Motivation & Reward June 20, 2014

1. Motivation & RewardJune 20, 2014

2. Complex Motivation

3. Motivation What does it mean to be “motivated”? • Organized actions -- acquisition of goal • Role of emotion, interpretation • Coping, dealing w/ stressors

4. Motivation What are we motivated toward? • Survival • Basic drives • Vigilance for removal of stress/danger • Reward • Pleasure, positive reinforcement • Success

5. Motivation Goal directed behavior • Already discussed “basic” motivations… • Hypothalamus • Some learning, higher order control • Many motivations involve more cognitive input

6. Motivation Influenced by… • Memory • Past events, consequences • Future outlook • Mood • Executive functioning • Personality, interpretation

7. Motivation Variable –frontal circuits  greater degree of choice Coordinated communication -- reward circuitry, “executive” frontal cortex, hypothalamic control

8. Reward & Pleasure

9. Reward • Positive/pleasurable consequence of an action - potent motivator • Satiety, sexual pleasure are “natural rewards” - survival based behaviors • Repetition • Common motivational circuits

10. Reward Circuits Must be sensitive, and not very malleable – why? • Mesolimbic pathway – midbrain & limbic system • Hippocampus, amygdala, nucleus accumbens (striatum) • Projections to prefrontal cortex • Medial forebrain bundle (MFB) – specifically between ventral tegmental areaof midbrain and nucleus accumbens

12. Nucleus Accumbens • Striatum • Near frontal, limbic cortices • MFB projects through hypothalamus • Brain self-stimulation - so-called “pleasure center” • Direct access to reward circuit? • Stimulate at cost of natural rewards (food, sex) http://youtu.be/aNXhyPj-RsM

13. Reward Circuits • “Experience” and expectationof reward • Note discrepancy from what is actually delivered • Natural stimulation reinforce appropriate response • Perseverative behaviors • Habits, rituals

14. Dopamine • Midbrain  striatum (motor behavior) • Reward pathways • Role in addiction, drugs of abuse (Will discuss specific drugs of abuse next)

15. Reward & Addiction • Remember – drugs can mimic, alter neurotransmitters, impact targets • Dopamine agonists can “hijack” reward circuit • Alter physiology of circuit • Create association between drug & reward

16. Addiction • Addiction is not universal – properties of drug, individual variability • Animals chose drugs over most other actual needs (food, etc) – true also of addicts

17. Tolerance & Sensitization • Repeated use changes rewarding properties • Tolerance – more to achieve effect • Sensitization – less to achieve effect • Effect of drug can depend on environment • Anticipatory responses • Internal & external

18. Higher Order Processing

19. Prefrontal Cortex • Prefrontal cortex as “executive control” • Complex motivation - long term planning, decision making • Orchestration of thoughts/actions to meet goals • Remember - effect of frontal lobotomies?

20. Prefrontal Cortex • Choose between conflicting goals • Consider ethical concerns • What is appropriate, “good” or “bad” • Social control • Representation of past, future

21. Prefrontal Cortex • Set-shifting – flexibility in the face of change • Adjust to changing rules • Wisconsin Card Sorting Task • Sort cards based on undetermined properties • “Rules” change • Adjust strategy

22. Wisconsin Card Sort May be: • Color • Shape • Number Feedback – “right” or “wrong”

23. Personality • Motivation also influenced by “personality” - internal characteristics of individual • Extroversion, impulsivity, adaptability, etc. • Highly dependent on prefrontal cortex

24. The Case of Phineas Gage • 3 ½ foot rod (1 ¼ inch diameter) through skull • Damage to left frontal hemisphere • No long term motor, speech or intellectual deficits

25. The Case of Phineas Gage • Impact on personality exaggerated… but, noted changes in impulsivity, restraint, planning • May have been relatively short-term

26. Drugs & Addiction

27. Drug Abuse

28. Drug Abuse What is a drug? What is a “drug of abuse”? Issues w/ definition based on legality…

29. Drug Abuse • 100s of classifications • Produces effect when introduced into the body (human/animal) (not food) • Most any drug can be abused • Inappropriate dose, period of time, purpose • Even if designed for other purpose (ex., paint thinner)

30. Drug Abuse • Drug use/abuse is not new • Opiates • Ergot poisoning (toxic rye fungus) – “bewitchment”, supernatural visions • Is addiction a “disease” – how define complications from drug taking & reward?

31. Drug Abuse • Variability in how impact reward & likelihood of becoming addictive • Health & economic cost • Push to find “cure” for addiction, dependency Anything consumed to alter behavior can be a drug…

32. Mode of Drug Action - REVIEW • Physiological effects • Release, reuptake of neurotransmitter • Mimic neurotransmitter (receptor binding) • Compensatory physiological changes • Can be general or specific • Psychological effects • Activation, alteration of the reward circuit • Learning and association

34. Mode of Drug Action - REVIEW So what makes a drug “abusable”? Capacity to alter behavior in desired way Capacity to alter reward … Entry into the CNS (pass BBB)

35. Mechanisms of Drug Use

36. Administration Different speed/strength of drug delivery Oral ingestion – digested, absorbed into bloodstream Injection – muscle, veins, fatty tissue Inhalation – lungs, into bloodstream Mucous membrane – nose, mouth, rectum

37. Metabolism • Inactivation/elimination by liver enzymes • Rate (metabolism) is drug dependent • Excreted in urine, sweat, breath, feces • Prevent toxicity • Lethal dose differs by drug • Compare to therapeutic dose • Drug combinations – dangerous (why?)

38. Dosing Tolerance/sensitization – shift in dose-response curve • Tolerance to some effects, sensitization to others • Amount of drug reaching target • Physical changes at site of action

39. Dosing • One drug can alter effects of another • Learning & conditioning • Pairing drug w/ reward, environment • Role in relapse

41. Withdrawal • Decrease or cessation of regular drug taking • Physical, psychological dependency • Effects depend on exposure (duration, type, amount of drug), site of action

42. Commonly Abused Drugs

43. Stimulants • Temporarily improve mental or physical function • Generally increase CNS/PNS activity • Wakefulness, motor activity, awareness, motivation, arousal

44. Stimulants • Many different modes of action • Increase in NE • Increase in DA • ACh receptor agonist • Abuse - effect on mood

45. Stimulants - Caffeine • Mild stimulant - coffee, tea, chocolate… • Caffeine pills, energy drinks • Reduce drowsiness • Combined w/ other drugs (OTC cold/flu, etc.)

46. Stimulants - Nicotine Extracted from some plants (incl. tobacco plant) Cigarettes, cigars Natural insecticide Most commonly chewed or inhaled

47. Stimulants - Nicotine • Effects on sympathetic NS, reward pathway • Indirect effects on other neurotransmitters/systems • Mood, concentration, metabolism… • One of the most addictive drugs • Mostly psychological • Notoriously difficult to stop use

48. Stimulants - Nicotine Long term effects on health – respiratory infections, oral/lung cancers, cardiovascular disease Teratogenic, secondhand effects Withdrawal – dizziness, nausea, tremors

49. Stimulants - Cocaine • Extract from leaves of coca plant • Method of preparation varies (derivatives) • Often cut w/ other stimulants • Different modes of administration (snorting, injection, etc.) • Anesthetic

50. Stimulants - Cocaine • Reward pathway, dopamine transporter; interference w/ Na channels • Euphoria, alertness, increased energy, anxiety, restlessness, reduced need for sleep • Tremors, convulsions w/ very high doses • Highly addictive over time