Clinically Relevant Functional Neuroanatomy 3: Working Memory and Executive Skills

1. Clinically Relevant Functional Neuroanatomy 3: Working Memory and Executive Skills Russell M. Bauer, Ph.D. University of Florida, USA Vivian Smith Summer Institute 28 June, 2006

2. From Memory to Executive Skills:The Anatomy of Working Memory

3. Who invented “working memory? a. Mark D’Esposito Alan Baddeley Monte Buchsbaum Patricia Goldman-Rakic William James

4. G.A. Miller E. Galanter Miller, G. A., Galanter, E. & Pribram, K. H. (1960). Plans and the structure of behavior. New York: Holt, Rinehart & Winston. K.H. Pribram

5. Alan Baddeley

8. Episodic Buffer

9. Clinical Techniques and Methods • Verbal • Memory Span (digits, consonants, words) • Free Recall • Short-term forgetting (Peterson/Peterson) • Memory Probe Techniques • Prose Recall

10. Experimental Techniques and Methods • Spatial delayed response • Oculomotor delayed response • Delayed matching-to-sample • Attentional set-shifting • N-back

11. Working memory and associative memory may be distinguished using the delayed response task • When PFC-lesioned monkey must remember which well is baited from trial to trial, performance is poor • When PFC-lesioned monkey must remember which symbol is baited from trial to trial, performance is good

12. Patricia Goldman-Rakic (1937-2003)

15. Goldman-Rakic, 1996

17. Wilson, O’Scalaidhe, & Goldman-Rakic, 1993

20. A question to think about: why would you have spatially-sensitive neurons in preMOTOR cortex? Smith & Jonides, 1999

21. Frontal and parietal neurons are linked systemically – note similar patterns of delay period response

22. Cohen et al., 1998

23. Cohen et al (1998); memory structures active during delay

24. Two views about specificity in WM • Domain-specificity(Goldman-Rakic, Ungerleider, Courtney) • Ventral prefrontal: object working memory • Dorsal prefrontal: spatial working memory • Process-specificity(Petrides, D’Esposito) • Ventral prefrontal: sequential organization and storage • Dorsal prefrontal: executive control and monitoring

25. Exec + Storage Storage Smith & Jonides 1999

26. Petit, Courtney, Ungerleider, & Haxby, 1998

27. Medial Wall Activity in WM • Primary activity in Pre-SMA and Caudal AC • Extensive connections with DLPFC • Pre-SMA: response selection and output preparation • Caudal AC: attention for action, response selection

28. D’Esposito, Postle, and Rypma, 2000

29. Curtis & D’Esposito, 2003 (from Rowe et al, 2000)

30. D’Esposito, M., Zarahn, E., Balard, D., Shin, R.K., and Lease, J. (1998) Functional MRI studies of spatial and nonspatial working memory. Cogn. Brain Res. 7:1-13

31. Curtis & D’Esposito, 2003

32. PFC’s role in working memory may be as a buffer for activated long-term memories

33. Anatomy of Executive Skills

34. Executive Functions • Attention and inhibition • Task management/switching • Planning • Monitoring • Coding representations in WM for time/place of appearance • Response selection

35. Frontal Lobe Cortex • Functional subdivisions: • Lateral (4, 6, 8-10, 43-47) • Medial (6, 8-12, 24, 25, 32, 22) • Inferior (11-15, 25, 47) • Another division: • Motor (4) • Premotor (6, 8, 43, 44, 45) • Prefrontal (9-15, 46, 47)

36. Neuropsychological Manifestations of Frontal Lesions I Frontal Operculum (44,45,47) A) Left: Broca’s aphasia B) Right: ‘expressive’ aprosodia Superior Mesial (mesial 6, 24) A) Left: akinetic mutism B) Right: akinetic mutism Bilateral lesions of mesial SMA (6) and anterior cingulate (24) produce more severe form of akinetic mutism Tranel, 1992

37. Neuropsychological Manifestations of Frontal Lobe Lesions II Inferior Mesial Region A)Orbital Region(10, 11) Lesions in this region produce disinhibition, altered social conduct, “acquired sociopathy”, and other disturbances due to impairment in fronto-limbic relationships B)Basal Forebrain(posterior extension of inferior mesial region, including diagonal band of Broca, nucleus accumbens, septal nuclei, substantia innominata) Lesions here produce prominent anterograde amnesia with confabulation (material specificity present, but relatively weak) Tranel, 1992

38. Neuropsychological Manifestations of Frontal Lobe Lesions III Lateral Prefrontal Region (8,9,46) Lesions in this region produce impairment in a variety of “executive” skills that cut across domains. Some degree of material-specificity is present, but relatively weak. A) Fluency: impaired verbal fluency (left) or design fluency (right) B) Memory impairments: defective recency judgment, metamemory defects, difficulties in memory monitoring C) Impaired abstract concept formation and hypothesis testing D) Defective planning, motor sequencing E) Defective cognitive judgement and estimation Tranel, 1992

39. Phineas Gage (1823-1861, accident in 1848)

40. Phineas Gage’s lesion reconstructed (H. Damasio and R. Frank, 1992)

41. Keys to Understanding Frontal Lobe Function • Realize that it is as far away from the external world as any cortical region • Appreciate patterns of connectivity (you can tell a lot about someone by getting to know their friends) • Appreciate inhibitory/excitatory (modulatory) aspects in addition to idea of specialized information-processors

42. General Organization of Frontal cortical-striatal-pallidal-thalamic-cortical loops

44. Blumenfeld, 2002

45. Blumenfeld, 2002

47. Blumenfeld, 2002

48. Dorsolateral Loop • Critical for executive function • Damage produces • Inflexibility • Planning • Problem-solving • Goal-directed behavior

49. Orbitofrontal Loop • Involved in social and emotional functioning • Damage produces: • Disinhibition • Hyperactivity • Emotional lability • Aggressiveness • Reduce self-awareness

50. Medial Frontal/Cingulate Loop • Important in behavioral activation/intentional disorders • Damage results in • Akinetic mutism • Abulia • Impairments in spontaneous initiation of behavior