even a single dose of suppression of an item in working memory can (if engaged with sufficient strength) produce lasting changes in its neural representation, particularly weakening the unique, item-specific features, which leads to forgetting. Our study sheds light on the underlying mechanisms that contribute to the suppression of unwanted thoughts and highlights the dynamic interplay between working memory and long-term memory.

Composite Measures of Brain Activation Predict Individual Differences in Behavioral Stroop Interference.

The goal of the current study was to interrogate aspects of the cascade-of-control model [Banich, M. T. Executive function: The search for an integrated account. Current Directions in Psychological Science, 18, 89-94, 2009; Banich, M. T. The Stroop effect occurs at multiple points along a cascade of control: Evidence from cognitive neuroscience approaches. Frontiers in Psychology, 10, 2164, 2019], a neurocognitive model that posits how portions of pFC interact in a cascade-like manner to overcome interference from task-irrelevant information, and to test whether it could be used to predict individual differences in cognitive control outside the scanner. Participants (n = 62) completed two fMRI Word-Picture Stroop tasks, one containing emotional stimuli and one containing non-emotional stimuli, as well as a behavioral out-of-scanner Color-Word Stroop task at each of two time points. In a departure from the traditional approach of using a single task contrast to index neural activation across all ROIs, the current study utilized specific ROI by contrast pairings selected based on the specific level of control hypothesized by the cascade-of-control model to occur within that region. In addition, data across both tasks and both time points were combined to create composite measures of neural activation and of behavior. Consistent with the cascade-of-control model, individual differences in brain activation for specific contrasts within each of the three ROIs were associated with behavioral interference on the standard Color-Word Stroop task. Testing of alternative models revealed that these brain-behavior relationships were specific to the theoretically driven ROI by contrast pairings. Furthermore, such relationships were not observed across single-task and single-time point measures, but instead emerged from the composite measures. These findings provide evidence that brain activation observed across multiple regions of frontal cortex, each of which likely exerts cognitive control in a differential manner, is capable of predicting individual differences in behavioral performance.

Genetic and Environmental Variation in Continuous Phenotypes in the ABCD Study®.

Twin studies yield valuable insights into the sources of variation, covariation and causation in human traits. The ABCD Study® (abcdstudy.org) was designed to take advantage of four universities known for their twin research, neuroimaging, population-based sampling, and expertise in genetic epidemiology so that representative twin studies could be performed. In this paper we use the twin data to: (i) provide initial estimates of heritability for the wide range of phenotypes assessed in the ABCD Study using a consistent direct variance estimation approach, assuring that both data and methodology are sound; and (ii) provide an online resource for researchers that can serve as a reference point for future behavior genetic studies of this publicly available dataset. Data were analyzed from 772 pairs of twins aged 9-10 years at study inception, with zygosity determined using genotypic data, recruited and assessed at four twin hub sites. The online tool provides twin correlations and both standardized and unstandardized estimates of additive genetic, and environmental variation for 14,500 continuously distributed phenotypic features, including: structural and functional neuroimaging, neurocognition, personality, psychopathology, substance use propensity, physical, and environmental trait variables. The estimates were obtained using an unconstrained variance approach, so they can be incorporated directly into meta-analyses without upwardly biasing aggregate estimates. The results indicated broad consistency with prior literature where available and provided novel estimates for phenotypes without prior twin studies or those assessed at different ages. Effects of site, self-identified race/ethnicity, age and sex were statistically controlled. Results from genetic modeling of all 53,172 continuous variables, including 38,672 functional MRI variables, will be accessible via the user-friendly open-access web interface we have established, and will be updated as new data are released from the ABCD Study. This paper provides an overview of the initial results from the twin study embedded within the ABCD Study, an introduction to the primary research domains in the ABCD study and twin methodology, and an evaluation of the initial findings with a focus on data quality and suitability for future behavior genetic studies using the ABCD dataset. The broad introductory material is provided in recognition of the multidisciplinary appeal of the ABCD Study. While this paper focuses on univariate analyses, we emphasize the opportunities for multivariate, developmental and causal analyses, as well as those evaluating heterogeneity by key moderators such as sex, demographic factors and genetic background.

The Angular Gyrus as a Hub for Modulation of Language-related Cortex by Distinct Prefrontal Executive Control Regions.

It has become clear in recent years that reading, while relying on domain-specific language processing regions, also involves regions that implement executive processes more broadly. Such executive control is generally considered to be implemented by prefrontal regions, which exert control via connectivity that allows them to modulate processing in target brain regions. The present study examined whether three previously identified and distinct executive control regions in the pFC [Wang, K., Banich, M. T., Reineberg, A. E., Leopold, D. R., Willcutt, E. G., Cutting, L. E., et al. Left posterior prefrontal regions support domain-general executive processes needed for both reading and math. Journal of Neuropsychology, 14, 467-495, 2020] show similar patterns of functional connectivity (FC) during a reading comprehension task as compared with a symbol identification condition. Our FC results in a sample of adolescents (n = 120) suggest all three regions commonly show associations with activity in "classic" left hemisphere reading areas, including the angular and supramarginal gyri, yet each exhibits differential connectivity as well. In particular, precentral regions show differential FC to parietal portions of the dorsal language stream, the inferior frontal junction shows differential FC to middle temporal regions of the right hemisphere and other regions involved in semantic processing, and portions of the inferior frontal gyrus show differential FC to an extensive set of right hemisphere prefrontal regions. These results suggest that prefrontal control over language-related regions occurs in a coordinated yet discrete manner.

Context-specific activations are a hallmark of the neural basis of individual differences in general executive function.

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.

Neuroanatomical Correlates of Perceived Stress Controllability in Adolescents and Emerging Adults.

Stressful life events predict changes in brain structure and increases in psychopathology, but not everyone is equally affected by life stress. The learned helplessness theory posits that perceiving life stressors as uncontrollable leads to depression. Evidence supports this theory for youth, but the impact of perceived control diverges based on stressor type: perceived lack of control over dependent (self-generated) stressors is associated with greater depression symptoms when controlling for the frequency of stress exposure, but perceived control over independent (non-self-generated) stressors is not. However, it is unknown how perceived control over these stressor types is associated with brain structure. We tested whether perceived lack of control over dependent and independent life stressors, controlling for stressor exposure, is associated with gray matter (GM) in a priori regions of interest (ROIs; mPFC, hippocampus, amygdala) and across the cortex in a sample of 108 adolescents and emerging adults ages 14-22. There were no associations across the full sample between perceived control over either stressor type and GM in the ROIs. However, less perceived control over dependent stressors was associated with greater amygdala gray matter volume in female youth and greater medial prefrontal cortex thickness in male youth. Furthermore, whole-cortex analyses revealed less perceived control over dependent stressors was associated with greater GM thickness in cortical regions involved in cognitive and emotional regulation. Thus, appraisals of control have distinct associations with brain morphology while controlling for stressor frequency, highlighting the importance of differentiating between these aspects of the stress experience in future research.

Identifying brain regions supporting amygdalar functionality: Application of a novel graph theory technique.

Effective amygdalar functionality depends on the concerted activity of a complex network of regions. Thus, the role of the amygdala cannot be fully understood without identifying the set of brain structures that allow the processes performed by the amygdala to emerge. However, this identification has yet to occur, hampering our ability to understand both normative and pathological processes that rely on the amygdala. We developed and applied novel graph theory methods to diffusion-based anatomical networks in a large sample (n = 1,052, 54.28% female, mean age=28.75) to identify nodes that critically support amygdalar interactions with the larger brain network. We examined three graph properties, each indexing a different emergent aspect of amygdalar network communication: current-flow betweenness centrality (amygdalar influence on information flowing between other pairs of nodes), node communicability (clarity of communication between the amygdala and other nodes), and subgraph centrality (amygdalar influence over local network processing). Findings demonstrate that each of these aspects of amygdalar communication is associated with separable sets of regions and, in some cases, these sets map onto previously identified sub-circuits. For example, betweenness and communicability were each associated with different sub-circuits that have been identified in previous work as supporting distinct aspects of memory-guided behavior. Other regions identified span basic (e.g., visual cortex) to higher-order (e.g., insula) sensory processing and executive functions (e.g., dorsolateral prefrontal cortex). Present findings expand our current understanding of amygdalar function by showing that there is no single 'amygdala network', but rather multiple networks, each supporting different modes of amygdalar interaction with the larger brain network. Additionally, our novel method allowed for the identification of how such regions support the amygdala, which has not been previously explored.

Heritability of brain resilience to perturbation in humans.

Resilience is the capacity of complex systems to persist in the face of external perturbations and retain their functional properties and performance. In the present study, we investigated how individual variations in brain resilience, which might influence response to stress, aging and disease, are influenced by genetics and/or the environment, with potential implications for the implementation of resilience-boosting interventions. Resilience estimates were derived from in silico lesioning of either brain regions or functional connections constituting the connectome of healthy individuals belonging to two different large and unique datasets of twins, specifically: 463 individual twins from the Human Connectome Project and 453 individual twins from the Colorado Longitudinal Twin Study. As has been reported previously, moderate heritability was found for several topological indexes of brain efficiency and modularity. Importantly, evidence of heritability was found for resilience measures based on removal of brain connections rather than specific single regions, suggesting that genetic influences on resilience are preferentially directed toward region-to-region communication rather than local brain activity. Specifically, the strongest genetic influence was observed for moderately weak, long-range connections between a specific subset of functional brain networks: the Default Mode, Visual and Sensorimotor networks. These findings may help identify a link between brain resilience and network-level alterations observed in neurological and psychiatric diseases, as well as inform future studies investigating brain shielding interventions against physiological and pathological perturbations.

Genetic and Environmental Influence on the Human Functional Connectome.

Detailed mapping of genetic and environmental influences on the functional connectome is a crucial step toward developing intermediate phenotypes between genes and clinical diagnoses or cognitive abilities. We analyzed resting-state functional magnetic resonance imaging data from two adult twin samples (Nos = 446 and 371) to quantify genetic and environmental influence on all pairwise functional connections between 264 brain regions (~35 000 functional connections). Nonshared environmental influence was high across the whole connectome. Approximately 14-22% of connections had nominally significant genetic influence in each sample, 4.6% were significant in both samples, and 1-2% had heritability estimates greater than 30%. Evidence of shared environmental influence was weak. Genetic influences on connections were distinct from genetic influences on a global summary measure of the connectome, network-based estimates of connectivity, and movement during the resting-state scan, as revealed by a novel connectome-wide bivariate genetic modeling procedure. The brain's genetic organization is diverse and not as one would expect based solely on structure evident in nongenetically informative data or lower resolution data. As follow-up, we make novel classifications of functional connections and examine highly localized connections with particularly strong genetic influence. This high-resolution genetic taxonomy of brain connectivity will be useful in understanding genetic influences on brain disorders.

Structural Brain Architectures Match Intrinsic Functional Networks and Vary across Domains: A Study from 15 000+ Individuals.

Brain structural networks have been shown to consistently organize in functionally meaningful architectures covering the entire brain. However, to what extent brain structural architectures match the intrinsic functional networks in different functional domains remains under explored. In this study, based on independent component analysis, we revealed 45 pairs of structural-functional (S-F) component maps, distributing across nine functional domains, in both a discovery cohort (n = 6005) and a replication cohort (UK Biobank, n = 9214), providing a well-match multimodal spatial map template for public use. Further network module analysis suggested that unimodal cortical areas (e.g., somatomotor and visual networks) indicate higher S-F coherence, while heteromodal association cortices, especially the frontoparietal network (FPN), exhibit more S-F divergence. Collectively, these results suggest that the expanding and maturing brain association cortex demonstrates a higher degree of changes compared with unimodal cortex, which may lead to higher interindividual variability and lower S-F coherence.

Children's Knowledge of Cannabis and Other Substances in States with Different Cannabis Use Regulations.

Background: Public acceptance of cannabis continues to increase across the US, yet there has been little research on how cannabis legalization affects young children. The present study compared knowledge of cannabis and other substances among children living in states with different cannabis laws and examined whether the association between such substance knowledge and externalizing behavior varies by state cannabis regulations. Methods: Participants were from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) at the baseline assessment (N = 11,875, ages 9-11, collected from 2016 to 2018). Chi-square difference tests were used to compare nested models testing group differences in knowledge of substances and the association between externalizing disorder/behavior and substance knowledge as a function of state legality of cannabis use (recreational, medical, low THC/CBD, none). Results: Children living in states with more permissive cannabis laws had a greater knowledge of cannabis and reported more alcohol experimentation. In contrast, knowledge regarding alcohol, tobacco, and other illicit drugs was not greater in children from states with more permissive cannabis laws. Externalizing disorder/behavior was not significantly associated with cannabis knowledge in any group and not significantly different across groups. The association between externalizing disorder/behavior and illicit drug knowledge was significant only in states with the recreational and medical use laws but did not differ significantly across groups. Conclusion: Children living in environments with more permissive cannabis regulations have greater knowledge of cannabis, but not other substances, and report more experimentation with alcohol.

Striatal-frontal network activation during voluntary task selection under conditions of monetary reward.

During voluntary task selection, a number of internal and external biases may guide such a choice. However, it is not well understood how reward influences task selection when multiple options are possible. To address this issue, we examined brain activation in a voluntary task-switching paradigm while participants underwent fMRI (n = 19). To reinforce the overall goal to choose the tasks randomly, participants were told of a large bonus that they would receive at the end of the experiment for making random task choices. We also examined how occasional, random rewards influenced both task performance and brain activation. We hypothesized that these transient rewards would increase the value of the just-performed task, and therefore bias participants to choose to repeat the same task on the subsequent trial. Contrary to expectations, transient reward had no consistent behavioral effect on subsequent task choice. Nevertheless, the receipt of such rewards did influence activation in brain regions associated with reward processing as well as those associated with goal-directed control. In addition, reward on a prior trial was found to influence activation during task choice on a subsequent trial, with greater activation in a number of executive function regions compared with no-reward trials. We posit that both the random presentation of transient rewards and the overall task bonus for random task choices together reinforced the goal to choose the tasks randomly, which in turn influenced activation in both reward-related regions and those regions involved in abstract goal processing.

Correction to: Striatal-frontal network activation during voluntary task selection under conditions of monetary reward.

Conflict of interest statement: Although co-author Marie T. Banich is the Editor-in-Chief of Cognitive, Affective, and Behavioral Neuroscience, Stan Floresco served as the action editor for this manuscript.

Large-scale Meta-analysis Suggests Low Regional Modularity in Lateral Frontal Cortex.

Extensive fMRI study of human lateral frontal cortex (LFC) has yet to yield a consensus mapping between discrete anatomy and psychological states, partly due to the difficulty of inferring mental states from brain activity. Despite this, there have been few large-scale efforts to map the full range of psychological states across the entirety of LFC. Here, we used a data-driven approach to generate a comprehensive functional-anatomical mapping of LFC from 11 406 neuroimaging studies. We identified putatively separable LFC regions on the basis of whole-brain co-activation, revealing 14 clusters organized into 3 whole-brain networks. Next, we generated functional preference profiles by using multivariate classification to identify the psychological states that best predicted activity within each cluster. We observed large functional differences between networks, suggesting brain networks support distinct modes of processing. Within each network, however, we observed relatively low functional specificity, suggesting discrete psychological states are not strongly localized to individual regions; instead, our results are consistent with the view that individual LFC regions work as part of distributed networks to give rise to flexible behavior. Collectively, our results provide a comprehensive synthesis of a diverse neuroimaging literature using relatively unbiased data-driven methods.

Association Between Initial Age of Exposure to Childhood Abuse and Cognitive Control: Preliminary Evidence.

Cognitive control, which relies on the protracted development of frontal-parietal regions into adolescence, is a brain process that may be particularly vulnerable to the impact of childhood abuse. In this study, we used functional magnetic resonance imaging (fMRI) to examine associations between the age of onset of childhood abuse and alterations to the neural mechanisms supporting cognitive control in early adulthood, which have not been previously examined. During fMRI scanning, participants completed hybrid block/event-related versions of a classic color-word Stroop task as well as emotional Stroop tasks (threat and positive words). Participants were young adult women (N = 15; age range: 23-30 years) who had a history of childhood physical or sexual abuse that began prior to 13 years of age. Results indicated that earlier age of onset of childhood abuse was robustly associated with increased transient (i.e., event-related) recruitment of medial cognitive control regions in the classic color-word paradigm as well as with less suppression of medial frontal regions that are part of the default mode network, ßs = -.16 to -.87. In comparison, increased activation in dorsolateral prefrontal regions was associated with earlier age of abuse onset under conditions of sustained (i.e., blocked) cognitive control in the emotional Stroop task for blocks of positive distracting words versus fixation, ßs = -.50 to -.60. These results provide preliminary evidence that earlier age of exposure to childhood abuse impacts the functional activation of neural systems involved in cognitive control in adulthood.

Flexible brain network reconfiguration supporting inhibitory control.

The ability to inhibit distracting stimuli from interfering with goal-directed behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory tools to functional magnetic resonance imaging data collected while a large sample of adults (n = 101) performed a color-word Stroop task. Higher demand for inhibitory control was associated with restructuring of the global network into a configuration that was more optimized for specialized processing (functional segregation), more efficient at communicating the output of such processing across the network (functional integration), and more resilient to potential interruption (resilience). In addition, there were regional changes with right inferior frontal sulcus and right anterior insula occupying more central positions as network hubs, and dorsal anterior cingulate cortex becoming more tightly coupled with its regional subnetwork. Given the crucial role of inhibitory control in goal-directed behavior, present findings identifying functional network organization supporting inhibitory control have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties.

Large-Scale Meta-Analysis of Human Medial Frontal Cortex Reveals Tripartite Functional Organization.

UNLABELLED: The functional organization of human medial frontal cortex (MFC) is a subject of intense study. Using fMRI, the MFC has been associated with diverse psychological processes, including motor function, cognitive control, affect, and social cognition. However, there have been few large-scale efforts to comprehensively map specific psychological functions to subregions of medial frontal anatomy. Here we applied a meta-analytic data-driven approach to nearly 10,000 fMRI studies to identify putatively separable regions of MFC and determine which psychological states preferentially recruit their activation. We identified regions at several spatial scales on the basis of meta-analytic coactivation, revealing three broad functional zones along a rostrocaudal axis composed of 2-4 smaller subregions each. Multivariate classification analyses aimed at identifying the psychological functions most strongly predictive of activity in each region revealed a tripartite division within MFC, with each zone displaying a relatively distinct functional signature. The posterior zone was associated preferentially with motor function, the middle zone with cognitive control, pain, and affect, and the anterior with reward, social processing, and episodic memory. Within each zone, the more fine-grained subregions showed distinct, but subtler, variations in psychological function. These results provide hypotheses about the functional organization of medial prefrontal cortex that can be tested explicitly in future studies. SIGNIFICANCE STATEMENT: Activation of medial frontal cortex in fMRI studies is associated with a wide range of psychological states ranging from cognitive control to pain. However, this high rate of activation makes it challenging to determine how these various processes are topologically organized across medial frontal anatomy. We conducted a meta-analysis across nearly 10,000 studies to comprehensively map psychological states to discrete subregions in medial frontal cortex using relatively unbiased data-driven methods. This approach revealed three distinct zones that differed substantially in function, each of which were further subdivided into 2-4 smaller subregions that showed additional functional variation. Each individual region was recruited by multiple psychological states, suggesting subregions of medial frontal cortex are functionally heterogeneous.

Functional connectivity at rest is sensitive to individual differences in executive function: A network analysis.

Graph theory provides a means to understand the nature of network characteristics and connectivity between specific brain regions. Here it was used to investigate whether the network characteristics of the brain at rest are associated with three dimensions thought to underlie individual differences in executive function (EF)-common EF, shifting-specific EF, and updating-specific EF (Miyake and Friedman [2012]). To do so, both an a priori analysis focused mainly on select frontoparietal regions previously linked to individual differences in EF as well as a whole-brain analysis were performed. The findings indicated that individual differences in each of the three dimensions of EF were associated with specific patterns of resting-state connectivity both in a priori and other brain regions. More specifically, higher common EF was associated with greater integrative (i.e., more hublike) connectivity of cuneus and supplementary motor area but less integrative function of lateral frontal nodes and left temporal lobe nodes. Higher shifting-specific EF was associated with more hublike motor-related nodes and cingulo-opercular nodes. Higher updating-specific EF was associated with less hublike lateral and medial frontoparietal nodes. In general, these results suggested that higher ability in each of these three dimensions of EF was not solely characterized by the connectivity characteristics of frontoparietal regions. The pattern was complicated in that higher EF was associated with the connectivity profile of nodes outside of the traditional frontoparietal network, as well as with less hublike or centrality characteristics of some nodes within the frontoparietal network. Hum Brain Mapp 37:2959-2975, 2016. © 2016 Wiley Periodicals, Inc.