1. Category Learning and Dopaminergic Personality Traits: Evidence for a Hippocampal Contribution to Some Task Variants? Alan Pickering Department of Psychology a.pickering@gold.ac.uk

2. Collaborators Various students from Psychology Departments within the University of London: Harry Pidd (Goldsmiths College) Rozmin Halari (Institute of Psychiatry) Lucy Schomberg & Luke Jones (St Georges Hospital Medical School)

3. Evidence for Influence of DA on (Category) Learning Neuropsychological Studies with patients with damage to DA-rich striatal brain regions are impaired on some category learning tasks Neurophysiological Studies suggest synaptic plasticity in striatal brain regions require appropriately timed DA signal

4. Category Learning in Parkinsons Disease Weather task: Knowlton et al, 1996

5. Category Learning in Parkinsons Disease Main Findings: Knowlton et al, 1996

6. What Processes in Learning Tasks Might be DA-Related? Two main candidates are widely proposed: 1.Appetitive reinforcement and motivation DA activity has been viewed as provided a reinforcement signal which is required for synaptic plasticity (3-factor learning rule)

7. DA-Related Processes (cont) 2.Input Modulation Schultz (1998): DA lets only the strongest cortical influences pass to striatal neurons, whereas weaker inputs become ineffective Floresco et al (2001): DA receptor activity serves to strengthen salient inputs while inhibiting weaker ones

8. Logic of The Present Studies Certain biologically-based personality traits in the healthy population reflect variation in dopaminergic neurotransmission Therefore, these traits should correlate with performance on DA- sensitive category learning tasks (e.g. those involving reinforcement or input modulation)

9. Which Personality Traits Are DA-Related? Extraversion-Introversion (Depue, Rammsayer) Example measures: EPQ-E; Introvertive Anhedonia (IntAnh) Impulsive Antisocial Sensation Seeking: ImpASS (Gray, Cloninger, Zuckerman, Pickering) Example measures: EPQ-P; Novelty Seeking; Sensation Seeking Scale Positive Schizotypy (many) Example measures: Unusual Experiences

10. Example Questionnaire Items ImpASS: Measure = EPQ-P (25 items) -Have people said that you sometimes act too rashly? -Should people always respect the law? -Would you take drugs which may have strange or dangerous effects? Positive Schizotypy: Measure = Unusual Experiences (30 items) -I have felt that I have special, almost magical powers -Do you ever feel that your thoughts dont belong to you -Sometimes my thoughts are as real as actual events in my life

11. What Evidence Implicates DA in Personality Traits? Direct evidence for extraversion and ImpASS -Traits correlate with psycho- physiological response to DA drugs -Traits correlate with DA-binding in neuroimaging studies -Traits correlate with DA receptor gene variations No evidence for positive schizotypy but argument by analogy with schizophrenia schizotypal personality disorder

12. DA and ImpASS: Sample Evidence Gray, Pickering & Gray (1994) SPET D2-binding in basal ganglia and EPQ-P

13. Category Learning & ImpASS Scores: Early Studies Ball & Zuckerman (1990): positive correlation between Sensation Seeking scores and learning of a concept formation task Pickering (2 studies): positive correlations for Novelty Seeking and EPQ-P scores with learning of a filtration category learning task Suggestive but uninformative about what DA-related processes might be involved

14. My Personality and Category Learning Research Programme Series of studies which attempt to relate specific task processes to specific (DA-related) traits Model results using biologically- constrained neural networks, varying DA parameters to try to model trait variation Results show dissociable relationships across traits and tasks

15. Overview of Results Anx = anxiety (control trait) Trait correlation with task Task Involves ExtraPos SzImpASSAnx Input Modulation NoYesNo +ve Rein- forcement YesNo Mismatch Processing No Yes

16. Aims of Current Talk To illustrate some of the results: Reinforcement Study suggesting extraversion and positive reinforcement link Focus on the possible links between ImpASS traits (esp. the EPQ-P measure) and hippocampal system processes during category learning and related tasks

17. Reinforcement Study Pickering and Halari Within-Ss design using 2 equivalent probabilistic category learning tasks: Weather task and a Symptoms-Disease task Training Task 1:enhanced reinforcement £0.10 per correct response Task 2:paired-associate training meant no reinforcement Testing Categorise each stimulus without reinforcement

18. Details 40 healthy male participants, mostly students Personality Measures Extraversion: Introvertive Anhedonia (IntAnh) ImpAss:EPQ-P Schizotypy:Unusual Experinces (UnEx) Dependent Variable = Accuracy of responses during test

19. Results: Correlations RF= reinforcement task score PA= paired-associate task score Pos SZExtraImpASS RFUnExIntAnhEPQ-P PA0.14-0.01-0.060.30* RF0.20-0.35*0.00 UnEx0.020.34* IntAnh0.13

20. Summary of Findings DA-related personality traits again correlated with performance on DA- sensitive category learning tasks Extraversion-introversion (but not ImpAss or schizotypal traits) correlated with learning under appetitive reinforcement component ImpAss correlated with learning under paired-associate training

21. Interpretation of ImpASS Result Could the paired-associate training encourage a greater dependency on hippocampally-mediated explicit remembering? Do ImpASS traits relate to functioning of hippocampal system? Cons:Probabilistic training Pros:Subsequent paper by Poldrack et al (Nature, 2001)

22. Poldrack et al 2001 fMRI study in healthy volunteers with weather task under standard feedback (FB) and also paired associate (PA) training Medial temporal lobe (MTL) activity higher for PA than for FB task Reverse was true for caudate nucleus (CN) activity Negative correlation between MTL and CN activation in both tasks

23. ImpASS Traits and Hippocampal Functioning Little existing evidence Some evidence from human Latent Inhibition tasks We carried out several studies to test the link further: - latent inhibition study - paired-associate learning - associative mismatch detection

24. ImpASS Traits and Latent Inhibition (LI) LI tasks in animals are sensitive to hippocampal lesions Human LI analogues studied in relation to positive schizotypy and ImpASS Pickering & Gray (2001) review shows LI associated with either type of trait tested separately High trait scores and hippocampal lesions affect performance in same direction

25. LI Study: Pickering & Pidd Studied LI in relation to measures of both positive schizotypy and ImpASS Used standard human LI task (learning association between a specific sound on a tape and a counter increment after preexposure to sound without increment) Tested 86 subjects mostly students

26. Pickering & Pidd: Details Trait Measures Positive Schizotypy - Unusual Experinces (UnEx) ImpASS - Impulsive Nonconformity (ImpNon) - Sensation Seeking Scale (SSS) Nonparametric correlations between LI task performance (trials to criterion) and trait measures

27. Pickering & Pidd: Results After partialling out UnEx: R 2 =0.29 Trials to criterion UnEx-0.49 ImpNon-0.60 SSS-0.45 Spearmans rho (all p<0.001)

28. Conclusions ImpASS and positive schizotypy trait measures make independent contributions to learning in the preexposed condition of a human LI task In both cases, high trait scores facilitate learning (reduce LI) – the same effect as hippocampal lesions Suggests ImpASS trait scores may reflect individual differences in hippocampal system functioning

29. ImpASS and Paired Associate Learning: I Pickering and Schomberg Unrelated verbal paired-associates (e.g. SOIL-MILE; SIDE-BRAVE) were used This is the quintessential explicit memory task sensitive to hippocampal lesions 40 healthy subjects (students) Extraversion (Ext), ImpASS (EPQ-P), and positive schizotypy (UnEx) were measured

30. ImpASS and Paired Associate Learning: II 12 word pairs (A-B) used 3 study-test learning trials Test= cued recall for B using A as cue 1 unexpected 10-min delayed cued recall test trial DVs=Number correct on each test (NC1, NC2, NC3, & NCD) Measured IQ subtest performance for each subject (WAIS-III Matrices)

31. ImpASS and Paired Associate Learning: Results *denotes correlation with EPQ-P after partialling out IQ ExtEPQ-PEPQ-P*UnExIQ NC10.170.430.400.150.26 NC2-0.030.330.290.090.28 NC3-0.100.330.290.080.27 NCD-0.040.370.35-0.010.15

32. Interpretation & Conclusions ImpASS traits appear to be positively associated with performance on hippocampal- sensitive tasks Given ImpASS traits also correlate with performance on standard and paired-associate category learning (CL) tasks (see above), this suggests a possible hippocampal contribution to CL tasks

33. Key Questions Raised What specific processes in explicit remembering might be linked to ImpASS traits? What about links between ImpASS traits and DA neurotransmission? What evidence exists on role of DA activity in hippocampal system?

34. Dopamine and Hippocampus Work by Otmakhova & Lisman has demonstrated that DA reduces transmission in the perforant path projection to CA1 but not in the CA3-CA1 pathway (Schaffer collaterals) This modulatory DA effect depended on both D1-like and D2- like receptors

35. Otmakhova & Lisman (1999) J Neurosci., 19, 1437-1445

36. Otmakhova-Lisman Model I Input at time t CA3 CA1 Input at time t+1 CA3 outputs prediction for input at time t+1 based on input at time t Dopamine suppresses this input specifically CA1 compares predicted input with actual input Match or Mismatch

37. Otmakhova-Lisman Model II Many similar models (Vinogradova, 1984; Levy, 1989; Gray & McNaughton, 2000) but how do they account for explicit memory functions? Underactivity of D1/D2 DA receptors would make hippocampus oversensitive to mismatch High ImpASS scoring subjects have hypofunctional D2 receptors Prediction : High ImpASS subjects will have higher mismatch sensitivity than low ImpASS

38. Associative Mismatch Study Pickering and Jones Choice reaction time (RT) task Warning stimuli for RT trials manipulated to create regular sequence which subjects learn incidentally Observe effect on RT task during critical trials (e.g. when mismatching warning stimulus sequence is used)

39. + A Standard Trial Sequence

40. + L Associative Mismatch Sequence

41. Choice RT Task Measures Mean RT and % errors on: critical trials (e.g. associative mismatch, AM) compared with matched control trials (i.e. immediately preceding standard trials) For correlations use difference measures: (critical RT – matched control RT)

42. AM Study: Details Investigated effects of AM and secondary reinforcers (SRs), of 4 different types (aversive and appetitive) 40 healthy volunteers (male medical students) Used preconditioning procedure to create secondary reinforcers 350 choice RT trials (1-50 practice), including 6 AM and 4x6 SR trials

43. AM Study: Questionnaires Used Extraversion-Introversion - EPQ-E - Introvertive Anhedonia (IntAnh) ImpASS - EPQ-P - Novelty Seeking Scale: NS Anxiety various (results not reported here)

44. Mismatch Study: Overall RTs AM= associative mismatch trials Trials with various reinforcer types

45. Mismatch Study: Results Mean (±s.d.) mismatch RT difference: 40.1 ±57.8 ms Outliers: So we used nonparametric correlations and parametric correlations on Winsorized data

46. Mismatch Study: Results Correlations with mean RT difference on Mismatch Trials ExtraversionImpASS NEPQ-EIntAnhEPQ-PNS Spearman400.14-0.090.32*0.31* Pearson (winsord) 380.16-0.130.34*0.17

47. Summary of Mismatch Results As predicted, ImpAss traits are positively associated with sensitivity to associative mismatch Other data from our lab (e.g. Gray, Pickering, et al, 2002) on rule learning tasks is consistent with these observations: High ImpASS subjects are more affected by unpredicted rule shifts than low ImpASS

48. General Conclusions These data reinforce the view that dopaminergic activity plays multiple roles in category learning (CL) A significant association between CL performance and some personality traits may be a signature for involvement of particular psychological processes ImpASS traits may influence CL particularly when the task engages hippocampal mismatch detection mechanisms