Introduction

Adolescence is a transitional period of development when there are many changes experienced concomitantly, including physical maturation, drive for independence, increased salience of social and peer interaction, and brain development ^1–3. This developmental period is also a time characterized by an inflection in risky behaviors including experimentation with drugs and alcohol, criminal activity and unprotected sex. Understanding the neural basis of these risky behaviors is key in identifying which teens may be at risk for poor outcomes, such as substance dependence and abuse.

A number of hypotheses have been postulated for why adolescents may engage in impulsive and risky behaviors. Traditional accounts of adolescence suggest that it is a period of development associated with progressively greater efficiency of cognitive control capacities. This efficiency in cognitive control is described as dependent on maturation of the prefrontal cortex as evidenced by imaging ^4–7 and post mortem studies^8–10 showing continued structural and functional development of this region well into young adulthood.

Improved cognitive control with development of the prefrontal cortex is consistent with a linear increase in this ability from childhood to adulthood. Yet suboptimal choices and actions observed during adolescence represent an inflection in development ¹¹ that is unique from either childhood or adulthood, as evidenced by the National Center for Health Statistics on adolescent behavior and mortality ¹². If cognitive control and an immature prefrontal cortex were the basis for suboptimal choice behavior alone, then children should look remarkably similar or presumably worse than adolescents, given their less developed prefrontal cortex and cognitive abilities ². This review addresses the primary question of how the brain is changing during adolescence that may explain inflections in risky and impulsive behavior. In addition, we provide examples of how alcohol and drug use during this period of development may further exacerbate these changes and can lead to subsequent abuse and dependence.

To accurately capture cognitive and neurobiological changes during adolescence, this period must be treated as a transitional one rather than a single snapshot in time ³. In other words, to understand this developmental period, transitions into and out of adolescence are necessary for distinguishing distinct attributes of this period relative to other time points in development. Therefore, empirical data that establishes developmental trajectories from childhood to adulthood for cognitive and neural processes are essential in characterizing these transitions and more importantly in constraining any interpretations about changes in brain or behavior in adolescence.

Second, accurate depictions of adolescence require a refinement in the phenotypic characterization of this period. For example, on a behavioral level, adolescents are often characterized as impulsive and greater risk-takers with these constructs used almost synonymously. Yet, these constructs are distinct and appreciating this distinction is important for describing their developmental trajectories and neural underpinnings. We provide behavioral, clinical and neurobiological evidence that suggest that risk-taking is more tightly coupled with sensitivity to environmental incentives (sensation-seeking) whereas impulsivity is associated with poor top down cognitive control.

To theoretically ground the empirical findings, we provide a plausible neurobiological model for adolescence and suggest how development during this time may lead to an enhancement in vulnerabilities for alcohol and drug abuse. The intention of this review is not to psychopathologize adolescence, but rather to explain why some teens but not others are vulnerable to substance abuse. As such, we attempt to identify potential biological and behavioral markers for early identification and for outcome assessments of interventions.

Neurobiological Model of Adolescence

A neurobiological model of adolescent development ² that builds on rodent models ^{13, 14} and recent imaging studies of adolescence ^{6, 7, 15–20} is depicted Figure 1. This model illustrates how subcortical and prefrontal top-down control regions must be considered together as a circuit. The cartoon shows different developmental trajectories for signaling of these regions, with limbic projections developing earlier than prefrontal control regions. According to the model, the adolescent is biased by functionally mature subcortical relative to less mature cortical circuitry during adolescence (i.e., imbalance in reliance of systems), compared to children, for whom this frontolimbic circuitry is still developing; and compared to adults, for whom these systems are fully mature. With development and experience, the functional connectivity between these regions is strengthened and provides a mechanism for top down modulation of the subcortical systems ⁷. Thus it is the frontostriatal circuitry, along with functional strengthening of connections within this circuitry, that may provide a mechanism to explain changes in both impulsivity and risk-taking observed across development.

This model is consistent with previous ones ^21–24 in that it provides a basis for nonlinear inflections observed in behavior from childhood to adulthood, due to earlier maturation of subcortical projections relative to less mature top down prefrontal ones. Specifically, the triadic model ²¹ proposes that motivated behavior has three distinct neural circuits (approach, avoidance and regulatory). The approach system is largely controlled by the ventral striatum, avoidance system by the amygdala and lastly, the regulatory system by the prefrontal cortex ²⁵. The current model differs largely from others in that it is grounded in empirical evidence for brain changes not only in the transition from adolescence to adulthood, but rather the transition into adolescence from childhood and later out of adolescence into adulthood. Moreover, the model does not suggest that the striatum and amygdala are specific to approach and avoidant behavior given recent studies showing valence independence of these structures ²⁶, but rather are systems that are important in detecting motivationally and emotionally relevant cues in the environment that can bias behavior. In this review, we describe the most recent evidence from behavioral and human imaging studies of adolescence in the context of our model that illustrates the transition from childhood to adulthood.

Go to:

Phenotypic Characterization of Adolescence

The ability to resist temptation in favor of long-term goals is a form of cognitive control. Lapses in this ability have been suggested to be at the very core of adolescent risky behavior ²⁷. Cognitive control, which includes resistance from temptation or delay of immediate gratification has been studied in the context of social, developmental and cognitive psychology. Developmentally, this ability has been measured by assessing how long a toddler can resist an immediate reward (e.g., a cookie) in favor of a larger reward later (e.g., two cookies) ²⁸. Although individuals vary in this ability even as adults, developmental studies suggest windows of development when an individual may be particularly susceptible to temptations. This ability has been described as a form of impulse control ²⁹ and it is multi-faceted ^{30, 31}, but can be operationally defined as the ability to accomplish goal-directed behavior in the face of salient, competing inputs and actions ³².

Historically, developmental studies have shown a steady improvement in cognitive control capacity from infancy to adulthood ³³. This observation is supported by a wealth of behavioral evidence from experimental paradigms in controlled laboratory settings including paradigms such as the Go-NoGo task, Simon task, and task-switching paradigms that require participants to override a prepotent response in order to achieve a correct one ^{32, 34}. However, when it is advantageous to suppress a response to incentive-related cues, cognitive control suffers ²⁰. This reduced control is especially evident during the period of adolescence, when suboptimal choices in sexual and drug related behaviors peak ^{3, 11, 12, 14}. These observations imply that developmental trajectories in cognitive control are complex and can be modulated by emotionally charged or reinforcing contexts (e.g., social and sexual interactions), in which cognitive control demands interact with motivational drives or processes.

Motivation can modulate cognitive control in at least two ways. First, being rewarded for performance on a given task can make people work harder and ultimately perform better than when not rewarded ¹⁷. Second, the capacity to exert control can be challenged when required to suppress thoughts and actions toward appetitive cues ²⁰. Recent studies of adolescent development have begun to compare cognitive control capacity in relatively neutral versus motivational contexts. These studies suggest a change in sensitivity to environmental cues, especially reward-based ones at different points in development, and suggest a unique influence of motivation on cognition during the adolescent years.

In the following section, we highlight some of the most recent studies of how adolescent behavior is differentially biased in emotionally charged contexts relative to adults.

For example, Ernst and colleagues ^{35, 36} examined performance on an antisaccade task with a promise of financial reward for accurate performance on some trials but not others. Results showed that promise of a reward, facilitated adolescent cognitive control behavior more than for adults, a finding that has been replicated ¹⁷ and recently been extended to social rewards (e.g. happy faces ²⁰).

While the previous examples provide instances of enhanced performance in teens with incentives, rewards can also diminish performance when suppressing responses to rewards that lead to high gain. For example, using a gambling task in which reward feedback was provided immediately during decision-making (“hot” trials which heightened task-elicited affective arousal) or withheld until after the decision (“cold” deliberate decision making trials), Figner and colleagues ³⁷ showed that adolescents made disproportionately more risky gambles compared to adults but only in the “hot” condition. Using a similar task, the Iowa Gambling Task, Cauffman and colleagues ³⁸ have shown that this sensitivity to rewards and incentives actually peaks during adolescence, with a steady increase from late childhood to adolescence in tendency to play with more advantageous decks of cards and then a subsequent decline from late adolescence to adulthood. These findings illustrate a curvilinear function, peaking roughly between 13 and 17, and then declining ²⁷. While prior findings with the Iowa Gambling task have shown a linear increase in performance with age ³⁹, these studies did not look at age continuously nor did they examine only trials with advantageous decks of cards.

Recent studies have suggested that social contexts, particularly peers, may also serve as a motivational cue and can diminish cognitive control during adolescence. It has been shown that the degree to which an adolescent’s peers are using substances is directly proportional to the amount of alcohol or illegal substances that the adolescent themselves will use ⁴⁰. Using a simulated driving task, Gardner and colleagues ⁴¹ have shown that adolescents make riskier decisions in the presence of peers than when alone and that these risky decisions decrease linearly with age ^{23, 40}.

Taken together, these studies suggest that during adolescence, motivational cues of potential reward are particularly salient and can lead to improved performance when provided as a reinforcer or rewarded outcome, but to riskier choices or suboptimal choices when provided as a cue. In the latter case, the motivational cue can diminish effective goal-oriented behavior. Furthermore, these studies suggest that sensitivity to rewards and sensation- seeking behavior are distinct from impulsivity with very different developmental patterns (curvilinear function versus a linear function, respectively). This distinction is further evident in a recent study by Steinberg et al. ⁴² using self- report measures of sensation- seeking and impulsivity. They tested whether the often-conflated constructs of sensation-seeking and impulsivity develop along different timetables in nearly 1000 individuals between the ages of 10 and 30. The results showed that differences in sensation-seeking with age followed a curvilinear pattern, with peaks in sensation-seeking increasing between 10 and 15 years and declining or remaining stable thereafter. In contrast, age differences in impulsivity followed a linear pattern, with decreasing impulsivity with age in a linear fashion (see Figure 2 panel A). These findings together with the laboratory based findings, suggest heightened vulnerability to risk- taking in adolescence “may be due to the combination of relatively higher inclinations to seek excitement and relatively immature capacities for self-control that are typical of this period of development” ⁴².

Neurobiology of Adolescence

As denoted in our model of adolescence, two key regions implicated in cognitive and motivational behavior are the prefrontal cortex, known to be important for cognitive control ⁴³ and the striatum critical in detecting and learning about novel and rewarding cues in the environment ⁴⁴. We highlight recent animal and human imaging work on neurobiological changes supporting these motivational and cognitive systems across development in the context of the previous behavioral findings on the development of sensation-seeking and impulsivity. We use the previously described imbalance model of linear development of top down prefrontal regions relative to a curvilinear function for development of bottom-up striatal regions involved in detecting salient cues in the environment to ground the findings. The importance of examining circuitry rather than specific regional change, especially within frontostriatal circuits that underlie different forms of goal-oriented behavior is key. This perspective moves the field away from examination of how each region matures in isolation to how they may interact in the context of interconnected circuits.

Seminal animal and human work has shown how striatal and prefrontal cortical regions shape goal-directed behavior ^{7, 27, 37, 38, 44}. Using single-unit recordings in monkeys, Pasupathy & Miller ⁴⁵ demonstrated that when flexibly learning a set of reward contingencies, very early activity in the striatum provides the foundation for reward-based associations, whereas later, more deliberative prefrontal mechanisms are engaged to maintain the behavioral outputs that can optimize the greatest gains, these findings have been replicated in lesion studies ^46–48. A role for the striatum in early temporal coding of reward contingencies prior to the onset of activation in prefrontal regions has also been extended to humans ⁴⁹. These findings suggest that understanding the interactions between regions (along with their component functions); within frontostriatal circuitry is critical for developing a model of cognitive and motivational control in adolescence.

Frontostriatal circuits undergo considerable elaboration during adolescence ^50–53 that are particularly dramatic in the dopamine system. Peaks in the density of dopamine receptors, D1 and D2 in the striatum occur early in adolescence, followed by a loss of these receptors by young adulthood ^54–56. In contrast, the prefrontal cortex does not show peaks in D1 and D2 receptor density until late adolescence and young adulthood ^{57, 58}. Similar developmental changes have been shown in other reward related systems including cannabinoid receptors ⁵⁹. It remains unclear how changes in the dopamine systems may relate to motivated behavior as controversy remains as to whether reward sensitivity is modulated by dopamine systems (e.g., ^{60, 61}) and whether it is a result of less active or hypersensitive dopamine systems (e.g., ^{62, 63}). However, given the dramatic changes in dopamine rich circuitry during adolescence, it is likely to be related to changes in sensitivity to rewards distinct from childhood or adulthood ^{50, 64}. Beyond the significant changes in dopamine receptors, there are also dramatic hormonal changes which occur during adolescence that lead to sexual maturity, and influence functional activity in frontostriatal circuits ⁶⁵, however, a detailed discussion is beyond the scope of this paper, see ^{66, 67} for detailed reviews on the subject.

Human imaging studies have begun to provide support for strengthening in the connections of dopamine rich frontostriatal circuitry, across development. Using diffusion tensor imaging and functional magnetic resonance (fMRI), Casey and colleagues ^{68, 69} and others ⁷⁰ have shown greater strength in distal connections within these circuits across development and have linked connection strength between prefrontal and striatalregions with the capacity to effectively engage cognitive control in typically and atypically developing individuals ^{68, 69}. These studies illustrate the importance of signaling within corticostriatal circuitry which support the capacity to effectively engage in cognitive control.

Likewise, there is mounting evidence from human functional neuroimaging studies on how subcortical systems like the striatum and the prefrontal cortex interact to give rise to risky behavior observed in adolescents ⁷¹. The majority of imaging studies have focused on one or the other regions showing that the prefrontal cortex, thought to subserve age-related improvement in cognitive control ^72–78 undergoes delayed maturation ^{4, 79, 80} while striatal regions sensitive to novelty and reward manipulations develop earlier ^{74, 81}. Several groups have shown that adolescents show heightened activation of the ventral striatum in anticipation and/or receipt of rewards compared to adults ^{6, 15, 17, 18}, but others report a hypo-responsiveness ⁸².

One of the first studies to examine reward related processes across the full spectrum of development from childhood to adulthood was completed by Galvan and colleagues ⁶ in 6 to 29 year olds. They showed that ventral striatal activation was sensitive to varying magnitudes of monetary reward ⁴⁹ and that this response was exaggerated during adolescence, relative to children and adolescents ⁶ (see Figure 3), indicative of signal increases ⁶ or more sustained activation ⁸³. In contrast to the pattern in the ventral striatum, orbital prefrontal regions, showed protracted development across these ages (Figure 2b).

But, how does this enhancement of signaling in the ventral striatum relate to behavior? In a follow-up study, Galvan and colleagues ¹⁶ examined the association between activity in the ventral striatum to large monetary reward with personality trait measures of risk-taking and impulsivity. Anonymous self-report rating scales of risky behavior, risk perception and impulsivity were acquired in her sample of 7 to 29 year olds. Galvan et al. showed a positive association between ventral striatal activity to large reward and the likelihood of engaging in risky behavior (see Figure 3) These findings are consistent with adult imaging studies showing ventral striatal activity with risky choices ^{84, 85}.

To further support an association between adolescents' risky behavior and sensitivity to reward as indexed by an exaggerated ventral striatal response, Van Leijenhorst and colleagues ¹⁸ tested this association using a gambling task. The task included Low-Risk gambles with a high probability of obtaining a small monetary reward and High-Risk gambles with a smaller probability of obtaining a larger monetary reward. The fMRI results confirmed that High-Risk choices were associated with ventral striatal recruitment whereas Low-Risk choices were associated with activation in ventral medial prefrontal cortex. These findings are consistent with the hypothesis that risky behavior in adolescence is associated with an imbalance caused by different developmental trajectories of subcortical reward and prefrontal regulatory brain regions consistent with our neurobiological model of adolescence.

While there appears to be an association between risk-taking behavior and ventral striatal activation, in the Galvan study ¹⁶ no correlation was reported between ventral striatal activity with impulsivity. Rather, impulsivity ratings were correlated with age, consistent with numerous imaging studies showing linear development with age in prefrontal cortical recruitment during impulse control tasks ^{7, 75, 77} (and see reviews by ^{34, 86}). Moreover, recent studies have shown that impulsivity ratings inversely correlate with volume of the ventral medial prefrontal cortex in a sample of healthy boys (7–17yrs) ⁸⁷. Finally, studies of clinical populations characterized by impulsivity problems like ADHD, show impaired impulse control and reduced activity in prefrontal regions compared to controls, ^{88, 89} but do not show heightened responses to incentives ⁹⁰.

These findings provide neurobiological empirical support for a dissociation of the constructs related to risk-taking and reward sensitivity from that of impulsivity with the former showing an curvilinear pattern and the latter a linear pattern (see Figure 2 B). Thus adolescent choices and behavior cannot be explained by impulsivity or protracted development of the prefrontal cortex alone. Rather, motivational subcortical regions must be considered to elucidate why adolescent behavior is not only different from adults, but from children as well. Thus, the ventral striatum appears to play a role in levels of excitement ^{82, 91} and positive affect ¹⁵ when receiving rewards, as well as the propensity for sensation-seeking and risk-taking ^{16, 91}. More importantly, these findings suggest that during adolescence, some individuals may be more prone to engage in risky behaviors due to developmental changes in concert with variability in a given individual’s predisposition to engage in risky behavior, rather than to simple changes in impulsivity.

A scientific area that has received less attention is determining how cognitive control and motivational systems interact over the course of development. As mentioned earlier, Ernst and colleagues ^{35, 36} showed that promise of a monetary reward facilitated adolescent cognitive control behavior more than for adults. Geier et al. ¹⁷ recently identified the neural substrates of this cognitive up-regulation using a variant of an antisaccade task during functional brain imaging. In adolescents and adults, trials for which money was at stake speeded performance and facilitated accuracy, but this effect was larger in adolescents. Following a cue that the next trial would be rewarded, adolescents showed exaggerated activation in the ventral striatum while preparing for and subsequently executing the antisaccade. An exaggerated response was observed in adolescents within prefrontal regions along the precentral sulcus, important for controlling eye movements, suggesting a reward-related up-regulation in control regions as well.

Rewards, as suggested above, can enhance as well as diminish goal-directed behavior. The observation that adolescents take more risks when appetitive cues are present versus absent during gambling tasks makes this point (e.g., ³⁷). In a recent imaging study ²⁰, Somerville et al. identified the neural substrates of down-regulation of control regions with appetitive cues. Somerville et al. tested child, adolescent, and adult participants while they performed a go nogo task with appetitive social cues (happy faces) and neutral cues. Task performance to neutral cues showed steady improvement with age on this impulse control task. However, on trials for which the individual had to resist approaching appetitive cues, adolescents failed to show the expected age-dependent improvement. This performance decrement during adolescence was paralleled by enhanced activity in the striatum. Conversely, activation in the inferior frontal gyrus was associated with overall accuracy and showed a linear pattern of change with age for the nogo versus go trials. Taken together, these findings implicate exaggerated ventral striatal representation of appetitive cues in adolescents in the absence of a mature cognitive control response.

Collectively, these data suggest that although adolescents as a group are considered risk-takers ⁴¹, some adolescents will be more prone than others to engage in risky behaviors, putting them at potentially greater risk for negative outcomes. These findings underscore the importance of considering individual variability when examining complex brain-behavior relationships related to risk-taking and impulsivity in developmental populations. Further, these individual and developmental differences may help to explain vulnerability in some individuals to risk-taking which is associated with substance use, and ultimately, addiction ⁶⁴.

Substance Use and Abuse in Adolescents

Adolescence marks a period of increased experimentation with drugs and alcohol ⁹², with alcohol being the most abused of illegal substances by teens ^{11, 93, 94}. Early use of these substances, such as alcohol, is a reliable predictor of later dependence and abuse ⁹⁵. Given the surge in alcohol dependence between adolescence and adulthood that is unequaled at any other developmental stage ⁹⁶, we focus predominantly on a select review here of its use and abuse in adolescents and motivational properties.

Alcohol as well as other substances of abuse, including cocaine and cannabinoids, have been shown to have reinforcing properties. These substances influence mesolimbic dopamine transmission with acute activations of neurons in frontolimbic circuitry rich in dopamine, including the ventral striatum ^97–99. As suggested by Hardin and Ernst (2009) ⁹², the use of these substances may exacerbate an already enhanced ventral striatum response resulting in heightened or strengthening of reinforcement properties to the drug. Robinson and Berridge ^{61, 63, 100} have suggested that these drugs of abuse can “hijack” the systems associated with drug incentives like the ventral striatum, thus down regulating top down prefrontal control regions.

The majority of empirical work on adolescent use of alcohol has been done in animals, given ethical constraints in performing such studies in human adolescents. Animal models of ethanol also provide the most evidence for differential effects of alcohol in adolescents relative to adults and are consistent with human findings of adolescents having relative insensitivity to ethanol effects. Spear and colleagues have shown that adolescent rats relative to adults, are less sensitive to the social, motor, sedation, acute withdrawal and “hangover effects” of ethanol ^101–103. These findings are significant in that many of these effects serve as cues to limit intake in adults ¹¹. Likewise, at the same time when adolescents are insensitive to cues that may help to limit their alcohol intake, positive influences of alcohol such as social facilitation may further encourage alcohol use ¹⁰⁴. Most risky behaviors in humans- including alcohol abuse- occur in social situations ²³, potentially pushing adolescents towards greater use of alcohol and drugs when this behavior is valued by their peers.

How is the brain altered with alcohol use and abuse in adolescence relative to adults? Whereas adolescents may be less sensitive to some of the behavioral effects of alcohol, they appear to be more sensitive to some of the neurotoxic effects ⁹⁴. For example, physiological studies (e.g., ¹⁰⁵) show greater ethanol induced inhibition of NMDA-mediated synaptic potentials and long-term potentiation in hippocampal slices in adolescents than in adults. Repeated exposure of intoxicating doses of ethanol also produces greater hippocampal dependent memory deficits ^{106, 107} and prolonged ethanol exposure has been associated with increased dendritic spine size ¹⁰⁸. These latter findings of dendritic spine changes are suggestive of modification of brain circuitry that may stabilize addictive behavior ⁹⁴.

Data from brain imaging studies provide parallel evidence in humans of neurotoxic effects of alcohol on the brain. A number of studies have reported altered brain structure and function in alcohol-dependent or -abusing adolescents and young adults compared to healthy individuals. These studies show smaller frontal and hippocampal volumes, altered white matter microstructure and poorer memory ^109–113. Moreover, these studies show positive associations between hippocampal volumes and age of first use ¹⁰⁹ suggesting that early adolescence may be a period of heightened risk to alcohol’s neurotoxic effects. Duration, which was negatively correlated with hippocampal volume, may compound this effect.

Currently, only a few studies have examined functional brain activity to drug or alcohol related stimuli (i.e. pictures of alcohol) in adolescents ¹¹⁴, although this is an area of future research (see ¹¹⁵). Studies of high-risk populations (e.g. familial load of alcohol dependence) suggest impairments in frontal functioning are apparent prior to drug use exposure (e.g. ^{116, 117}) and can predict later substance use ^{118, 119}. However, in an early behavioral study of the effects of alcohol in 8 to 15 year old boys of low and high familial risk ¹²⁰, the most significant finding was little if any behavioral change or problem on tests of intoxication -even after given doses which had been intoxicating in an adult population were observed. These neurotoxic effects together with increased sensitivity to the motivational effects of alcohol and evidence of poorer top down prefrontal control apparent even prior to drug use exposure ¹¹⁶ may set up a long-term course of alcohol and drug abuse well beyond adolescence ^{118, 119}.

Conclusions

Together, the studies described support a view of adolescent brain development as characterized by a tension between early emerging “bottom-up” systems that express exaggerated reactivity to motivational stimuli and later maturing “top-down” cognitive control regions. This bottom-up system which is associated with sensation- seeking and risk-taking behavior gradually loses its competitive edge with the progressive emergence of “top-down” regulation (e.g., ^{2, 7, 15, 23, 64, 121–123}). This imbalance between these developing systems during adolescence may lead to heightened vulnerability to risk-taking behaviors and increased susceptibility to the motivational properties of substances of abuse.

This review provides behavioral, clinical and neurobiological evidence for dissociating these subcortico-cortico systems developmentally. Behavior data from laboratory tasks and self -report ratings administered to children, adolescents and adults (e.g., ^{18, 20, 37, 42}) suggest curvilinear development of sensation-seeking with a peak inflection roughly between 13 and 17 years, while impulsivity decreases across development in a linear fashion from childhood to young adulthood. Human imaging studies show patterns of activity in subcortical brain regions sensitive to reward (ventral striatum) that parallel the behavioral data. Specifically, they show a curvilinear pattern of development in these regions and the magnitude of their response is associated with risk-taking behaviors. In contrast, prefrontal regions, important in top down regulation of behavior, show a linear pattern of development that parallels those seen in behavioral studies of impulsivity. Moreover, clinical disorders with impulse control problems show less prefrontal activity, further linking neurobiological substrates with the phenotypic construct of impulsivity.

The tension between subcortical regions relative to prefrontal cortical regions during this period may serve as a possible mechanism for the observed heightened risk-taking, including use and abuse of alcohol and drugs. The majority of adolescents have tried alcohol ⁹³, but this does not necessarily lead to abuse. Individuals with less top-down regulation may be particularly susceptible to alcohol and substance abuse as suggested by studies of high-risk populations showing impairments in frontal functioning prior to alcohol and drug exposure (e.g. ^{116, 117}). In the context of our neurobiological model of adolescence, these individuals would have an even greater imbalance in cortico-subcortical control. These findings are also in accordance with clinical findings in ADHD populations who show reduced prefrontal activity and are four times as likely to develop a substance use disorder compared to healthy controls ¹²⁴. This imbalance in cortico-subcortical control would be further compounded by the insensitivity of adolescence to the motor and sedative effects of alcohol that otherwise may help to limit intake, and the positive influences of alcohol in social facilitation which may further encourage alcohol use ¹⁰⁴. As shown by Steinberg and colleagues ^{23, 41}, most risky behaviors- including alcohol and substance abuse- occur in social situations. Thus use of alcohol and drugs may be encouraged and maintained by peers when this behavior is valued.

One of the challenges in addiction related work is the development of biobehavioral markers for early identification of risk for substance abuse and/or for outcomes assessments for interventions/treatments. Our findings suggest that behavioral challenges that require both cognitive control in the presence of tempting appetitive cues may be useful potential markers. Example of such behavioral assays include gambling tasks with high and low risk or “hot” and “cold” conditions described in this review ^{18, 37} or simple impulse control tasks that require suppressing a response to an appetitive/tempting cue ²⁰. These tasks are reminiscent of the delay of gratification task developed by Mischel ¹²⁵. In fact, performance on simple impulse control tasks such as these in adolescents and adults has been associated with their performance as toddlers on the delay of gratification task ^{28, 29}. Mischel and colleagues have shown the high level of stability and predictive value of this task in later life. Relevant to substance abuse, they showed that the ability to delay gratification as a toddler, predicted less substance abuse (e.g., cocaine) later in life ¹²⁶. In our current work, we are beginning to use a combination of these tasks to identify the neural substrates of this ability to further understand potential risk factors for substance abuse.

Collectively, these data suggest that although adolescents as a group are considered risk- takers ⁴¹, some adolescents will be more prone than others to engage in risky behaviors, putting them at potentially greater risk for negative outcomes. However, risk-taking can be quite adaptive in the right environments. So rather than trying to eliminate adolescent risk-taking behavior that has not been a successful enterprise to date ²³, a more constructive strategy may be to provide access to risky and exciting activities (e.g., after school programs with in-door wall climbing) under controlled settings and limit harmful risk-taking opportunities. As the adolescent brain is a reflection of experiences, with these safe risk-taking opportunities, the teenager can shape long-term behavior by fine tuning the connections between top-down control regions and bottom-up drives with maturity of this circuitry. Other successful strategies are cognitive behavioral therapies which focus on refusal skills, or cognitive control, to reduce risky behaviors ¹²⁷. The findings underscore the importance of considering individual variability when examining complex brain–behavior relationships related to risk-taking and impulsivity in developmental populations. Further, these individual and developmental differences may help explain vulnerability in some individuals to risk-taking associated with substance use, and ultimately, addiction.

Neurobiological Development of Human Adolescence

Introduction

Adolescence is a developmental period characterized by numerous, simultaneous changes, including physical maturation, a desire for independence, the increasing importance of social and peer interactions, and significant brain development [1–3]. This period also sees a marked increase in risky behaviors such as drug and alcohol experimentation, criminal activity, and unprotected sex. To develop effective interventions for adolescents at risk of negative outcomes like substance dependence and abuse, it is crucial to understand the neural underpinnings of these behaviors.

Several hypotheses attempt to explain why adolescents engage in risky and impulsive behaviors. Traditional perspectives suggest adolescence is a period of increasing cognitive control efficiency, primarily attributed to the maturation of the prefrontal cortex. This maturation is supported by imaging [4–7] and post-mortem studies [8–10] demonstrating ongoing structural and functional development of this region well into young adulthood.

The concept of improved cognitive control alongside prefrontal cortex development aligns with a linear increase in this ability from childhood to adulthood. However, suboptimal decision-making during adolescence represents a developmental inflection point [11] distinct from both childhood and adulthood, as evidenced by national statistics on adolescent behavior and mortality [12]. If cognitive control and prefrontal cortex immaturity were the sole drivers of suboptimal choices, children should exhibit similar, if not more pronounced, behaviors compared to adolescents, given their less developed prefrontal cortex and cognitive capabilities [2].

This review addresses how brain changes during adolescence might explain these inflections in risky and impulsive behavior. We also explore how substance use during this developmental period can exacerbate these changes and potentially lead to subsequent abuse and dependence.

Accurately representing cognitive and neurobiological changes during adolescence necessitates treating it as a transitional phase rather than a static point in time [3]. To understand this period fully, we must examine the transitions both into and out of adolescence, differentiating its characteristics from other developmental stages. Therefore, empirical data establishing developmental trajectories from childhood to adulthood for cognitive and neural processes are essential for characterizing these transitions and refining interpretations of brain and behavioral changes during adolescence.

Furthermore, accurate depictions of adolescence require a nuanced understanding of the phenotypic characteristics of this period. For example, adolescents are frequently described as impulsive and prone to risk-taking, with these constructs often used interchangeably. However, these constructs are distinct, and recognizing this distinction is crucial for describing their developmental trajectories and neural underpinnings. We present behavioral, clinical, and neurobiological evidence suggesting that risk-taking is more closely associated with sensitivity to environmental incentives (sensation-seeking), while impulsivity is linked to poor top-down cognitive control.

To provide a theoretical framework for these empirical findings, we propose a plausible neurobiological model of adolescence and explore how development during this time might increase vulnerability to alcohol and drug abuse. This review does not aim to pathologize adolescence but rather to explain why some teenagers are more susceptible to substance abuse than others. As such, we aim to identify potential biological and behavioral markers for early identification and outcome assessment of interventions.

Neurobiological Model of Adolescence

We propose a neurobiological model of adolescent development [2] based on rodent models [13, 14] and recent adolescent imaging studies [6, 7, 15–20] (Figure 1). This model emphasizes the need to consider subcortical and prefrontal top-down control regions as interconnected components of a circuit. It illustrates the divergent developmental trajectories of these regions, with limbic projections maturing earlier than prefrontal control regions.

According to this model, adolescents exhibit a bias towards functionally mature subcortical circuitry relative to less mature cortical circuitry compared to children, whose frontolimbic circuitry is still under development, and adults, who possess fully mature systems. Through development and experience, functional connectivity between these regions strengthens, enabling top-down modulation of subcortical systems [7]. Therefore, the maturation of frontostriatal circuitry, along with the strengthening of connections within this circuitry, may explain the changes observed in both impulsivity and risk-taking throughout development.

This model aligns with previous models [21–24] in that it provides a framework for the nonlinear inflections observed in behavior from childhood to adulthood, attributed to the earlier maturation of subcortical projections relative to top-down prefrontal ones. Specifically, the triadic model [21] posits that motivated behavior involves three distinct neural circuits: approach, avoidance, and regulatory. The ventral striatum primarily governs the approach system, the amygdala controls the avoidance system, and the prefrontal cortex oversees the regulatory system [25].

Our model differs from others in that it is grounded in empirical evidence for brain changes occurring not only in the transition from adolescence to adulthood, but also in the transition into adolescence from childhood and out of adolescence into adulthood. Moreover, this model does not posit that the striatum and amygdala are specific to approach and avoidant behaviors, given recent studies demonstrating the valence independence of these structures [26]. Instead, they are viewed as systems crucial for detecting motivationally and emotionally salient environmental cues that can influence behavior.

This review will discuss the most recent evidence from behavioral and human imaging studies of adolescence within the context of our proposed model, illustrating the transition from childhood to adulthood.

Phenotypic Characterization of Adolescence

The capacity to resist temptation in favor of long-term goals, a facet of cognitive control, is often cited as a central factor in adolescent risky behavior [27]. Cognitive control, encompassing resistance to temptation and delay of gratification, has been studied extensively in social, developmental, and cognitive psychology. Developmentally, this ability has been measured by assessing a toddler's ability to resist an immediate reward (e.g., one cookie) in favor of a larger, delayed reward (e.g., two cookies) [28].

Although individuals vary in this capacity even as adults, developmental studies suggest there are periods during development when individuals may be particularly susceptible to temptation. This ability has been described as a form of impulse control [29], and while it is multi-faceted [30, 31], it can be operationally defined as the capacity to execute goal-directed behavior in the presence of salient, competing stimuli and actions [32].

Historically, developmental studies have demonstrated a consistent improvement in cognitive control capacity from infancy to adulthood [33]. This observation is supported by extensive behavioral evidence from controlled laboratory paradigms, including the Go/No-Go task, Simon task, and task-switching paradigms, which require participants to override prepotent responses to achieve correct ones [32, 34].

However, cognitive control can be compromised when suppressing responses to incentive-related cues is advantageous [20]. This diminished control is particularly evident during adolescence, coinciding with a peak in suboptimal choices related to sexual and drug-related behaviors [3, 11, 12, 14]. These observations suggest that developmental trajectories in cognitive control are complex and can be modulated by emotionally charged or rewarding contexts (e.g., social and sexual interactions) where cognitive control demands intersect with motivational drives and processes.

Motivation can influence cognitive control in at least two ways. Firstly, being rewarded for task performance can increase effort and lead to improved performance compared to unrewarded conditions [17]. Secondly, the capacity to exert control can be challenged when suppressing thoughts and actions directed towards desirable cues [20]. Recent adolescent development studies have begun to compare cognitive control capacity in both neutral and motivational contexts. These studies suggest that sensitivity to environmental cues, particularly reward-based cues, changes across development and that motivation exerts a unique influence on cognition during adolescence.

The following section highlights recent studies examining how adolescent behavior, compared to adult behavior, is differentially biased in emotionally charged contexts.

For instance, Ernst and colleagues [35, 36] investigated performance on an antisaccade task with the promise of financial reward for accurate performance on a subset of trials. The results showed that the promise of reward facilitated cognitive control behavior more strongly in adolescents than in adults, a finding that has been replicated [17] and recently extended to include social rewards (e.g., happy faces) [20].

While the previous examples illustrate instances of enhanced performance in teenagers when incentives are present, rewards can also hinder performance when individuals need to suppress responses to potentially high-gain rewards. For example, using a gambling task in which reward feedback was provided either immediately during decision-making ("hot" trials designed to heighten affective arousal) or withheld until after the decision ("cold" trials promoting deliberate decision-making), Figner and colleagues [37] demonstrated that adolescents made riskier gambles compared to adults, but only during the "hot" condition. Using a similar task, the Iowa Gambling Task, Cauffman and colleagues [38] found that this sensitivity to rewards and incentives peaks during adolescence, with a steady increase from late childhood to adolescence in the tendency to choose advantageous decks of cards, followed by a decline from late adolescence to adulthood. These findings illustrate a curvilinear function peaking around 13-17 years old before declining [27]. Although previous Iowa Gambling Task studies have reported a linear increase in performance with age [39], these studies did not examine age continuously or focus solely on trials involving advantageous decks of cards.

Recent research suggests that social contexts, particularly those involving peers, can also act as motivational cues that diminish cognitive control during adolescence. The extent to which an adolescent's peers use substances is directly proportional to the amount of alcohol or illicit substances the adolescent will use [40]. Using a simulated driving task, Gardner and colleagues [41] observed that adolescents make riskier decisions in the presence of peers than when alone, and that these risky decisions decline linearly with age [23, 40].

In summary, these studies suggest that, during adolescence, motivational cues signaling potential rewards are particularly salient. This can result in enhanced performance when rewards are presented as reinforcers or outcomes but can also lead to riskier or suboptimal choices when rewards are presented as cues. In the latter case, the motivational cue can undermine effective goal-directed behavior.

Furthermore, these studies suggest that sensitivity to rewards and sensation-seeking behavior are distinct from impulsivity, each exhibiting different developmental patterns (curvilinear versus linear, respectively). This distinction is further supported by a recent study by Steinberg et al. [42] using self-report measures of sensation-seeking and impulsivity in nearly 1000 individuals between 10 and 30 years old. Their results showed that age-related differences in sensation-seeking followed a curvilinear pattern, with peaks in sensation-seeking increasing between 10 and 15 years and declining or remaining stable thereafter. In contrast, age-related differences in impulsivity followed a linear pattern, with impulsivity decreasing linearly with age (Figure 2A).

These findings, along with laboratory-based evidence, suggest that heightened risk-taking vulnerability in adolescence "may be due to the combination of relatively higher inclinations to seek excitement and relatively immature capacities for self-control that are typical of this period of development" [42].

Neurobiology of Adolescence

As highlighted in our model of adolescence, two brain regions are crucial for understanding cognitive and motivational behavior: the prefrontal cortex, associated with cognitive control [43], and the striatum, critical for detecting and learning about novel and rewarding environmental cues [44]. We review recent animal and human imaging studies on the neurobiological changes underpinning these motivational and cognitive systems across development, considering the previously discussed behavioral findings on sensation-seeking and impulsivity development. We use the imbalance model, characterized by linear development of top-down prefrontal regions and a curvilinear function for bottom-up striatal regions involved in detecting salient environmental cues, to provide context for these findings.

Examining circuitry rather than isolated regional changes, particularly within frontostriatal circuits underpinning various forms of goal-directed behavior, is crucial. This perspective shifts the focus from the isolated maturation of individual regions to their interactions within interconnected circuits.

Seminal animal and human research has elucidated how striatal and prefrontal cortical regions shape goal-directed behavior [7, 27, 37, 38, 44]. Using single-unit recordings in monkeys, Pasupathy & Miller [45] showed that, when flexibly learning reward contingencies, early striatal activity establishes reward-based associations, while later, more deliberate prefrontal mechanisms are recruited to maintain behavioral outputs that maximize gains. These findings have been replicated in lesion studies [46–48]. A similar role for the striatum in the early temporal coding of reward contingencies before prefrontal activation has also been observed in humans [49]. These findings highlight the importance of understanding how regions interact within frontostriatal circuitry, along with their individual functions, to develop a comprehensive model of cognitive and motivational control in adolescence.

Frontostriatal circuits, particularly the dopamine system, undergo substantial elaboration during adolescence [50–53]. Dopamine receptor density (D1 and D2) in the striatum peaks in early adolescence, followed by a decline in receptor density by young adulthood [54–56]. In contrast, the prefrontal cortex doesn't exhibit peak D1 and D2 receptor density until late adolescence and young adulthood [57, 58]. Similar developmental changes have been observed in other reward-related systems, including the cannabinoid system [59]. While the relationship between changes in the dopamine system and motivated behavior remains unclear due to ongoing debates about whether dopamine systems modulate reward sensitivity (e.g., [60, 61]) and whether these changes reflect hypoactive or hypersensitive dopamine systems (e.g., [62, 63]), the dramatic changes in dopamine-rich circuitry during adolescence suggest a link to age-specific changes in reward sensitivity [50, 64]. In addition to changes in dopamine receptors, significant hormonal changes during adolescence contribute to sexual maturity and influence functional activity in frontostriatal circuits [65]. However, a detailed discussion of these hormonal changes is beyond the scope of this review (see [66, 67] for comprehensive reviews on this topic).

Human imaging studies have begun to provide evidence for the strengthening of connections within dopamine-rich frontostriatal circuitry across development. Using diffusion tensor imaging and fMRI, Casey and colleagues [68, 69], as well as other researchers [70], have demonstrated increased strength in distal connections within these circuits throughout development. They have linked the strength of connections between prefrontal and striatal regions with the capacity to effectively engage cognitive control in both typically and atypically developing individuals [68, 69]. These findings highlight the significance of signaling within corticostriatal circuitry for successful cognitive control.

Similarly, accumulating evidence from human functional neuroimaging studies reveals how subcortical systems, such as the striatum, and the prefrontal cortex interact to produce the risky behaviors observed in adolescents [71]. Most imaging studies have focused on one region or the other, demonstrating that the prefrontal cortex, thought to underlie age-related improvements in cognitive control [72–78], undergoes delayed maturation [4, 79, 80], while striatal regions sensitive to novelty and reward manipulations mature earlier [74, 81]. Several studies have reported heightened activation in the ventral striatum during reward anticipation and/or receipt in adolescents compared to adults [6, 15, 17, 18], while others report hypo-responsiveness [82].

One of the first studies to examine reward-related processes across the developmental spectrum from childhood to adulthood was conducted by Galvan and colleagues [6] in participants aged 6 to 29 years. They found that ventral striatal activation was sensitive to varying magnitudes of monetary reward [49] and that this response was exaggerated in adolescents compared to children and adults [6] (Figure 3). This exaggeration could reflect increased signal [6] or more sustained activation [83]. In contrast to the ventral striatum, orbital prefrontal regions exhibited protracted development across these ages (Figure 2B).

How does this enhanced ventral striatal signaling relate to behavior? In a follow-up study, Galvan and colleagues [16] investigated the relationship between ventral striatal activity in response to large monetary rewards and personality trait measures of risk-taking and impulsivity. Anonymous self-report measures of risky behavior, risk perception, and impulsivity were collected from their sample of 7 to 29 year olds. Galvan et al. found a positive correlation between ventral striatal activity to large rewards and the likelihood of engaging in risky behavior (Figure 3). These findings are consistent with adult imaging studies linking ventral striatal activity to risky choices [84, 85].

To further investigate the association between adolescent risky behavior and reward sensitivity as indexed by an exaggerated ventral striatal response, Van Leijenhorst and colleagues [18] employed a gambling task involving Low-Risk gambles with a high probability of a small monetary reward and High-Risk gambles with a lower probability of a larger monetary reward. Their fMRI results confirmed that High-Risk choices were associated with ventral striatal recruitment, whereas Low-Risk choices were associated with ventromedial prefrontal cortex activation. These findings support the hypothesis that risky behavior in adolescence is linked to an imbalance caused by different developmental trajectories of subcortical reward and prefrontal regulatory brain regions, consistent with our neurobiological model of adolescence.

Although there seems to be an association between risk-taking behavior and ventral striatal activation, Galvan's study [16] did not find a correlation between ventral striatal activity and impulsivity. Instead, impulsivity ratings were correlated with age, aligning with numerous imaging studies demonstrating a linear increase in prefrontal cortex recruitment with age during impulse control tasks [7, 75, 77] (see reviews by [34, 86]). Additionally, recent studies have shown that impulsivity ratings are inversely correlated with ventromedial prefrontal cortex volume in healthy boys (7-17 years) [87]. Furthermore, studies of clinical populations characterized by impulsivity problems, such as ADHD, show impaired impulse control and reduced activity in prefrontal regions compared to controls [88, 89], but no heightened response to incentives [90].

These findings provide neurobiological support for dissociating risk-taking and reward sensitivity from impulsivity. Risk-taking and reward sensitivity exhibit a curvilinear developmental pattern, while impulsivity shows a linear pattern (Figure 2B). Therefore, adolescent choices and behaviors cannot be solely attributed to impulsivity or protracted prefrontal cortex development. Subcortical regions involved in motivation must also be considered to understand why adolescent behavior differs not only from adults, but from children as well.

The ventral striatum seems to play a role in the experience of excitement [82, 91] and positive affect [15] during reward receipt, as well as in the propensity for sensation-seeking and risk-taking [16, 91]. Importantly, these findings suggest that during adolescence, individual variability in the predisposition for risky behavior, along with developmental changes, may contribute to the increased likelihood of engaging in risky behaviors, rather than impulsivity alone.

A research area that has received less attention is the interaction between cognitive control and motivational systems across development. As previously mentioned, Ernst and colleagues [35, 36] showed that the promise of monetary reward facilitated adolescent cognitive control behavior more than adult cognitive control behavior. Geier et al. [17] recently identified the neural correlates of this cognitive upregulation using a modified antisaccade task during functional brain imaging. In both adolescents and adults, trials with monetary stakes were associated with faster and more accurate performance, but this effect was more pronounced in adolescents. Following a cue signaling an upcoming rewarded trial, adolescents exhibited exaggerated ventral striatum activation during both preparation for and execution of the antisaccade. An exaggerated response was also observed in adolescent prefrontal regions along the precentral sulcus, an area crucial for controlling eye movements, suggesting reward-related upregulation in control regions as well.

As mentioned earlier, rewards can both enhance and diminish goal-directed behavior. The observation that adolescents take more risks in gambling tasks when appetitive cues are present versus absent supports this notion (e.g., [37]). In a recent imaging study [20], Somerville et al. investigated the neural substrates of downregulation in control regions in the presence of appetitive cues. They tested children, adolescents, and adults on a go/no-go task involving appetitive social cues (happy faces) and neutral cues. Task performance to neutral cues showed a steady, age-related improvement in impulse control. However, on trials requiring participants to resist approaching appetitive cues, adolescents did not show this expected age-dependent improvement. This performance decrement during adolescence was accompanied by enhanced activity in the striatum. Conversely, inferior frontal gyrus activation, a region associated with overall accuracy, showed a linear increase with age for no-go versus go trials. These findings implicate exaggerated representation of appetitive cues in the adolescent ventral striatum, in the absence of a mature cognitive control response, in adolescent behavior.

Overall, although adolescents are often characterized as risk-takers [41], these data suggest that some adolescents might be more susceptible to engaging in risky behaviors than others, potentially putting them at greater risk for negative outcomes. These findings emphasize the importance of considering individual variability when examining the complex brain-behavior relationships underlying risk-taking and impulsivity in developmental populations. These individual and developmental differences may also elucidate why some individuals are more vulnerable to risk-taking behaviors associated with substance use and, ultimately, addiction [64].

Substance Use and Abuse in Adolescents

Adolescence is a period of increased experimentation with drugs and alcohol [92], with alcohol being the most abused substance in this age group [11, 93, 94]. Early substance use, including alcohol, is a strong predictor of later dependence and abuse [95]. Given the surge in alcohol dependence from adolescence to adulthood, a trend not observed in any other developmental stage [96], we will focus primarily on alcohol use and abuse in adolescents and its motivational properties in this review.

Alcohol, along with other addictive substances such as cocaine and cannabinoids, has reinforcing properties. These substances influence mesolimbic dopamine transmission, acutely activating neurons in dopamine-rich frontolimbic circuitry, including the ventral striatum [97–99]. Hardin and Ernst (2009) [92] propose that substance use may exacerbate an already heightened ventral striatum response, leading to an increase in the reinforcement properties of the drug. Robinson and Berridge [61, 63, 100] suggest that addictive substances can "hijack" brain systems associated with drug-related incentives, like the ventral striatum, thereby downregulating top-down prefrontal control regions.

Most empirical research on adolescent alcohol use has been conducted in animals due to ethical constraints in human adolescent research. Animal models of ethanol consumption provide substantial evidence for the differential effects of alcohol in adolescents compared to adults, aligning with human findings indicating that adolescents are relatively insensitive to the effects of ethanol.

Spear and colleagues have demonstrated that adolescent rats are less sensitive than adult rats to the social, motor, sedative, acute withdrawal, and "hangover" effects of ethanol [101–103]. This is significant because many of these effects typically serve to limit alcohol consumption in adults [11]. Moreover, while adolescents are less attuned to cues that might curb their alcohol intake, the positive reinforcing effects of alcohol, such as social facilitation, might further encourage alcohol use [104]. Notably, most human risky behaviors, including alcohol abuse, occur in social situations [23], potentially increasing adolescent alcohol and drug use when such behavior is socially reinforced.

How does alcohol use and abuse affect the adolescent brain compared to the adult brain? While adolescents may be less sensitive to certain behavioral effects of alcohol, they appear to be more susceptible to some of its neurotoxic effects [94]. For example, physiological studies (e.g., [105]) show that ethanol causes greater inhibition of NMDA-mediated synaptic potentials and long-term potentiation in adolescent hippocampal slices than in adult slices. Additionally, repeated exposure to intoxicating doses of ethanol results in greater hippocampal-dependent memory deficits [106, 107], and prolonged ethanol exposure has been linked to increased dendritic spine size [108]. This latter finding suggests that alcohol-induced changes in dendritic spines might contribute to modifications in brain circuitry that solidify addictive behavior [94].

Brain imaging studies in humans provide converging evidence for the neurotoxic effects of alcohol on the brain. Several studies have reported alterations in brain structure and function in alcohol-dependent or -abusing adolescents and young adults compared to healthy individuals, including smaller frontal and hippocampal volumes, altered white matter microstructure, and poorer memory performance [109–113]. Furthermore, these studies reveal positive associations between hippocampal volume and age of first use [109], implying that early adolescence might be a period of heightened vulnerability to the neurotoxic effects of alcohol. The duration of alcohol use, which is negatively correlated with hippocampal volume, may exacerbate this effect.

Currently, few studies have investigated functional brain activity in response to drug or alcohol-related stimuli (e.g., pictures of alcohol) in adolescents [114], although this is an active area of research (see [115]). Studies of high-risk populations (e.g., individuals with a family history of alcohol dependence) suggest that impairments in frontal lobe function are present before drug exposure (e.g., [116, 117]) and can predict later substance use [118, 119]. However, an early behavioral study examining the effects of alcohol in boys aged 8 to 15 years with low and high familial risk [120] found surprisingly minimal behavioral change or impairment on intoxication tests, even after administering doses that were intoxicating to adults. These neurotoxic effects, combined with increased sensitivity to the motivational effects of alcohol and evidence of weaker top-down prefrontal control even before drug use [116], might contribute to a prolonged trajectory of alcohol and drug abuse extending beyond adolescence [118, 119].

Conclusions

The studies discussed in this review support a view of adolescent brain development characterized by a dynamic interplay between early-maturing "bottom-up" systems, which exhibit exaggerated reactivity to motivational stimuli, and later-maturing "top-down" cognitive control regions. This bottom-up system, associated with sensation-seeking and risk-taking behavior, gradually becomes less dominant with the progressive emergence of "top-down" regulation (e.g., [2, 7, 15, 23, 64, 121–123]). This imbalance between developing systems during adolescence may contribute to heightened vulnerability to risk-taking behaviors and increased susceptibility to the motivational properties of addictive substances.

This review presents behavioral, clinical, and neurobiological evidence supporting the dissociation of these subcortico-cortical systems developmentally. Behavioral data from laboratory tasks and self-report measures administered to children, adolescents, and adults (e.g., [18, 20, 37, 42]) indicate a curvilinear developmental trajectory for sensation-seeking, peaking around 13-17 years, whereas impulsivity declines linearly from childhood to young adulthood. Human imaging studies reveal parallel activity patterns in subcortical brain regions associated with reward processing (ventral striatum). Specifically, these regions exhibit a curvilinear developmental pattern, and the magnitude of their response correlates with risk-taking behaviors. In contrast, prefrontal regions involved in top-down behavioral regulation show a linear developmental pattern mirroring those observed in behavioral studies of impulsivity. Furthermore, clinical disorders characterized by impaired impulse control exhibit reduced prefrontal activity, further linking neurobiological substrates to the phenotype of impulsivity.

The tension between subcortical and prefrontal cortical regions during this period might explain the observed increase in risk-taking behaviors, including alcohol and drug use and abuse. While most adolescents experiment with alcohol [93], this does not inevitably lead to abuse. Individuals with weaker top-down regulation may be particularly vulnerable to alcohol and substance abuse, as suggested by studies in high-risk populations demonstrating frontal lobe impairments before alcohol and drug exposure (e.g., [116, 117]). In the context of our proposed neurobiological model of adolescence, these individuals would exhibit an even greater imbalance in cortico-subcortical control. These findings are also consistent with clinical observations in ADHD populations, who show reduced prefrontal activity and are four times more likely to develop a substance use disorder than healthy controls [124]. This imbalance in cortico-subcortical control could be further exacerbated by adolescents' insensitivity to the motor and sedative effects of alcohol, which might otherwise limit intake, and by the positive reinforcing effects of alcohol in social contexts, which may encourage alcohol use [104]. As demonstrated by Steinberg and colleagues [23, 41], most risky behaviors, including alcohol and substance abuse, occur in social settings. As such, alcohol and drug use might be encouraged and maintained by peers when such behavior is socially valued.

One of the main challenges in addiction research is developing biobehavioral markers for the early identification of individuals at risk for substance abuse and/or for assessing the effectiveness of interventions and treatments. Our findings suggest that behavioral tasks requiring cognitive control in the presence of tempting appetitive cues might be useful as potential markers. Examples of such tasks include gambling tasks involving high- and low-risk or "hot" and "cold" conditions, as described in this review [18, 37], or simple impulse control tasks requiring response inhibition to appetitive/tempting cues [20]. These tasks are reminiscent of the delay of gratification paradigm developed by Mischel [125]. Indeed, performance on simple impulse control tasks in adolescents and adults has been associated with their performance on the delay of gratification task as toddlers [28, 29]. Mischel and colleagues have shown the remarkable stability and predictive validity of this task later in life. Importantly, they found that the ability to delay gratification as a toddler predicted lower rates of substance abuse (e.g., cocaine) later in life [126]. Our current research aims to use a combination of these tasks to identify the neural substrates of this ability and to further our understanding of potential risk factors for substance abuse.

In conclusion, although adolescents, as a group, are often labeled as risk-takers [41], these data emphasize the substantial individual variability within this population. Some adolescents are more likely to engage in risky behaviors than others, potentially placing them at increased risk for negative outcomes. However, risk-taking can be adaptive in certain environments. Therefore, instead of attempting to eliminate adolescent risk-taking, which has not been successful [23], a more constructive approach might involve providing access to risky and exciting activities (e.g., indoor rock climbing) in controlled settings and limiting opportunities for harmful risk-taking. Given the plasticity of the adolescent brain, providing teenagers with safe outlets for risk-taking might help them shape long-term behavior by fine-tuning the connections between top-down control regions and bottom-up drives as these circuits mature. Other successful approaches include cognitive behavioral therapies that focus on refusal skills and cognitive control to reduce risky behaviors [127]. These findings underscore the need to consider individual differences when investigating the complex interplay between brain and behavior related to risk-taking and impulsivity in developmental populations. Ultimately, understanding these individual and developmental differences may be the key to understanding why some individuals are more vulnerable to risk-taking behaviors associated with substance use and, ultimately, addiction.

Why Are Teens So Impulsive? A Look at the Developing Brain

Introduction

Adolescence is a time of huge change – physically, emotionally, and mentally. Teens are dealing with physical development, a growing need for independence, navigating complex social interactions, and all while their brains are still developing 1–3. It's no surprise that this period is often linked to an increase in risky behaviors like experimenting with drugs and alcohol, criminal activity, and unsafe sex. To understand why some teens are more vulnerable to negative outcomes like addiction, we need to understand what's happening in their brains.

We used to think that teen risky behavior was simply due to an immature prefrontal cortex, the part of the brain responsible for decision-making and impulse control. This area is still developing well into adulthood, as shown by brain imaging 4–7 and post-mortem studies 8–10. However, if this were the whole story, we'd expect children to make even worse decisions than teenagers, since their prefrontal cortex is even less developed. But statistics on teen behavior and mortality 11, 12 tell a different story. Clearly, there's more to it than just an immature prefrontal cortex.

This paper explores the brain changes during adolescence that might explain these risky behaviors. We'll delve into how alcohol and drug use during this critical period can worsen these changes and increase the risk of addiction.

To understand this, we need to view adolescence as a transition, not a fixed state 3. This means looking at how the brain develops from childhood, through adolescence, and into adulthood. We also need to be precise with our terms. While we often use "impulsivity" and "risk-taking" interchangeably when talking about teens, these are distinct concepts with different developmental trajectories and underlying brain mechanisms. We'll explore evidence suggesting that risk-taking is closely tied to a sensitivity to environmental rewards (sensation-seeking), while impulsivity is more about struggles with cognitive control.

We'll outline a neurobiological model of adolescence and explain how these developmental changes can make teens more susceptible to alcohol and drug abuse. Our aim isn't to paint all teenagers as troubled, but to understand why some are more vulnerable than others. By identifying potential biological and behavioral warning signs, we can work towards early intervention and better support systems.

A Look Inside the Teenage Brain

Our model of adolescent brain development 2 is based on research with rodents 13, 14 and brain imaging studies of human teens 6, 7, 15–20 (see Figure 1). It highlights how the brain's reward system (including areas like the striatum) and the control system (primarily the prefrontal cortex) develop at different paces. The reward system, driven by emotional responses, develops earlier than the control system, which is responsible for rational thinking and planning.

[Figure 1 should be inserted here]

This model explains why teenage behavior can seem so unpredictable – it's a period where the reward system is in overdrive while the control system is still playing catch-up. In essence, teenagers experience a temporary imbalance, relying more on immediate gratification and less on long-term consequences.

Over time, as the prefrontal cortex matures, the connection between these two systems strengthens 7. This allows for better control over impulses and more reasoned decision-making, eventually leading to a more balanced brain in adulthood. Our model builds on earlier models 21–24 by emphasizing the transition phases – into, during, and out of adolescence. It also stresses the interplay between brain regions, rather than just focusing on their individual development.

Teens, Temptation, and Taking Risks

Resisting temptation and delaying gratification are key aspects of cognitive control. Think of a toddler who has to choose between eating one cookie now or waiting for two cookies later. This ability develops over time, and while individuals differ, adolescence seems to be a period of increased vulnerability to temptation 27, 28.

Studies show that cognitive control generally improves with age 33. However, teenagers, compared to adults, seem to struggle when faced with tempting rewards 3, 11, 12, 14. Interestingly, rewards can sometimes be beneficial, motivating teens to perform better when offered as incentives 17, 35, 36.

However, when the reward itself is the problem (like making risky choices to get a bigger reward), teens tend to make riskier decisions than adults, especially in the heat of the moment 37. Studies using gambling tasks show that this sensitivity to rewards peaks during adolescence 27, 38. This means that while teenagers' ability to resist impulsive urges generally improves with age, their desire for rewards and excitement also peaks, creating a perfect storm for risk-taking.

Adding fuel to the fire, the social environment plays a significant role. The influence of peers is particularly potent during adolescence, with studies showing a direct link between peer substance use and an individual's own use 40. For example, in simulated driving tasks, teenagers take more risks when their friends are present 41.

A key takeaway is that while risk-taking and impulsivity often go hand-in-hand in our perception of teenagers, they have distinct developmental trajectories. A large study found that sensation-seeking (the drive for new and exciting experiences) follows a curve, peaking in mid-adolescence and then declining, while impulsivity steadily decreases with age 42 (see Figure 2A).

[Figure 2A should be inserted here]

These findings highlight the importance of understanding the complex interplay of brain development, individual differences, and environmental factors in shaping adolescent behavior.

The Brain's Reward System: Wired for Excitement

The striatum, a brain region crucial for processing rewards and learning from our experiences, undergoes significant changes during adolescence [44](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099425/#R44]. This area is particularly sensitive to dopamine, a neurochemical associated with pleasure and motivation. During adolescence, dopamine receptors in the striatum peak and then decline as we reach adulthood 54–56. In contrast, the prefrontal cortex, responsible for regulating these impulses, develops at a slower pace, with dopamine receptor density peaking later in adolescence and young adulthood 57, 58. These developmental differences contribute to the imbalance we discussed earlier, making teenagers more sensitive to rewards and less equipped to control their impulses.

[Figure 2B should be inserted here]

Brain imaging studies support this model. One study found that adolescents, compared to children and adults, showed heightened activity in the ventral striatum (a part of the striatum) when anticipating or receiving rewards 6, indicating a heightened sensitivity to rewards (see Figure 3). This heightened activity was also linked to self-reported risky behavior 16.

[Figure 3 should be inserted here]

In contrast, impulsivity appears to be more closely related to the development of the prefrontal cortex. Studies consistently show that as the prefrontal cortex matures, our ability to control our impulses improves 7, 75, 77. This is further supported by studies of individuals with ADHD, a condition characterized by impulsivity, who often show reduced prefrontal cortex activity 88, 89.

These findings reinforce the idea that risk-taking and impulsivity, while related, have distinct neural underpinnings. Understanding this is crucial for developing effective interventions for risky behaviors in teenagers.

The Double-Edged Sword of Alcohol and Drugs

Adolescence is a period of increased experimentation with drugs and alcohol 92. Alcohol, in particular, is a major concern, as it's the most commonly abused substance among teenagers 11, 93, 94. Early use significantly increases the risk of developing dependence and abuse later in life 95.

Substances like alcohol directly affect the brain's reward system, leading to the release of dopamine in areas like the ventral striatum 97–99. This reinforces drug-seeking behavior, creating a cycle of addiction. Studies suggest that substance use during adolescence might "hijack" the developing reward system, making it even more sensitive to drug-related cues and weakening the control mechanisms of the prefrontal cortex 61, 63, 100.

While adolescents might be less sensitive to some of the immediate negative effects of alcohol (like sedation or motor impairment), research suggests they are more vulnerable to its long-term damaging effects on the brain 94, 101–103. Animal studies show that alcohol exposure during adolescence leads to greater memory impairments and structural changes in the brain compared to exposure during adulthood 105–108. Similarly, human imaging studies reveal that teenagers who abuse alcohol show alterations in brain structure and function, including reduced volume in areas like the prefrontal cortex and hippocampus (crucial for memory) 109–113. These studies underscore the heightened vulnerability of the adolescent brain to the damaging effects of alcohol.

Conclusion: Navigating the Challenges of the Teenage Brain

The adolescent brain is a work in progress, a dynamic system in constant flux. While this period is marked by increased risk-taking, it's also a time of immense opportunity for growth and learning. By understanding the unique challenges posed by the developing brain, we can develop effective strategies to support teenagers as they navigate this critical period.

This review emphasizes the need to differentiate between risk-taking and impulsivity and highlights the importance of considering individual differences. Some teenagers may be more vulnerable than others due to a combination of genetic predispositions, environmental influences, and the timing of brain development.

Further research is needed to fully understand these complex interactions. However, the existing evidence offers valuable insights for early identification of at-risk individuals and the development of targeted interventions. Instead of focusing on eliminating risk-taking altogether, which is unrealistic and potentially counterproductive, perhaps a more effective approach is to provide opportunities for safe and healthy exploration. By channeling their natural drive for excitement and novelty in positive directions, we can help teenagers develop into healthy and well-adjusted adults.

The Teen Brain: Why Risky Business Feels So Good

Being a teenager is all about change. Your body is changing, you want more independence, and your brain is going through a major upgrade, too! This mix can make things exciting and, yeah, sometimes a little bit risky. You might feel drawn to trying new things, like experimenting with drugs or alcohol, or taking chances you wouldn't have before. Scientists are working hard to figure out exactly what's happening in the brain during these years to explain these risky choices.

Lots of people think teens are just impulsive, but there's more to the story. To really understand teenage behavior, we need to look at the brain. Our brains have different parts, and some of them, like the parts that get excited about rewards, develop faster than others, like the parts that help us make careful decisions.

Picture This: Your Brain on Teenager

Imagine your brain like a car. The part that loves rewards, called the striatum, is like a powerful engine that's ready to go full speed ahead. It gets fired up by exciting things like trying something new or hanging out with friends. But the part that helps you hit the brakes, called the prefrontal cortex, is still under construction during your teenage years. It's like having a steering wheel that's not quite connected right – you can steer, but it takes more effort.

This "imbalance" in your brain – a strong reward system and a still-developing control system – is what makes teenagers more likely to take risks. It's not that you're trying to make bad decisions, it's just that the "reward engine" is extra powerful and the "control steering wheel" is still being fine-tuned.

Go to:

Taking Risks vs. Being Impulsive: Not the Same Thing

Even though people use the words "risk-taking" and "impulsivity" interchangeably, they're actually different. Think of it this way:

• Risk-taking is like being a thrill-seeker. You're drawn to exciting and new experiences, even if there are potential downsides. This peaks in your mid-teens and then starts to level off.

• Impulsivity is like acting without thinking. It's like blurting out an answer in class without raising your hand. Impulsivity actually decreases steadily as you get older.

Scientists see this difference in how the brain develops. The reward center (that powerful engine) is super active during the teen years, which explains the peak in risk-taking. Meanwhile, the prefrontal cortex (our trusty steering wheel) gets stronger with age, which is why impulsivity goes down.

What's Up with the Reward System?

Research has shown that a part of the brain called the ventral striatum is really sensitive to rewards during adolescence. It's like this part of the brain is on high alert for anything exciting or pleasurable. When teenagers see a potential reward, this area lights up like a Christmas tree! And the bigger the reward, the more activity you see.

This excitement about rewards makes a lot of sense when you think about what teenagers are going through. You're exploring your independence, figuring out who you are, and navigating the social world. All of these things involve seeking out new experiences and rewards.

So, What Does This Mean for Me?

First of all, don't freak out! Just because your brain is wired for excitement doesn't mean you're destined to make a bunch of bad decisions. It just means you need to be extra aware of the power of the reward system and work on strengthening your "control steering wheel."

Here are a few things that can help:

• Find healthy ways to get your thrills. Instead of turning to drugs or alcohol, explore activities that give you a rush in a safe environment, like sports, music, or art.

• Think before you act. Take a moment to consider the potential consequences of your choices, both good and bad.

• Surround yourself with positive influences. Hang out with people who make smart choices and support your goals.

The teenage years can be a wild ride, but understanding how your brain works can help you make choices that support your well-being and set you up for success in the long run. Remember, even though your brain is still developing, you have the power to shape its development through your choices and experiences.

Growing Up: How Teen Brains Work

Being a teenager is like being on a rollercoaster! Your body is changing, you want more freedom, and hanging out with friends feels more important than ever [1]. It's also a time when some teens try risky things like smoking, drinking, or breaking rules. To understand why, scientists study how teenage brains work.

Some people think teenagers make risky choices because their brains aren't done growing yet, especially the front part of the brain called the prefrontal cortex [4]–[10]. This part helps us make good decisions and think about the consequences of our actions. Since it's still developing in teens, it's like their brakes aren't working as well as adults'.

But wait! If that were the whole story, then little kids should make even riskier choices because their brains are even less developed, right? But that's not always true [11], [12]. So, something else must be going on in teenage brains.

Scientists have discovered that while the prefrontal cortex is still under construction, the parts of the brain that love excitement and rewards, like the striatum, are working at full speed! This creates an imbalance [2], [13], [14], like having a powerful engine in a car but weak brakes Figure 1.

What Makes Teenagers Tick?

Let's talk about two important things: being impulsive and being a risk-taker. Being impulsive means doing something without thinking, like blurting out an answer in class before raising your hand. This gets better as you grow up. Being a risk-taker means enjoying exciting and sometimes dangerous activities, like riding a rollercoaster or trying a new sport [27]–[31]. Teenagers are often drawn to these kinds of things.

Scientists have found that risk-taking actually peaks in the teenage years and then goes down [38], [42]. It's like a wave that rises and then falls Figure 2. On the other hand, impulsivity steadily decreases as you get older. This means that teenagers are more likely to take risks, not just because they're impulsive, but because their brains are wired to find excitement rewarding.

The Science Behind Teenage Brains

Deep inside your brain, there are special pathways that connect different areas [44]–[49]. One important pathway links the prefrontal cortex (the "brake pedal") with the striatum (the "gas pedal"). This pathway is like the communication system between your brain and your foot when driving a car.

During the teenage years, this pathway is still under development [50]–[53]. The striatum, full of excitement, is sending strong signals, while the prefrontal cortex is still learning how to control those signals. This is why teenagers sometimes have trouble resisting exciting or rewarding things, even when they know they shouldn't [6], [15]–[20].

When Fun Turns into Trouble

Imagine your brain's reward system is like a muscle [92]. When you do something pleasurable, like eating cake or playing a game, this muscle gets a little workout. Alcohol and drugs can give this muscle a super-charged workout, making it crave those feelings even more [97]–[99].

The problem is, teenage brains are already wired to find excitement and rewards super-rewarding! [6], [15]–[20]. So, when alcohol or drugs enter the picture, it's like giving a super-charged workout to an already strong muscle. This can make it even harder for teenagers to control their impulses and make healthy choices [92].

To make matters worse, teenagers' brains are still developing, making them more vulnerable to the harmful effects of alcohol and drugs [94], [105]–[108]. Think of it like this: if you drop a phone with a cracked screen, it's more likely to break than a phone with a strong, undamaged screen.

What Does It All Mean?

Growing up is a time of great change and excitement. It's also a time when some teenagers might be more likely to experiment with risky behaviors, like using alcohol or drugs. This doesn't mean that all teenagers will develop problems. But it does mean that it's important for teenagers to understand how their brains work and to make healthy choices.

Scientists are still learning about the teenage brain [114], but we already know enough to help teenagers make smart decisions. By understanding how their brains work, teenagers can learn to navigate the challenges of adolescence and make choices that will help them grow into healthy and successful adults.