1. Goal directed behaviour and its disorders Lecture 9 John Done

2. Frontal lobe dysfuntion and the dysexecutive syndrome 2 Examples of Goal Directed behaviour. Deciding where to take your Summer holiday. Choosing to come to this lecture. Choosing what to have for your lunch at the canteen. Gear shift together with pedal control ( learning to drive) Examples of Automatic behaviour/ Habit Gear shift and pedal control( experienced driver) Implicit/procedural skills ( see Confabulation lecture). Well learnt instrumental behaviours.

3. Frontal lobe dysfuntion and the dysexecutive syndrome 3 What is intentional Behaviour –philosophers accounts ? Wittgenstein,Brand and other philosophers suggest 2 general categories of behaviour: 1. ‘Actions’ e..g. John walks into a restaurant; John reads the menu. 2. ‘Mere Doings’ ( or automated behaviour) e.g. John puts hand out to break fall; John grimaces with pain. Wittgenstein - A critical difference is that with ‘Actions’, the actor knows what s/he is doing. In ‘Mere Doings’ s/he doesn’t unless given sensory feedback.

4. Duncan (1986) model for action planning and control. M o n I t o r I n g (frrontal cortex) Intention or Goal identified ( frontal cortex) Motor/Cognitive subroutine selected ( basal ganglia ?) Subroutine executed Response Frontal lobe provides : intention,goal selection, monitoring

5. Model of organization of goal-directed behaviors. Levy R, Dubois B Cereb. Cortex 2006;16:916-928

6. The Case of Phineas Gage

7. Frontal lobe dysfuntion and the dysexecutive syndrome 7 The Case of Phineas Gage Before accident Harlow 1848 “..vigorous physical organization, temperate habits, and possessed considerable energy of character.” “Well balanced mind”; “looked upon by those that knew him as shrewd”; “smart businessman”; “very energetic”; “persistent in executing all his plans of operation”; “ a most efficient and capable foreman”. 28 days post accident Memory and orientation okay, but does not estimate size and monetary value of objects. 6 months post accident Harlow 1849 “ His physical health is good...he has fully recovered.”But, “...he was gross, profane, coarse, and vulgar...intolerable to decent people” 20 years post accident. “Impatient of restraint or advice when it conflicts with his desires...obstinate, yet capricious and vacillating, devising many plans of future operation, which are no sooner arranged than they are abandoned in turn for others...he has the animal passions of a strong man.” ( Harlow 1868) Harlow in 1868 also reported “ the change of his mind so marked that ( the railroad contractors) could not give him his place again”.

8. The Prefrontal Cortex (PFC)

9. Executive Functions They are all necessary for appropriate, socially responsible, effectively self-serving adult conduct (Lezak, 1982a) Executive functions can be conceptualized as having 4 components: Volition Planning Purposive action Effective performance

10. Purposive action The translation of an intention or plan into productive, self-serving activity requires the actor to initiate, maintain, switch and stop sequences of complex behaviour in an orderly and integrated manner (Lezak, 1982a). Patient swith programming activity troubles may display a marked dissociation between their verbalized intentions and plans and their actions (Lezak, 1982a).

11. Neuropsychological impairments following frontal lobe damage : BehaviourBehaviour - Failure to shift response set ( e.g. Wisconsin Card Sort - perseveration) - Perseverative behaviour. - Organising and planning behaviour - Tower of London/Hanoi task. - Generating novel actions ( Design Fluency) CognitiveCognitive - Impaired Recency judgement - Impaired estimation ability ( Cognitive Estimates Test ) - Retrieval from Memory ( e.g.Verbal Fluency) - Alternative Uses Test. - Distracted by other stimuli ( e.g. Stroop Test) - Self Ordered Memory - Source memory Dysexecutive Syndrome

12. Wisconsin Card Sort test

13. Tower of London task Participants are asked to preplan mentally a sequence of moves to match a start set of discs to a goal, and then to execute the moves one by one. The mental preplanning stage has been identified as critical to efficient performance.

14. Norman and Shallice (1986) - Theoretical Model of Executive System: - Most behaviours are automatic (e.g.driving a car/ entering a cafe). - ‘Contention Scheduling’ (i.e. ordering and timing) of these packets of action is normally okay. - When the scheduling breaks down (slips of action) voluntary ( goal directed) adjustments are made to behaviour. N and S considered these voluntary adjustments could be accounted for by a Supervisory Activating System (SAS). -N&S propose that : -frontal lobes operate as if they were the SAS. -Damage to the SAS > disorders seen in patients with prefrontal lobe damage. Original Theory of the Role of Prefrontal Cortex

15. Norman and Shallice (1986) Theoretical Model of Executive System:

16. Shallice & Burgess (1991) Shallice and Burgess (1991) Brain114,727-741 Case1 RTA, bifrontal damage. 4.5 years after accident could not carry out even the simplest activity because of an inability to keep his mind on the task e.g. he was discovered on the local golf course having originally stepped outside to fetch some coffee. Verbal IQ 121, Performance IQ 120 and performed satisfactorily on all perceptual, language, arithmetic and memory tests. Case 2 RTA extensive right and mild left frontal lobe injury. Wife’s report indicates that when she gives him a task she has to specify exactly what is required and even so he might carry out some parts only and then starts reading a newspaper. She organises all trips, outings and social contacts. Occasionally he is irresponsible with money. Verbal IQ 126, Performance IQ 112. Performed well on a wide range of perceptual,language and memory tasks.

17. Shallice & Burgess (1991) Shallice and Burgess (1991) Brain114,727-741 3 patients dysfunctional at home and work, but perform normally on classic tests of frontal dysfunction. 2 tests developed to assess real life scheduling i) Six Elements Test (in 15 mins devise a simple plan,scheduling the 6 subtests efficiently and checking on time) ii) Multiple Errands Test. Dovetailing a number of tasks in situations where minor unforeseen events can occur. Results In i) patients tackled fewer subtasks and took longer on any subtask. In ii) patients produced inefficiencies, rule breaks, interpretation failures,task failure.

18. Used to describe the pattern of deficits commonly found in patients with dorsolateral prefrontal DLPFC lobe damage Cognition& behaviour characterised by failures to : Organise. Plan. Monitor All features of Levy and Duncan models of Goal Direct cognition and behaviour. The Dysexecutive Syndrome

19. Fronto-Striatal Circuits 5 fronto-striatal circuits are as follows : 1.Dorsolateral Prefrontal (DLPFC) Circuit. (Associative) 2.Motor Circuit (Supplementary Motor Area). (Motor) 3. Anterior Cingulate (ACC) Circuit. ( Limbic/Motivational) 4.OrbitoFrontal (OFC) Circuit. ( Limbic/Motivational) 5. Oculomotor Circuit (Frontal Eye Fields)

20. Direct Pathway (aka the Express Route) CORTEX PUTAMEN (GPe) (STN) GP interna VA/VL THALAMUS Glutamate (+) GABA (-)

21. Indirect Pathway (aka, scenic route) CORTEX PUTAMEN GP externa STN GP interna VA/VL THALAMUS Glutamate (+) GABA (-) Glutamate (+) GABA (-) Glutamate (+)

22. Frontal Sub-Cortical Circuits

23. Herrero et al (2002) Functional Anatomy of Thalamus and basal ganglia. Child’s Nerv syst,18,386-404 Basal Ganglia: Caudate Putamen

24. Motor loop cognitive Medial Lateral Separation cognitive Motor loop Anterior Posterior Separation

25. Topographic links : Cortex - Striatum Motor Motor cortex > Putamen > Pallidum/SNr etc ( dl striatum) Cognitive DLPFC > Caudate > Pallidum /SNr etc dm striatum Motivational OFC > Caudate > Pallidum / SNr etc vm striatum dl= dorsolateral ; dm=dorsomedial vm= ventromedial

26. Yin et al. Nature Reviews Neuroscience 7, 464–476 (June 2006) | doi:10.1038/nrn1919

27. Cognitive Loop Motor loop Division of TD into two parts Caudate Putamen Nacc MRI view Reconstructed View DLPFC MC

28. Parkinson’s Disease Loss of Dopamine (DA) neurons in substantia nigra (SNr) > major dysfunction of Basal ganglia. Symptoms only appear after >=60% of DA loss in SNr. Key (clinical) symptoms: motor dysregulation, akinesis/bradykinesia, bradyphrenia. Psychological deficits depend on Hoehn & Yahr severity ( 1,2=mild/mod; 3,4=severe) Frontal lobe dysfuntion and the dysexecutive syndrome 28

29. Parkinson’s Disease Lima et al (2008) Parkinsons P (H&Y = 3-4) ie severe Patients impaired on a range of executive tasks. Frontal lobe dysfuntion and the dysexecutive syndrome 29

30. Parkinson’s Disease Owen et al (1992) PD (H&Y = 1,2 & 3-4) Severe PD(H&Y 3&4) – impaired on a range of executive tasks like frontal patients, except they are also impaired on: 1.Spatial memory 2.Initial thinking time ( ToL)- ( accuracy and speed)-bradyphrenia Frontal lobe dysfuntion and the dysexecutive syndrome 30

31. Parkinson’s Disease Owen et al (1992) Mild PD (H&Y1&2) 1.Slow initial RT on ToL. Normal RT on subsequent moves ( unlike frontal P). 2.Impaired performance on attention set shifting. 3.Spatial WM impaired. Frontal lobe dysfuntion and the dysexecutive syndrome 31

32. Parkinson’s Disease and Goal vs Habit Redgrave et al 2010 1.Projections from SNr to posterior putamen go first in PD. 2.Habit route is lost in early stages of PD so all behaviour thru Goal directed route. Frontal lobe dysfuntion and the dysexecutive syndrome 32

33. Conclusions 1.Goal directed behaviour and cognition controlled thru a fronto-striatal loop. 2.Automatic (habit ) controlled thru a Motor-striatal loop. 3.Early PD – deficit in automatic-route 4.Late-PD –deficit in both automatic and goal directed route. 5.DLPFC damage- deficit in goal directed route. Frontal lobe dysfuntion and the dysexecutive syndrome 33

34. Frontal lobe dysfuntion and the dysexecutive syndrome 34 References Essential Most general text books on neuropsychology : 1. Gazzaniga et al (2002). Cognitive Neuroscience: the biology of the mind. Chapter on frontal cortex (?Ch11?) 2. Parkin (1996) Explorations in Cognitive Neuropsychology CH 10 (covers dysexecutive syndrome only). Numerous copies in LRC 3. Code C et al (1996)Classical Cases in Neuropsychology. Ch 18 Phineas Gage. (LRC and Pinked). 4. Duncan J (1986) Disorganisation of behaviour after frontal lobe damage. Cognitive Neuropsychology,3,271-290. More advanced 5. Shallice T and BurgessPW (1991) Deficits in Strategy Applicaton following Frontal Lobe Damage in Man. Brain 114, 727-741. (LRC and Pinked). 6. Lima, C.F. (2008) The Frontal Assessment Battery (FAB) in Parkinson’s disease and correlations with formal measures of executive functioning. J Neurol (2008) 255:1756–1761 DOI 10.1007/s00415-008-0024-6

35. Frontal lobe dysfuntion and the dysexecutive syndrome 35 References Advanced ( cont) Advanced 1.Owen et al (1992) Frontal-striatal cognitive deficits at different stages of Parkinson’s disease. Brain,115,1727-1751. 2.YinHH and Knowlton BJ (2006) The role of the basal ganglia in habit formation. Nature Reviews Neuro. June, Vol 7, pp464- 476doi:10.1038/nrn1919 3. Redgrave et al (2010) Goal Directed and habitual control in the basal ganglia: Implicatiuons for parkinson’s Disease. Nature Reviews Neuro, Vol11, 760-772 Parallel Circuits: Alexander GE and DeLong MR & Strick (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience 9, 357-81 ( Google Scholar e-copy.