1. Perception and Processing of Representations of Emotional and Physical Pain: Does It All Hurt the Same Way? Petra E. Pajtás December 12, 2006

2. How do we experience pain? The “pain pathway”: from input to cortex (Image courtesy of Sigma- Aldrich.com)

3. What is physical pain? Provoked by noxious stimulus Designed to warn of potential harm Usually results in a motor response to “get you out of the noxious situation” Mediators: noci-receptors or hypersensitization of regular receptors

4. Breaking physical pain into components Sensory discriminative component -location, intensity, quality “Oh my head, I feel a bad, sharp pain!” Motivational-affective component -depression, anxiety “Oh, I feel like $*&%! I think I might die!” Cognitive evaluation + Reflexive component -figuring out why it hurts, responding “Someone just hit me with a hammer upside the head; let me run away…” Willis, 1985

5. What about emotional pain? “I know it was wrong, but I got hecka suspicious about her and Charles so I went into her email one day and I saw a letter that she sent to Charles...And after I saw that, it was over. I was so [expletive deleted] mad and so [expletive deleted] hurt, mostly mad. I wanted to throw EVERYTHING and just punch everything I saw... That night that I found out, I couldn't even sleep. I thought I was just gonna die in bed that night, it was just hella hurting. I was just lying there, and the heartache was hurting so bad, it's unexplainable. It starts from the heart, and it spreads throughout your body so the whole body hurts. The heart, the mind, everything about me was dying.” (uclamangoboy, 2003) MacDonald, Kingsbury, & Shaw, 2005 So does this guy hurt, physically? Is there a noxious stimulus per say? Is there a different way to characterize how he feels other than words describing physical pain? If we asked him to describe the intensity and quality of the pain, what would he say?

6. The Question: Does emotional pain (which comes without all the nociceptive processing – suppose) hurt the same way as physical pain? Cognition? Where does the input go?

7. Are there any shared cortical mechanisms? The ACC? Activation in response to painful stimuli (processing/looking for a way out?) (Davis et al., 1997) Activation to social exclusion (Eisenberger et al., 2003) Activation correlating with empathy ratings in witnessing the pain of a significant other (Singer et al., 2004)

8. What does the ACC do? Regulation of autonomic behavior (Critchley et al., 2003) ACC activation in conflict resolution (Cohen et al., 1999; Ochsner et al., 2001) Activation to detect error when a response is possible (Hadland et al., 2002) Lesions: apathetic, unconcerned, prone to mistakes (Eslinger & Damasio, 1985) Detecting when strategic control is required (MacDonald et al., 2000) Metabolically highly active even at rest (Raichle et al., 2001)

9. Problems with the ACC Very large region; localizations for each of the references in the previous slide remains inconsistent and often the experiments have not yet been replicated. If we’re going to look at ACC functioning, we may as well start from scratch.

10. Hypothesis In the event that emotional pain and the motivational/affective component of physical pain (“physical pain”) are processed by the same mechanisms, overlapping activation of the ACC is predicted. If emotional and “physical” pain are processed by different mechanisms – even if these overlap or are similar – only partially overlapping or distinct activation of the ACC is predicted.

11. Methods – Participants 16 participants (8 female) Right-handed; 18-40 years old Normal or corrected-to-normal vision No color blindness; no past or current psychiatric or neurological conditions Participants to undergo SCID before experiment

12. Methods – Task Participants will be told that they would be presented images with both physically and emotionally painful stimuli as well as neutral pictures. They are told that their job is to focus on identifying with the events presented in each of the images; they are also asked to evaluate the degree of pain in each presentation (without providing verbal responses).

13. Sets of images depicting emotional or physical pain Sets of images of neutral matched control images Images normalized for stim intensity; hue and saturation are similar Images piloted for emotional vs. physical pain depiction… Methods – Task

14. Methods – Image Examples Suggests physical pain (courtesy of fotosearch.com) Suggests emotional pain (this is debatable – but this is just an example; it’s difficult to find matching pictures) (courtesy of picsearch.com)

15. Methods – Design -6 functional scans + structurals -block-design, 5 blocks -emotional p, physical p, emotional n., physical n., fixation -10 stim per block, presented 2x -begins with fixation for 500 ms -stimulus on screen for 2.5 sec -blank screen for 750 ms -blocks counterbalanced across scans -new set of 10 stimuli for each scan Total scan length: 5.4 min each

16. One-back task 1x per block Just for attentional engagement Methods – Design & Acquisition Acquisition: -TR=1.173, TE=30 ms, flip angle = 90° -3 mm slice thickness, 3x3x3 mm voxel size -realignment, normalization, spatial smoothing (FreeSurfer) -HR function via gamma function + derivative (found to be best for this region)

17. Data Analysis – Whole Brain Random effects analysis of variance for whole brain data to be conducted Expected results: increased activity in the ACC for emotional AND physical pain compared to neutral picture viewing Also, remember that we have to also separate by gender.

18. Data Analysis – Matched Sets We split the data into even and odd runs: set 1 (scans 1, 3, 5) and set 2 (scans 2, 4, 6) We perform the same analyses we do in whole brain ANOVAs, only on half the set this time (we can look at how much power we lost…) Take the coordinates for the regions we find in set 1 and: We do the equiv. of whole brain on set 2; then we subtract from the activation maps the coordinates for the regions found in set 1 (one set for ROI EMO, one for ROI PHYS). What we are left with is everything outside the region of subtraction; with t-tests corrected for multiple comparisons, we can compare voxel-by-voxel activation between what we found in set 1 (including what became ROIs and what we found in set 2). If we do a SET2EMO – PHYS_ROI and SET2PHYS – EMO_ROI, we can figure out whether the regions for EMO and PHYS overlap. THIS IS COMPLICATED, make sure you ask me questions (it’s also a good opportunity to confuse me… )

19. How We Do the Analyses: SET 1: EMO_FUL BLOCKS – EMO_NEU BLOCKS = EMO1 PHYS_FUL BLOCKS – PHYS_NEU BLOCKS = PHYS1 … ANOVA  EMO_ROI & PHYS_ROI SET 2: EMO_FUL BLOCKS – EMO_NEU BLOCKS = EMO2 PHYS_FUL BLOCKS – PHYS_NEU BLOCKS = PHYS2 … EMO2 – PHYS_ROI = EMO2_clean PHYS2 – EMO_ROI = PHYS2_clean We check if EMO2_clean and PHYS2_clean overlap… -if EMO2_clean and PHYS2_clean >0, there is a non- overlapping region in processing physical and emotional pain; -if subtraction leads a close to 0 result, the processing of physical and emotional pain is done via the same regions.

20. Expected Results This says the same thing, just a bit differently; the point is still that results should look something like this with no significant diff. in ACC activity for PHY vs. EMO pain. Percent Signal of Voxel Activity Accounted For by Each Component 0 20 40 60 80 100 EMO PainPHYS Pain Stimulus Separation by Pain Type Percent Signal EMO ROI PHYS ROI

21. Interpretations Is the subjective experience still different despite the ACC being involved in both? Are there differences between women and men in emotional reactivity? Are our findings How can we inform the field with out findings? What follow-ups do we need? Why aren’t these follow-ups feasible? (I’ll tell ya…)

22. Importance What we find can help inform what we know about ACC lesions, disorders where emotion and empathy are compromised (alexithymia) We learn about how the brain processes fear/pain/emotional stressors

23. Potential Problems Gender, individual variability in capacity to empathize (despite self-report similarities) Task engagement (one-back task may not be enough) Splitting into 2 sets may be decimating our power, but … Because the lit is inconsistent it would be silly to do ROIs based on other people’s published results… We shouldn’t have phobics, but what if someone responds aversively to the stimuli… moving in the scanner – trashing data…

24. Costs 16 hrs. scan time = $8592 (+ $1500 wiggle room for data loss) $50 / subject = $800 $1000 for conference presentation Publication expenses: 5 figures x $600 = $3000 We have RAs working for free…. the beauty of dedicated students and aspiring grad students Estimated total cost = $14,892+

25. Questions, Comments, Suggestions? Thanks Yuhong for breaking down the data analysis to intelligible bits…! Thanks everyone!