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The Adolescent Developmental Stageo Physical maturation
o Drive for independence
o Increased salience of social and peerinteractions
o Brain development
o Inflection in risky behaviors includingexperimentation with drugs and alcoholcriminal activity and unprotected sex
Neural Underpinningso Understanding the neural basis of these risky behaviors
is important to identify which teens may be at risk forpoor outcomes, such as substance dependence andabuse.
o Traditional accounts of adolescence suggest that it is aperiod of development associated with greater efficiencyof cognitive control.
o Dependent on maturation of the prefrontal cortex asevidenced by imaging and postmortem studies, thebrain shows continued structural and functionaldevelopment well into young adulthood.
Challenging Traditional Viewso It is accurate that Improved Cognitive Control with
development of the Pre-Frontal Cortex is consistent with alinear increase in this ability from Childhood to Adulthood.
o However, sub-optimal choices and actions observedduring Adolescence represent an inflection indevelopment, which is unique from Childhood orAdulthood.
o If Cognitive Control and an Immature Pre-Frontal Cortexwere the basis for sub-optimal choice behavior, thenChildren should look similar to (or worse than) Adolescents,given their less developed Pre-Frontal Cortex and cognitiveabilities.
New Research Contributionso Primary question of how the brain is changing
during Adolescence, which may explain inflectionsin risky and impulsive behavior.
o Examples provided for how alcohol and drug usemay further exacerbate these changes and lead tosubstance abuse/dependence.
o Attempt to identify potential biological andbehavioral markers for early identification and foroutcome assessments of interventions.
Framework Io To accurately capture cognitive and
neurobiological changes during Adolescence,this period must be treated as a transitional onerather than a single snapshot in time.
o Empirical data that establishes developmentaltrajectories from Childhood to Adulthood forcognitive and neural processes are essential incharacterizing these transitions and moreimportantly, in constraining any interpretationsabout changes in brain or behavior inAdolescence.
Framework IIo Refinement in the phenotypic characterization of this period
of development is needed: Adolescents are oftencharacterized as impulsive and as greater risk-takers withthese constructs used synonymously.
o These constructs are distinct
o Appreciating this distinction is important for describing theirdevelopmental trajectories and neural underpinnings.
o There is behavioral, clinical, and neurobiologicalevidences that suggest
o Risk-Taking is associated more with sensitivity to environmentalincentives (sensation seeking) and
o Impulsivity is associated with poor top-down cognitive control.
Neurobiological Model of Adolescence I
o Sub-Cortical regions of the Striatum and the Pre-Frontaltop-down control must be considered together as a circuit.
o Limbic Projections develop sooner than Pre-Frontal Controlregions.
o Adolescence is biased by a functionally matureSub-Cortical Limbic region relative to less matureCortical Circuitry (i.e. imbalance in reliance ofsystems)
o compared with children for whom this Fronto-LimbicCircuitry is still developing and
o compared with Adults for whom both systems are fullymature.
Neurobiological Model of Adolescence II
o With development and experience, the functionalconnectivity between these regions is strengthenedand provides a mechanism for top-down modulationof the subcortical systems.
o The Fronto-Striatal circuitry and functionalstrengthening of connections within the circuitry mayprovide a mechanism to explain changes in impusivity and risk-taking across development.
o This model provides a basis for nonlinear inflectionsobserved in behavior from Childhood to Adulthood,due to earlier maturation of subcortical projectionsrelative to less mature top-down prefrontal ones.
Neurobiological Model of Adolescence III o
The Triadic Model proposes that motivatedbehavior has three distinct(approach, avoidance, andregulatory)
oApproach - Ventral Striatum (VS)
oAvoidance - Amygdala (AMG)
neural circuits
o Regulatory - Pre-Frontal Cortex (PFC)
Neurobiological Model of Adolescence IV
o The Triadic Model does not suggest that thestriatum and amygdala are specific toapproach and avoidant behaviors, givenrecent studies showing valence independentof these structures
o It rather suggests they are “systems” that areimportant in detecting motivationally andemotionally relevant cues in the environmentthat can bias behavior.
Phenotypic Characterization of Adolescence I
o Impulse control is multifaceted, but generally defined asthe ability to accomplish goal-directed behavior in theface of salient, competing inputs and actions.
o Developmental studies have shown a steadyimprovement in cognitive control capacity fromInfancy to Adulthood.
o Developmental trajectories in cognitive control arecomplex and can be modulated by emotionally chargedor reinforcing contexts (e.g. social and sexualinteractions), in which cognitive control demandsinteract with motivational drives or processes.
Phenotypic Characterization of Adolescence II
o Motivation can modulate cognitive control in at least two ways:
Being rewarded for performance on a given task can makepeople work harder and ultimately perform better than when notrewarded.
2. The capacity to exert control can be challenged whenrequired to suppress thoughts and actions toward appetitivecues.
o These studies suggested:
o a change in sensitivity to environmental cues, especiallyreward-based ones at different points in development and
o a unique influence of motivation on cognition during theAdolescent years.
Research Results - What Influences Teens? Io Promise of financial and social rewards facilitated
Adolescent cognitive control behavior more than foradults.
o Although there is evidence of enhanced performancesin teens with incentives, rewards can also diminishperformance when suppressing responses to rewardsthat lead to high gain.
o Sensitivity to rewards and incentives actually peakduring Adolescence, with a steady increase from lateChildhood to Adolescence then a decrease from lateAdolescence to Adulthood. Curvilinear function peaksfrom 13-17 then declines.
Research Results -What Influences Teens?
o Social contexts, particularly peers, may also serve as amotivational cue and can diminish cognitive controlduring adolescence.
The degree to which an adolescent’s peers are usingsubstances is directly proportional to the amount ofalcohol or illegal substances that an adolescent willuse.
o Adolescents make riskier decisions in the presence ofpeers than when alone and that these risky decisionsdecrease linearly with age.
Research Results - What Influences Teens? III
o During Adolescence, motivational cues of potentialreward are particularly salient and can lead to improvedperformance when provided as a reinforcer or rewardedoutcome, but to riskier choices or suboptimal choiceswhen provided as a cue.
o The motivational cue can diminish effectivegoal-oriented behavior.
o Sensitivity to rewards and sensation-seeking behaviorare distinct from impulsivity with very differentdevelopmental patterns (curvilinear function versus alinear function, respectively).
Research Results-What Influences Teens? IV
curvilinear pattern with peaksincreasing from 10 to 15 yearsremaining stable thereafter.
in sensation-seekingand decreasing or
o In contrast, age differences in impulsivity followed alinear pattern, with decreasing impulsivity with age ina linear fashion.
o These findings suggest heightened vulnerability torisk-taking in adolescence that may be due to thecombination of relatively higher inclinations to seekexcitement and relatively immature capacities forself-control that are typical for this period of
o Differences in sensation-seeking with age followed a
development.
Neurobiology of Adolescence I
o Cognitive ControlPrefrontal Cortex
Impulsivity
o Motivational Behaviors(Sensation Seeking)Striatum - Nucleus AccumbensCritical in detecting and learning aboutnovel and rewarding cues in theenvironment.
Neurobiology of Adolescence II
o There is an imbalance model of lineardevelopment of top-down prefrontal regionscompared with a curvilinear function fordevelopment of bottom-up striatal regionsinvolved in detecting salient cues in theenvironment to ground the findings.
o Research is moving away from examining howeach region matures in isolation to how theseregions may interact in the context ofinterconnected circuits.
Neurobiology of Adolescence III
o Striatal and Pre-Frontal Cortical regions shapegoal-directed behavior.
o When flexibly learning a set of rewardcontingencies:
o very early activity in the Striatum provides thefoundation for reward-based associations,
whereas later in the activity, more deliberativePre-Frontal mechanisms are engaged to maintainthe behavioral outputs that can optimize the greatestgains.
Neurobiology of Adolescence IVUnderstanding the interactions between regions (and their componentfunctions) within the Fronto-Striatal Circuitry is critical for developing amodel of cognitive and motivational control in Adolescence:
o Fronto-Striatal Circuits undergo considerable elaboration duringAdolescence, particularly dramatic in the dopamine system.
o Peaks in the density of dopamine receptors D1 and D2 in the striatumoccur early in Adolescence, followed by a loss of these receptors byYoung Adulthood.
o In contrast the Pre-Frontal Cortex does not show peaks in D1 and D2receptor density until Late Adolescence and Young Adulthood.
Given the dramatic changes in dopamine-rich circuitry duringAdolescence, it is likely to be related to changes in sensitivity torewards distinct from Childhood or Adulthood.
Neurobiology of Adolescence VDTI and fMRI studies show the importance ofsignaling within the corticostriatal circuitry thatsupports the capacity to effectively engage incognitive control.
o Imaging studies show the prefrontal cortex, thoughtto sub-serve age-related improvement in cognitivecontrol, undergoes delayed maturation, whereasstriatal regions sensitive to novelty and rewardmanipulations develop sooner.
> Adolescents show heightened activation of theventral striatum in anticipation and/or receipt ofrewards compared with Adults.
Neurobiology of Adolescence VIo Ventral striatal-large reward and the likelihood of
engaging in high risk-taking behavior.
o Ventral Medial Pre-Frontal cortex-low risk choices.Impulsivity ratings were inversely correlated with thevolume of the ventral medial prefrontal cortex inteenage boys.
o Risky behavior in adolescence is associated with animbalance caused by different developmentaltrajectories of subcortical reward and prefrontalregulatory brain regions consistent with outneurobiological model of adolescence.
Neurobiology of Adolescence VII
o Studies of clinical populations characterized byimpulsivity problems such as attention-deficithyperactivity disorder have shown impaired impulsecontrol and decreased activity in prefrontal regionscompared with controls but not heightened responses toincentives.
o These findings provide neurobiological empirical supportfor a dissociation of the constructs related to risk-takingand reward sensitivity from that of impulsivity, with theformer showing a curvilinear pattern and the latter alinear pattern.
Neurobiology of Adolescence VIIIAdolescent choices and behavior cannot be explained byimpulsivity or protracted development of the Pre-Frontal Cortex(PFC) alone, rather
o Motivational Sub-Cortical regions must be considered to elucidatewhy adolescent behavior is not only different from Adults but alsofrom Children
o Thus, the Ventral Striatum appears to play a role in levels ofexcitement and positive affect when receiving rewards and thepropensity for sensation-seeking and risk-taking.
During Adolescence some individuals may be more prone toengage in risky behaviors due to developmental changes inconcert with variability in a given individual’s predisposition toengage in risky behavior, rather than to simple changes inimpulsivity.
Neurobiology of Adolescence IXo Task performance to neutral cues showed steady
improvement with age on this impulse control task.
o However, on trials for which the individual had to resistapproaching appetitive cues, adolescents failed toshow the expected age-dependent improvement.
o This performance decrement during adolescence wasparalleled by enhanced activity in the Striatum.
. This shows exaggerated Ventral Striatalrepresentation of appetitive cues in adolescence in theabsence of a mature cognitive control response.
Neurobiology of Adolescence Xo Overall, the data suggests although adolescents as a
group are considered risk-takers, some adolescentswill be more prone than others to engage in riskybehaviors, putting them at potentially greater risk fornegative outcomes.
o These findings underscore the importance ofconsidering individual variability when examiningcomplex brain-behavior relations related to risk-takingand impulsivity in developmental populations, further
o These individual and developmental differences mayhelp to explain vulnerability in some individuals torisk-taking, which is associated with substance use,and ultimately addiction.
Substance Use and Abuse in Adolescence I
o Early use of substances is a reliable predictorof later dependence and abuse.
o Alcohol and other substances of abuse, includingCocaine and Cannabinoids have been shown tohave reinforcing properties.
o These substances influence MesoLimbicDopamine transmission with acute activationsof neurons in FrontoLimbic circuitry rich indopamine, including the Ventral Striatum.
Substance Use and Abuse in Adolescence II
o The use of these substances may exacerbate analready enhanced Ventral Striatum responseresulting in heightened or strengthening ofreinforcement properties to the drug.
o These drugs can “Hijack” the systems associatedwith drug incentives, such as the Ventral Striatum,thus down-regulating top-down Pre-Frontal controlregions.
o Adolescents may be insensitive to cues to limitusage and
o Positive influences of alcohol such as socialfacilitation may further encourage alcohol use.
Substance Use and Abuse in Adolescence III
o Although Adolescents may be less sensitive to somebehavioral effects of alcohol, they appear to be moresensitive to some of the neurotoxic effects.
o Greater ethanol-induced inhibition of N-methyl-D asparticacid-mediated synaptic potentials and long-termpotentiation in Hippocampal slices in adolescents than nadults
o Repeated exposure of intoxicating doses of ethanol alsoproduces greater Hippocampal-dependent memory deficits
o Prolonged ethanol exposure has been associated withincreased Dendritic Spine size, which is suggestive ofmodification of brain circuitry that may stabilize addictivebehavior.
Substance Use and Abuse in Adolescence IV
o There is evidence of altered brain structure andfunction in alcohol-dependent or abusingAdolescents and Young Adults compared withhealthy individuals.
o There has also been smaller Frontal andHippocampal volumes, altered White Matter mcrostructure and poorer memory.
o There are also positive associations betweenHippocampal volumes and age of first use, suggestingthat Early Adolescence may be a period of heightenedrisk to alcohol’s neurotoxic effects.
o Duration, which was negatively correlated toHippocampal volume, may compound this effect.
Substance Use and Abuse in Adolescence V
o Studies of high-risk populations (e.g., familial loadof alcohol dependence) have suggested thatimpairments in Frontal functioning are apparentbefore drug-use exposure and can predict latersubstance use.
o The Neurotoxic Effects of Alcohol, An IncreasedSensitivity to the Motivational Effects of Alcoholand Evidence of Poorer Top-Down Pre-Frontalcontrol apparent even before drug-use exposuremay set up a long-term course of alcohol and drugabuse well beyond Adolescence.
Substance Use and Abuse in Adolescenceo Research supports a view of Adolescent brain
development as characterized by a tension betweenearly emerging “bottom-up” systems that expressexaggerated reactivity to motivational stimuli and latermaturing “top-down” cognitive control regions.
o The bottom-up system, which is associated withsensation-seeking and risk-taking behavior, graduallyloses its competitive edge with the progressiveemergence of “top down” regulation.
o The imbalance between these developing systemsduring adolescence may lead to heightenedvulnerability to risk-taking behaviors and an increasedsusceptibility to the motivational properties ofsubstances of abuse.
Substance Use and Abuse in Adolescence VI
o Individuals with less top-down regulation may beparticularly susceptible to alcohol and substanceabuse as suggested by studies of high-riskpopulations showing impairments in Frontalfunctioning before alcohol and drug exposure.
o In the context of our Neurobiological Model ofAdolescence, these individuals would have an evengreater imbalance in Cortico-Sub-Cortical control.
o These findings are also in accordance with clinicalfindings in ADHD who show decreased prefrontalactivity and are four times as likely to develop asubstance use disorder compared with healthycontrols.
Substance Use and Abuse in Adolescence VII
o This imbalance in Cortico-Subcortical control would befurther compounded by the insensitivity of Adolescents tothe motor and sedative effects of alcohol that otherwisemay help to limit intake and the positive influences ofalcohol in social facilitation that may further encouragealcohol use.
o One of the challenges in addiction-related work is thedevelopment of bio-behavioral markers for earlyidentification of risk for substance abuse and/or foroutcome assessments for interventions/treatments.
o The behavioral challenges that require cognitive control inthe presence of tempting appetitive cues may be usefulpotential markers, such as impulse control and delayedgratification tasks.
Substance Use and Abuse in Adolescence VIII
o Although Adolescents as a group are consideredrisk-takers, some Adolescents will be more prone thanothers to engage in risky behaviors, putting them atpotentially greater risk for negative outcomes.
o Instead of limiting risk taking behavior, which may beadaptive in some situations, providing access to riskyand exciting activities under controlled settings may behelpful to limit harmful activities.
Substance Use and Abuse in Adolescence IX
Prevention and Treatment Strategies:o Instead of limiting risk taking behavior, which may be
adaptive in some situations, providing access to riskyand exciting activities under controlled settings may behelpful to limit harmful activities.
o By engaging in safe risk-taking opportunities, theTeenager can shape long-term behavior by fine-tuningthe connections between top-down control regions andbottom-up drives with maturity of this circuitry.
o Cognitive Behavioral Therapies that focus on RefusalSkills, or Cognitive Control can decrease risky behaviors.
Resources for Presentationo B.J. Casey, Ph.D. and Rebecca M. Jones, M.S.,
“Neurobiology of the Adolescent Brain and Behavior:Implications for Substance Use Disorders” ReviewArticle. Journal of the American Academy of Child andAdolescent Psychiatry. Vol . 49, No. 12 December2010.
