1. Last Lecture The Wernicke-Geschwind Model of Reading The Wernicke-Geschwind Model of Reading Category-specific semantic deficts and the representation of meaning Category-specific semantic deficts and the representation of meaning Introduction to the Frontal Lobes Introduction to the Frontal Lobes

2. This Lecture Frontal Lobe Anatomy Frontal Lobe Anatomy Inhibition and voluntary control Inhibition and voluntary control A model task: working memory A model task: working memory

3. Announcements FINAL EXAM: 182 Dennison 182 Dennison Wednesday, 4/19 Wednesday, 4/19 4:00 pm - 6:00 pm. 4:00 pm - 6:00 pm. Please contact us immediately if this poses a conflict. Please contact us immediately if this poses a conflict.

4. Prefrontal cortex ~ 1/3 of cortical surface ~ 1/3 of cortical surface Most recently evolved Most recently evolved Well developed only in primates Well developed only in primates the advent of the human species: "age of the frontal lobe" the advent of the human species: "age of the frontal lobe" develops late in ontogeny develops late in ontogeny differentiation through age 1 differentiation through age 1 maturation through age 6 maturation through age 6

5. Connectivity of Prefrontal regions input from association cortex (occipital, parietal, temporal & olfactory areas) input from association cortex (occipital, parietal, temporal & olfactory areas) convergence of higher- order input from all modalities. convergence of higher- order input from all modalities. reciprocal connections: prefrontal processing modulates perceptual processing. reciprocal connections: prefrontal processing modulates perceptual processing. LIMBIC connections (memory/emotion) LIMBIC connections (memory/emotion) Input to premotor areas - controls/programs behavior. Input to premotor areas - controls/programs behavior.

6. Premotor & Motor Areas Premotor areas (6) - input from prefrontal regions and parietal association areas (5,7). Premotor areas (6) - input from prefrontal regions and parietal association areas (5,7). Area 4: primary motor cortex Area 4: primary motor cortex input from premotor area (6) and area 44 input from premotor area (6) and area 44 sends output to spinal cord, and other motor structures (basal ganglia) sends output to spinal cord, and other motor structures (basal ganglia) Frontal network controls voluntary, planned actions. Frontal network controls voluntary, planned actions.

7. Frontal Release signs Re-emergence of "primitive" reflexes following frontal damage. grasp reflex: forceful grasping of an object that contacts palm or sole of foot. grasp reflex: forceful grasping of an object that contacts palm or sole of foot. sucking reflex: elicited by touching the lip sucking reflex: elicited by touching the lip groping reflex: involuntary following with hand /eyes of moving object groping reflex: involuntary following with hand /eyes of moving object stimulus capture: utilization behavior stimulus capture: utilization behavior The frontal lobes normally inhibit stimulus- bound reflexes.

8. Mediate voluntary control of behavior... ANTI-saccade task saccade AWAY from an eccentric target saccade AWAY from an eccentric target patients w/ prefrontal damage including FEF (Area 8): patients w/ prefrontal damage including FEF (Area 8): reflexive saccades to the target. reflexive saccades to the target. Cannot correct error and make anti-saccades Cannot correct error and make anti-saccades e.g., left lesion patients impaired on right anti-saccades e.g., left lesion patients impaired on right anti-saccades +

9. Poor performance on Anti-saccade task Why more reflexive saccades ? Why more reflexive saccades ? Superior colliculus- control rapids, stimulus-driven eye movements. Superior colliculus- control rapids, stimulus-driven eye movements. Disinhibited by frontal lobe damage, "releasing" reflexive glances Disinhibited by frontal lobe damage, "releasing" reflexive glances Why were Anti saccades impaired? Why were Anti saccades impaired? Difficulty forming representation of goal to control voluntary behavior. Difficulty forming representation of goal to control voluntary behavior.

10. Model task to study frontal lobe function: Delayed Response Task Correct response requires keeping baited well in mind. Correct response requires keeping baited well in mind. Monkeys and humans w/lesions of LPFC fail these tasks. Monkeys and humans w/lesions of LPFC fail these tasks. Infants younger than 12 months also fail versions of these tasks. Infants younger than 12 months also fail versions of these tasks.

11. Delayed Saccade Task (Goldman-Rakic) Single unit recordings from principal sulcus (Brodmann's 46). Single unit recordings from principal sulcus (Brodmann's 46).TASK: Cue one of 8 locations Cue one of 8 locations 3 sec. delay 3 sec. delay fixation removed signaling GO fixation removed signaling GO Saccades to remembered location Saccades to remembered location

12. Cognitive Role of area 46 Delay activity -- location specific Delay activity -- location specific Delay activity reduced when monkeys made errors. Delay activity reduced when monkeys made errors. Lesions of 46 impair performance on this task. Lesions of 46 impair performance on this task.Interpretation: Neural activity corresponds to mental representation of a GOAL Neural activity corresponds to mental representation of a GOAL The goal is maintained "on-line" available for use. The goal is maintained "on-line" available for use. This is working memory. This is working memory.

13. Without goal representation... Behavior is determined by reflex reflex habit habit past-reward (perseveration) past-reward (perseveration) immediate stimulus conditions immediate stimulus conditions Rather than by intentions that integrate the relevant current spatial and temporal context.

14. Frontal Lobes and Working memory... A system for maintaining and manipulating information to perform complex cognitive activities (Baddeley, 1992).

15. Working Memory on-line store on-line store short-term retention (approx. 10 sec) short-term retention (approx. 10 sec) executive processes executive processes rehearsal processes rehearsal processes material specific buffers material specific buffers verbal (phonological loop) left hem. verbal (phonological loop) left hem. spatial (visuo-spatial sketchpad) right hem. spatial (visuo-spatial sketchpad) right hem. EXECUTIVE phono- logical loop visuo- spatial sketch pad

16. Executive Functions of Prefrontal Cortex Aleksandr Luria (1966) Programming, regulating, monitoring Smith & Jonides (1999) Attention/inhibition, task management, contextual coding, planning, monitoring

17. Verbal WM Tasks M M M M 500 msec 3000 msec 1500 msec 3200 msec 500 msec 300 msec 1500 msec Verbal Memory Verbal Control m M K R D m

18. Spatial WM Tasks + 500 msec 3000 msec 1500 msec + 3300 msec 500 msec 200 msec 1500 msec Spatial Memory Spatial Control + + + + + +

19. Regions of Significant Activation

20. Hypothesized Working Memory Circuitry Frontal sites control rehearsal and manipulation of stored information. Frontal sites control rehearsal and manipulation of stored information. Parietal sites control the storage of this information. Parietal sites control the storage of this information. Anterior Posterior

21. Aging and Working Memory WM - contributes broadly to higher cognition. WM - contributes broadly to higher cognition. WM declines w/age. WM declines w/age. PFC atrophies w/ age. PFC atrophies w/ age. How does the neural substrate of WM change w/age? How does the neural substrate of WM change w/age? Birth 1 yr 60 100 Synapses in LPFC (after Huttenlocher, 1979)

22. Seniors made more Verbal errors than Young (p = 0.02) Seniors made more Verbal errors than Young (p = 0.02) Senior and Young groups had equal Spatial accuracies (p = 0.6) Senior and Young groups had equal Spatial accuracies (p = 0.6) Performance Results SPATIAL-Recognition Errors 0 1 2 3 4 5 6 7 8 9 10 YoungSeniors Errors (%) VERBAL-Recognition Errors 0 2 4 6 8 10 YoungSeniors Errors( %)

23. Regions of Activation (Reuter-Lorenz et al., 2000) Regions of Activation (Reuter-Lorenz et al., 2000)

24. Neuroimaging Results (verbal) Anterior Regions Posterior Regions (* = p <.05 ** = p ≤.02 *** = p <.005) -0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Younger Older *** RHLH -0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 YoungerOlder *** RHLH Percent Activation Change

25. Neuroimaging Results Spatial Anterior ROIs Posterior ROIs (* = p <.05 ** = p ≤.02 *** = p <.005) -0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 YoungerOlder *** ** -0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 YoungerOlder ** RHLHRHLH Percent Activation Change

26. Aging and Working Memory: Summary Neural substrate for WM is affected by aging. Neural substrate for WM is affected by aging. Selectivity: Frontal circuitry more vulnerable. Selectivity: Frontal circuitry more vulnerable. Decreased lateralization. Decreased lateralization. Compensatory? Compensatory? Recruitment as a “neural strategy” to cope with age-related loss of neural efficiency. Recruitment as a “neural strategy” to cope with age-related loss of neural efficiency.

27. Long Term Memory and its Dysfunction Memory: the ability to retain & recollect the contents of our experience Memory: the ability to retain & recollect the contents of our experience typically multimodal typically multimodal rich in associations rich in associations Expanding the definition to include... the ability to acquire new skills & demonstrate improved performance as a result of experience. Expanding the definition to include... the ability to acquire new skills & demonstrate improved performance as a result of experience.

28. Human Amnesia Anterograde: Inability to acquire NEW memories. Anterograde: Inability to acquire NEW memories. Retrograde: Inability to recollect OLD memories. Retrograde: Inability to recollect OLD memories.