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As public access to longitudinal developmental datasets like the Adolescent Brain Cognitive Development Study

Establishing brain-behavior associations that map brain organization to phenotypic measures and generalize to novel individuals remains a challenge in neuroimaging. Predictive modeling approaches that define and validate models with independent datasets offer a solution to this problem. While these methods can detect novel and generalizable brain-behavior associations, they can be daunting, which has limited their use by the wider connectivity community. Here, we offer practical advice and examples based on functional magnetic resonance imaging (fMRI) functional connectivity data for implementing these approaches. We hope these ten rules will increase the use of predictive models with neuroimaging data.

Cognitive states, such as rest and task engagement, share an 'intrinsic' functional network organization that is subject to minimal variation over time and yields stable signatures within an individual. Importantly, there are also transient state-specific functional connectivity (FC) patterns that vary across neural states. Here, we examine functional brain organization differences that underlie distinct states in a cross-sectional developmental sample. We compare FC fMRI data acquired during naturalistic viewing (i.e., movie-watching) and resting-state paradigms in a large cohort of 157 children and young adults aged 6-20. Naturalistic paradigms are commonly implemented in pediatric research because they maintain the child's attention and contribute to reduced head motion. It remains unknown, however, to what extent the brain-wide functional network organization is comparable during movie-watching and rest across development. Here, we identify a widespread FC pattern that predicts whether individuals are watching a movie or resting. Specifically, we develop a model for prediction of multilevel neural effects (termed PrimeNet), which can with high reliability distinguish between movie-watching and rest irrespective of age and that generalizes across movies. In turn, we characterize FC patterns in the most predictive functional networks for movie-watching versus rest and show that these patterns can indeed vary as a function of development. Collectively, these effects highlight a 'core' FC pattern that is robustly associated with naturalistic viewing, which also exhibits change across age. These results, focused here on naturalistic viewing, provide a roadmap for quantifying state-specific functional neural organization across development, which may reveal key variation in neurodevelopmental trajectories associated with behavioral phenotypes.

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback is a non-invasive, non-pharmacological therapeutic tool that may be useful for training behavior and alleviating clinical symptoms. Although previous work has used rt-fMRI to target brain activity in or functional connectivity between a small number of brain regions, there is growing evidence that symptoms and behavior emerge from interactions between a number of distinct brain areas. Here, we propose a new method for rt-fMRI, connectome-based neurofeedback, in which intermittent feedback is based on the strength of complex functional networks spanning hundreds of regions and thousands of functional connections. We first demonstrate the technical feasibility of calculating whole-brain functional connectivity in real-time and provide resources for implementing connectome-based neurofeedback. We next show that this approach can be used to provide accurate feedback about the strength of a previously defined connectome-based model of sustained attention, the saCPM, during task performance. Although, in our initial pilot sample, neurofeedback based on saCPM strength did not improve performance on out-of-scanner attention tasks, future work characterizing effects of network target, training duration, and amount of feedback on the efficacy of rt-fMRI can inform experimental or clinical trial designs.

Attention is a critical cognitive function, allowing humans to select, enhance, and sustain focus on information of behavioral relevance. Attention contains dissociable neural and psychological components. Nevertheless, some brain networks support multiple attentional functions. Connectome-based Predictive Models (CPM), which associate individual differences in task performance with functional connectivity patterns, provide a compelling example. A sustained attention network model (saCPM) successfully predicted performance for selective attention, inhibitory control, and reading recall tasks. Here we constructed a visual attentional blink (VAB) model (vabCPM), comparing its performance predictions and network edges associated with successful and unsuccessful behavior to the saCPM’s. In the VAB, attention devoted to a target often causes a subsequent item to be missed. Although frequently attributed to attentional limitations, VAB deficits may attenuate when participants are distracted or deploy attention diffusely. Participants (n=73; 24 males) underwent fMRI while performing the VAB task and while resting. Outside the scanner, they completed other cognitive tasks over several days. A vabCPM constructed from these data successfully predicted VAB performance. Strikingly, the network edges that predicted better VAB performance (positive edges) predicted worse selective and sustained attention performance, and vice versa. Predictions from the saCPM mirrored these results, with the network’s negative edges predicting better VAB performance. Furthermore, the vabCPM’s positive edges significantly overlapped with the saCPM’s negative edges, and vice versa. We conclude that these partially overlapping networks each have general attentional functions. They may indicate an individual’s propensity to diffusely deploy attention, predicting better performance for some tasks and worse for others.Significance statementA longstanding question in psychology and neuroscience is whether we have general capacities or domain-specific ones. For such general capacities, what is the common function? Here we addressed these questions using the attentional blink (AB) task and neuroimaging. Individuals searched for two items in a stream of distracting items; the second item was often missed when it closely followed the first. How often the second item was missed varied across individuals, which was reflected in attention networks. Curiously, the networks’ pattern of function that was good for the AB was bad for other tasks, and vice versa. We propose that these networks may represent not a general attentional ability, but rather the tendency to attend in a less focused manner.

Sustaining attention to the task at hand is a crucial part of everyday life, from following a lecture at school to maintaining focus while driving. Lapses in sustained attention are frequent and often problematic, with conditions such as attention deficit hyperactivity disorder affecting millions of people worldwide. Recent work has had some success in finding signatures of sustained attention in whole-brain functional connectivity (FC) measures during basic tasks, but since FC can be dynamic and task-dependent, it remains unclear how fully these signatures would generalize to a more complex and naturalistic scenario. To this end, we used a previously defined whole-brain FC network - a marker of attention that was derived from a sustained attention task - to predict the ability of participants to recall material during a free-viewing reading task. Though the predictive network was trained on a different task and set of participants, the strength of FC in the sustained attention network predicted reading recall significantly better than permutation tests where behavior was scrambled to simulate chance performance. To test the generalization of the method used to derive the sustained attention network, we applied the same method to our reading task data to find a new FC network whose strength specifically predicts reading recall. Even though the sustained attention network provided significant prediction of recall, the reading network was more predictive of recall accuracy. The new reading network's spatial distribution indicates that reading recall is highest when temporal pole regions have higher FC with left occipital regions and lower FC with bilateral supramarginal gyrus. Right cerebellar to right frontal connectivity is also indicative of poor reading recall. We examine these and other differences between the two predictive FC networks, providing new insight into the task-dependent nature of FC-based performance metrics.

Connectome-based predictive modeling (CPM; Finn et al., 2015; Shen et al., 2017) was recently developed to predict individual differences in traits and behaviors, including fluid intelligence (Finn et al., 2015) and sustained attention (Rosenberg et al., 2016a), from functional brain connectivity (FC) measured with fMRI. Here, using the CPM framework, we compared the predictive power of three different measures of FC (Pearson's correlation, accordance, and discordance) and two different prediction algorithms (linear and partial least square [PLS] regression) for attention function. Accordance and discordance are recently proposed FC measures that respectively track in-phase synchronization and out-of-phase anti-correlation (Meskaldji et al., 2015). We defined connectome-based models using task-based or resting-state FC data, and tested the effects of (1) functional connectivity measure and (2) feature-selection/prediction algorithm on individualized attention predictions. Models were internally validated in a training dataset using leave-one-subject-out cross-validation, and externally validated with three independent datasets. The training dataset included fMRI data collected while participants performed a sustained attention task and rested (N = 25; Rosenberg et al., 2016a). The validation datasets included: 1) data collected during performance of a stop-signal task and at rest (N = 83, including 19 participants who were administered methylphenidate prior to scanning; Farr et al., 2014a; Rosenberg et al., 2016b), 2) data collected during Attention Network Task performance and rest (N = 41, Rosenberg et al., in press), and 3) resting-state data and ADHD symptom severity from the ADHD-200 Consortium (N = 113; Rosenberg et al., 2016a). Models defined using all combinations of functional connectivity measure (Pearson's correlation, accordance, and discordance) and prediction algorithm (linear and PLS regression) predicted attentional abilities, with correlations between predicted and observed measures of attention as high as 0.9 for internal validation, and 0.6 for external validation (all p's

There are well-characterized age-related differences in behavioral and neural responses to tasks of attentional control. However, there is also increasing recognition of individual variability in the process of neurocognitive aging. Using connectome-based predictive modeling, a method for predicting individual-level behaviors from whole-brain functional connectivity, a sustained attention connectome-based prediction model (saCPM) has been derived in young adults. The saCPM consists of two large-scale functional networks: a high-attention network whose strength predicts better attention and a low-attention network whose strength predicts worse attention. Here we examined the generalizability of the saCPM for predicting inhibitory control in an aging sample. Forty-two healthy young adults (n = 21, ages 18–30) and older adults (n = 21, ages 60–80) performed a modified Stroop task, on which older adults exhibited poorer performance, indexed by higher reaction time cost between incongruent and congruent trials. The saCPM generalized to predict reaction time cost across age groups, but did not account for age-related differences in performance. Exploratory analyses were conducted to characterize the effects of age on functional connectivity and behavior. We identified subnetworks of the saCPM that exhibited age-related differences in strength. The strength of two low-attention subnetworks, consisting of frontoparietal, medial frontal, default mode, and motor nodes that were more strongly connected in older adults, mediated the effect of age group on performance. These results support the saCPM's ability to capture attention-related patterns reflected in each individual's functional connectivity signature across both task context and age. However, older and younger adults exhibit functional connectivity differences within components of the saCPM networks, and it is these connections that better account for age-related deficits in attentional control.

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.

Although fluctuations in sustained attention are ubiquitous, most psychological experiments treat them as noise, averaging performance over many trials. The current study uses multi-voxel pattern analysis (MVPA) to decode whether, on each trial of a cognitive task, participants are in an optimal or suboptimal attentional state. During fMRI, participants performed n-back tasks, composed of central face images overlaid on distractor scenes, with low, perceptual, and working memory load. Instructions were to respond to novel faces and withhold response to rare repeats. To index attentional state, reaction time variability was calculated at each correct response. Participants' 50% least variable trials were labeled optimal, or "in the zone," and their 50% most erratic trials were labeled suboptimal, or "out of the zone." Support vector machine classifiers trained on activity in the default mode network (DMN), dorsal attention network (DAN), and task-relevant fusiform face area (FFA) distinguished in-the-zone and out-of-the-zone trials in all tasks. Consistent with evidence that distractors are processed when central task load is low, parahippocampal place area (PPA) classifiers were only successful in the low load task. Classification in anatomical regions across the brain revealed widespread coding of attentional state. In contrast to these robust pattern analyses, univariate signal in DMN, DAN, FFA, and PPA did not distinguish states, suggesting a nuanced relationship to sustained attention. In sum, MVPA can be used to decode trial-by-trial attentional state throughout much of cortex, helping to characterize how attention network fluctuations correlate with performance variability.