Linguistic measures of psychological distance track symptom levels and treatment outcomes in a large set of psychotherapy transcripts.

SignificanceUsing language to "distance" ourselves from distressing situations (i.e., by talking less about ourselves and the present moment) can help us manage emotions. Here, we translate this basic research to discover that such "linguistic distancing" is a replicable measure of mental health in a large set of therapy transcripts (N = 6,229). Additionally, clustering techniques showed that language alone could identify participants who differed on both symptom severity and treatment outcomes. These findings lay the foundation for 1) tools that can rapidly identify people in need of psychological services based on language alone and 2) linguistic interventions that can improve mental health.

Age-related differences in resting-state functional connectivity from childhood to adolescence.

The human brain is active at rest, and spontaneous fluctuations in functional MRI BOLD signals reveal an intrinsic functional architecture. During childhood and adolescence, functional networks undergo varying patterns of maturation, and measures of functional connectivity within and between networks differ as a function of age. However, many aspects of these developmental patterns (e.g. trajectory shape and directionality) remain unresolved. In the present study, we characterised age-related differences in within- and between-network resting-state functional connectivity (rsFC) and integration (i.e. participation coefficient, PC) in a large cross-sectional sample of children and adolescents (n = 628) aged 8-21 years from the Lifespan Human Connectome Project in Development. We found evidence for both linear and non-linear differences in cortical, subcortical, and cerebellar rsFC, as well as integration, that varied by age. Additionally, we found that sex moderated the relationship between age and putamen integration where males displayed significant age-related increases in putamen PC compared with females. Taken together, these results provide evidence for complex, non-linear differences in some brain systems during development.

Examining the Association between Punishment and Reward Sensitivity and Response Inhibition to Previously-Incentivized Cues across Development.

Processing and learning from affective cues to guide goal-directed behavior may be particularly important during adolescence; yet the factors that promote and/or disrupt the ability to integrate value in order to guide decision making across development remain unclear. The present study (N = 1046) assessed individual difference factors (self-reported punishment and reward sensitivity) related to whether previously-rewarded and previously-punished cues differentially impact goal-directed behavior (response inhibition) in a large developmental sample. Participants were between the ages of 8-21 years (Mage = 14.29, SD = 3.97, 50.38% female). Previously-rewarded cues improved response inhibition among participants age 14 and older. Further, punishment sensitivity predicted overall improved response inhibition among participants aged 10 to 18. The results highlight two main factors that are associated with improvements in the ability to integrate value to guide goal-directed behaviour - cues in the environment (e.g., reward-laden cues) and individual differences in punishment sensitivity. These findings have implications for both educational and social policies aimed at characterizing the ways in which youth integrate value to guide decision making.

Graded Variation in T1w/T2w Ratio during Adolescence: Measurement, Caveats, and Implications for Development of Cortical Myelin.

Adolescence is characterized by the maturation of cortical microstructure and connectivity supporting complex cognition and behavior. Axonal myelination influences brain connectivity during development by enhancing neural signaling speed and inhibiting plasticity. However, the maturational timing of cortical myelination during human adolescence remains poorly understood. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (HCP-D; N = 628, ages 8-21). We characterize microstructural changes relevant to myelination by estimating age-related differences in T1w/T2w throughout the cerebral neocortex from childhood to early adulthood. We apply Bayesian spline models and clustering analysis to demonstrate graded variation in age-dependent cortical T1w/T2w differences that are correlated with the sensorimotor-association (S-A) axis of cortical organization reported by others. In sensorimotor areas, T1w/T2w ratio measures start at high levels at early ages, increase at a fast pace, and decelerate at later ages (18-21). In intermediate multimodal areas along the S-A axis, T1w/T2w starts at intermediate levels and increases linearly at an intermediate pace. In transmodal/paralimbic association areas, T1w/T2w starts at low levels and increases linearly at the slowest pace. These data provide evidence for graded variation of the T1w/T2w ratio along the S-A axis that may reflect cortical myelination changes during adolescence underlying the development of complex information processing and psychological functioning. We discuss the implications of these results as well as caveats in interpreting magnetic resonance imaging (MRI)-based estimates of myelination.SIGNIFICANCE STATEMENT Myelin is a lipid membrane that is essential to healthy brain function. Myelin wraps axons to increase neural signaling speed, enabling complex neuronal functioning underlying learning and cognition. Here, we characterize the developmental timing of myelination across the cerebral cortex during adolescence using a noninvasive proxy measure, T1w/T2w mapping. Our results provide new evidence demonstrating graded variation across the cortex in the timing of T1w/T2w changes during adolescence, with rapid T1w/T2w increases in lower-order sensory areas and gradual T1w/T2w increases in higher-order association areas. This spatial pattern of microstructural brain development closely parallels the sensorimotor-to-association axis of cortical organization and plasticity during ontogeny.

Physical Effort Exertion for Peer Feedback Reveals Evolving Social Motivations From Adolescence to Young Adulthood.

Peer relationships and social belonging are particularly important during adolescence. Using a willingness-to-work paradigm to quantify incentive motivation, we examined whether evaluative information holds unique value for adolescents. Participants (N = 102; 12-23 years old) rated peers, predicted how peers rated them, and exerted physical effort to view each peer's rating. We measured grip force, speed, and opt-out behavior to examine the motivational value of peer feedback, relative to money in a control condition, and to assess how peer desirability and participants' expectations modulated motivated effort across age. Overall, when compared with adolescents, adults were relatively less motivated for feedback than money. Whereas adults exerted less force and speed for feedback when expecting rejection, adolescents exerted greater force and speed when expecting to be more strongly liked or disliked. These findings suggest that the transition into adulthood is accompanied by a self-protective focus, whereas adolescents are motivated to consume highly informative feedback, even if negative.

History of conditioned reward association disrupts inhibitory control: an examination of neural correlates.

The neural processes that support inhibitory control in the face of stimuli with a history of reward association are not yet well understood. Yet, the ability to flexibly adapt behavior to changing reward-contingency contexts is important for daily functioning and warrants further investigation. This study aimed to characterize neural and behavioral impacts of stimuli with a history of conditioned reward association on motor inhibitory control in healthy young adults by investigating group-level effects as well as individual variation in the ability to inhibit responses to stimuli with a reward history. Participants (N = 41) first completed a reward conditioning phase, during which responses to rewarded stimuli were associated with money and responses to unrewarded stimuli were not. Rewarded and unrewarded stimuli from training were carried forward as No-Go targets in a subsequent go/no-go task to test the effect of reward history on inhibitory control. Participants underwent functional brain imaging during the go/no-go portion of the task. On average, a history of reward conditioning disrupted inhibitory control. Compared to inhibition of responses to stimuli with no reward history, trials that required inhibition of responses to previously rewarded stimuli were associated with greater activity in frontal and striatal regions, including the inferior frontal gyrus, insula, striatum, and thalamus. Activity in the insula and thalamus during false alarms and in the ventromedial prefrontal cortex during correctly withheld trials predicted behavioral performance on the task. Overall, these results suggest that reward history serves to disrupt inhibitory control and provide evidence for diverging roles of the insula and ventromedial prefrontal cortex while inhibiting responses to stimuli with a reward history.

Voluntary pursuit of negatively valenced stimuli from childhood to early adulthood.

Although common sense suggests that we are motivated to pursue positive and avoid negative experiences, previous research shows that people regularly seek out negative experiences. In the current study, we characterized this tendency from childhood to young adulthood. Due to the known increases in risky behavior and sensation seeking in adolescence, we hypothesized that adolescents would show an increased engagement with negatively valenced stimuli compared to children and adults. Participants aged 4-25 (N = 192) completed a behavioral task assessing motivation to engage with negative, positive, and neutral images. On each trial, participants viewed two small images and selected one to view at a larger size for up to 10s. Trials were organized into three valence conditions: negative versus positive images (matched on arousal), negative versus neutral images, and positive versus neutral images. Although participants chose positive images more than neutral or negative images, participants selected negative images frequently, even when given a positive (28% of trials) or neutral (42% of trials) alternative. Contrary to expectations, the tendency to choose negative images was highest in early childhood and decreased linearly with increasing age, and the tendency to choose positive images increased linearly with age. These results provide insight into how motivation to engage with emotional stimuli varies across age. It is possible that the novelty and rarity of negative experiences drives children to pursue these stimuli. Alternatively, children may find negative images less aversive, which would caution against assuming that these stimuli elicit the same motivational states in individuals of all ages.

Examining the Causal Effects of Sleep Deprivation on Emotion Regulation and Its Neural Mechanisms.

Cognitive reappraisal (CR) is a strategy used to regulate emotions that is thought to be effective but effortful, relying on higher-order cognitive control systems to engage in active regulation. Sleep deprivation is believed to impair the functioning of these control systems, suggesting that it may impede the ability to implement CR effectively. This study tested the causal effects of sleep deprivation on emotional reactivity and the neurobiological systems underlying CR. We employed a within-subject crossover design in which participants underwent fMRI scanning twice, once when fully rested and once after a night of total sleep deprivation. During scans, participants passively viewed or used CR to down-regulate their emotional response to negative and neutral images. Contrary to hypotheses, both self-reported negative affect ratings and neural responses to the images indicated no difference in the way participants implemented CR when sleep deprived and when fully rested. Meanwhile, neural regions that showed distinct reactivity responses to negative relative to neutral images lost this specificity under deprived conditions. Negative affect ratings and heart rate deceleration, a physiological response typically evoked by aversive pictures, exhibited a similar blunting. Together, these results suggest that, although sleep deprivation may reduce the discrimination between emotional reactivity responses to negative and neutral stimuli, it does not impact CR the way it is presently studied.

Registration-free analysis of diffusion MRI tractography data across subjects through the human lifespan.

Diffusion MRI tractography produces massive sets of streamlines that need to be clustered into anatomically meaningful white-matter bundles. Conventional clustering techniques group streamlines based on their proximity in Euclidean space. We have developed AnatomiCuts, an unsupervised method for clustering tractography streamlines based on their neighboring anatomical structures, rather than their coordinates in Euclidean space. In this work, we show that the anatomical similarity metric used in AnatomiCuts can be extended to find corresponding clusters across subjects and across hemispheres, without inter-subject or inter-hemispheric registration. Our proposed approach enables group-wise tract cluster analysis, as well as studies of hemispheric asymmetry. We evaluate our approach on data from the pilot MGH-Harvard-USC Lifespan Human Connectome project, showing improved correspondence in tract clusters across 184 subjects aged 8-90. Our method shows up to 38% improvement in the overlap of corresponding clusters when comparing subjects with large age differences. The techniques presented here do not require registration to a template and can thus be applied to populations with large inter-subject variability, e.g., due to brain development, aging, or neurological disorders.

Development of self-protective biases in response to social evaluative feedback.

Adolescence is a developmental period marked by heightened attunement to social evaluation. While adults have been shown to enact self-protective processes to buffer their self-views from evaluative threats like peer rejection, it is unclear whether adolescents avail themselves of the same defenses. The present study examines how social evaluation shapes views of the self and others differently across development. N = 107 participants ages 10-23 completed a reciprocal social evaluation task that involved predicting and receiving peer acceptance and rejection feedback, along with assessments of self-views and likability ratings of peers. Here, we show that, despite equivalent experiences of social evaluation, adolescents internalized peer rejection, experiencing a feedback-induced drop in self-views, whereas adults externalized peer rejection, reporting a task-induced boost in self-views and deprecating the peers who rejected them. The results identify codeveloping processes underlying why peer rejection may lead to more dramatic alterations in self-views during adolescence than other phases of the lifespan.

Development of Prefrontal Cortical Connectivity and the Enduring Effect of Learned Value on Cognitive Control.

Inhibitory control, the capacity to suppress an inappropriate response, is a process employed for guiding action selection in the service of goal-directed behavior. Under neutral circumstances, inhibitory control success improves from childhood to adulthood and has been associated with developmental shifts in functional activation and connectivity of the PFC. However, the ability to exercise inhibitory control is challenged in certain contexts by including appetitive cues, a phenomenon that may be particularly pronounced in youths. Here, we examine the magnitude and temporal persistence of learned value's influence on inhibitory control in a cross-sectional sample of 8- to 25-year-olds. Participants first underwent conditioning of a motor approach response to two initially neutral cues, with one cue reinforced with monetary reward and the other with no monetary outcome. Subsequently, during fMRI, participants reencountered these cues as no-go targets in a nonreinforced go/no-go paradigm. Although the influence of learned value increasingly disrupted inhibitory control with increasing age, in young adults this pattern remitted over the course of the task, whereas during adolescence the impairing effect of reward history persisted. Successful no-go performance to the previously rewarded target was related to greater recruitment of the right inferior frontal gyrus and age-related increase in functional connectivity between the inferior frontal gyrus and the ventromedial PFC for the previously rewarded no-go target over the control target. Together, results indicate the complex influence of value on goals over development relies upon the increased coordination of distinct higher-order regions in the PFC.

The Lifespan Human Connectome Project in Aging: An overview.

The original Human Connectome Project yielded a rich data set on structural and functional connectivity in a large sample of healthy young adults using improved methods of data acquisition, analysis, and sharing. More recent efforts are extending this approach to include infants, children, older adults, and brain disorders. This paper introduces and describes the Human Connectome Project in Aging (HCP-A), which is currently recruiting 1200 + healthy adults aged 36 to 100+, with a subset of 600 + participants returning for longitudinal assessment. Four acquisition sites using matched Siemens Prisma 3T MRI scanners with centralized quality control and data analysis are enrolling participants. Data are acquired across multimodal imaging and behavioral domains with a focus on factors known to be altered in advanced aging. MRI acquisitions include structural (whole brain and high resolution hippocampal) plus multiband resting state functional (rfMRI), task fMRI (tfMRI), diffusion MRI (dMRI), and arterial spin labeling (ASL). Behavioral characterization includes cognitive (such as processing speed and episodic memory), psychiatric, metabolic, and socioeconomic measures as well as assessment of systemic health (with a focus on menopause via hormonal assays). This dataset will provide a unique resource for examining how brain organization and connectivity changes across typical aging, and how these differences relate to key characteristics of aging including alterations in hormonal status and declining memory and general cognition. A primary goal of the HCP-A is to make these data freely available to the scientific community, supported by the Connectome Coordination Facility (CCF) platform for data quality assurance, preprocessing and basic analysis, and shared via the NIMH Data Archive (NDA). Here we provide the rationale for our study design and sufficient details of the resource for scientists to plan future analyses of these data. A companion paper describes the related Human Connectome Project in Development (HCP-D, Somerville et al., 2018), and the image acquisition protocol common to both studies (Harms et al., 2018).

Commentary: Building the developmental foundations of developmental computational psychiatry: reflections on Hauser et al. (2019).

There is a growing interest in applying the conceptual and analytical frameworks of computational psychiatry to developmental populations. This is motivated by appreciation that psychiatric illness needs to be understood from a neurodevelopmental perspective. The target article by Hauser and colleagues highlights progress in applying the computational psychiatry perspectives to identifying the developmental mechanisms of mental illness. We share the enthusiasm and optimism for this venture, while recognizing the substantial theoretical and pragmatic challenges associated with applying computational frameworks to developing populations. In this commentary, we highlight the ways that taking a developmental perspective in this arena stretches beyond merely identifying age differences in a computational parameter of interest. These include the need for experimental and computational frameworks to recognize that developmental changes can be quantitative or qualitative in nature, the need to consider developmental stage beyond age groupings or even numerical age, and the need for large quantities of data to model age-related changes in a reproducible manner. In doing so, we hope to stimulate progress in uncovering the mechanisms of psychiatric illness in a way that is developmentally informed.

Developmental patterns of change in the influence of safe and risky peer choices on risky decision-making.

Adolescents take more risks when peers monitor their behavior. However, it is largely unknown how different types of peer influence affect adolescent decision-making. In this study, we investigate how information about previous choices of peers differentially influences decision-making in adolescence and young adulthood. Participants (N = 99, age range 12-22) completed an economic choice task in which choice options were systematically varied on levels of risk and ambiguity. On each trial, participants selected between a safer choice (low variability in outcome) and a riskier choice (high variability in outcome). Participants made choices in three conditions: a solo condition in which they made choices with no additional information, a social condition in which they saw choices of supposed peers, and a computer condition in which they saw choices of a computer. Results showed that participants' choices conform to the choices made by the peers, but not a computer. Furthermore, when peers chose the safe option, late adolescents were especially likely to make a safe choice. Conversely, when the peer made a risky choice, late adolescents were least likely to follow choices made by the peer. We did not find evidence for differential influence of social information on decisions depending on their level of risk and ambiguity. These results show that information about previous decisions of peers are a powerful modifier for behavior and that the effect of peers on adolescents' decisions is less ubiquitous and more specific than previously assumed.

Stress impacts the fidelity but not strength of emotional memories.

Psychological stress during memory encoding influences resulting memory representations. However, open questions remain regarding how stress interacts with emotional memory. This interaction has mainly been studied by characterizing the correct identification of previously observed material (memory "hits"), with few studies investigating how stress influences the endorsement of unobserved material as remembered (memory "false alarms"). While hits can provide information about the presence or strength of a memory representation, false alarms provide insight into memory fidelity, indicating to what extent stored memories are confused with similar information presented at retrieval. This study examined the effects of stress on long-term memory for negative and neutral images, considering the separate contributions of hits and false alarms. Participants viewed images after repeated exposure to either a stress or a control manipulation. Stress impaired memory performance for negative pictures and enhanced memory performance for neutral pictures. These effects were driven by false alarms rather than hits: stressed participants false alarmed more often for negative and less often for neutral images. These data suggest that stress undermines the benefits of emotion on memory by changing individuals' susceptibility towards false alarms, and highlight the need to consider both memory strength and fidelity to characterize differences in memory performance.

Dissecting "Peer Presence" and "Decisions" to Deepen Understanding of Peer Influence on Adolescent Risky Choice.

This study evaluated the aspects of complex decisions influenced by peers, and components of peer involvement influential to adolescents' risky decisions. Participants (N = 140) aged 13-25 completed the Columbia Card Task (CCT), a risky choice task, isolating deliberation-reliant and affect-reliant decisions while alone, while a friend monitors choices, and while a friend is merely present. There is no condition in which a nonfriend peer is present. Results demonstrated the risk-increasing peer effect occurred in the youngest participants in the cold CCT and middle-late adolescents in the hot CCT, whereas other ages and contexts showed a risk-decreasing peer effect. Mere presence was not sufficient to influence risky behavior. These boundaries in age, decision, and peer involvement constrain prevailing models of adolescent peer influence.

The Lifespan Human Connectome Project in Development: A large-scale study of brain connectivity development in 5-21 year olds.

Recent technological and analytical progress in brain imaging has enabled the examination of brain organization and connectivity at unprecedented levels of detail. The Human Connectome Project in Development (HCP-D) is exploiting these tools to chart developmental changes in brain connectivity. When complete, the HCP-D will comprise approximately ∼1750 open access datasets from 1300 + healthy human participants, ages 5-21 years, acquired at four sites across the USA. The participants are from diverse geographical, ethnic, and socioeconomic backgrounds. While most participants are tested once, others take part in a three-wave longitudinal component focused on the pubertal period (ages 9-17 years). Brain imaging sessions are acquired on a 3 T Siemens Prisma platform and include structural, functional (resting state and task-based), diffusion, and perfusion imaging, physiological monitoring, and a battery of cognitive tasks and self-reports. For minors, parents additionally complete a battery of instruments to characterize cognitive and emotional development, and environmental variables relevant to development. Participants provide biological samples of blood, saliva, and hair, enabling assays of pubertal hormones, health markers, and banked DNA samples. This paper outlines the overarching aims of the project, the approach taken to acquire maximally informative data while minimizing participant burden, preliminary analyses, and discussion of the intended uses and limitations of the dataset.

Extending the Human Connectome Project across ages: Imaging protocols for the Lifespan Development and Aging projects.

The Human Connectome Projects in Development (HCP-D) and Aging (HCP-A) are two large-scale brain imaging studies that will extend the recently completed HCP Young-Adult (HCP-YA) project to nearly the full lifespan, collecting structural, resting-state fMRI, task-fMRI, diffusion, and perfusion MRI in participants from 5 to 100+ years of age. HCP-D is enrolling 1300+ healthy children, adolescents, and young adults (ages 5-21), and HCP-A is enrolling 1200+ healthy adults (ages 36-100+), with each study collecting longitudinal data in a subset of individuals at particular age ranges. The imaging protocols of the HCP-D and HCP-A studies are very similar, differing primarily in the selection of different task-fMRI paradigms. We strove to harmonize the imaging protocol to the greatest extent feasible with the completed HCP-YA (1200+ participants, aged 22-35), but some imaging-related changes were motivated or necessitated by hardware changes, the need to reduce the total amount of scanning per participant, and/or the additional challenges of working with young and elderly populations. Here, we provide an overview of the common HCP-D/A imaging protocol including data and rationales for protocol decisions and changes relative to HCP-YA. The result will be a large, rich, multi-modal, and freely available set of consistently acquired data for use by the scientific community to investigate and define normative developmental and aging related changes in the healthy human brain.

The Nonlinear Development of Emotion Differentiation: Granular Emotional Experience Is Low in Adolescence.

People differ in how specifically they separate affective experiences into different emotion types-a skill called emotion differentiation or emotional granularity. Although increased emotion differentiation has been associated with positive mental health outcomes, little is known about its development. Participants ( N = 143) between the ages of 5 and 25 years completed a laboratory measure of negative emotion differentiation in which they rated how much a series of aversive images made them feel angry, disgusted, sad, scared, and upset. Emotion-differentiation scores were computed using intraclass correlations. Emotion differentiation followed a nonlinear developmental trajectory: It fell from childhood to adolescence and rose from adolescence to adulthood. Mediation analyses suggested that an increased tendency to report feeling emotions one at a time explained elevated emotion differentiation in childhood. Importantly, two other mediators (intensity of emotional experiences and scale use) did not explain this developmental trend. Hence, low emotion differentiation in adolescence may arise because adolescents have little experience conceptualizing co-occurring emotions.

Does Psychosocial Stress Impact Cognitive Reappraisal? Behavioral and Neural Evidence.

Cognitive reappraisal (CR) is regarded as an effective emotion regulation strategy. Acute stress, however, is believed to impair the functioning of prefrontal-based neural systems, which could result in lessened effectiveness of CR under stress. This study tested the behavioral and neurobiological impact of acute stress on CR. While undergoing fMRI, adult participants ( n = 54) passively viewed or used CR to regulate their response to negative and neutral pictures and provided ratings of their negative affect in response to each picture. Half of the participants experienced an fMRI-adapted acute psychosocial stress manipulation similar to the Trier Social Stress Test, and a control group received parallel manipulations without the stressful components. Relative to the control group, the stress group exhibited heightened stress as indexed by self-report, heart rate, and salivary cortisol throughout the scan. Contrary to our hypothesis, we found that reappraisal success was equivalent in the control and stress groups, as was electrodermal response to the pictures. Heart rate deceleration, a physiological response typically evoked by aversive pictures, was blunted in response to negative pictures and heightened in response to neutral pictures in the stress group. In the brain, we found weak evidence of stress-induced increases of reappraisal-related activity in parts of the PFC and left amygdala, but these relationships were statistically fragile. Together, these findings suggest that both the self-reported and neural effects of CR may be robust to at least moderate levels of stress, informing theoretical models of stress effects on cognition and emotion.