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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.

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.

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.

One critical aspect of reward-feedback is the impact of local outcome history – how past experiences with choices and outcomes influences current behavior and neural activity. Yet, prior event-related potential (ERP) work in this area has been contentious. This study contributes to this field by using time-frequency measures to better isolate constituent processes. Specifically, we identify how theta and delta are differentially sensitive to local outcome history. Participants completed a binary monetary choice task while we collected EEG data. Unbeknownst to them, trial outcomes were manipulated into pre-determined sequences, ranging from one to eight gains or losses in a row. Analyses were arranged by sequence establishment (first 2 trials of a sequence) and continuation (prolonged sequences of 3–8 trials). During the establishment of a sequence, delta activity to gains and losses were virtually identical on the first (change) trial, demonstrating marked divergence only on the second trial. This difference grew throughout the continuation period, as delta activity was sustained with accruing gains but declined with multiple losses. Theta activity, conversely, demonstrated a maximal loss-gain difference on the change trial but was insensitive to the establishment of a new sequence. Differential theta activity between outcomes decreased as sequences continued, with theta activity increasing over accruing gains and remaining stable over losses. Results indicate that delta-gain and theta-loss signals are relatively stable across sequential outcomes. Furthermore, theta is most sensitive to loss-gain differences on the initial change trial, while delta is more sensitive to gain-loss differences with the continuation of a sequence.

Contains fulltext : 241693.pdf (Publisher’s version ) (Open Access) 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. 11 p.

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.

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.

Objectives Bipolar disorders' (BD) onset before age 18 is a potential marker for a more severe illness course. Adolescence is also a period of significant normative maturation of inhibitory control and reward-relevant decision-making processes, such as decreased delay discounting (i.e., decreased preference for smaller, immediate versus larger, delayed rewards). Adults with BD exhibit elevated delay discounting rates. Very little is known about developmental changes in delay discounting in adolescents with BD, or about associations between inhibitory control and delay discounting in BD. The present study addresses these questions. Methods The sample included 78 participants, ages 13 to 23, with BD or without history of mental illness. Group differences and group by age interaction effects on delay discounting (32 BD, 32 controls with valid responses), probability discounting (34 BD, 37 controls) and inhibitory control indices (34 BD, 38 controls) were assessed. Results Among healthy controls, less discounting of delayed rewards was associated with older age, whereas adolescents with BD did not show age-related associations. There were no group differences in probability discounting or inhibitory control. Limitations The cross-sectional nature of the study cannot fully rule out the less likely interpretation of group differences in cohort effects. Conclusions The lack of age-related improvement in delay tolerance in BD suggests disrupted development of executive control processes within reward contexts, which in turn may contribute to understanding more severe course of pediatric onset BD. Longitudinal studies are needed to examine delay discounting in relation to maturation of neural reward systems among adolescents with BD.

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.

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 non-using controls. Both groups completed a neuropsychological battery at study intake and again two years later. RESULTS: Baseline group differences have been published (Becker, Collins, & Luciana, 2014) 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 non-users 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.

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.

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, Body Mass Index percentile 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.

RATIONALE: lcohol impairs the brain’s detection of performance errors as evidenced by attenuated error-related negativity (ERN), an event-related potential (ERP) thought to reflect a brain system that monitors one’s behavior. However, it remains unclear whether alcohol impairs performance-monitoring capacity across a broader range of contexts, including those entailing external feedback. OBJECTIVE: This study sought to determine whether alcohol-related monitoring deficits are specific to internal recognition of errors (reflected by the ERN) or occur also in external cuing contexts. We evaluated the impact of alcohol consumption on the feedback-related negativity (FRN), an ERP thought to engage a similar process as the ERN but elicited by negative performance feedback in the environment. METHODS: In an undergraduate sample randomly assigned to drink alcohol (n=37; average peak BAC=0.087 g/100 ml, estimated from breath alcohol sampling) or placebo beverages (n =42), ERP responses to gain and loss feedback were measured during a two-choice gambling task. Time–frequency analysis was used to parse the overlapping theta-FRN and delta-P3 and clarified the effects of alcohol on the measures. RESULTS: Alcohol intoxication attenuated both the theta-FRN and delta-P3 brain responses to feedback. The theta-FRN attenuation was stronger following loss than gain feedback. CONCLUSIONS: Attenuation of both theta-FRN and delta-P3 components indicates that alcohol pervasively attenuates the brain’s response to feedback in this task. That theta-FRN attenuation was stronger following loss trials is consistent with prior ERN findings and suggests that alcohol broadly impairs the brain’s recognition of negative performance outcomes across differing contexts.

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.

Healthy participants (n = 79), ages 9–23, completed a delay discounting task assessing the extent to which the value of a monetary reward declines as the delay to its receipt increases. Diffusion tensor imaging (DTI) was used to evaluate how individual differences in delay discounting relate to variation in fractional anisotropy (FA) and mean diffusivity (MD) within whole-brain white matter using voxel-based regressions. Given that rapid prefrontal lobe development is occurring during this age range and that functional imaging studies have implicated the prefrontal cortex in discounting behavior, we hypothesized that differences in FA and MD would be associated with alterations in the discounting rate. The analyses revealed a number of clusters where less impulsive performance on the delay discounting task was associated with higher FA and lower MD. The clusters were located primarily in bilateral frontal and temporal lobes and were localized within white matter tracts, including portions of the inferior and superior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, and splenium of the corpus callosum. FA increased and MD decreased with age in the majority of these regions. Some, but not all, of the discounting/DTI associations remained significant after controlling for age. Findings are discussed in terms of both developmental and age-independent effects of white matter organization on discounting behavior.

Studies have investigated planning skill development using the Tower of London (TOL). Reports conflict regarding maturational trajectories and associations with IQ, other executive functions, and impulsivity. A convenience sample of 9- to 20-year-olds completed the TOL and other measures. TOL accuracy improved until ages 15-17. Digit span backwards (DSB), response inhibition, and IQ were correlated with TOL performance. DSB contributed to TOL accuracy above and beyond age and IQ. Inhibitory control and DSB both contributed to the modulation of planning times across problems. Self-reported inattention and hyperactivity were associated with low performance. Task approaches reflecting planning and psychometric issues are discussed.

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. (C) 2013 Elsevier Inc. All rights reserved.

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.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).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.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.

This longitudinal study examines associations between baseline individual differences and developmental changes in reward [i.e. behavioral approach system (BAS)] sensitivity and relevant brain structures' volumes to prospective substance use initiation during adolescence. A community sample of adolescents ages 15-18 with no prior substance use was assessed for substance use initiation (i.e. initiation of regular alcohol use and/or any use of other substances) during a 2-year follow-up period and for alcohol use frequency in the last year of the follow-up. Longitudinal 'increases' in BAS sensitivity were associated with substance use initiation and increased alcohol use frequency during the follow-up. Moreover, adolescents with smaller left nucleus accumbens at baseline were more likely to initiate substance use during the follow-up period. This study provides support for the link between developmental increases in reward sensitivity and substance use initiation in adolescence. The study also emphasizes the potential importance of individual differences in volumes of subcortical regions and their structural development for substance use initiation during adolescence.

Adolescence is characterized by complex developmental processes that impact behavior, biology, and social functioning. Two such adolescence-specific processes are puberty and increases in reward sensitivity. Relations between these processes are poorly understood. The present study focused on examining unique effects of puberty, age, and sex on reward and threat sensitivities and volumes of subcortical brain structures relevant for reward/threat processing in a healthy sample of 9 to 18 year-olds. Unlike age, pubertal status had a significant unique positive relationship with reward sensitivity. In addition, there was a trend for adolescent females to exhibit higher threat sensitivity with more advanced pubertal development and higher reward and threat sensitivity with older age. Similarly, there were significant puberty by sex interaction effects on striatal volumes, i.e., left nucleus accumbens and right pallidum. The present pattern of results suggests that pubertal development, independent of chronological age, is uniquely associated with reward hypersensitivity and with structural differences in striatal regions implicated in reward processing.

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.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.Participants (n = 55) completed MRI scans and behavioral assessments.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.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.

A fundamental question in frontal lobe function is how motivational and emotional parameters of behavior apply to executive processes. Recent advances in mood and personality research and the technology and methodology of brain research provide opportunities to address this question empirically. Using event-related-potentials to track error monitoring in real time, the authors demonstrated that variability in the amplitude of the error-related negativity (ERN) is dependent on mood and personality variables. College students who are high on negative affect (NA) and negative emotionality (NEM) displayed larger ERN amplitudes early in the experiment than participants who are low on these dimensions. As the high-NA and -NEM participants disengaged from the task, the amplitude of the ERN decreased. These results reveal that affective distress and associated behavioral patterns are closely related with frontal lobe executive functions.

Extraversion has two central characteristics: (1) interpersonal engagement, which consists of affiliation (enjoying and valuing close interpersonal bonds, being warm and affectionate) and agency (being socially dominant, enjoying leadership roles, being assertive, being exhibitionistic, and having a sense of potency in accomplishing goals) and (2) impulsivity, which emerges from the interaction of extraversion and a second, independent trait (constraint). Agency is a more general motivational disposition that includes dominance, ambition, mastery, efficacy, and achievement. Positive affect (a combination of positive feelings and motivation) is closely associated with extraversion. Extraversion is accordingly based on positive incentive motivation.Parallels between extraversion (particularly its agency component) and a mammalian behavioral approach system based on positive incentive motivation implicate a neuroanatomical network and modulatory neurotransmitters in the processing of incentive motivation. A corticolimbic-striatal-thalamic network (1) integrates the salient incentive context in the medial orbital cortex, amygdala, and hippocampus; (2) encodes the intensity of incentive stimuli in a motive circuit composed of the nucleus accumbens, ventral pallidum, and ventral tegmental area dopamine projection system; and (3) creates an incentive motivational state that can be transmitted to the motor system.Individual differences in the functioning of this network arise from functional variation in the ventral tegmental area dopamine projections, which are directly involved in coding the intensity of incentive motivation. The animal evidence suggests that there are three neurodevelopmental sources of individual differences in dopamine: genetic, “experience-expectant,” and “experience-dependent.” Individual differences in dopamine promote variation in the heterosynaptic plasticity that enhances the connection between incentive context and incentive motivation and behavior.Our psychobiological threshold model explains the effects of individual differences in dopamine transmission on behavior, and their relation to personality traits is discussed.

The commentaries on our target article address three main areas: (1) the relative importance of extraversion and other related traits to DA functioning, (2) how the long-term stability of extraversion can be conceptualized within a highly plastic central nervous system, and (3) the nature of DA functioning in the MOC network and in extraversion. We have organized our Response, therefore, into three major sections.

Neurocognitive research has focused on monoaminergic influences over broad behavior patterns. For example, dopamine (DA) generally facilitates informational transfer within limbic and cortical networks to promote reward-seeking behavior. Specifically, DA activity in prefrontal cortex modulates the ability for nonhuman primates and humans to perform spatial working memory tasks. Serotonin (5HT) constrains the activity of DA, resulting in an opposing relationship between DA and 5HT with respect to emotional and motor behaviors. A role for 5HT in constraining prefrontally guided spatial working memory (WM) processes in humans has not been empirically demonstrated but is a logical avenue for study if these principles of neurotransmitter activity hold within cortical networks. In this study, normal humans completed a visuospatial WM task under pharmacological challenge with (i) bromocriptine, a DA agonist and (ii) fenfluramine, a serotonin agonist, in a double-blind, repeated-measures, placebo-controlled design. Findings indicate that bromocriptine facilitated spatial delayed, but not immediate, memory performance. Fenfluramine resulted in impaired delayed spatial memory. These effects were not due to nonspecific arousal, attentional, sensorimotor or perceptual changes. These findings suggest that monoaminergic neurotransmitters (DA and 5HT) may interact within cortical networks to modulate the expression of specific cognitive behaviors, particularly effortful processes associated with goal-directed activity.

It appears that functionally segregated visual pathways exist in the primate brain for the processing of visuospatial versus nonspatial information. Functional segregation has been demonstrated for the early associative processing of sensory information but may also exist at higher levels of cognitive analysis. Namely, connections between the dorsal visual system and dorsolateral prefrontal cortex (PFC) appear to mediate spatial working memory, which is modulated by dopamine receptor fields in the principal sulcal region of the PFC. It is speculated that nonspatial working memory may be modulated within connections between ventral visual processing regions and the inferior convexity of the PFC. Whether dopamine facilitates nonspatial memory through connections between the ventral visual system and ventral PFC has not been examined. In this study, normal humans completed spatial and nonspatial working memory tasks under pharmacological challenges with a dopamine receptor agonist (bromocriptine) and antagonist (haloperidol) in a double-blind placebcxontrolled repeated measures design. Findings indicated facilitation of spatial delayed working memory functions by bromocriptine and impairment of spatial working memory functions by haloperidol. Neither drug was effective in manipulating nonspatial memory performance. Control tasks were included to measure drug effects on basic sensorimotor and attentional processes. Findings suggest that separate processing mechanisms for remembering “What” versus “Where” an object is may exist at structural, but also neurochemical, levels in the human brain.

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. There were 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., Highlights • The neurochemical profile of the basal ganglia was examined in young marijuana users. • Glutamate/glutamine levels were lower in female users versus male users and controls. • Higher myo-inositol levels were observed in female users as compared to other groups. • Neurochemical impacts of marijuana may be particularly pronounced in females.

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.

International audience; 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. There were 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.

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.

Figure 2 was distorted in production. The correct version is presented in the erratum.] Adolescence is a period of radical normative changes and increased risk for substance use, mood disorders, and physical injury. Researchers have proposed that increases in reward sensitivity (i.e., sensitivity of the behavioral approach system [BAS]) and/or increases in reactivity to all emotional stimuli (i.e., reward and threat sensitivities) lead to these phenomena. The present study is the first longitudinal investigation of changes in reward (i.e., BAS) sensitivity in 9- to 23-year-olds across a 2-year follow-up. Support was found for increased reward sensitivity from early to late adolescence, and evidence was found for decline in the early 20s. This decline is combined with a decrease in left nucleus accumbens (Nacc) volume, a key structure for reward processing, from the late teens into the early 20s. Furthermore, we found longitudinal increases in sensitivity to reward to be predicted by individual differences in the Nacc and medial orbitofrontal cortex (OFC) volumes at baseline in this developmental sample. Similarly, increases in sensitivity to threat (i.e., behavioral inhibition system sensitivity) were qualified by sex, with only females participants experiencing this increase, and predicted by individual differences in lateral OFC volumes at baseline.

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.

Modern trait theories of personality include a dimension reflecting positive emotionality (PE) based on sensitivity to signals of incentive-reward. In animals, responsivity within an emotional system analog of PE is dependent on brain dopamine (DA) activity. To determine whether human PE trait levels are also associated with central DA, effects of a specific DA D2 receptor agonist were assessed in Ss who were widely distributed along the trait dimension of PE. The degree of agonist-induced reactivity in two distinct central DA indices was strongly and specifically associated with trait levels of PE, but not with other personality traits. The results suggest that the trait structure of personality may be related to individual differences in brain DA functioning.

The neural correlates of cross-modal recognition memory were examined in 8-month-old infants by using event-related potentials. Testing began by having all Ss feel (but not see) an object for 60 s. Test trials then followed. Infants in Condition 1 received 15 presentations of a picture of the familiar object, followed by alternating pictures of that object and a novel object. Infants in Condition 2 received 15 presentations of a picture of the novel object, followed by the same test sequence as infants in Condition 1. Infants in Condition 3 were presented with 2 test trials during which looking times were recorded to pictures of the familiar and novel objects; they then received the same test sequence as infants in Conditions 1 and 2. Infants in Condition 4 were presented only with the same test sequence as infants in Conditions 1, 2, and 3. Only in Conditions 1 and 4 was a late positive slow wave invoked by the novel object (indicative of recognition memory), although infants in Condition 3 did show a significant looking preference for the novel object

The neural and behavioral correlates of the 4- and 8-month-old infant's ability to distinguish between frequently and infrequently presented familiar and novel events was examined. Cortical event-related potentials (ERPs) were recorded as infants were familiarized to two faces. During the test trials that followed, one of these faces was presented frequently, and the other infrequently; on each of the remaining 20% of the trials, a previously unseen, novel face was presented. Following the ERP phase, infants' looking times were recorded to pairs of faces, some of which had been seen during the ERP testing, and some of which had not. At 4 months the ERP activity invoked by the three classes of events was similar, suggesting that infants were unable to distinguish among them. At 8 months the ERP activity differed only between the Infrequent Novel events and the two classes of familiar events, but did not differ between the frequently and infrequently presented familiar events. The ERP findings complement previously reported data from 6-month-old infants in describing a trend whereby infants become increasingly able to respond to stimuli on the basis of whether they have been seen before, and not on the basis of how often they had been seen. The behavioral data at both 4 and 8 months were less clear cut than the ERP data. These findings are discussed in the context of the neural and cognitive processes involved in dissociating probability information from novelty detection.

Adolescence is characterized by increased risk-taking, novelty-seeking, and locomotor activity, all of which suggest a heightened appetitive drive. The neurotransmitter dopamine is typically associated with behavioral activation and heightened forms of appetitive behavior in mammalian species, and this pattern of activation has been described in terms of a neurobehavioral system that underlies incentive-motivated behavior. Adolescence may be a time of elevated activity within this system. This review provides a summary of changes within cortical and subcortical dopaminergic systems that may account for changes in cognition and affect that characterize adolescent behavior. Because there is a dearth of information regarding neurochemical changes in human adolescents, models for assessing links between neurochemical activity and behavior in human adolescents will be described using molecular genetic techniques. Furthermore, we will suggest how these techniques can be combined with other methods such as pharmacology to measure the impact of dopamine activity on behavior and how this relation changes through the lifespan.

• Event-related potentials were recorded over occipital and parietal scalp from 20 patients suffering from intractable partial complex seizures prior to undergoing a temporal lobectomy. Subjects were presented with language and nonlanguage visual stimuli using a divided-field, "oddball" paradigm. Although behavioral performance (button-press accuracy, reaction time, and running counts) was comparable across all groups (although accuracy was worse for those in the left temporal group), patients showed tremendous variability in both the amplitude and latency of the P300 response. Particularly notable was the observation that more slow wave activity was present among the patients than among the control subjects, and those scheduled for a left temporal resection evinced more amplitude reduction than those scheduled for a right temporal resection. In addition, a number of patients appeared not to show a P300 response at all. These results are discussed in the context of the utility of using noninvasive event-related potential measures to examine both memory impairment and the integrity of the neural structures that mediate memory functioning in certain patient populations.

Event-related potentials (ERPs) and fixation duration were used to examine 6-month-old infants' responses to frequently and infrequently presented familiar and novel events.

Healthy adolescents, ages 9–23, completed delay and probability discounting tasks and measures of verbal and nonverbal intelligence, executive functioning, and self-reported internalizing and externalizing behavior. Delay but not probability discounting decreased with age. Delay discounting was also associated with verbal intelligence and Go-NoGo and Iowa Gambling Task performance. Probability discounting was associated only with externalizing behavior. Findings conform to an accumulation of evidence that while delay and probability discounting may have some overlapping components, they also reflect some fundamentally different processes in this age group.

The present study examined subjects' cognitive processing of pictures of emotional and neutral facial expressions, as measured by Event-Related Potentials (ERPs). In Experiment 1, 10 subjects viewed two slides of a woman modelling angry and happy expressions; in Experiment 2, 10 subjects viewed slides of two women modelling neutral expressions. One face appeared on 20% of the trials and the other on 80% of the trials. Subjects counted the low frequency target face. In both experiments, the area of the P300 component was larger at Pz than Cz. In Experiment 1, P300 area was larger when the target was happy; peak amplitude was greater when the target was angry. No differences between neutral target faces were found for P300 amplitude or area in Experiment 2. These results suggest that emotional versus neutral facial expressions elicit different electrophysiological responses; responses are further differentiated to positive versus negative expressions.

Event‐Related Potentials (ERPs) were recorded as 6‐month‐old infants were presented with a picture whose appearance was cued by a preceding tone. On a subset of these trials the picture was deleted. ERPs reflecting “surprise” to the stimulus deletion were observed on the trial following the deleted trial. These results are discussed in the context of the degree to which physically absent events act as novel events, and the limits of infants’ short‐term memory.

Cross-sectional and longitudinal volumetric studies suggest that the corpus callosum (CC) continues to mature structurally from infancy to adulthood. Diffusion tensor imaging (DTI) provides in vivo information about the directional organization of white matter microstructure and shows potential for elucidating even more subtle brain changes during adolescent development. We used DTI to examine CC microstructure in healthy right-handed adolescents (n=92, ages 9-24 years) and correlated the imaging data with motor task performance. The primary DTI variable was fractional anisotropy (FA), which reflects the degree of white matter's directional organization. Participants completed an alternating finger tapping test to assess interhemispheric transfer and motor speed. Task performance was significantly correlated with age. Analyses of variance indicated that 9- to 11-year-olds generally performed worse than each of the older groups. Males outperformed females. Significant positive correlations between age and FA were observed in the splenium of the CC, which interconnects posterior cortical regions. Analyses of variance indicated that individuals older than 18 years had significantly higher FA than 9- to 11-year-olds. FA levels in the genu and splenium correlated significantly with task performance. Regression analyses indicated that bimanual coordination was significantly predicted by age, gender, and splenium FA. Decreases in alternating finger tapping time and increases in FA likely reflect increased myelination in the CC and more efficient neuronal signal transmission. These findings expand upon existing neuroimaging reports of CC development by showing associations between bimanual coordination and white matter microstructural organization in an adolescent sample.