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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.

Previous research has shown beneficial cognitive changes following exercise training in older adults. However, the work on the potential moderating effects of Apoliprotein E (APOE) ε4 carrier status has been mixed, and the role of exercise intensity remains largely unexplored. The present study sought to examine the influence of APOE ε4 status and exercise intensity on measures of cognitive performance in a group of older adults. Cross-sectional comparisons between a group of younger inactive adults (n=44, age=28.86±0.473 SD, 60.5% female) and a group of older inactive adults (n=142, age=67.8±5.4, 62.7% female) were made on baseline measurements of APOE ε4 status, VO(2)peak, and cognitive performance in the domain of executive functioning. The older adults also participated in a randomized controlled exercise trial, exercising three times per week for 16-weeks in either a low-intensity continuous training (LICT) group or a moderate-intensity continuous training plus interval training (MICT+IT) group at the Center for Health and Neuroscience, Genes, and Environment (CUChange) Exercise Laboratory. Follow-up measurements of VO(2)peak and cognitive performance were collected on the older adults after the exercise intervention. Cross-sectional comparisons between the older and younger adults demonstrated significant impairments among older adults in Stroop effect on error and time, Category Switch mixing effects, and Keep Track task. This impairment was not moderated by APOE ε4 carrier status. Improvements from pre- to post-exercise intervention were observed in both exercise groups in Stroop effect on error ([F(1, 256) = 9.381, p < 0.01, η(2)= 0.031] ) and Category Switch switching effect reaction time ([F(1, 274) = 4.442, p < 0.05, η(2)=0.020]), with no difference between exercise groups. The moderating effects of APOE ε4 carrier status were mixed. Exercise did not improve the Stroop effect on error among ε4 carriers assigned to MICT+IT when improvements were seen in all other groups. Further research is needed to examine the mechanisms of action by which exercise impacts cognitive task performance, and possible moderators such as genetic variability and exercise intensity.

The ability to enact cognitive control under changing environmental demands is commonly studied using set-shifting paradigms. While the control processes required for task set reconfiguration (switch costs) have been studied extensively, less research has focused on the control required during task repetition in blocks containing multiple tasks as compared to those containing a single task (mixing costs). We investigated how individual differences in mixing costs related to other executive functions (EFs) in a large sample (N = 749) of young adults. Individual differences in mixing costs across three different set-shifting paradigms loaded significantly onto a mixing cost latent variable. This Mixing Cost factor moderately correlated with a Common EF factor capturing variance shared across nine EF tasks designed to tap response inhibition, working memory updating, and mental set-shifting. It did not correlate with Updating-Specific and Shifting-Specific factors. Results indicate that the additional cognitive control required during mixed-task block repeat trials relies on general executive processes, as well as unique abilities distinct from both set-shifting and working memory updating. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

One major question in the cognitive neuroscience of cognitive control is whether prefrontal regions contribute to control by upregulating the processing of task-relevant material or by downregulating the processing of task-irrelevant material. Here we take a unique approach to addressing this question by using multi-voxel pattern analysis, which allowed us to determine the degree to which each of the task-relevant and task-irrelevant dimensions of a stimulus are being processed in posterior cortex on a trial-by-trial basis. In our study, adolescent participants performed an emotion word – emotional face Stroop task requiring them to determine the emotional valence (positive, negative) of a task-relevant word in the context of a task-irrelevant emotional face. Using mediation models, we determined whether activation of a major cognitive control region, the dorsolateral prefrontal cortex (DLPFC), influences reaction time on a trial-by-trial basis directly or if it does so indirectly by modulating processing of the task-relevant and/or task-irrelevant information in posterior brain regions. To examine the specificity of the effects observed for the DLPFC, similar analyses were performed for the amygdala, a brain region involved in processing of the salient task-irrelevant emotional information. For both congruent and incongruent trials, increased DLPFC activity on a given trial was associated with reduced perceptual processing of the task-irrelevant face, consistent with the idea that top-down cognitive control can modulate processing of task-irrelevant information. No effect of DLPFC activity was observed on processing of the task-relevant word. However, increased processing of the task-relevant word was associated with longer RT on congruent trials but not incongruent trials, which may reflect a need for greater processing of the task-relevant word to overcome any influence of the pre-potent task-irrelevant face. In a more exploratory aspect of our investigation, multi-level moderated mediation models were used to examine the influence of individual differences on the observed brain-behavior relationships. For congruent trials, the influence of task-irrelevant face processing on RT was decreased in individuals with higher self-reported Executive Control and increased in those with higher levels of self-reported Negative Affect. These results suggest that cognitive control regions in prefrontal cortex during adolescence can suppress the processing of task-irrelevant information in sensory cortex to influence performance (RT). The processing of task-relevant information may also influence performance, but such processing did not reveal evidence of being modulated by cognitive control regions. Moreover, these effects are sensitive to individual differences in the self-reported ability to exert cognitive and affective control. As such, we provide insights into the more precise mechanisms by which cognitive control influences task performance on a trial-by-trial basis during adolescence.

During voluntary task selection there are a number of internal and external biases that 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 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 as compared to 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.

Introduction Performance in the executive function (EF) domain has been linked to symptoms and functional outcomes in psychosis. Studies have found that UHR populations have difficulty with verbal fluency, which involves multiple facets of EF. Two potentially implicated EF facets were examined to explore whether these could be dissociated in UHR populations: selection among alternatives (measured by selection costs) and retrieval from semantic memory retrieval (measured by retrieval costs). Methods A total of 45 UHR individuals and 46 healthy controls (HVs) were assessed with a verb generation task. Differences in selection cost (RT difference between high and low selection demand conditions) and retrieval cost (RT difference between high and low retrieval demand conditions) were examined and participants were also assessed for clinical symptoms. Results The UHR group showed greater selection costs relative to HVs, F (1, 91) = 4.39, p = 0.039. However, there were no group differences on retrieval cost, F (1, 91) = 0.63, p = 0.43. A positive association (r = 0.41) was found between disorganized and negative symptoms and selection costs (but not retrieval costs) in the UHR group. There was no significant association between selection costs and positive symptoms. Discussion Increased selection costs may reflect impaired performance in the neural inhibition domain of EF in the UHR population, potentially underlying a mechanistically distinct EF subdomain that affects the group's ability to efficiently select between competing options. Findings suggest that UHR individuals may exhibit impairment in selecting among alternatives, but not in retrieval from semantic memory.

Executive functions (EF) are a set of higher-order cognitive abilities that enable goal-directed behavior by controlling lower-level operations. In the brain, those functions have been traditionally associated with activity in the Frontoparietal Network, but recent neuroimaging studies have challenged this view in favor of more widespread cortical involvement. In the present study, we aimed to explore whether the network that serves as critical hubs at rest, which we term network reliance, differentiate individuals as a function of their level of EF. Furthermore, we investigated whether such differences are driven by genetic as compared to environmental factors. For this purpose, resting-state functional magnetic resonance imaging data and the behavioral testing of 453 twins from the Colorado Longitudinal Twins Study were analyzed. Separate indices of EF performance were obtained according to a bifactor unity/diversity model, distinguishing between three independent components representing: Common EF, Shifting-specific and Updating-specific abilities. Through an approach of step-wise in silico network lesioning of the individual functional connectome, we show that interindividual differences in EF are associated with different dependencies on neural networks at rest. Furthermore, these patterns show evidence of mild heritability. Such findings add knowledge to the understanding of brain states at rest and their connection with human behavior, and how they might be shaped by genetic influences. Supplementary Information The online version contains supplementary material available at 10.1007/s00429-021-02388-4.

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.

This chapter shows that the processing power of the hemispheres working together can surpass that of the separate capabilities of each hemisphere added together. The major quest in the field of cognitive neuroscience is to understand how the neural wiring of the brain constrains and shapes the information processing capacity of the human mind. One of the primary features of the neurological organization of the human brain is lateral asymmetry. One could view interhemispheric processing as merely a simple shuttling mechanism allowing for passive transport of information between the hemispheres. The chapter argues that interhemispheric interaction is a means whereby the overall processing capacity of the brain is enhanced. The fact that the distribution model is a better description of performance than the concentration model is important, because it suggests that, indeed, interhemispheric interaction allows processing to be dispersed over as much neural space as possible.

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, βs = -.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, βs = -.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.

Importance Incidental findings (IFs) are unexpected abnormalities discovered during imaging and can range from normal anatomic variants to findings requiring urgent medical intervention. In the case of brain magnetic resonance imaging (MRI), reliable data about the prevalence and significance of IFs in the general population are limited, making it difficult to anticipate, communicate, and manage these findings. Objectives To determine the overall prevalence of IFs in brain MRI in the nonclinical pediatric population as well as the rates of specific findings and findings for which clinical referral is recommended. Design, setting, and participants This cohort study was based on the April 2019 release of baseline data from 11 810 children aged 9 to 10 years who were enrolled and completed baseline neuroimaging in the Adolescent Brain Cognitive Development (ABCD) study, the largest US population-based longitudinal observational study of brain development and child health, between September 1, 2016, and November 15, 2018. Participants were enrolled at 21 sites across the US designed to mirror the demographic characteristics of the US population. Baseline structural MRIs were centrally reviewed for IFs by board-certified neuroradiologists and findings were described and categorized (category 1, no abnormal findings; 2, no referral recommended; 3; consider referral; and 4, consider immediate referral). Children were enrolled through a broad school-based recruitment process in which all children of eligible age at selected schools were invited to participate. Exclusion criteria were severe sensory, intellectual, medical, or neurologic disorders that would preclude or interfere with study participation. During the enrollment process, demographic data were monitored to ensure that the study met targets for sex, socioeconomic, ethnic, and racial diversity. Data were analyzed from March 15, 2018, to November 20, 2020. Main outcomes and measures Percentage of children with IFs in each category and prevalence of specific IFs. Results A total of 11 679 children (52.1% boys, mean [SD] age, 9.9 [0.62] years) had interpretable baseline structural MRI results. Of these, 2464 participants (21.1%) had IFs, including 2013 children (17.2%) assigned to category 2, 431 (3.7%) assigned to category 3, and 20 (0.2%) assigned to category 4. Overall rates of IFs did not differ significantly between singleton and twin gestations or between monozygotic and dizygotic twins, but heritability analysis showed heritability for the presence or absence of IFs (h2 = 0.260; 95% CI, 0.135-0.387). Conclusions and relevance Incidental findings in brain MRI and findings with potential clinical significance are both common in the general pediatric population. By assessing IFs and concurrent developmental and health measures and following these findings over the longitudinal study course, the ABCD study has the potential to determine the significance of many common IFs.

Post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are two of the most common consequences of combat deployment. Estimates of comorbidity of PTSD and mTBI are as high as 42% in combat exposed Operation Enduring Freedom, Operation Iraqi Freedom and Operation New Dawn (OEF/OIF/OND) Veterans. Combat deployed Veterans with PTSD and/or mTBI exhibit deficits in classic executive function (EF) tasks. Similarly, the extant neuroimaging literature consistently indicates abnormalities of the ventromedial prefrontal cortex (vmPFC) and amygdala/hippocampal complex in these individuals. While studies examining deficits in classical EF constructs and aberrant neural circuitry have been widely replicated, it is surprising that little research examining reward processing and decision-making has been conducted in these individuals, specifically, because the vmPFC has long been implicated in underlying such processes. Therefore, the current study employed the modified Iowa Gambling Task (mIGT) and structural neuroimaging to assess whether behavioral measures related to reward processing and decision-making were compromised and related to cortical morphometric features of OEF/OIF/OND Veterans with PTSD, mTBI, or co-occurring PTSD/mTBI. Results indicated that gray matter morphometry in the lateral prefrontal cortex (lPFC) predicted performance on the mIGT among all three groups and was significantly reduced, as compared to the control group.

While Enkavi et al.’s (1) examination of the reliability of self-regulation dependent variables (DVs) from online assessments is an important addition to the field, their conclusion that “survey DVs are more appropriate for individual differences analyses [than behavioral tasks]” (p. 5476) is likely overstated. Existing research indicates that task-based constructs of self-regulation 1) are highly reliable at the latent variable level and 2) predict variance in real-world behavior that is 3) independent of variance predicted by questionnaires. Thus, both questionnaires and task-based measures are important to understand self-regulation and associated behavioral outcomes. First, the psychological constructs assessed by self-regulation questionnaires and behavioral tasks are not interchangeable. Enkavi et al.'s (1) finding of low associations … [↵][1]1To whom correspondence may be addressed. Email: Naomi.Friedman{at}colorado.edu. [1]: #xref-corresp-1-1

Alterations in neural systems underlying cognitive control are well-documented across individuals with various internalizing disorders. The current study examined how individual differences in underlying traits related to internalizing disorders influence brain activation, as assessed by fMRI, when cognitive control must be exerted to make a decision about the emotional valence (positive, negative) of a task-relevant word displayed concurrently with a task-irrelevant emotional face. Taking a bi-factor model approach, fifty-five middle-aged female participants were characterized on symptom level on a common internalizing latent factor representing shared symptoms across anxiety and depression, as well as on specific factors remaining after taking the common internalizing factor into account: low positive affect, anxious arousal, and anxious apprehension. Contrasting activation on trials requiring higher vs. lower control revealed that higher levels of the Common Internalizing factor are associated with less deactivation of regions of the default mode network. Higher levels of the Low Positive Affect-specific factor are associated with less differentiation in engagement of portions of the fronto-parietal control network, while higher levels of the Anxious Arousal-specific factor are associated with less of a differentiation in activation of the thalamus. No effects were observed for level of the Anxious Apprehension-specific factor. These results suggest that prior findings of alterations in default mode activity associated with depression may not be specific to depressive symptoms per se but may characterize internalizing symptoms more generally. In addition, they suggest that reduced engagement of cognitive control regions may be more associated with low positive affect than depressive symptoms more generally.

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.HighlightsAn overview of the MRI processing pipeline for the ABCD StudyA discussion on the challenges of large, multisite population studiesA methodological reference for users of publicly shared data from the ABCD Study

Brain regions in the default mode network (DMN) display greater functional connectivity at rest or during self-referential processing than during goal-directed tasks. The present study assessed resting-state connectivity as a function of anxious apprehension and anxious arousal, independent of depressive symptoms, in order to understand how these dimensions disrupt cognition. Whole-brain, seed-based analyses indicated differences between anxious apprehension and anxious arousal in DMN functional connectivity. Lower connectivity associated with higher anxious apprehension suggests decreased adaptive, inner-focused thought processes, whereas higher connectivity at higher levels of anxious arousal may reflect elevated monitoring of physiological responses to threat. These findings further the conceptualization of anxious apprehension and anxious arousal as distinct psychological dimensions with distinct neural instantiations.

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.

A recent shift in legal and social attitudes toward marijuana use has also spawned a surge of interest in understanding the effects of marijuana use on the brain. There is considerable evidence that an adolescent onset of marijuana use negatively impacts white matter coherence. On the other hand, a recent well-controlled study demonstrated no effects of marijuana use on the morphometry of subcortical or cortical structures when users and non-users were matched for alcohol use. Regardless, most studies have involved small, carefully selected samples, so the ability to generalize to larger populations is limited. In an attempt to address this issue, we examined the effects of marijuana use on white matter integrity and cortical and subcortical morphometry using data from the Human Connectome Project (HCP) consortium. The HCP data consists of ultra-high resolution neuroimaging data from a large community sample, including 466 adults reporting recreational marijuana use. Rather than just contrasting two groups of individuals who vary significantly in marijuana usage as typifies prior studies, we leveraged the large sample size provided by the HCP data to examine parametric effects of recreational marijuana use. Our results indicate that the earlier the age of onset of marijuana use, the lower was white matter coherence. Age of onset also also affected the shape of the accumbens, while the number of lifetime uses impacted the shape of the amygdala and hippocampus. Marijuana use had no effect on cortical volumes. These findings suggest subtle but significant effects of recreational marijuana use on brain structure., Highlights • Effects of marijuana use on brain morphology in 466 recreational users were investigated. • Age of first use impacted white matter integrity. • Age of first use and lifetime times used impacted shape of the hippocampus and accumbens • Marijuana use did not affect cortical volume.

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. Historical attempts to estimate the genetic etiology of the connectome have focused on large-scale brain networks - obscuring possible heterogeneity among or novel communities of small network subcomponents. In the current study, we analyze resting-state data from two, adult twin samples - 198 twins from the Colorado Longitudinal Twin Sample and 422 twins from the Human Connectome Project - to examine genetic and environmental influence on all pairwise functional connections between 264 brain regions (~35,000 functional connections). We find high non-shared environmental influence across the entire connectome, moderate heritability in roughly half of all connections, and weak-to-moderate shared environmental influences. The pattern of genetic influence across the connectome is related to a priori notions of functional brain networks but also highly heterogeneous as confirmed by a hierarchical clustering analysis of the genetic profile of all 264 regions. Additionally, we confirm genetic influences on connections are independent of genetic influences shared with a global summary measure of brain connectivity - an important validation analysis for future, high-dimensionality genetic neuroimaging studies. Together, our analyses reveal a novel genetic taxonomy of brain regions and have implications for studies employing multivariate signals for prediction purposes. Variation across the population in those neurobiological signals is influenced by genes and the environment in different spatial locations and to different degrees suggesting genetic risk factors may be limited to a subset of the connectome.

To better characterize the neural correlates of the full spectrum of reading ability, this fMRI study examined how variations in reading ability correlate with task-based brain activity during reading among a large community sample of adolescents (N = 234). In addition, complimentary approaches taking advantage of empirical as well as independent meta-analytic information were employed to isolate neural substrates of domain-general executive processes that are predictive of reading ability. Age-related differences in brain activity were also examined. Better reading was associated with increased activation in left anterior and inferior temporal regions and parts of orbitofrontal cortex, along with reduced activation in the thalamus and left frontal eye field (FEF). Converging evidence suggests that FEF activity corresponds to executive processes during reading. In contrast, activity in temporal regions is likely to reflect cognitive processes specific to reading. Older adolescents also demonstrated increased activation in an orbitofrontal region that overlaps with the aforementioned age-independent, reading-related regions, along with reduced activity in parietal and occipital regions. These results suggest that comparedto poor readers, proficient readers benefit from efficient reading-specific processes and require less executive effort, implemented via the FEF, during a reading comprehension task. Keywords: Executive Function, Reading, Frontal eye field, fMRI, Individual differences

Fatigue is one of the most debilitating symptoms of multiple sclerosis (MS), and the underlying mechanisms are poorly understood. When exposed to a physical or cognitive challenge, individuals with MS tend to exhibit greater declines in task performance (performance fatigability) and increased levels of self-reported fatigue (perceived fatigability), but these effects may be attenuated by greater intellectual capacity. The purpose of our study was to examine the influence of intelligence on fatigability in persons with MS. We hypothesized that greater intellectual capacity confers some protection against heightened levels of fatigue and fatigability associated with MS. Twelve adults with relapsing-remitting MS were compared with 12 control (CO) subjects who were matched for age, sex, and premorbid intellectual capacity. Performance fatigability was measured as the decline in maximal voluntary contraction (MVC) torque after 60 isometric contractions (10 s contraction at 25% MVC, 5 s rest) performed with the knee extensor muscles. Perceived fatigability was assessed with the modified fatigue impact scale (MFIS) questionnaire (trait fatigability) and the Borg rating of perceived exertion (RPE, state fatigability). Persons with MS reported greater MFIS scores (MS: 43 ± 14; CO: 11 ± 8, P ≤ 0.001). Initial MVC torque for the knee extensors did not differ between the groups (MS: 112 ± 38 N⋅m; CO: 107 ± 44 N⋅m) and the decline (performance fatigability) was similar for both groups (MS: -16 ± 19 N⋅m; CO: -13 ± 16 N⋅m). RPE increased during the fatiguing contraction for both groups (P < 0.001) but was significantly greater in magnitude (main effect for group, P = 0.03) and increased more for the MS group (group × time interaction, P = 0.05). Torque steadiness declined during the fatiguing contractions (main effect for time, P = 0.05) and was less steady for the MS group (main effect for group, P = 0.02). Performance and full-4 IQ was correlated with the decline in torque steadiness for the MS group (r = -0.63, P < 0.05; r = -0.64, P < 0.05). Intellectual capacity was not associated with fatigability in persons with MS but was associated with adjustments in muscle activation during the fatiguing contractions.

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9–10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data is a resource of unprecedented scale and depth for studying typical and atypical development. The aim of this manuscript is to describe the baseline neuroimaging processing and subject-level analysis methods used by ABCD. Processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI. This manuscript serves as a methodological reference for users of publicly shared neuroimaging data from the ABCD Study.

Inhibitory control/regulation is critical to adapt behavior in accordance with changing environmental circumstances. Dysfunctional inhibitory regulation is ubiquitous in neurological and psychiatric populations. These populations exhibit dysfunction across psychological domains, including memory/thought, emotion/affect, and motor response. Although investigation examining inhibitory regulation within a single domain has begun outlining the basic neural mechanisms supporting regulation, it is unknown how the neural mechanisms of these domains interact. To investigate the organization of inhibitory neural networks within and across domains, we used neuroimaging to outline the functional and anatomical pathways that comprise inhibitory neural networks regulating cognitive, emotional, and motor processes. Networks were defined at the group level using an array of analyses to indicate their intrinsic pathway structure, which was subsequently assessed to determine how the pathways explained individual differences in behavior. Results reveal how neural networks underlying inhibitory regulation are organized both within and across domains, and indicate overlapping/common neural elements.

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.

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.

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, βs = -.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, βs = -.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.

The ABCD study is recruiting and following the brain development and health of over 10,000 9–10 year olds through adolescence. The imaging component of the study was developed by the ABCD Data Analysis and Informatics Center (DAIC) and the ABCD Imaging Acquisition Workgroup. Imaging methods and assessments were selected, optimized and harmonized across all 21 sites to measure brain structure and function relevant to adolescent development and addiction. This article provides an overview of the imaging procedures of the ABCD study, the basis for their selection and preliminary quality assurance and results that provide evidence for the feasibility and age-appropriateness of procedures and generalizability of findings to the existent literature. Keywords: Addiction, Adolescence, Development, Impulsivity, Memory, Reward

The ABCD twin study will elucidate the genetic and environmental contributions to a wide range of mental and physical health outcomes in children, including substance use, brain and behavioral development, and their interrelationship. Comparisons within and between monozygotic and dizygotic twin pairs, further powered by multiple assessments, provide information about genetic and environmental contributions to developmental associations, and enable stronger tests of causal hypotheses, than do comparisons involving unrelated children. Thus a sub-study of 800 pairs of same-sex twins was embedded within the overall Adolescent Brain and Cognitive Development (ABCD) design. The ABCD Twin Hub comprises four leading centers for twin research in Minnesota, Colorado, Virginia, and Missouri. Each site is enrolling 200 twin pairs, as well as singletons. The twins are recruited from registries of all twin births in each State during 2006–2008. Singletons at each site are recruited following the same school-based procedures as the rest of the ABCD study. This paper describes the background and rationale for the ABCD twin study, the ascertainment of twin pairs and implementation strategy at each site, and the details of the proposed analytic strategies to quantify genetic and environmental influences and test hypotheses critical to the aims of the ABCD study. Keywords: Twins, Heritability, Environment, Substance use, Brain structure, Brain function

Behavioral approach, defined as behavior directed toward a reward or novel stimulus, when elevated, may increase one's vulnerability to substance use disorder. Behavioral approach has been associated with relatively greater left compared to right frontal activity; behavioral inhibition may be associated with relatively greater right compared to left frontal brain activity. We hypothesized that substance dependent individuals (SDI) would have higher behavioral approach than controls and greater prefrontal cortical activity during decision-making involving reward. We hypothesized that behavioral approach would correlate with left frontal activity during decision-making and that the correlation would be stronger in SDI than controls. 31 SDI and 21 controls completed the Behavioral Inhibition System/Behavioral Approach System (BIS/BAS) scales and performed a decision-making task during fMRI. Orbitofrontal (OFC) and dorsolateral prefrontal activity were correlated with BIS and BAS scores. Compared to controls, SDI had higher BAS Fun Seeking scores (p

Background: Advancing research on the etiology, prevention, and treatment of psychopathology requires the field to move beyond modular conceptualizations of neural dysfunction toward understanding disturbance in key brain networks. Although some studies of anxiety and depression have begun doing so, they typically suffer from several drawbacks, including: (1) a categorical approach ignoring transdiagnostic processes, (2) failure to account for substantial anxiety and depression comorbidity, (3) examination of networks at rest, which overlooks disruption manifesting only when networks are challenged. Accordingly, the present study examined relationships between transdiagnostic dimensions of anxiety/depression and patterns of functional connectivity while goal maintenance was challenged. Methods: Participants (n = 179, unselected community members and undergraduates selected to be high/low on anxiety/depression) performed a task in which goal maintenance was challenged (color-word Stroop) while fMRI data were collected. Analyses examined moderation by anxiety/depression of condition-dependent coupling between regions of dorsolateral prefrontal cortex (dlPFC) previously associated with approach and avoidance motivation and amygdala/orbitofrontal cortex (OFC). Results: Anxious arousal was positively associated with amygdala↔right dlPFC coupling. Depression was positively associated with OFC↔right dlPFC coupling and negatively associated with OFC↔left dlPFC coupling. Conclusions: Findings advance the field toward an integrative model of the neural instantiation of anxiety/depression by identifying specific, distinct dysfunctions associated with anxiety and depression in networks important for maintaining approach and avoidance goals. Specifically, findings shed light on potential neural mechanisms involved in attentional biases in anxiety and valuation biases in depression and underscore the importance of examining transdiagnostic dimensions of anxiety/ depression while networks are challenged. Depression and Anxiety 31:805–813, 2014. C � 2014 Wiley Periodicals, Inc.

Although the relationship between structural differences within the prefrontal cortex (PFC) and executive function (EF) has been widely explored in cognitively impaired populations, little is known about this relationship in healthy young adults. Using optimized voxel-based morphometry (VBM), surface-based morphometry (SBM), and fractional anisotropy (FA) we determined the association between regional PFC grey matter (GM) morphometry and white matter tract diffusivity with performance on tasks that tap different aspects of EF as drawn from Miyake et al.'s three-factor model of EF. Reductions in both GM volume (VBM) and cortical folding (SBM) in the ventromedial PFC (vmPFC), ventrolateral PFC (vlPFC), and dorsolateral PFC (dlPFC) predicted better common EF, shifting-specific, and updating-specific performance, respectively. Despite capturing different components of GM morphometry, voxel- and surface-based findings were highly related, exhibiting regionally overlapping relationships with EF. Increased white matter FA in fiber tracts that connect the vmPFC and vlPFC with posterior regions of the brain also predicted better common EF and shifting-specific performance, respectively. These results suggest that the neural mechanisms supporting distinct aspects of EF may differentially rely on distinct regions of the PFC, and at least in healthy young adults, are influenced by regional morphometry of the PFC and the FA of major white matter tracts that connect the PFC with posterior cortical and subcortical regions.

a b s t r a c t Background: Adolescents with conduct disorder (CD) and substance use disorders (SUD) experience dif- ficulty evaluating and regulating their behavior in anticipation of future consequences. Given the role of the brain's default mode network (DMN) in self-reflection and future thought, this study investigates whether DMN is altered in adolescents with CD and SUD, relative to controls. Methods: Twenty adolescent males with CD and SUD and 20 male controls of similar ages underwent functional magnetic resonance imaging as they completed a risk-taking decision task. We used indepen- dent component analysis as a data-driven approach to identify the DMN spatial component in individual subjects. DMN activity was then compared between groups. Results: Compared to controls, patients showed reduced activity in superior, medial and middle frontal gyrus (Brodmann area (BA) 10), retrosplenial cortex (BA 30) and lingual gyrus (BA 18), and bilateral middle temporal gryus (BA 21/22) - DMN regions thought to support self-referential evaluation, memory, foresight, and perspective taking. Furthermore, this pattern of reduced activity in patients remained robust after adjusting for the effects of depression and attention-deficit hyperactivity disorder (ADHD). Conversely, when not adjusting for effects of depression and ADHD, patients demonstrated greater DMN activity than controls solely in the cuneus (BA 19). Conclusions: Collectively, these results suggest that comorbid CD and SUD in adolescents is characterized by atypical activity in brain regions thought to play an important role in introspective processing. These functional imbalances in brain networks may provide further insight into the neural underpinnings of conduct and substance use disorders.

A significant portion of previously deployed combat Veterans from Operation Enduring Freedom and Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) are affected by comorbid posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI). Despite this fact, neuroimaging studies investigating the neural correlates of cognitive dysfunction within this population are almost nonexistent, with the exception of research examining the neural correlates of diagnostic PTSD or TBI. The current study used both voxel-based and surface-based morphometry to determine whether comorbid PTSD/mTBI is characterized by altered brain structure in the same regions as observed in singular diagnostic PTSD or TBI. Furthermore, we assessed whether alterations in brain structures in these regions were associated with behavioral measures related to inhibitory control, as assessed by the Go/No-go task, self-reports of impulsivity, and/or PTSD or mTBI symptoms. Results indicate volumetric reductions in the bilateral anterior amygdala in our comorbid PTSD/mTBI sample as compared to a control sample of OEF/OIF Veterans with no history of mTBI and/or PTSD. Moreover, increased volume reduction in the amygdala predicted poorer inhibitory control as measured by performance on the Go/No-go task, increased self-reported impulsivity, and greater symptoms associated with PTSD. These findings suggest that alterations in brain anatomy in OEF/OIF/OND Veterans with comorbid PTSD/mTBI are associated with both cognitive deficits and trauma symptoms related to PTSD.

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.

Individuals with drug addictions report increased willingness to approach rewards. Approach behaviors are thought to involve executive control processes and are more strongly represented in the left compared to right prefrontal cortex. A direct link between approach tendencies and left hemisphere activity has not been shown in the resting brain. We hypothesized that compared to controls, substance dependent individuals (SDI) would have greater left hemisphere activity in the left executive control network (ECN) at rest.Twenty-five SDI and 25 controls completed a Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) questionnaire and underwent a resting-state fMRI scan. Group independent component analysis was performed. We used template matching to identify the left and right ECN separately and compared the corresponding components across groups. Across group, BAS scores were correlated with signal fluctuations in the left ECN and BIS scores with right ECN.BAS scores were higher in SDI compared to controls (p.003) and correlated with signal fluctuation in the left ECN. SDI showed significantly more activity than controls in the left prefrontal cortex of the left ECN. Conversely, SDI showed less activity than controls in the right prefrontal cortex of the right ECN.Results from this study suggest that approach tendencies are related to the left ECN, even during rest. Higher resting-state signal in the left ECN may play a role in heightened approach tendencies that contribute to drug-seeking behavior.

The goal of this study was to cast light on the existence of functional callosal channels for the interhemispheric transfer (IHT) of spatial and semantic information. To do so, we recorded event-related potentials in healthy humans while performing a primed odd-even discrimination task. Targets were visually presented numbers preceded by single-letter primes signaling the probable presentation of an odd or an even number. Primes and targets could appear either in the same or in different visual fields, thus requiring an IHT in the latter case. The P1 and N2 components were influenced by IHT of spatial information only, whereas the later N400 was influenced by IHT of both spatial and semantic information. This was not the case for the P3b, which was modulated by semantic validity only. These results provide novel evidence of the existence of a temporally separated interhemispheric exchange of spatial and semantic information.

This study used functional magnetic resonance imaging (fMRI) to examine the neural systems activated during an intertemporal choice task in a group of 14- to 19-year-old adolescents, as well as the relationship of such activation patterns to individual differences in the self-reported ability to engage in nonimmediate thinking (i.e., less impulsive and more future-oriented thoughts and action). With increasing age, there was greater differentiation between patterns of brain activity for immediate versus future choices across three distinct brain systems involved in intertemporal choice--those involved in exerting control over behavior, attributing affective value to choices, and imagining future outcomes. Furthermore, a greater propensity toward self-reported nonimmediate thinking was associated with decreased activity in the systems involved in cognitive control, possibly suggesting that individuals with greater self-reported nonimmediate thinking need to rely less on cognitive control regions during conditions of intertemporal choice. These results highlight the role that both developmental age and individual differences play in influencing neural systems involved in intertemporal choice. Implications for understanding the onset of substance abuse disorders during adolescence are discussed.

We sought to identify brain activation differences in conduct-problem youth with limited prosocial emotions (LPE) compared to conduct-problem youth without LPE and community adolescents, and to test associations between brain activation and severity of callous-unemotional traits. We utilized a novel task, which asks subjects to repeatedly decide whether to accept offers where they will benefit but a beneficent other will be harmed. Behavior on this task has been previously associated with levels of prosocial emotions and severity of callous-unemotional traits, and is related to empathic concern. During fMRI acquisition, 66 male adolescents (21 conduct-problem patients with LPE, 21 without, and 24 typically-developing controls) played this novel game. Within typically-developing controls, we identified a network engaged during decision involving bilateral insula, and inferior parietal and medial frontal cortices, among other regions. Group comparisons using non-parametric (distribution-free) permutation tests demonstrated LPE patients had lower activation estimates than typically-developing adolescents in right anterior insula. Additional significant group differences emerged with our a priori parametric cluster-wise inference threshold. These results suggest measurable functional brain activation differences in conduct-problem adolescents with LPE compared to typically-developing adolescents. Such differences may underscore differential treatment needs for conduct-problem males with and without LPE.

Some youths develop multiple substance use disorders early in adolescence and have severe, persistent courses. Such youths often exhibit impulsivity, risk-taking, and problems of inhibition. However, relatively little is known about the possible brain bases of these behavioral traits, especially among females. Methods We recruited right-handed female patients, 14–19 years of age, from a university-based treatment program for youths with substance use disorders and community controls similar for age, race and zip code of residence. We obtained 43 T1-weighted structural brain images (22 patients and 21 controls) to examine group differences in cortical thickness across the entire brain as well as six a priori regions-of-interest: 1) medial orbitofrontal cortex; 2) rostral anterior cingulate cortex; and 3) middle frontal cortex, in each hemisphere. Age and IQ were entered as nuisance factors for all analyses. Results A priori region-of-interest analyses yielded no significant differences. However, whole-brain group comparisons revealed that the left pregenual rostral anterior cingulate cortex extending into the left medial orbitofrontal region (355.84 mm2 in size), a subset of two of our a priori regions-of-interest, was significantly thinner in patients compared to controls (vertex-level threshold p = 0.005 and cluster-level family wise error corrected threshold p = 0.05). The whole-brain group differences did not survive after adjusting for depression or externalizing scores. Whole-brain within-patient analyses demonstrated a positive association between cortical thickness in the left precuneus and behavioral disinhibition scores (458.23 mm2 in size). Conclusions Adolescent females with substance use disorders have significant differences in brain cortical thickness in regions engaged by the default mode network and that have been associated with problems of emotional dysregulation, inhibition, and behavioral control in past studies.

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.