1. Cognitive Neuroscience (Psychology 460) Summer Quarter Mondays & Wednesdays 12:00 – 2:10pm This course will focus on answering the question, “How are cognitive behaviors produced by the human brain?” Topics include language, attention, action, cognitive control, and memory. The course will involve lectures, discussions, demonstrations, and tours of some of the neuroscientific tools we have on the UW campus.

2. Retrieval, Memory Modification and The Cycle of Consolidation Psychology 355: Cognitive Psychology Instructor: John Miyamoto 05/09/2016: Lecture 07-1 Note: This Powerpoint presentation may contain macros that I wrote to help me create the slides. The macros aren’t needed to view the slides. You can disable or delete the macros without any change to the presentation.

3. Outline Brunet’s treatment of unwanted memories in PTSD patients. The cycle of consolidation Introduction to autobiographical memory Psych 355, Miyamoto, Spr ‘16 3 OLD SLIDE: Nader’s Method for Undoing Fear Conditioning Lecture probably ends here

4. Psych 355, Miyamoto, Spr '16 4 Undoing Fear Conditioning in the Rat Nader, K., Schafe, G. E., & Le Doux, J. E. (2000). Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature, 406, 722-726. If a tone is paired with an electric shock, a rat will learn to freeze when it hears the tone (classical conditioning of fear). Anisomycin – antibiotic that inhibits protein synthesis that is required in the formation of new memories. Administering anisomycin to a rat can cause it to fail to learn. Experimental Design (Diagram of Rat Learning or Unlearning) Skim past:

5. Summary of Main Finding Psych 355, Miyamoto, Spr '16 5 Retrieval Makes Day 1 Learning Vulnerable to Change Drug on Day 2 does not undo fear conditioning. Combining drug with tone & shock on Day 1 prevents fear conditioning. Combining drug with retrieval of fear conditioning on Day 2 undoes fear conditioning. Condition 2: Day 1: Tone + Shock Day 2: Drug; no tone; no shock Day 3: Freezes to tone (shows learning) Condition 1: Day 1: Tone + Shock + anisomycin Day 2: No drug; no tone; no shock Day 3: Does not freeze to tone (shows no learning) Condition 3: Day 1: Tone + Shock Day 2: Drug + tone, no shock. Day 3: Does not freeze to tone (shows no learning) Skim past:

6. Psych 355, Miyamoto, Spr '16 6 Retrieval makes the fear conditioning from Day 1 vulnerable to change. Combining retrieval with drug prevents reconsolidation of memory of fear conditioning, thereby causing loss of conditioning. Condition 3 displayed to the right: Nader et al. (2000) state that the memory trace is "labile" during retrieval, i.e., its form can be changed at that time. Interpretation Using Fragility of Memories During Retrieval to Treat PTSD Day 1 Day 2 Day 3

7. Psych 355, Miyamoto, Spr '16 7 Using the Fragility of Memories During Retrieval to Treat PTSD Brunet, A., Orr, S. P., Tremblay, J., Robertson, K., Nader, K., & Pitman, R. K. (2008). Effect of post- retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. Journal of Psychiatric Research, 42, 503-506. Post-traumatic stress disorder (PTSD): Strong fear and stress responses are evoked by reminders of the initial traumatic event. Brunet et al. asked whether human PTSD patients can lose or at least diminish their fear and stress conditioning by techniques that are similar to Nader et al.'s demonstration that rats can lose their fear conditioning. ♦ Study used propranolol, a drug that is used to prevent traumatic memories if administered immediately following a traumatic event. Propranolol reduces the fear & stress conditioning of trauma. Brunet et al.'s Subjects Were PTSD Patients Skim past:

8. Psych 355, Miyamoto, Spr '16 8 Brunet et al.'s Study of PTSD Subjects PTSD patients: Childhood sexual abuse, motor vehicle accident, rape, being taken hostage. ♦ Comorbid mental disorders included: major depressive disorder, panic disorder, social phobia, bulimia, generalized anxiety disorder. Two scripts were prepared for each patient that described the events that produced the trauma for that patient. 19 PTSD patients were randomly assigned to either a TREATMENT Condition or a CONTROL Condition. (Conditions described on next slide.) Test of Treatment - Was It Efficacious? Skim past:

9. Brunet et al.'s Study: Treatment and Control Conditions 9 Psych 355, Miyamoto, Spr '16 Test of Treatment - Was It Efficacious? Patient hears recorded description of traumatic experience Patient hears another recorded description of traumatic experience Patient is injected with propranolol. Patient is injected with placebo. Measure anxiety 7 Days

10. Psych 355, Miyamoto, Spr '16 10 Test of Treatment One week later, the patients listened to a taped version of the scripts that described their traumatic experience, and are asked to imagine the traumatic events while listening to the tape. ♦ Physiological measures of stress and anxiety are taken while patients listen to the tape. Question: When the patients hear the taped version of traumatic experience, will they experience fear, anxiety, etc. of PTSD? ♦ I.e., has the drug treatment reduced or eliminated their tendency to associate fear responses with these memories. Analogy Between Rat Conditioning and PTSD Treatment Skim past:

11. HUMANRAT Traumatic experienceTone + shock conditioning in the rat Listen to taped Rat hears tone without the shock description of traumatic experience Injection of propranolol Injection of anisomycin immediately after recallimmediately after rat hears tone Later, the rat seems to have unlearned the fear conditioning to the tone. Psych 355, Miyamoto, Spr '16 11 Later, will the human seem to have unlearned the fear conditioning to the traumatic memories? Analogy Between PTSD Treatment & Conditioning Experimental Results ?

12. Psych 355, Miyamoto, Spr '16 12 Brunet et al. Results Grey = placebo group; Black = propranolol group Result: Therapy reduces original fear conditioning. Heart Rate Skin Conductance Corrugator EMG Tensing of Frowning Muscles Return to Malleability of Memory During Retrieval Y-Axis Are Z-Scores Relative to Base Rate

13. Psych 355, Miyamoto, Spr '16 13 Brunet et al. Results Grey = placebo group; Black = propranolol group Result: Therapy reduces original fear conditioning. Heart Rate Skin Conductance Corrugator EMG Return to Malleability of Memory During Retrieval Y-Axis Are Z-Scores Relative to Base Rate Tensing of Frowning Muscles

14. Psych 355, Miyamoto, Spr '16 14 Malleability of Memories During Retrieval Learned associations can be lost during retrieval ♦ Rats unlearned tone-shock connection ♦ Humans unlearn (to some degree) the association between a traumatic episodic memory and the emotional response. This Slide + Retrieval Strengthens Memory (Consolidation/Reconsolidation)

15. Psych 355, Miyamoto, Spr '16 15 Malleability of Memories During Retrieval Learned associations can be lost during retrieval Consolidation & Reconsolidation – Memories can be strengthened during retrieval. ♦ Thinking about something produces better future recall. ♦ Practice testing (retrieval) produces better future recall. ♦ The memory becomes more primed, i.e., more easily retrieved as an associate of something else. This Slide + Query: Do These Facts Contradict Each Other?

16. Psych 355, Miyamoto, Spr '16 16 Malleability of Memories During Retrieval Learned associations can be lost during retrieval Consolidation & Reconsolidation – Memories can be strengthened during retrieval. Do these results contradict each other? Stored representations can change during retrieval. ♦ Usually the change makes the memory stronger, better organized, more linked to other memories. The memory becomes more primed, i.e., more easily retrieved as an associate of something else. ♦ The opposite can also happen, ○ E.g., rats unlearn their fear conditioning, or humans become desensitized to memories of trauma. This is a special case that is based on the injection of drugs that would not normally be present. ○ E.g., while we think about past events, i.e., during retrieval, we may distort the facts or even falsify what was once a true memory. Psychologists believe that this happens to everyone. No! Conclusions re Consolidation

17. Psych 355, Miyamoto, Spr '16 17 Conclusion re Consolidation Consolidation occurs through reactivation of memories, followed by re-encoding of the memories. Hippocampus plays a major role in reactivation of recent episodic memories. ♦ Standard Model of Consolidation: After the memories have been consolidated, the hippocampus plays a reduced role in retrieval of episodic memories. ♦ Multiple Trace Model of Consolidation: After the memories have been consolidated, the hippocampus plays a reduced role in retrieval of episodic memories that have been semanticized (turned into semantic memories, i.e., “remember” the memory), but not for episodic memories that continue to be episodic, i.e., “know” that this is what happened. Memories are malleable during or shortly after retrieval. PBS video titled “Memory Hackers”: https://www.youtube.com/watch?v=xS_OiKvoqbo Excellent discussion of how memories are created. Thank you, Lindsay. The Cycle of Consolidation

18. Cycle of consolidation (JM’s term) : ♦ Repeatedly retrieving some memories. ♦ Possibly modifying the memories. ♦ Reconsolidating the memories, possibly with modifications. The cycle of consolidation happens spontaneously in many different situations. Psych 355,, Miyamoto, Spr '16 18 Image of a Man Thinking About a Conflict with Significant Other

19. Not-So-Instant Replay of Interpersonal Conflict 19 Psych 355, Miyamoto, Spr '16... but she said ABC!...... so I said XYZ....... she doesn’t care if PQR!...... I asked her why EFG?...... she thinks JKL......., etc., etc., etc.,... Image of a Man Thinking About How to Compute a T-Test

20. Statistics Problem Solving 20 Psych 355, Miyamoto, Spr '16... How do I calculate a T-test?...... What’s the difference between the standard deviation and the standard error?...... What’s the formula for SE(X ̅ 1 – X ̅ 2 )?...... Does it matter if the sample sizes are different?...... What are the degrees of freedom of SS pooled ?......, etc., etc., etc.,... Dwelling On Something Involves Lots of Retrievals – END

21. Dwelling on Something Usually Involves Lots of Retrieval Retrieval creates a the potential for modification of memories. Retrieval induced memory change happens very often. We spontaneously engage in thinking patterns that cause retrieval-induced memory change. This is the cycle of consolidation. ♦ Retrieval induced memory change is not just a tool for better study habits. ♦ Retrieval induced memory change is not just a tool for clinical modification of memories. Psych 355, Miyamoto, Spr '16 21 END – OR – Start Autobiographical Memory

22. Autobiographical Memory (AM) Autobiographical memories are memories of one's personal experiences and history. Many autobiographical memories include episodic memories. ♦ E.g., I remember listening to a lecture on statistical theory last week, i.e., I remember where I was sitting in the room, who was around me, etc. Many autobiographical memories include semantic memories. ♦ E.g., I remember the name of my elementary school, but the name isn’t connected to a particular experience. Psych 355, Miyamoto, Spr '16 22 AM & Mental Imagery

23. AM’s often include memories of visual, auditory, olfactory or haptic aspects of the memory. ♦ Memory of a place might include a visual memory. ♦ Memory of food might include visual or olfactory aspects. Greenberg and Rubin (2003) ♦ Patients who cannot recognize objects also experience loss of autobiographical memory ♦ Visual experience plays a role in forming and retrieving AM Psych 355, Miyamoto, Spr '16 23 Do AM’s Involve Distinct Patterns of Brain Activity?

24. Subjects (Duke undergrads) took photos of campus landmarks. Later subjects viewed photos during fMRI scan. OWN Photos: Photos taken by the subject. LAB Photos: Photos taken by someone else, not by the subject. Psych 355, Miyamoto, Spr '16 24 Figure 8.1 Goldstein, p. 209, based on Cabeza, Prince, Daselaar, Greenberg, Budde, Dalcos, et. al. (2004). fMRI Results for OWN and LAB Photos (text description)

25. fMRI Results for OWN Photos & LAB Photos Both types of photos activated similar brain structures ♦ Medial temporal lobe (MTL) (typical of episodic memory) ♦ Parietal cortex (typical of scene processing) OWN-photos activated more of the ♦ Prefrontal cortex (PFC) (information about self) ♦ Hippocampus (recollection) Psych 355, Miyamoto, Spr '16 25 These interpretations involve theory (intelligent guesswork). fMRI Results for OWN and LAB Photos (fMRI Images)

26. fMRI Images that Support Interpretation on Preceding Slide Figure 8.2. fMRI response in three brain regions. Yellow lines: Response to OWN photos Blue lines: Response to LAB photos OWN photos produce stronger response than LAB photos in PFC & hippocampus. Psych 355, Miyamoto, Spr '16 26 (c) Hippocampus (a) Parietal cortex (b) Prefrontal cortex (PFC) END