Developmental trajectories of delay discounting from childhood to young adulthood: longitudinal associations and test-retest reliability.

Delay discounting (DD) indexes an individual's preference for smaller immediate rewards over larger delayed rewards, and is considered a form of cognitive impulsivity. Cross-sectional studies have demonstrated that DD peaks in adolescence; longitudinal studies are needed to validate this putative developmental trend, and to determine whether DD assesses a temporary state, or reflects a more stable behavioral trait. In this study, 140 individuals aged 9-23 completed a delay discounting (DD) task and cognitive battery at baseline and every-two years thereafter, yielding five assessments over approximately 10 years. Models fit with the inverse effect of age best approximated the longitudinal trajectory of two DD measures, hyperbolic discounting (log[k]) and area under the indifference-point curve (AUC). Discounting of future rewards increased rapidly from childhood to adolescence and appeared to plateau in late adolescence for both models of DD. Participants with greater verbal intelligence and working memory displayed reduced DD across the duration of the study, suggesting a functional interrelationship between these domains and DD from early adolescence to adulthood. Furthermore, AUC demonstrated good to excellent reliability across assessment points that was superior to log(k), with both measures demonstrating acceptable stability once participants reached late adolescence. The developmental trajectories of DD we observed from childhood through young adulthood suggest that DD may index cognitive control more than reward sensitivity, and that despite modest developmental changes with maturation, AUC may be conceptualized as a trait variable related to cognitive control vs impulsivity.

Does pubertal stage mediate the association between family environment and structure and function of the amygdala-mPFC circuit? A replication study of the longitudinal ABCD cohort.

Psychosocial acceleration theory suggests that early stress accelerates pubertal development. Using half of the baseline Adolescent Brain and Cognitive Development (ABCD) cohort, Thijssen et al. (2020) provide support that accelerated puberty following stressful family environments may promote neurodevelopment. Here, we replicate and extend those analyses using 1) data from the second half of the ABCD sample (n = 3300 +, ages 9-10), and 2) longitudinal imaging data from the original sample (n = 1800 +, ages 11-12). A family environment latent variable was created and related to anterior cingulate cortex (ACC) thickness, area, white matter fractional anisotropy, amygdala volume, and cingulo-opercular network (CON)-amygdala resting-state functional connectivity. Results from the independent sample replicate the mediating effects of family environment through pubertal stage on amygdala-CON functional connectivity. Sex-stratified analyses show indirect effects via pubertal stage in girls; boys show evidence for direct associations. Analyses using wave 2 imaging data or wave 2-wave 1 difference scores from the originally-analyzed sample replicate the resting-state indirect effects. The current paper replicates the mediating role for puberty in the association between family environment and neurodevelopment. As both direct and indirect associations were found, puberty may be one of multiple mechanisms driving accelerated neurodevelopment following environmental stress.

Neuroplasticity, the Prefrontal Cortex, and Psychopathology-Related Deviations in Cognitive Control.

A basic survival need is the ability to respond to, and persevere in the midst of, experiential challenges. Mechanisms of neuroplasticity permit this responsivity via functional adaptations (flexibility), as well as more substantial structural modifications following chronic stress or injury. This review focuses on prefrontally based flexibility, expressed throughout large-scale neuronal networks through the actions of excitatory and inhibitory neurotransmitters and neuromodulators. With substance use disorders and stress-related internalizing disorders as exemplars, we review human behavioral and neuroimaging data, considering whether executive control, particularly cognitive flexibility, is impaired premorbidly, enduringly compromised with illness progression, or both. We conclude that deviations in control processes are consistently expressed in the context of active illness but operate through different mechanisms and with distinct longitudinal patterns in externalizing versus internalizing conditions.

Is Adolescence a Sensitive Period for the Development of Incentive-Reward Motivation?

Human adolescence is broadly construed as a time of heightened risk-taking and a vulnerability period for the emergence of psychopathology. These tendencies have been attributed to the age-related development of neural systems that mediate incentive motivation and other aspects of reward processing as well as individual difference factors that interact with ongoing development. Here, we describe the adolescent development of incentive motivation, which we view as an inherently positive developmental progression, and its associated neural mechanisms. We consider challenges in applying the sensitive period concept to these maturational events and discuss future directions that may help to clarify mechanisms of change.

Initiation of Moderately Frequent Cannabis use in Adolescence and Young Adulthood is Associated with Declines in Verbal Learning and Memory: A Longitudinal Comparison of Pre- versus Post-Initiation Cognitive Performance.

OBJECTIVE: Cannabis use is associated with relative cognitive weaknesses as observed by cross-sectional as well as longitudinal research. Longitudinal studies, controlling for relevant confounds, are necessary to differentiate premorbid from post-initiation contributions to these effects. METHODS: We followed a sample of adolescents and young adults across ten years. Participants provided neurocognitive data and substance use information at two-year intervals. Participants who initiated cannabis and/or alcohol use were identified (n = 86) and split into alcohol-only initiators (n = 39) and infrequent (n = 29) and moderately frequent (n = 18) cannabis initiators. Participants completed the Rey Auditory Verbal Learning Task (RAVLT) and the Iowa Gambling Task (IGT). Group differences before and after substance use initiation and the extent to which alcohol, nicotine, and cannabis use frequencies contributed to cognitive functions over time were examined. RESULTS: After controlling for parental education, RAVLT new learning was worse in moderately frequent cannabis users prior to use initiation. RAVLT total learning and delayed recall showed significant declines from pre- to post-initiation in moderately frequent cannabis users. Regression analyses confirmed that frequencies of cannabis, but not alcohol, use contributed to post-initiation variations. Nicotine use showed an independent negative association with delayed memory. Findings for the IGT were not significant. CONCLUSIONS: Verbal learning and memory may be disrupted following the initiation of moderately frequent cannabis use while decreased new learning may represent a premorbid liability. Our use of a control group of alcohol-only users adds interpretive clarity to the findings and suggests that future studies should carefully control for comorbid substance use.

The longitudinal association between externalizing behavior and frontoamygdalar resting-state functional connectivity in late adolescence and young adulthood.

BACKGROUND: Externalizing behavior has been attributed, in part, to decreased frontolimbic control over amygdala activation. However, little is known about developmental trajectories of frontoamygdalar functional connectivity and its relation to externalizing behavior. The present study addresses this gap by examining longitudinal associations between adolescent and adult externalizing behavior and amygdala-anterior cingulate cortex (ACC) and amygdala-orbitofrontal cortex (OFC) resting-state functional connectivity in a sample of 111 typically developing participants aged 11-23 at baseline. METHODS: Participants completed two-to-four data waves spaced approximately two years apart, resulting in a total of 309 data points. At each data wave, externalizing behavior was measured using the Externalizing Behavior Broadband Scale from the Achenbach Youth/Adult Self-Report questionnaire. Resting-state fMRI preprocessing was performed using FSL. Amygdala functional connectivity was examined using AFNI. The longitudinal association between externalizing behavior and amygdala-ACC/OFC functional connectivity was examined using linear mixed effect models in R. RESULTS: Externalizing behavior was associated with increased amygdala-ACC and amygdala-OFC resting-state functional connectivity across adolescence and young adulthood. For amygdala-ACC connectivity, externalizing behavior at baseline primarily drove this association, whereas for amygdala-OFC functional connectivity, change in externalizing behavior relative to baseline drove the main effect of externalizing behavior on amygdala-OFC functional connectivity. No evidence was found for differential developmental trajectories of frontoamygdalar connectivity for different levels of externalizing behavior (i.e., age-by-externalizing behavior interaction effect). CONCLUSIONS: Higher externalizing behavior is associated with increased resting-state attunement between the amygdala and ACC/OFC, perhaps indicating a generally more vigilant state for neural networks important for emotional processing and control.

Pubertal development mediates the association between family environment and brain structure and function in childhood.

Psychosocial acceleration theory suggests that pubertal maturation is accelerated in response to adversity. In addition, suboptimal caregiving accelerates development of the amygdala-medial prefrontal cortex circuit. These findings may be related. Here, we assess whether associations between family environment and measures of the amygdala-medial prefrontal cortex circuit are mediated by pubertal development in more than 2000 9- and 10-year-old children from the Adolescent Brain Cognitive Development Study (http://dx.doi.org/10.15154/1412097). Using structural equation modeling, demographic, child-reported, and parent-reported data on family dynamics were compiled into a higher level family environment latent variable. Magnetic resonance imaging preprocessing and compilations were performed by the Adolescent Brain Cognitive Development Study's data analysis core. Anterior cingulate cortex (ACC) thickness, area, white matter fractional anisotropy, amygdala volume, and cingulo-opercular network-amygdala resting-state functional connectivity were assessed. For ACC cortical thickness and ACC fractional anisotropy, significant indirect effects indicated that a stressful family environment relates to more advanced pubertal stage and more mature brain structure. For cingulo-opercular network-amygdala functional connectivity, results indicated a trend in the expected direction. For ACC area, evidence for quadratic mediation by pubertal stage was found. Sex-stratified analyses suggest stronger results for girls. Despite small effect sizes, structural measures of circuits important for emotional behavior are associated with family environment and show initial evidence of accelerated pubertal development.

Longitudinal Alterations in Prefrontal Resting Brain Connectivity in Non-Treatment-Seeking Young Adults With Cannabis Use Disorder.

Background: Cannabis is increasingly perceived as a harmless drug by recreational users, yet chronic use may impact brain changes into adulthood. Repeated cannabis exposure has been associated with enduring synaptic changes in executive control and reward networks. It is important to determine whether there are brain functional alterations within these networks in individuals that do not seek treatment for chronic cannabis abuse. Methods: This longitudinal study compared resting-state functional connectivity changes in executive control and reward networks between 23 non-treatment-seeking young adults with cannabis use disorder (6 females; baseline age M = 19.3 ± 1.18) and 21 age-matched controls (10 females; baseline age M = 19.4 ± 0.65) to determine group differences in the temporal trajectories of resting-state functional connectivity across a 2-year span. Results: Results showed i) significant increases in resting-state functional connectivity between the caudal anterior cingulate cortex and precentral and parietal regions over time in the control group, but not in the cannabis use disorder group, and ii) sustained lower resting-state functional connectivity of anterior cingulate cortex seeds with frontal and thalamic regions in the cannabis use disorder group vs. the age-matched controls. Resting-state functional connectivity strength was correlated with cannabis use patterns in the cannabis use disorder sample. Conclusion: Longitudinal alterations in intrinsic functional organization of executive control networks found in non-treatment-seeking young adults with cannabis use disorder (when compared to age-matched controls) may impact regulatory control over substance use behavior. Current findings were limited to examining executive control and reward networks seeded in ACC and NAcc, respectively. Future studies with larger sample sizes and enough power are needed to conduct exploratory analyses examining rsFC of other networks beyond those within the scope of the current study.

Longitudinal changes in cognition in young adult cannabis users.

INTRODUCTION: Adolescent cannabis use (CU) is associated with impaired attention, executive function, and verbal learning/memory. These associations are generally observed in cross-sectional studies. Longitudinal studies of cannabis users are lacking. METHOD: The present study examines associations between CU and cognition over time in chronic daily adolescent-onset CUs, as compared to nonusing controls. Both groups completed a neuropsychological battery at study intake and again 2 years later. RESULTS: Baseline group differences have been published and indicated deficits in verbal learning and memory, motivated decision-making, planning, and working memory in CUs. In this follow-up report, the longitudinal performance of users is compared to that of sustained nonusers using the same battery. At follow-up, the majority of CUs continued to report regular and heavy cannabis use. Relative impairments in the domains of working memory, planning and verbal memory remained stable, suggesting that these are enduring vulnerabilities associated with continued CU during young adulthood. Improvements in motivated decision-making were evident in both groups. In addition, CUs demonstrated relatively better performance on short-duration speeded tasks. An earlier age of CU onset was associated with poorer verbal learning and memory and planning performance over time. CONCLUSIONS: Verbal learning and memory and planning processes, as well as their neural correlates, merit further scrutiny within etiological models of cannabis-induced cognitive impairments.

Higher Adolescent Body Mass Index Is Associated with Lower Regional Gray and White Matter Volumes and Lower Levels of Positive Emotionality.

Adolescent obesity is associated with an increased chance of developing serious health risks later in life. Identifying the neurobiological and personality factors related to increases in adiposity is important to understanding what drives maladaptive consummatory and exercise behaviors that result in obesity. Previous research has largely focused on adults with few findings published on interactions among adiposity, brain structure, and personality. In this study, Voxel Based Morphometry (VBM) was used to identify associations between gray and white matter volumes and increasing adiposity, as measured by Body Mass Index percentile (BMI%), in 137 adolescents (age range: 9-20 years, BMI% range: 5.16-99.56). Variations in gray and white matter volume and BMI% were then linked to individual differences in personality measures from the Multidimensional Personality Questionnaire (MPQ). After controlling for age and other covariates, BMI% correlated negatively with gray matter volume in the bilateral caudate (right: partial r = -0.338, left: r = -0.404), medial prefrontal cortex (partial r = -0.339), anterior cingulate (partial r = -0.312), bilateral frontal pole (right: partial r = -0.368, left: r = -0.316), and uncus (partial r = -0.475) as well as white matter volume bilaterally in the anterior limb of the internal capsule (right: partial r = -0.34, left: r = -0.386), extending to the left middle frontal subgyral white matter. Agentic Positive Emotionality (PEM-AG) was correlated negatively with BMI% (partial r = -0.384). PEM-AG was correlated positively with gray matter volume in the right uncus (partial r = 0.329). These results suggest that higher levels of adiposity in adolescents are associated with lower trait levels in reward-related personality domains, as well as structural variations in brain regions associated with reward processing, control, and sensory integration.

Longitudinal changes in white matter microstructure after heavy cannabis use.

Diffusion tensor imaging (DTI) studies of cannabis users report alterations in brain white matter microstructure, primarily based on cross-sectional research, and etiology of the alterations remains unclear. We report findings from longitudinal voxelwise analyses of DTI data collected at baseline and at a 2-year follow-up on 23 young adult (18-20 years old at baseline) regular cannabis users and 23 age-, sex-, and IQ-matched non-using controls with limited substance use histories. Onset of cannabis use was prior to age 17. Cannabis users displayed reduced longitudinal growth in fractional anisotropy in the central and parietal regions of the right and left superior longitudinal fasciculus, in white matter adjacent to the left superior frontal gyrus, in the left corticospinal tract, and in the right anterior thalamic radiation lateral to the genu of the corpus callosum, along with less longitudinal reduction of radial diffusion in the right central/posterior superior longitudinal fasciculus, corticospinal tract, and posterior cingulum. Greater amounts of cannabis use were correlated with reduced longitudinal growth in FA as was relatively impaired performance on a measure of verbal learning. These findings suggest that continued heavy cannabis use during adolescence and young adulthood alters ongoing development of white matter microstructure, contributing to functional impairment.

Age-related changes in the intrinsic functional connectivity of the human ventral vs. dorsal striatum from childhood to middle age.

The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC) imaging in 106 healthy individuals, ages 9-44. Broadly, the dorsal striatum (DS) is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS) is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC) that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns) and dorsal anterior cingulate cortex (dACC) that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents' unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old.

Neurocognition in college-aged daily marijuana users.

BACKGROUND: Marijuana is the most commonly used illicit substance in the United States. Use, particularly when it occurs early, has been associated with cognitive impairments in executive functioning, learning, and memory. METHOD: This study comprehensively measured cognitive ability as well as comorbid psychopathology and substance use history to determine the neurocognitive profile associated with young adult marijuana use. College-aged marijuana users who initiated use prior to age 17 (n = 35) were compared to demographically matched controls (n = 35). RESULTS: Marijuana users were high functioning, demonstrating comparable IQs to controls and relatively better processing speed. Marijuana users demonstrated relative cognitive impairments in verbal memory, spatial working memory, spatial planning, and motivated decision making. Comorbid use of alcohol, which was heavier in marijuana users, was unexpectedly found to be associated with better performance in some of these areas. CONCLUSIONS: This study provides additional evidence of neurocognitive impairment in the context of adolescent and young adult marijuana use. Findings are discussed in relation to marijuana's effects on intrinsic motivation and discrete aspects of cognition.

Effects of alcohol use initiation on brain structure in typically developing adolescents.

BACKGROUND: Alcohol use in excessive quantities has deleterious effects on brain structure and behavior in adults and during periods of rapid neurodevelopment, such as prenatally. Whether similar outcomes characterize other developmental periods, such as adolescence, and in the context of less extensive use is unknown. Recent cross-sectional studies suggest that binge drinking as well as alcohol use disorders in adolescence are associated with disruptions in white matter microstructure and gray matter volumes. OBJECTIVES: The current study followed typically developing adolescents from a baseline assessment, where no experience with alcohol was present, through two years, after which some individuals transitioned into regular use. METHODS: Participants (n = 55) completed MRI scans and behavioral assessments. RESULTS: Alcohol initiators (n = 30; mean baseline age 16.7 ± 1.3 years), compared to non-users (n = 25; mean baseline age 17.1 ± 1.2 years), showed altered patterns of neurodevelopment. They showed greater-than-expected decreases in cortical thickness in the right middle frontal gyrus from baseline to follow-up as well as blunted development of white matter in the right hemisphere precentral gyrus, lingual gyrus, middle temporal gyrus and anterior cingulate. Diffusion tensor imaging revealed a relative decrease over time in fractional anisotropy in the left caudate/thalamic region as well as in the right inferior frontal occipital fasciculus. Alcohol initiators did not differ from non-users at the baseline assessment; the groups were largely similar in other premorbid characteristics. CONCLUSIONS: Subclinical alcohol use during mid-to-late adolescence is associated with deviations in neurodevelopment across several brain tissue classes. Implications for continued development and behavior are discussed.

In vivo 1H magnetic resonance spectroscopy in young-adult daily marijuana users.

To date, there has been little work describing the neurochemical profile of young, heavy marijuana users. In this study, we examined 27 young-adult marijuana users and 26 healthy controls using single-voxel magnetic resonance spectroscopy on a 3 T scanner. The voxel was placed in the dorsal striatum, and estimated concentrations of glutamate + glutamine, myo-inositol, taurine + glucose, total choline and total N-acetylaspartate were examined between groups. Therewere no overall group effects, but two metabolites showed group by sex interactions. Lower levels of glutamate + glutamine (scaled to total creatine) were observed in female, but not male, marijuana users compared to controls. Higher levels of myo-inositol were observed in female users compared to female non-users and to males in both groups. Findings are discussed in relation to patterns of corticostriatal connectivity and function, in the context of marijuana abuse.

Separable processes before, during, and after the N400 elicited by previously inferred and new information: evidence from time-frequency decompositions.

Successful comprehension during reading often requires inferring information not explicitly presented. This information is readily accessible when subsequently encountered, and a neural correlate of this is an attenuation of the N400 event-related potential (ERP). We used ERPs and time-frequency (TF) analysis to investigate neural correlates of processing inferred information after a causal coherence inference had been generated during text comprehension. Participants read short texts, some of which promoted inference generation. After each text, they performed lexical decisions to target words that were unrelated or inference-related to the preceding text. Consistent with previous findings, inference-related words elicited an attenuated N400 relative to unrelated words. TF analyses revealed unique contributions to the N400 from activity occurring at 1-6 Hz (theta) and 0-2 Hz (delta), supporting the view that multiple, sequential processes underlie the N400.

Associations between cortical thickness and general intelligence in children, adolescents and young adults.

Neuroimaging research indicates that human intellectual ability is related to brain structure including the thickness of the cerebral cortex. Most studies indicate that general intelligence is positively associated with cortical thickness in areas of association cortex distributed throughout both brain hemispheres. In this study, we performed a cortical thickness mapping analysis on data from 182 healthy typically developing males and females ages 9 to 24 years to identify correlates of general intelligence (g) scores. To determine if these correlates also mediate associations of specific cognitive abilities with cortical thickness, we regressed specific cognitive test scores on g scores and analyzed the residuals with respect to cortical thickness. The effect of age on the association between cortical thickness and intelligence was examined. We found a widely distributed pattern of positive associations between cortical thickness and g scores, as derived from the first unrotated principal factor of a factor analysis of Wechsler Abbreviated Scale of Intelligence (WASI) subtest scores. After WASI specific cognitive subtest scores were regressed on g factor scores, the residual score variances did not correlate significantly with cortical thickness in the full sample with age covaried. When participants were grouped at the age median, significant positive associations of cortical thickness were obtained in the older group for g-residualized scores on Block Design (a measure of visual-motor integrative processing) while significant negative associations of cortical thickness were observed in the younger group for g-residualized Vocabulary scores. These results regarding correlates of general intelligence are concordant with the existing literature, while the findings from younger versus older subgroups have implications for future research on brain structural correlates of specific cognitive abilities, as well as the cognitive domain specificity of behavioral performance correlates of normative gray matter thinning during adolescence.

Dopaminergic modulation of incentive motivation in adolescence: age-related changes in signaling, individual differences, and implications for the development of self-regulation.

Behavioral activation that is associated with incentive-reward motivation increases in adolescence relative to childhood and adulthood. This quadratic developmental pattern is generally supported by behavioral and experimental neuroscience findings. It is suggested that a focus on changes in dopamine neurotransmission is informative in understanding the mechanism for this adolescent increase in reward-related behavioral activation and subsequent decline into adulthood. Evidence is presented to indicate that incentive-reward motivation is modulated by mesoaccumbens dopamine, and that it increases in adolescence before declining into adulthood because of normative developmental changes at the molecular level. Potential mechanisms of variation in functional mesoaccumbens dopamine transmission are discussed with a focus on the interplay between tonic and phasic modes of dopamine transmission in modulating both general incentive-motivational biases and the efficacy of reward learning during exposure to novel reward experiences. Interactions between individual difference factors and these age-related trends are discussed.

Incentive Motivation, Cognitive Control, and the Adolescent Brain: Is It Time for a Paradigm Shift?

It can be argued that adolescents' decision making is biased more by motivational factors than by cognitively driven calculations of outcome probabilities. Brain-based models, derived from structural and functional neuroimaging perspectives to account for this bias, have focused on purported differences in rates of development of motivational and regulatory-control systems. This article proposes a neurochemically based framework for understanding adolescents' behavioral biases_and suggests that there should be an increased focus on the dopaminergic substrates of incentive motivation, which increases into adolescence and decreases thereafter. The article also discusses the manner in which this increase interacts with executive control systems in affecting self-regulation.

Associations between cortical thickness and verbal fluency in childhood, adolescence, and young adulthood.

Neuroimaging studies of normative human brain development indicate that the brain matures at differing rates across time and brain regions, with some areas maturing into young adulthood. In particular, changes in cortical thickness may index maturational progressions from an overabundance of neuropil toward efficiently pruned neural networks. Developmental changes in structural MRI measures have rarely been examined in relation to discrete neuropsychological functions. In this study, healthy right-handed adolescents completed MRI scanning and the Controlled Oral Word Association Test (COWAT). Associations of task performance and cortical thickness were assessed with cortical-surface-based analyses. Significant correlations between increasing COWAT performances and decreasing cortical thickness were found in left hemisphere language regions, including perisylvian regions surrounding Wernicke's and Broca's areas. Task performance was also correlated with regions associated with effortful verbal processing, working memory, and performance monitoring. Structure-function associations were not significantly different between older and younger subjects. Decreases in cortical thicknesses in regions that comprise the language network likely reflect maturation toward adult-like cortical organization and processing efficiency. The changes in cortical thicknesses that support verbal fluency are apparent by middle childhood, but with regionally separate developmental trajectories for males and females, consistent with other studies of adolescent development.