1. A B SAMPLE DELAY CHOICE A B A B 1st Reversal2nd Reversal etc…. 05001500 Trial Time (ms) Conditional Visuomotor Learning Task Asaad, W.F., Rainer, G. and Miller, E.K. (1998) Neuron, 21:1399-1407.

3. RightLeftRightLeftRightLeft Movement DirectionStimulusMapping

4. Prefrontal cortex : May mediate learning of arbitrary associations. Many PF neurons coded both an object and a currently-associated directional response. During learning, information about the cue object and the action it instructed gradually merged together in PF activity. This may reflect the role of the PF cortex in acquiring and representing behavior-guiding rules, a function crucial for intelligent, adaptive behavior. Asaad, W.F., Rainer, G. and Miller, E.K. (1998) Neuron, 21:1399-1407.

5. Match (bar release) Nonmatch (bar release) Match Rule (DMS) Nonmatch rule (DNMS) Sample Delay Test We trained monkeys to switch between two abstract rules: “match” and “nonmatch” Four samples were used. New objects every day. Wallis, J.D., Anderson, K.C., and Miller, E.K. (2000) Soc. Neurosci. Abstr.

6. + reward + low tone Lever release Match + no reward + high tone Lever release Nonmatch Condition Rule Example Trial Sample Cue

7. + reward + low tone Lever release Match + no reward + high tone Lever release Nonmatch Novel objects were used on each day. Therefore, monkeys needed to learn two abstract rules (match and nonmatch) that could be applied to any object. We sought their neural correlate.

8. Sample Delay A Prefrontal Neuron Tuned to the Match Rule

9. A Prefrontal Neuron Tuned to the Nonmatch Rule Sample Delay

10. The prefrontal cortex: Selectively represents goal-relevant information (focal attention, recall). Synthesizes information from diverse sources to serve a common behavioral goal (sensory inputs, stored knowledge). Is plastic: it neural activity changes to meet behavioral demands. Knits together arbitrary associations between diverse, but behaviorally-related information. Conveys information about the behavioral context in which the animals are engaged and the rules used to guide behavior. This may reflect the role of the PF cortex in acquiring and representing the formal demands of behavior, rules or models of tasks that provide a foundation for complex, intelligent behavior. (Cohen and Servan-Schreiber, 1992; Passingham, 1993; Grafman, 1994;Wise et al., 1996; Dehaene et al., 1998; Miller, 1999, Miller, 2000, Miller and Cohen, 2001).

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

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

15. Active Inactive The PF cortex and cognitive control Phone rings Answer Don’t answer At home Guest PF cortex Reward signals (VTA neurons?)

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

17. Active Inactive The PF cortex and cognitive control Phone rings Answer Don’t answer At home Guest PF cortex Reward signals (VTA neurons?)

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

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24. PF cortex Its integrative anatomy allows it to rapidly acquire a “map” that specifies which pattern of “tracks” (neural pathways) are needed to solve a given task. The prefrontal cortex may be like a switch operator in a system of railroad tracks:

25. PF cortex Its integrative anatomy allows it to rapidly acquire a “map” that specifies which pattern of “tracks” (neural pathways) are needed to solve a given task. The PF cortex actively maintains this pattern during task performance, allowing feedback signals to bias the flow of activity in other brain areas along those tracks. The prefrontal cortex may be like a switch operator in a system of railroad tracks:

26. PF cortex Its integrative anatomy allows it to rapidly acquire a “map” that specifies which pattern of “tracks” (neural pathways) are needed to solve a given task. The PF cortex actively maintains this pattern during task performance, allowing feedback signals to bias the flow of activity in other brain areas along those tracks. The prefrontal cortex may be like a switch operator in a system of railroad tracks: Attention, retrieval, representation of rules and goals, response selection, inhibitory control, etc. can be explained by PF bias signals acting on different brain structures.