Adolescence is a developmental period that entails substantial changes in affective and incentive-seeking behavior relative to both childhood and adulthood, including a heightened propensity to engage in risky behaviors and experience persistent negative and labile mood states. This review discusses the emotional and incentive-driven behavioral changes in adolescents and their associated neural mechanisms, focusing on the dynamic interactions between the amygdala, ventral striatum, and prefrontal cortex. Common behavioral changes during adolescence may be associated with a heightened responsiveness to incentives and emotional cues while the capacity to effectively engage in cognitive and emotion regulation is still relatively immature. We highlight empirical work in humans and animals that addresses the interactions between these neural systems in adolescents relative to children and adults, and propose a neurobiological model that may account for the nonlinear changes in adolescent behavior. Finally, we discuss other influences that may contribute to exaggerated reward and emotion processing associated with adolescence, including hormonal fluctuations and the role of the social environment.

The amygdala was more responsive to fearful (larger) eye whites than to happy (smaller) eye whites presented in a masking paradigm that mitigated subjects' awareness of their presence and aberrant nature. These data demonstrate that the amygdala is responsive to elements of.

Adolescent risk-taking is a public health issue that increases the odds of poor lifetime outcomes. One factor thought to influence adolescents' propensity for risk-taking is an enhanced sensitivity to appetitive cues, relative to an immature capacity to exert sufficient cognitive control. We tested this hypothesis by characterizing interactions among ventral striatal, dorsal striatal and prefrontal cortical regions with varying appetitive load using functional magnetic resonance imaging (fMRI) scanning. Child, teen, and adult participants performed a go nogo task with appetitive (happy faces) and neutral cues (calm faces). Impulse control to neutral cues showed linear improvement with age, whereas teens showed a nonlinear reduction in impulse control to appetitive cues. This performance decrement in teens was paralleled by enhanced activity in the ventral striatum. Prefrontal cortical recruitment correlated with overall accuracy and showed a linear response with age for nogo versus go trials. Connectivity analyses identified a ventral frontostriatal circuit including the inferior frontal gyrus and dorsal striatum during nogo versus go trials. Examining recruitment developmentally showed that teens had greater between-subjects ventral-dorsal striatal coactivation relative to children and adults for happy nogo versus go trials. These findings implicate exaggerated ventral striatal representation of appetitive cues in adolescents relative to an intermediary cognitive control response. Connectivity and coactivity data suggest these systems communicate at the level of the dorsal striatum differentially across development. Biased responding in this system is one possible mechanism underlying heightened risk-taking during adolescence.

Mouse models are useful for studying genes involved in behavior, but whether they are relevant for human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat, and in the efficacy of treatments that rely on extinction mechanisms such as exposure therapy.Genetically modified mice provide useful model systems for testing the role of candidate genes in behavior. The extent to which such genetic manipulations in the mouse and the resulting phenotype can be translated across species, from mouse to human, is less clear. In this report we focused on identifying biologically valid phenotypes across species. We utilized a common single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene that leads to a valine (Val) to methionine (Met) substitution at codon 66 (Val66Met). In an inbred genetic knock-in mouse strain that expresses the variant BDNF allele to recapitulate the specific phenotypic properties of the human polymorphism in vivo, we found the BDNF Val66Met genotype was associated with treatment resistant forms of anxiety-like behavior (1). The objective of this study was to test if the Val66Met genotype could impact extinction learning in our mouse model, and if such findings could be generalized to human populations.BDNF mediates synaptic plasticity associated with learning and memory (2,3) specifically in fear learning and extinction (4,5). BDNF-dependent forms of fear learning have known biological substrates, and lie at the core of a number of clinical disorders (6,7) associated with the variant BDNF (8-10). Fear learning paradigms require the ability to recognize and +To whom correspondence should be addressed. fas2002@med.cornell.edu or bjc2002@med.cornell.edu. remember cues that signal safety or threat and to extinguish these associations when they no longer exist. These abilities are impaired in anxiety disorders such as posttraumatic stress disorder and phobias (11,12). Behavioral treatments for these disorders such as exposure therapy rely on basic principles of extinction learning (13) in which an individual is repeatedly exposed to an event that was previously associated with aversive consequences. Understanding the effect of the BDNF Met allele on these forms of learning can provide insight into the mechanism of risk for anxiety disorders, refine existing treatments, and may lead to genotypebased personalized medicine. NIH Public AccessWe examined the impact of the variant BDNF on classic fear...

One form of cognitive control is the ability to resist temptation in favor of long-term goal-oriented behavior. Historically, the development of cognitive control capacity has been described by a linear function from infancy to adulthood. However, the context in which control is required can impact this capacity, such that emotionally charged or rewarding contexts can diminish control. More recently, studies have begun to examine the development of cognitive control in contexts that vary in motivation. These studies suggest specific windows of development in which cognitive control capacity is more vulnerable to incentive-based modulation. In this review we highlight the most recent work on neurobiological changes supporting motivational and cognitive development, underscoring the importance of functional organization and development of the underlying circuitry implicated in these processes, and provide a theoretical perspective that moves away from discussing singular functional regions toward considering functional circuitry.

We examined the neural basis of self-regulation in individuals from a cohort of preschoolers who performed the delay-ofgratification task 4 decades ago. Nearly 60 individuals, now in their mid-forties, were tested on "hot" and "cool" versions of a go/ nogo task to assess whether delay of gratification in childhood predicts impulse control abilities and sensitivity to alluring cues (happy faces). Individuals who were less able to delay gratification in preschool and consistently showed low self-control abilities in their twenties and thirties performed more poorly than did high delayers when having to suppress a response to a happy face but not to a neutral or fearful face. This finding suggests that sensitivity to environmental hot cues plays a significant role in individuals' ability to suppress actions toward such stimuli. A subset of these participants (n = 26) underwent functional imaging for the first time to test for biased recruitment of frontostriatal circuitry when required to suppress responses to alluring cues. Whereas the prefrontal cortex differentiated between nogo and go trials to a greater extent in high delayers, the ventral striatum showed exaggerated recruitment in low delayers. Thus, resistance to temptation as measured originally by the delay-of-gratification task is a relatively stable individual difference that predicts reliable biases in frontostriatal circuitries that integrate motivational and control processes.reward | behavioral suppression | functional MRI | inferior frontal gyrus | longitudinal T he ability to resist temptation in favor of long-term goals is an essential component of individual, societal, and economical success. Developmentally, this ability has been assessed by measuring how long a young child can resist an immediate reward (e.g., a cookie) in favor of a larger, later reward (e.g., two cookies) (1). Even as adults we vary in our ability to resist temptations. Alluring situations can diminish our control (2-4); what serves as an alluring situation that requires a capacity to control our impulses, however, changes as a function of age (e.g., from cookies to social acceptance). In the present study we examined the extent to which individual differences in delay of gratification assessed when participants were in preschool and in their 20s and 30s predict control over impulses and sensitivity to social cues at the behavioral and neural level when the participants were in their 40s.Delay of gratification depends importantly on cognitive control (5). Cognitive control refers to the ability to suppress competing inappropriate thoughts or actions in favor of appropriate ones (6-11). Previously, we have shown that performance on the delay-of-gratification task in childhood predicts the efficiency with which the same individuals perform a cognitive control task (the go/nogo task) as adolescents and young adults (5). Individuals who as preschoolers directed their attention toward rewarding aspects of the classic delay-of-gratification situation, such as focusing on the cookie...

This study investigated human anterior cingulate cortex (ACC) involvement during a task that dissociated expectancy violation from social rejection. Across two studies, participants underwent functional magnetic resonance imaging while making social judgments and receiving fictitious feedback that was either positive or negative and consistent or inconsistent with their expectations. The results demonstrate that the dorsal ACC is sensitive to expectancy violations, whereas the ventral ACC is differentially responsive to social feedback.

Adolescence is a developmental period often characterized as a time of impulsive and risky choices leading to increased incidence of unintentional injuries and violence, alcohol and drug abuse, unintended pregnancy and sexually transmitted diseases. Traditional neurobiological and cognitive explanations for such suboptimal choices and actions have failed to account for nonlinear changes in behavior observed during adolescence, relative to childhood and adulthood. This review provides a biologically plausible conceptualization of the mechanisms underlying these nonlinear changes in behavior, as an imbalance between a heightened sensitivity to motivational cues and immature cognitive control. Recent human imaging and animal studies provide a biological basis for this view, suggesting differential development of subcortical limbic systems relative to top-down control systems during adolescence relative to childhood and adulthood. This work emphasizes the importance of examining transitions into and out of adolescence and highlights emerging avenues of future research on adolescent brain development.