Brain connectivity and academic skills in English learners.

English learners (ELs) are a rapidly growing population in schools in the United States with limited experience and proficiency in English. To better understand the path for EL's academic success in school, it is important to understand how EL's brain systems are used for academic learning in English. We studied, in a cohort of Hispanic middle-schoolers (n = 45, 22F) with limited English proficiency and a wide range of reading and math abilities, brain network properties related to academic abilities. We applied a method for localizing brain regions of interest (ROIs) that are group-constrained, yet individually specific, to test how resting state functional connectivity between regions that are important for academic learning (reading, math, and cognitive control regions) are related to academic abilities. ROIs were selected from task localizers probing reading and math skills in the same participants. We found that connectivity across all ROIs, as well as connectivity of just the cognitive control ROIs, were positively related to measures of reading skills but not math skills. This work suggests that cognitive control brain systems have a central role for reading in ELs. Our results also indicate that an individualized approach for localizing brain function may clarify brain-behavior relationships.

Brain tissue iron neurophysiology and its relationship with the cognitive effects of dopaminergic modulation in children with and without ADHD.

Children with attention-deficit/hyperactivity disorder (ADHD) exhibit impairments in response inhibition. These impairments are ameliorated by modulating dopamine (DA) via the administration of rewards or stimulant medication like methylphenidate (MPH). It is currently unclear whether intrinsic DA availability impacts these effects of dopaminergic modulation on response inhibition. Thus, we estimated intrinsic DA availability using magnetic resonance-based assessments of basal ganglia and thalamic tissue iron in 36 medication-naïve children with ADHD and 29 typically developing (TD) children (8-12 y) who underwent fMRI scans and completed standard and rewarded go/no-go tasks. Children with ADHD additionally participated in a double-blind, randomized, placebo-controlled, crossover MPH challenge. Using linear regressions covarying for age and sex, we determined there were no group differences in brain tissue iron. We additionally found that higher putamen tissue iron was associated with worse response inhibition performance in all participants. Crucially, we observed that higher putamen and caudate tissue iron was associated with greater responsivity to MPH, as measured by improved task performance, in participants with ADHD. These results begin to clarify the role of subcortical brain tissue iron, a measure associated with intrinsic DA availability, in the cognitive effects of reward- and MPH-related dopaminergic modulation in children with ADHD and TD children.

Resting-state cortical hubs in youth organize into four categories.

During childhood, neural systems supporting high-level cognitive processes undergo periods of rapid growth and refinement, which rely on the successful coordination of activation across the brain. Some coordination occurs via cortical hubs-brain regions that coactivate with functional networks other than their own. Adult cortical hubs map into three distinct profiles, but less is known about hub categories during development, when critical improvement in cognition occurs. We identify four distinct hub categories in a large youth sample (n = 567, ages 8.5-17.2), each exhibiting more diverse connectivity profiles than adults. Youth hubs integrating control-sensory processing split into two distinct categories (visual control and auditory/motor control), whereas adult hubs unite under one. This split suggests a need for segregating sensory stimuli while functional networks are experiencing rapid development. Functional coactivation strength for youth control-processing hubs are associated with task performance, suggesting a specialized role in routing sensory information to and from the brain's control system.

Brain Engagement During a Cognitive Flexibility Task Relates to Academic Performance in English Learners.

English Learners (ELs), students from non-English-speaking backgrounds, are a fast-growing, understudied, group of students in the U.S. with unique learning challenges. Cognitive flexibility-the ability to switch between task demands with ease-may be an important factor in learning for ELs as they have to manage learning in their non-dominant language and access knowledge in multiple languages. We used functional MRI to measure cognitive flexibility brain activity in a group of Hispanic middle school ELs (N = 63) and related it to their academic skills. We found that brain engagement during the cognitive flexibility task was related to both out-of-scanner reading and math measures. These relationships were observed across the brain, including in cognitive control, attention, and default mode networks. This work suggests the real-world importance of cognitive flexibility for adolescent ELs, where individual differences in brain engagement were associated with educational outcomes.

Effect of methylphenidate on functional controllability: a preliminary study in medication-naïve children with ADHD.

Methylphenidate (MPH) is the recommended first-line treatment for attention-deficit/hyperactivity disorder (ADHD). While MPH's mechanism of action as a dopamine and noradrenaline transporter blocker is well known, how this translates to ADHD-related symptom mitigation is still unclear. As functional connectivity is reliably altered in ADHD, with recent literature indicating dysfunctional connectivity dynamics as well, one possible mechanism is through altering brain network dynamics. In a double-blind, placebo-controlled MPH crossover trial, 19 medication-naïve children with ADHD underwent two functional MRI scanning sessions (one on MPH and one on placebo) that included a resting state scan and two inhibitory control tasks; 27 typically developing (TD) children completed the same protocol without medication. Network control theory, which quantifies how brain activity reacts to system inputs based on underlying connectivity, was used to assess differences in average and modal functional controllability during rest and both tasks between TD children and children with ADHD (on and off MPH) and between children with ADHD on and off MPH. Children with ADHD on placebo exhibited higher average controllability and lower modal controllability of attention, reward, and somatomotor networks than TD children. Children with ADHD on MPH were statistically indistinguishable from TD children on almost all controllability metrics. These findings suggest that MPH may stabilize functional network dynamics in children with ADHD, both reducing reactivity of brain organization and making it easier to achieve brain states necessary for cognitively demanding tasks.

Error-signaling in the developing brain.

While learning from mistakes is a lifelong process, the rate at which an individual makes errors on any given task decreases through late adolescence. Previous fMRI adult work indicates that several control brain networks are reliably active when participants make errors across multiple tasks. Less is known about the consistency and localization of error processing in the child brain because previous research has used single tasks. The current analysis pooled data across three studies to examine error-related task activation (two tasks per study, three tasks in total) for a group of 232 children aged 8-17 years. We found that, consistent with the adult literature, the majority of applied cingulo-opercular brain regions, including medial superior frontal cortex, dorsal anterior cingulate, and bilateral anterior insula, showed consistent error processing engagement in children across multiple tasks. Error-related activity in many of these cingulo-opercular regions correlated with task performance. However, unlike in the adult literature, we found a lack of error-related activation across tasks in dorsolateral frontal areas, and we also did not find any task-consistent relations with age in these regions. Our findings suggest that the task-general error processing signal in the developing brain is fairly robust and similar to adults, with the exception of lateral frontal cortex.

Pediatric ADHD symptom burden relates to distinct neural activity across executive function domains.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent childhood disorder marked by inattention and/or hyperactivity symptoms. ADHD may also relate to impaired executive function (EF), but is often studied in a single EF task per sample. The current study addresses the question of unique vs. overlapping relations in brain activity across multiple EF tasks and ADHD symptom burden. Three in-scanner tasks drawn from distinct EF domains (cognitive flexibility, working memory, and inhibition) were collected from children with and without an ADHD diagnosis (N = 63). Whole-brain activity and 11 regions of interest were correlated with parent reports of inattention and hyperactivity symptoms. Across the three EF domains, brain activity related to ADHD symptom burden, but the direction and location of these associations differed across tasks. Overall, activity in sensory and default mode network regions related to ADHD, and these relations did not consistently overlap across EF domains. We observed both distinct and overlapping patterns for inattention and hyperactivity symptoms. By studying multiple EF tasks in the same sample, we identified a heterogenous neural profile related to attention symptom burden in children. Our results inform ADHD characterization and treatment and explain some of the variable brain results related to EF and ADHD reported in the literature.

Functional Connectivity Fingerprints at Rest Are Similar across Youths and Adults and Vary with Genetic Similarity.

Distinguishing individuals from brain connectivity, and studying the genetic influences on that identification across different ages, improves our basic understanding of functional brain network organization. We applied support vector machine classifiers to two datasets of twins (adult, pediatric) and two datasets of repeat-scan individuals (adult, pediatric). Classifiers were trained on resting state functional connectivity magnetic resonance imaging (rs-fcMRI) data and used to predict individuals and co-twin pairs from independent data. The classifiers successfully identified individuals from a previous scan with 100% accuracy, even when scans were separated by months. In twin samples, classifier accuracy decreased as genetic similarity decreased. Our results demonstrate that classification is stable within individuals, similar within families, and contains similar representations of functional connections over a few decades of life. Moreover, the degree to which these patterns of connections predict siblings' data varied by genetic relatedness, suggesting that genetic influences on rs-fcMRI connectivity are established early in life.

How Does Motivation Modulate the Operation of the Mentalizing Network in Person Evaluation?

The mentalizing network is theorized to play a central role in making sense of people (compared with nonsocial targets), but is its involvement affected when we make sense of people in a nondispassionate manner (e.g., favoritism toward others on the basis of group membership)? First, mixed findings and small samples have prevented strong conclusions about whether intergroup evaluation increases or decreases activation regions associated with the mentalizing network. Second, little is known about the psychological mechanism underlying mentalizing network activation shaped by ingroup versus outgroup evaluations. Psychological models suggest two hypotheses that can be challenging to disentangle with self-report: Ingroup trait evaluations may benefit from a priori expectations and/or preferential evidence accumulation. Therefore, the current study (n = 50) drew on a combination of drift diffusion modeling and fMRI to examine how group membership affects the engagement of the mentalizing network for trait evaluation and whether group-differentiated activation is associated with a priori expectations and/or preferential evidence accumulation. Outgroup trait evaluations engaged dorsomedial pFC activation, whereas ingroup trait evaluations engaged ventromedial pFC activation as well as other regions associated with mentalizing such as precuneus, posterior cingulate cortex, and right TPJ. Furthermore, the ventromedial pFC and posterior cingulate cortex activation was associated with differential expectations applied to ingroup trait evaluation. The current findings demonstrate the importance of combining motivational factors, computational modeling, and fMRI to deepen our understanding of the neural basis of person evaluation.

Brain activity in struggling readers before intervention relates to future reading gains.

Neural markers for reading-related changes in response to intervention could inform intervention plans by serving as a potential index of the malleability of the reading network in struggling readers. Of particular interest is the role of brain activation outside the reading network, especially in executive control networks important for reading comprehension. However, it is unclear whether any intervention-related executive control changes in the brain are specific to reading tasks or reflect more domain general changes. Brain changes associated with reading gains over time were compared for a sentence comprehension task as well as for a non-lexical executive control task (a behavioral inhibition task) in upper-elementary struggling readers, and in grade-matched non-struggling readers. Functional MRI scans were conducted before and after 16 weeks of reading intervention. Participants were grouped as improvers and non-improvers based on the consistency and size of post-intervention gains across multiple post-test measures. Engagement of the right fusiform during the reading task, both before and after intervention, was related to gains from remediation. Additionally, pre-intervention activation in regions that are part of the default-mode network (precuneus) and the fronto-parietal network (right posterior middle temporal gyrus) separated improvers and non-improvers from non-struggling readers. None of these differences were observed during the non-lexical inhibitory control task, indicating that the brain changes seen related to intervention outcome in struggling readers were specific to the reading process.

Dynamic neural architecture for social knowledge retrieval.

Social behavior is often shaped by the rich storehouse of biographical information that we hold for other people. In our daily life, we rapidly and flexibly retrieve a host of biographical details about individuals in our social network, which often guide our decisions as we navigate complex social interactions. Even abstract traits associated with an individual, such as their political affiliation, can cue a rich cascade of person-specific knowledge. Here, we asked whether the anterior temporal lobe (ATL) serves as a hub for a distributed neural circuit that represents person knowledge. Fifty participants across two studies learned biographical information about fictitious people in a 2-d training paradigm. On day 3, they retrieved this biographical information while undergoing an fMRI scan. A series of multivariate and connectivity analyses suggest that the ATL stores abstract person identity representations. Moreover, this region coordinates interactions with a distributed network to support the flexible retrieval of person attributes. Together, our results suggest that the ATL is a central hub for representing and retrieving person knowledge.

Dissociable frontostriatal white matter connectivity underlies reward and motor impulsivity.

Dysfunction of cognitive control often leads to impulsive decision-making in clinical and healthy populations. Some research suggests that a generalized cognitive control mechanism underlies the ability to modulate various types of impulsive behavior, while other evidence suggests different forms of impulsivity are dissociable, and rely on distinct neural circuitry. Past research consistently implicates several brain regions, such as the striatum and portions of the prefrontal cortex, in impulsive behavior. However the ventral and dorsal striatum are distinct in regards to function and connectivity. Nascent evidence points to the importance of frontostriatal white matter connectivity in impulsivity, yet it remains unclear whether particular tracts relate to different control behaviors. Here we used probabilistic tractography of diffusion imaging data to relate ventral and dorsal frontostriatal connectivity to reward and motor impulsivity measures. We found a double dissociation such that individual differences in white matter connectivity between the ventral striatum and the ventromedial prefrontal cortex and dorsolateral prefrontal cortex was associated with reward impulsivity, as measured by delay discounting, whereas connectivity between dorsal striatum and supplementary motor area was associated with motor impulsivity, but not vice versa. Our findings suggest that (a) structural connectivity can is associated with a large amount of behavioral variation; (b) different types of impulsivity are driven by dissociable frontostriatal neural circuitry.

Individual differences in white matter microstructure predict semantic control.

In everyday conversation, we make many rapid choices between competing concepts and words in order to convey our intent. This process is termed semantic control, and it is thought to rely on information transmission between a distributed semantic store in the temporal lobes and a more discrete region, optimized for retrieval and selection, in the left inferior frontal gyrus. Here, we used diffusion tensor imaging in a group of neurologically normal young adults to investigate the relationship between semantic control and white matter tracts that have been implicated in semantic memory retrieval. Participants completed a verb generation task that taps semantic control (Snyder & Munakata, 2008; Snyder et al., 2010) and underwent a diffusion imaging scan. Deterministic tractography was performed to compute indices representing the microstructural properties of the inferior fronto-occipital fasciculus (IFOF), the uncinate fasciculus (UF), and the inferior longitudinal fasciculus (ILF). Microstructural measures of the UF failed to predict semantic control performance. However, there was a significant relationship between microstructure of the left IFOF and ILF and individual differences in semantic control. Our findings support the view put forth by Duffau (2013) that the IFOF is a key structural pathway in semantic retrieval.