1. WPA Early SPECT Studies David Ingvar and Niels Lassen Daniel Weinberger and Karen Berman

2. WPA Ingvar and Lassen Normals Patients (Hypofrontality)

3. WPA Frontal Functions Fluency of thought and speechFluency of thought and speech Emotional attachmentsEmotional attachments Social and moral judgmentSocial and moral judgment Volition and driveVolition and drive Planning and identifying goalsPlanning and identifying goals Formulating abstract conceptsFormulating abstract concepts

4. WPA Weinberger and Berman Normals Patients NumberWCS

5. WPA PET Studies

6. WPA Normals: Remembering Words Increased blood flow in frontal operculum, thalamus, cerebellumIncreased blood flow in frontal operculum, thalamus, cerebellum

7. WPA Patients: Remembering Words Failure to activate regions used by normalsFailure to activate regions used by normals Decreased frontal flowDecreased frontal flow

8. WPA Using PET to Study Anhedonia Examine changes in blood flow in response to visual emotional stimuliExamine changes in blood flow in response to visual emotional stimuli Comparison of pleasant vs unpleasant picturesComparison of pleasant vs unpleasant pictures Examine the final stage in emotional processing— attribution—which is the interface between cognition and emotionExamine the final stage in emotional processing— attribution—which is the interface between cognition and emotion

9. WPA Unpleasant

10. WPA Pleasant

11. WPA Activations in Normals: Visual Stimuli Subtraction images: Unpleasant minus pleasantSubtraction images: Unpleasant minus pleasant “Unpleasant” activations: areas of increased flow are red“Unpleasant” activations: areas of increased flow are red “Pleasant” activations: areas of increased flow are blue“Pleasant” activations: areas of increased flow are blue

12. WPA “Unpleasant” Activations Extrastriate and visual cortexExtrastriate and visual cortex CerebellumCerebellum AmygdalaAmygdala

13. WPA “Pleasant” Activations: Medial, orbital, and dorsolateral prefrontal cortexMedial, orbital, and dorsolateral prefrontal cortex

14. WPA Interpretation: Emotion Attribution in Normals The system that assigns positive emotional valence to stimuli is primarily prefrontalThe system that assigns positive emotional valence to stimuli is primarily prefrontal Pleasure attribution in human beings activates phylogenetically younger “higher” cortical regionsPleasure attribution in human beings activates phylogenetically younger “higher” cortical regions

15. WPA Randomization Analysis of PET Data A non-parametric statistical method that is robust to differences in varianceA non-parametric statistical method that is robust to differences in variance Displays areas where patients differ from controlsDisplays areas where patients differ from controls Blue: flow is decreased in patients during unpleasant stimuliBlue: flow is decreased in patients during unpleasant stimuli Red: flow is increased during unpleasant stimuli (?compensatory?)Red: flow is increased during unpleasant stimuli (?compensatory?)

16. WPA Unpleasant Pictures: Areas of Decreased Flow ThalamusThalamus Extrastriate visual cortexExtrastriate visual cortex HippocampusHippocampus

17. WPA Unpleasant Pictures: Areas of Increased Flow InsulaInsula Putamen/ accumbensPutamen/ accumbens Superior frontalSuperior frontal

18. WPA Focusing Visual Attention

19. WPA Remembering Faces

20. WPA Recalling Complex Narratives