1. ANATOMIC BASIS FOR LATERALIZATION speech lateralization in right-handers –following left hemisphere insult in 97% of stroke patients –following left hemisphere insult in 95% of head trauma patients –following left carotid Wada test in 95% of patients

2. ANATOMIC BASIS FOR LATERALIZATION most right-handed adults have speech represented in the left hemisphere

3. Two hemispheres Four lobes –Frontal –Temporal –Parietal –Occipital Anatomic features –Sylvian fissure –Central sulcus –Broca’s area –Wernicke’s area –Arcuate fasciculus BW

4. ANATOMIC BASIS FOR LATERALIZATION planum temporale larger in left hemisphere than right hemisphere in dextrals left Sylvian fissure longer and more horizontal than right Sylvian fissure in dextrals left inferior frontal cortex larger in left hemisphere than right hemisphere similar asymmetries in neonates, early hominids, some great apes

5. ANATOMIC BASIS FOR LATERALIZATION less overlapping dendritic trees in left Wernicke’s area than right Wernicke’s area –more discrete processing for rapid transition of speech sounds

6. ANATOMIC BASIS FOR LATERALIZATION speech lateralization in left-handers –sinistrals more likely to be aphasic following left hemisphere insult or right hemisphere insult aphasia milder and briefer in left-handers aphasia milder and briefer in mixed-handers and in patients with mixed family handedness

7. ENVIRONMENTAL BASIS FOR LATERALIZATION speech lateralization is affected by experience –right-handed illiterates and partial illiterates are less likely to have strongly lateralized speech aphasia follows insult to the left hemisphere or the right hemisphere in illiterate right-handers –aphasia for a recently acquired second language can follow right hemisphere insult in a right-hander, sparing the mother tongue in left hemisphere

8. APHASIA SYNDROMES

9. FLUENCY Non-fluent speech –effortful –telegraphic –agrammatic Fluent speech –melodic –circumlocutory –empty content

10. COMPREHENSION Single word comprehension –Point to the pencil –[present two objects] - point to the pencil –[present one object] - is this a pencil?

11. SENTENCE COMPREHENSION sentence-picture matching Fran showed her baby the pictures Fran showed her the baby pictures

12. SENTENCE COMPREHENSION “make the blue block be above the white block” Object manipulation

13. REPETITION Multi-syllabic words –“constitutional” Phrases –“methodist episcopal” Sentences –“no ifs, ands, or buts”

14. NAMING Confrontation naming –name demonstrated object spontaneously Recognition naming –choose correct name for demonstrated object Prompts –semantic –phonemic

15. APHASIA SYNDROMES BW

16. BROCA’S APHASIA non-fluent speech effortful, telegraphic, agrammatic comprehension intact single word comprehension agrammatic sentence comprehension

17. SENTENCE COMPREHENSION IN BROCA’S APHASIA Good comprehension of sentences with typical word order Poor comprehension of sentences with non- canonical word order

18. SENTENCE COMPREHENSION grammatical role is assigned indirectly via a trace that is phonetically silent The eagle i that t i chased the hawk was fast. grammatical role assignment in sentences with subject-relative center-embedded clauses

19. SENTENCE COMPREHENSION word order is non-canonical the antecedent noun must be kept in mind for many words until the trace is encountered The eagle i that the hawk chased t i was fast. grammatical role assignment in sentences with object-relative center-embedded phrases

20. impaired grammatical phrase structure knowledge –loss of traces –without traces, grammatical roles assigned on the basis of alternative strategies use of semantic constraint –The worm that the eagle ate was tasty dependence on word order strategy –First noun is subject/agent SENTENCE COMPREHENSION IN BROCA’S APHASIA

21. processing limitations –slowed lexical retrieval impairs grammatical processing on-line processing of grammatical phrases limited by failure to retrieve words exactly when needed in course of sentence processing SENTENCE COMPREHENSION IN BROCA’S APHASIA

22. slowed lexical retrieval during semantic priming slowed trace retrieval in object-relative center- embedded sentences –cross-modality lexical decision priming the trace at gap and pregap locations –Swinney et al, 1996 The eagle that the hawk with brown feathers *P* chased *G* was fast. * SENTENCE COMPREHENSION IN BROCA’S APHASIA

23. processing limitations –Verbal short-term memory limitation Poor retention of head noun until trace is encountered while processing sentence material –Broca’s aphasics have impaired verbal short-term memory SENTENCE COMPREHENSION IN BROCA’S APHASIA

24. fMRI SENTENCE COMPREHENSION subject-relative –Short linkage –Long linkage object-relative –short linkage –long linkage FOUR SENTENCE CONDITIONS PROBE AGENT OF ACTION –did male or female perform action in sentence?

25. fMRI SENTENCE COMPREHENSION GRAMMATICAL FACTOR –subject-relative center-embedded sentence grammatically simpler (typical word order) The boy i from Boston that t i chased the girl with the long brown hair is friendly –object-relative center-embedded sentence grammatically more complex (non-canonical word order) The boy i that the girl chased t i with the long brown hair from Boston is friendly

26. fMRI SENTENCE COMPREHENSION COGNITIVE RESOURCE FACTOR –short linkage sentence less working memory demands The boy i from Boston that t i chased the girl with the long brown hair is friendly –long linkage sentence more working memory demands The boy i with the long brown hair from Boston that t i chased the girl is friendly

27. SENTENCE COMPREHENSION Sentence comprehension compared to pseudofont baseline in 15 young healthy adults –A: subject-relative short linkage –B: subject-relative long linkage –C: object-relative short linkage –D: object-relative long linkage

28. SENTENCE COMPREHENSION Sentence comprehension compared to pseudofont baseline in 11 healthy seniors with good comprehension –A: subject-relative short linkage –B: subject-relative long linkage –C: object-relative short linkage –D: object-relative long linkage

29. SENTENCE COMPREHENSION Sentence comprehension comparing 11 healthy seniors and 13 young subjects for object-relative long linkage sentences –A: seniors > young –B: seniors < young

30. FRONTOTEMPORAL DEGENERATION Clinical subgroups –Progressive aphasia –Executive limitation –Personality change MRI scan –Relative atrophy in frontal and temporal distribution LR

31. PROGRESSIVE NON-FLUENT APHASIA Expression –hesitant, effortful, telegraphic speech oral, written Comprehension –agrammatic sentence comprehension oral, reading

32. PERFUSION fMRI IN FTD Grammatical aspects of sentence comprehension in FTD are correlated with left frontal defect

33. DYSEXECUTIVE SYNDROME limited working memory impaired planning, problem-solving inhibitory control deficit –perseverative, echolalic, perceptually bound, impulsive

34. PERFUSION fMRI IN FTD Semantically-guided category naming fluency in FTD is correlated with left frontal defect

35. SENTENCE COMPREHENSION IN FTD SUBGROUPS Comprehension of sentences with subordinate clauses PNFA patients more impaired than EXEC patients 100% of individual PNFA patients differ significantly from healthy controls

36. CORTICAL RECRUITMENT DURING SENTENCE COMPREHENSION IN FTD –PNFA patients (n=3) with grammatical comprehension difficulty do not recruit left inferior frontal cortex (BA 45/47) –EXEC patients (n=5) with limited short-term memory do not recruit BA 6/44 PNFA patients EXEC patients