Prefrontal cortex: categories, concepts and cognitive control Earl K. Miller

1. Prefrontal cortex: categories, concepts and cognitive control Earl K. Miller Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology www.millerlab.org

2. Sensory Motor Basic sensory, memory, and motorprocesses.

3. Sensory Motor Memories, habits and skills Learning and memory (Hippocampus, basal ganglia, etc.)

4. Learning and memory (Hippocampus, basal ganglia, etc.) Executive Functionsgoal-related information Sensory Motor

5. Learning and memory (Hippocampus, basal ganglia, etc.) Executive Functionsgoal-related information Top-down selection Bottom-up Sensory Motor

7. Sensory Motor Memories, habits and skills Learning and memory (Hippocampus, basal ganglia, etc.)

8. Learning and memory (Hippocampus, basal ganglia, etc.) Executive Functionsgoal-related information Top-down selection Sensory Motor Bottom-up

9. Miller Lab @ MIT (www.millerlab.org) Perceptual Categories David Freedman Maximillian RiesenhuberTomaso Poggio Earl Miller

10. Perceptual Categorization: “Cats” Versus “Dogs” 60% Dog Morphs 60% Cat Morphs 80% Cat Morphs 80% Dog Morphs Prototypes 100% Dog Prototypes 100% Cat Category boundary Freedman, D.J., Riesenhuber, M., Poggio, T. and Miller, E.K. (2001) Science, 291:312-316

11. Delayed match to category task . . . . (Match) Fixation Sample 500 ms. . Delay 600 ms. Test object is a “match” if it the same category (cat or dog) as the sample . 1000 ms. . Test (Nonmatch) Delay Test (Match)

12. A “Dog Neuron” in the Prefrontal Cortex

13. 60% Dog Morphs 60% Cat Morphs 80% Cat Morphs 80% Dog Morphs Prototypes 100% Dog Prototypes 100% Cat Category boundary

14. A “Dog Neuron” in the Prefrontal Cortex

15. 60% Dog Morphs 60% Cat Morphs 80% Cat Morphs 80% Dog Morphs Prototypes 100% Dog Prototypes 100% Cat Category boundary To test the contribution of experience, we moved the category boundaries and retrained a monkey

16. To test the contribution of experience, we moved the category boundaries and retrained a monkey New boundaries This created three categories whose boundaries were orthogonal to the two original categories Original boundary

17. New boundaries Original boundary Neural activity shifted to reflect the new (and not the old) category boundaries

18. Freedman, D.J., Riesenhuber, M., Poggio, T. and Miller, E.K. (2001) Science, 291:312-316 Prefrontal cortex: Cognition, decisions, etc. ??? Inferior temporal cortex:Visual recognition, memory Freedman, D.J., Riesenhuber, M., Poggio, T. and Miller, E.K. (in prep)

19. Fixation Sample Delay Choice 12 DOG 60% DOG 80% DOG 100% 8 CAT 100% CAT 80% Spike rate (Hz) CAT 60% 4 0 -500 0 500 1000 1500 2000 Time from sample stimulus onset (ms) An ITC neuron that responded more strongly to DOGS than CATS.

20. Delay Sample Time course of category-related activity:Inferior Temporal Cortex

21. Delay Sample Time course of category-related activity:Prefrontal Cortex

22. D1 C1 C1 D1 C1 D2 C1 D2 D3 D3 C1 C1 C2 D1 C2 D1 D1 C1 D2 C2 D2 C2 D2 C1 D3 C2 D3 D3 C2 C1 D1 C3 D1 C3 D1 C2 D2 C3 D2 C3 D2 C2 C3 C3 D3 D3 D3 C2 D1 C3 D2 C3 C2 D3 C3 ITC C3 C1 D1 C1 D2 C1 “cats” D3 C1 D1 C2 D2 C2 D3 C2 category boundary D1 C3 D2 C3 D3 C3 “dogs” D1 D3 D2 Category Effects were Stronger in the PFC than ITC: Single neurons Activity to individual stimuli along the 9 morph lines that crossed the category boundary PFC PFC neurons showed greater between-category differences and more uniformity within categories. ITC neurons showed stronger tuning for individual stimuli.

23. PFC ITC Stronger category effects Category Effects were Stronger in the PFC than ITC: Population Index of the difference in activity to stimuli from different, relative to same, category

24. Familiar categories are encoded onthe single neuron level. • Category representations are malleable byexperience. • Category tuning is stronger in the PFC than ITC. • Category signals are transient in the ITC and sustained in the PFC. • Behavioral factors (e.g., category match/non-match judgments)are more strongly encoded in the PFC than ITC.The PFC and ITC play complementary roles in category-basedbehaviors. The ITC is more “visual” while the PFC is more “behavioral”. Freedman, D.J., Riesenhuber, M., Poggio, T. and Miller, E.K. (2001) Science, 291:312-316Freedman, D.J., Riesenhuber, M., Poggio, T. and Miller, E.K. (in preparation)

25. Miller Lab @ MIT (www.millerlab.org) Quantity (numerosity) Andreas NiederDavid FreedmanEarl Miller

26. Behavioral protocol: delayed-match-to-numerosity task Numbers 1 – 5were used • Preventing the monkey from memorizing visual patterns: • Each numerosity tested with 100 different images per session. • All images newly generated after a session. • All relevant item features (position, size, identity) shuffled pseudo-randomly. • Sample and test images never identical. Nieder, Freedman, and Miller, submitted

27. Trained Standard stimulus Monkeys instantly generalized acrossthe stimulus sets Equal area Equal circumference Low density High density Variable features ‘Shape’ Linear

28. Standard stimulus Equal area

29. Standard stimulus Equal circumference

30. Standard stimulus Variable features

31. ‘Shape’ (Tri-, Quadrangle, Pentagon) Linear

32. Low density High density

33. EasyDiscrimination Difficult Discrimination Order 1 0 0 ) % ( e s 7 5 n *** *** o - - 4 4 - - 3 3 - - 2 2 - - 1 1 0 0 1 1 2 2 3 3 4 4 p s *** ** N N u u m m e e r r i i c c a a l l d d i i s s t t a a n n c c e e e 5 0 r d e z i l a 2 5 m r o N 0 - 4 - 3 - 2 - 1 0 1 2 3 4 N u m e r i c a l d i s t a n c e Characteristics of Numerosity • Preservation of numerical order – numbers are not isolatedcategories. • Numerical Distance Effect – discrimination between numbersimprove with increasing distance between them. PFC neurons show smooth tuning for number.

34. Characteristics of Numerosity • Preservation of numerical order – numbers are not isolatedcategories. • Numerical Distance Effect – discrimination between numbersimprove with increasing distance between them. • Numerical Magnitude Effect – discrimination between numbers ofequal numerical distance is increasingly difficult as their sizeincreases. 1 and 2 are easier to tell apart than 3 and 4.

35. 3 . 0 2 . 5 2 . 0 Bandwidth of tuning curves 1 . 5 1 . 0 0 5 1 2 3 4 5 N u m e r o s i t y ( s a m p l e ) Numerical Magnitude Effect Average tuning curve foreach number Average tuning curve widthfor each number Neural tuning becomes increasing imprecise with increasingnumber. Therefore, smaller size numbers are easier todiscriminate.

36. Numerosity in the PFC • Neurons in the lateral PFC represent high-level abstract informationrelated to numerosity judgments. • Neuronal activity preserve numerical order. • Neural activity generalizes across changes in the physical appearanceof displays. • Neuronal filter properties account for ‘numerical magnitude effect’ • and ‘numerical distance effect’. Nieder, Freedman, and Miller, submitted. PFC neurons selectively encode goal-relevant informationincluding the higher-order representations needed for intelligent behavior.

37. Miller Lab @ MIT (www.millerlab.org) Behavior-guiding rules Wael AsaadJonathan WallisKathleen AndersonGregor RainerEarl Miller

38. What is a rule? • A link between a sensory stimulus and motoric response that serves to guide the animal’s behavior CONCRETE ABSTRACT Asaad, Rainer, & Miller (1998)(also see Watanabe, Schall, Fuster, Wise et al) Asaad, Rainer, & Miller ( 2000)task context Wallis et al, 2000

39. Sample Test Release Hold Match Rule(same) Wallis, J.D., Anderson, K.C., and Miller, E.K. (2001) Nature, 411:953-956

40. Sample Test Release Hold Sample Test Hold Release Nonmatch Rule(different) Wallis, J.D., Anderson, K.C., and Miller, E.K. (2001) Nature, 411:953-956

41. Sample Test Release Hold Match Rule(same) Sample Test Hold Release Nonmatch Rule(different) The monkeys needed to remember the sample as well as which rule was currently in effect. Wallis, J.D., Anderson, K.C., and Miller, E.K. (2001) Nature, 411:953-956

42. Sample Test Release Hold Match Rule(same) Sample Test Hold Release Nonmatch Rule(different) The rules were made abstract by training monkeys until they couldperform the task with novel stimuli Wallis, J.D., Anderson, K.C., and Miller, E.K. (2001) Nature, 411:953-956

43. + juice OR Match + low tone OR + no juice Nonmatch + high tone Sample + cue Wallis, J.D., Anderson, K.C., and Miller, E.K. (2001) Nature, 411:953-956

44. Match Neuron Wallis, J.D., Anderson, K.C., and Miller, E.K. (2001) Nature, 411:953-956

45. Wallis, J.D., Anderson, K.C., and Miller, E.K. (2001) Nature, 411:953-956

46. Rule Selectivity Across the PFC Wallis, J.D., Anderson, K.C., and Miller, E.K. (2001) Nature, 411:953-956

47. The prefrontal cortex is at the top of the cortical hierarchy:It is more cognitive and behavioral (and less visual) than visual cortex, and less motor than premotor cortex. This ability of the PFC to convey categories and rules may reflect its role in acquiring and representing the formal demands of tasks, the internal models or concepts that provide a foundation for complex, intelligent behavior.(Fuster, 1985; Cohen and Servan-Schreiber, 1992; Passingham, 1993; Grafman, 1994;Wise et al., 1996; Dehaene et al., 1998; Miller, 1999, Miller, 2000, O’Reilly and Munakata, 2000; Miller and Cohen, 2001). A Model of PFC function:Miller, E.K. (2000) The prefrontal cortex and cognitive control. Nature Reviews Neuroscience, 1:59-65 Miller, E.K. and Cohen, J.D. (2001) An integrative theory of prefrontal cortex function. Annual Review of Neuroscience, 24:167-202 For reprints etc: www.millerlab.org

48. The PF cortex and cognitive control Phone rings Answer Don’t answer Inactive Active

49. The PF cortex and cognitive control Phone rings Answer Don’t answer Inactive Active

50. The PF cortex and cognitive control At home Guest Phone rings Answer Don’t answer Inactive Active