Discussion Overview

1. Danielle M. Bronk, PhD, ABPdNBoard Certified Pediatric NeuropsychologistNeurodevelopmental Health Services The Perfect Storm: Addictive Behavior and the Developing Brain: Understanding Adolescent Vulnerability to Addiction and the Impact on Development

2. Discussion Overview • A focus on relevant structural and neurochemical changes in the adolescent brain and the relationship of the developing brain on behavior. • We will review vulnerability factors associated with addictive behavior during adolescence. • We will discuss common addictions during adolescence and the effects of addiction on the developing brain. • Lastly, we will discuss screening as well as behavioral strategies and treatment resources for the more common adolescent addictions.

3. Poll Question #1 Is the adolescent brain more susceptible to addictive behavior? True or False

4. Part 1: The Significance of Adolescence • It’s not just about hormones….. • More important than the specific effects of hormones are the broader developmental changes that occur in the adolescent brain. • “Perhaps the most fundamental change—and the discovery that seems to have driven us to rethink how the teenage brain works—comes from neuroimaging studies revealing that white matter and gray matter in the brain undergo significant changes during the adolescent years” (Armstrong, 2016).

5. The Brain v. Hormones • Hormones certainly play in driving adolescent behaviors. • Estrogen and testosterone play a role in structural connections in the brain and affect neurotransmitters in the brain • However, structural changes in the brain during adolescence serve as the primary basis to understanding this key period in development.

6. The Adolescent Brain: Pedal to the Metal • The most profound changes that take place in the brain during adolescence involve rewiring, reassembling, and upgrading of neural tissue. • Beefing up white matter and reducing gray matter

7. Poll Question #2 Name one brain region that undergoes major development during adolescence?

8. The Adolescent Brain “Human brains are genetically engineered to prioritize emotions over logic in our adolescent and early adult years” (Shatkin, 2017).

9. Why is this? The answer lies in the specific regions and type of changes occurring in the adolescent brain– • Increased synaptic pruning and myelination in the prefrontal cortex • Enhanced amgydala reactivity to emotional stimuli • Exaggerated reactivity to rewarding stimuli • Reduced sensitivity to aversive stimuli

10. “The Brakes” - Prefrontal Cortex “The Accelerator” - Limbic System “The Gas Pedal” - Dopamine

11. Corticolimbic System: Thinking & Emotional Centers Prefrontal Cortex Limbic System Decision makingPlanningWorking memoryPrioritizingInhibiting impulsesReflectingOrganizingStrategizingSelf-controlCoordinating thought and emotionDelaying gratification Risk takingMotivationHungerSleep cycleLong-term memorySensation seekingReward seekingNovelty seekingImpulsivityPrimacy of emotional expressionImmediate needs

12. Corticolimbic System: Frontal Lobe • Frontal lobe is the brain’s action/direction cortex • The prefrontal cortex is the area responsible for planning, making decisions, setting priorities, forming strategies, and inhibiting impulses and inappropriate behavior. These activities are often referred to collectively as executive functions. • Different areas of the frontal lobe in particular, the prefrontal cortex are involved in different executive functions

13. Prefrontal Cortex & Executive Functions Metacognitive Strand - “Cold” EFs Social/Emotional Regulation Strand - “Hot”EFs • Goal Setting • Planning/Strategizing • Sequencing • Organization of Materials • Time management • Task Initiation • Goal Directed Attention • Task Persistence • Working Memory • Set Shifting • Response Inhibition (i.e., Impulse Control) • Emotional Control • Affective Decision-Making • Adaptability/Flexibility

14. Prefrontal Cortex Dorsolateral Prefrontal Cortex Anterior Cingulate Cortex Orbitomedial Cortex

15. Prefrontal Subcortical Circuits Dorsolateral Circuit: Working memory Planning Sustained attention Logical thinking Learning

16. Prefrontal Subcortical Circuits Anterior Cingulate Circuit: Motivational mechanisms; behavioral and emotional control; decision-making.

17. Prefrontal Subcortical Circuits Orbitofrontal Circuit – the inhibitory system, involved in inhibitory decision-making processes, especially involving reward-related behaviors.

18. CorticolimbicSystem: Limbic System Prefrontalcircuitry interacts with the limbic system to regulate affective arousal and modulation.

19. Limbic System - “The Accelerator” • Amygdala –Almond shaped set of neurons located in the medial temporal lobe that plays a key role in emotional processing and fear assessment. • Hippocampus – stores the memories of an experience and many related factors • Ventral Striatum (VS) –part of the limbic system involved in reward processing and motivation.

20. Dopamine “The Gasoline” Big distinction between the adolescent and the adult brain : the amount of dopamine. There is also a peak in the adolescent brain's sensitivity to dopamine.

21. Dopamine Continued…. Reward Prediction Error

22. Dopamine Continued…. Sex hormones - directly (e.g., adolescents' acquisition of sex-specific physical traits and sexual attraction to others) and indirectly (e.g., influencing neurotransmitter activity in the brain) influence dopamine and other neurotransmitters. During adulthood the brakes (PFC) and the accelerator (emotional center) are better connected and thus dopamine is better shared between the two, resulting in the brakes being more easily applied (less impulsive and more thoughtful in decision-making).

23. The Adolescent Brain As we age, the prefrontal cortex takes the driver seat unlike during adolescence where the amygdala has a greater role Adolescents display heightened attention and reactivity to reward and threat Adolescents display greater reliance on limbic emotional regions than on prefrontal control regions.

24. Neurodevelopmental Takeaways Sex hormones have an important role in affecting adolescent development During adolescence, white matter in the brain increases and gray matter decreases. Pruning of gray matter occurs from the back of the brain to the front, meaning that the prefrontal cortex , the site of executive functions is the last area of the brain to be fine-tuned in adolescence. The limbic system, or emotional brain, matures before the prefrontal cortex does, meaning that emotion, sensation seeking, and social salience often override more rational ways of thinking and behaving until late adolescence or the early 20s. During adolescence, fluctuations in neurotransmitter systems that involve dopamine, oxytocin, and serotonin can contribute to reward-based risk taking, intense desire for social connections, and mood disturbances.

25. Adolescent Brains are Engineered for Success Engineered for flexibility…..It is beneficial for the adolescent brain to be flexible, more “plastic” and not rigid like the adult brain. Engineered for risk-taking……Evolution shaped risk-taking in adolescence (think shorter life span) were best suited to take risks needed for exploring sources of food and land, procreating, etc. Engineered for sensation seeking… newer research tells us adolescents tolerate ambiguity better than adults. Therefore, adolescents may be more comfortable taking risks without all the information and uncertainty regarding potential outcomes.

26. The Critical Period of Adolescence Major structural and neurochemical changes that result in: Increased risk taking Less developed judgment Stronger emotional states And interact with multiple: Environmental Factors

27. Part 2:Neurobiological Models of Addiction It appears that the brain changes characteristic of adolescence are among the most dramatic and important to occur during the human life span.—Laurence Steinberg For this reason, exposure to addictive substances/behavior during this period is critical to our neurobiological understanding of addiction during adolescence.

28. The Dopamine Crave Theory • When we engage in a dopaminergic behavior (eating M&Ms), dopamine levels increase so the reward pathway is activated, thus telling the individual to repeat the behavior for more feel-good reward. • Addictive behaviors provide a short cut with less delay and a flooding of dopamine. Addicted individuals experience a dopamine reduction or shutdown to pause or reset overflooded receptors. • Addiction creates a reduced capacity to naturally produce dopamine so then the addicted individual needs to engage in the addicted behavior just to maintain dopamine levels.

29. The Dopamine Crave Continued…. Research has shown that those with a genetic predisposition to addiction have lower baseline levels of dopamine as well as endorphins and norepinephrine, and as a result are more likely become addicted on a substance or behavior that increases dopamine.

30. The Dopamine Crave Continued…. Eating foods like chocolate can raise dopamine by 50% Sex can raise dopamine levels by 100% 2-D videogames increase levels by 100% (Koepp, 1998) Snorting cocaine….350% Crystal meth….1,200%

31. The Dopamine Crave & Adolescence Adolescents do not have the benefit of the fully developed prefrontal cortex to apply the brakes to control impulsivity and exert greater levels of willpower.

32. Myelin Disruption Theory • When synapses are stimulated repeatedly, the neuronal connection pattern becomes hardwired via myelination. • Overstimulation of pathways can damage myelin in neural pathways too. • Oligodendrocytes = brain cells that produce cholesterol for proper myelination are easily damaged by head trauma, environmental stressors, toxins, stress hormones, certain drugs, and overstimulation.

33. Myelin Disruption Theory Continued…. • Recent brain imaging has also shown decreased myelination with tech addiction. • Indiana University School of Medicine 2011 study compared fMRI results for those that played violent videogames for one week versus controls. After one week of violent video game play, those individuals showed less activation in the left inferior frontal lobe and less activation in the anterior cingulate cortex in their baseline result and when compared to controls. • Once they refrained from VG play, the regions returned to a state closer to the control group highlighting the brain’s plasticity (bounce back and compensate).

34. The Environment • Environmental conditions seem to play a role in vulnerability to addiction. Rat studies by Canadian professor, Dr. Alexander highlight this as rats in cages were quick to become addicted to morphine, while rats in “parks” with other rats and opportunities for physical activities were much less likely to access the morphine. • Dr. Alexander applied this to humans and found those put in physical, mental or cultural isolation are more susceptible to addiction.

35. The Environment Continued…. Dr. Alexander went on to surmise that, “The view of addiction from Rat Park is that today’s flood of addiction is occurring because our hyperindividualistic, hypercompetitive, frantic, crisis-ridden society makes most people feel socially and culturally isolated…. “They find temporary relief in addiction to drugs or any of the other thousand other habits and pursuits because addiction allows them to escape from their feelings, to deaden their senses and to experience an addictive lifestyle as a substitute for a full life.”

36. Frontal Cognitive Dysfunction Theory • Chronic exposure to addictive substance or behavior negatively affects the frontal cortex….. • Frontal cortical cognitive dysfunction resulting in an inability to inhibit inappropriate unconditioned or conditioned responses elicited by drugs, related stimuli or internal drive states. • “Faulty Brakes” – the brain’s decision-maker (i.e., impulse control) makes it harder for the person to “just say no.”

37. Frontal Cognitive Dysfunction Theory Remember the PFC does the following: • Process the reward value and/or affective valence of environmental stimuli • Assess the future consequences of one’s actions and inhibit inappropriate behaviors Repeated exposure to addictive substance or behavior leads to dysfunction in OFC circuit that leads to an intensive drive to use or engage in the addictive behavior following exposure to “cues.”

38. Frontal Cognitive Dysfunction Theory Continued…. Executive dysfunction affects the addict’s ability to maintain the correspondence between intention and action, and to compile all of the necessary information to be aware of the consequences or one’s challenges as well as the repercussions on their family and social environment. In addition, the speed to understand the information is impaired.

39. Frontal Cognitive Dysfunction Theory & Denial/Lack of Awareness in Addiction • Interpreting and processing emotional signals – The insula in PFC is a key region for processing and integrating social engagement, perception, and emotional signals. • Impulsive Response Pattern – being able to perceive and anticipate the negative consequences of addiction. • Ability to imagine future consequences – medial orbitofrontal cortex, which is often considered one of the most affected regions of addiction.

40. The Adolescent Paradox: Overlearning • Adolescence is a stage of development where there is high rates of learning and memory due to the heightened synaptic plasticity of childhood. • This priming to learn leaves adolescents vulnerable to learning the wrong things, as anything learned (good or bad) that stimulates dopamine production is basically a reward to the brain. • According to Dr. Jensen, “This means a little bit of stimulation to a teenage brain whose synapses are firing all over the place leads to a craving for more stimulation that can, in certain situations, result in a kind of overlearning.”

41. Determinants of Addiction During Adolescence Risk & Protective Factors • Parent relationship • Family conflict • School environment • Relationships with adults in the community • Spiritual beliefs • Engagement in other risky behaviors

42. Poll Question #3 Tell me some common addictions during adolescence?

43. Part 3: Addiction in Adolescence For our purposes, we’ll examine….. • Alcohol • Vaping • Screen Addiction

44. Adolescence & Alcohol Use Disorder Some stats and facts…… Adolescents are less sensitive to the sedative effects of alcohol (Silveri & Spear, 1998). 25-35% of HS students begin drinking before age 13 (CESAR, 2006). Adolescents who begin drinking before age 15 are 4x more likely to become alcohol dependent during their lifetime (Grant & Dawson, 1998).

45. Alcohol & the Adolescent Brain • Adolescent brains are much better at handling the sedative aspects of drinking due to less GABA receptors (cerebellum) • Alcohol effects the size and efficiency of the prefrontal cortex and hippocampus • Animal studies have shown a reduction in hippocampi neurons when exposed to heavy drinking • Alcohol impairs memory more easily in adolescents than in adults Cocktail party memory deficit The blackout

46. Adolescence & Alcohol Use Disorder Research has shown adolescents with alcohol use disorder have smaller prefrontal gray and white matter volumes than age matched controls. Lower volumes correlated with a higher maximum number of drinks per drinking episode (De Bellis et al., 2005). Adolescents that engage in heavy binge drinking experience greater levels of negative mood and perform worse on executive function tasks (Townshend & Duka, 2003) secondary to disrupted synaptic remodeling (i.e., pruning and myelination) in prefrontal cortex (Crews et al., 2007).

47. Poll Questions # 4 & 5 Isn’t vaping less harmful than tobacco? True or False It is only water vaping, right? True or False

48. Vaping/Electronic Nicotine Devices (ENDS) ENDS deliver nicotine through a liquid that is heated into a vapor and inhaled, cutting out the cancer causing tar of combustible cigarettes. BUT….. The liquid usually contains glycerin or propylene glycol as well as nicotine, additives, and varying amounts of contaminants. The aerosol inhaled from these is often a mixture of nicotine, formaldehyde, and acrolein.

49. ENDS & the Developing Brain Animal studies regarding nicotine use during adolescence have demonstrated structural and functional changes in the brain, including: Upregulation of nAChRs Reduced cell number and size in midbrain, cerebral cortex, and hippocampus Changes in prefrontal cortex neurons

50. ENDS & the Developing Brain The research of Yuan et al., 2015 along with others revealed that adolescents exhibit greater behavioral sensitivity and susceptibility to other drugs of abuse after nicotine exposure.