1. Stimulating language: Insights from TMS
Joseph T. Devlin
MSc Neuroscience, Language &
Communication
16 November 2011 1

2. Lack of animal models
“I say, is that a banana?”

3. Neurology of language
Strokes & Disease
Intra-cortical mapping

4. MRI studies of brain structure PET and MRI studies of brain function
Non-invasive methods
MRI studies of brain structure
PET and MRI studies of brain function

5. Magnetic stimulation Magnetic stimulation elicited phosphenes
Not a new idea. As early as 1911, there were attempts to use magnets to non-invasively stimulate the brain. [Details in Vin’s book?]
Magnusson & Stevens ( )

6. Magnetic stimulation
11;1(8437):1106-7
Barker, Jalinous & Freeston (1985). Lancet, 11, 6

7. Transcranial magnetic stimulation

8. Induced electric field Induced tissue current
How does it work?
TMS coil current
8kA
Magnetic field pulse
2.5T
Rate of change of
magnetic field
30kT/s
The induced current can have several different effects. It can produce a physiological response such as a muscle twitch when stimulating motor cortex or outside of sensory-motor areas it can effectively disrupt processing in a region. If the region was required for a particular task, then this can slow responses or in some cases, lead to errors.
Induced electric field
500v/m
Induced tissue current
15mA/cm2

9. It’s fun -- really!

10. Speech arrest with TMS

11. Broca’s area re-visited
Categorisation
(man-made?)
Semantic decision
(Synonyms?)
Sentence
completion: Meaning
Meaning preferentially engages anterior, ventral Broca’s area

12. Broca’s area re-visited
Phonological decision
(Homophones?)
Sentence
Completion: Rhymes
Two syllables?
Sounds of words (or sentences) preferentially engage posterior, dorsal parts of Broca’s area

13. Common activations
Single words
Word pairs
Sentences
For instance, it’s become clear that that there is a rostral-caudal division of labour within Broca’s area related to semantic and phonological processing of information.
BUT… both sound and meaning engage all of Broca’s area relative to low level baselines

14. Two possibilities 1. Necessary processing  quantitative difference
Semantic Phonological
1. Necessary processing
 quantitative difference
2. Incidental processing
 qualitative difference
Theoretically there is a third possibility – namely that only one region region is necessary and the additional activation reflects incidental processing. But we can rule this out on the basis of two previous TMS studies.

15. Subdividing Broca’s area
Is there a double dissociation in LIFC for semantic and phonological processing?
Are both areas engaged by both types of processing?
Rostral Caudal
rTMS
rTMS
Semantic
Phonological
We also included a control task where participants pressed a button if two meaningless letter strings were identical. Because it was purely visual, we didn’t expect any significant TMS effects on the control task at either stimulation site.
None
None
rTMS
rTMS
None
None
Gough et al (2005). J Neuroscience

16. TMS Results

17. Anatomic localisation
MNI coordinates
Relative to C-T line
Rostral: -52, 35, -7 4 × 6cm
Caudal: -52, 15, 8 2 × 3cm
 Mean distance in cortex of 2.3cm apart
 Sites on scalp separated by 3.5cm, on average

18. Single pulse TMS * No TMS
Devlin et al (2003). J of Cognitive Neuroscience

19. Motor evoked potentials

20. Functional connectivity
MEP magnitude in hand during reading +
Before
Seyal et al. (1999). Clin Neurophysiol, 110(3),

21. Functional connectivity
MEP magnitude in hand during reading
After
officer
Before
Seyal et al. (1999). Clin Neurophysiol, 110(3),

22. Implications Evolutionary link?
Or inexplicable link between hand gestures and language
(most refined in Italian speakers)?

23. Actions and motor cortex
He turned the
key.
He kicked the
ball.
He forgot the
name.
Buccino et al. (2005). Brain Res Cogn Brain Res, 24(3),

24. Speech comprehension
Suggests that action-perception link may play a role in comprehending speech (akin to Lieberman’s dreaded Motor Theory of Speech Perception).
Watkins et al. (2003). Neuropsychologia, 41(8),

25. Somatotopy of speech Results
D’Ausilio et al. (2009). Current Biology, 19,

26. Disrupting speech perception
TMS Results
Meister et al. (2007). Current Biology, 17,

27. Recovery from aphasia peri-lesional activation Contralateral
L R
peri-lesional
activation
Contralateral
activation

28. Stimulating IFG in patients
No effect
Thiel et al. (2006). Brain Lang. 98(1):

29. Pre-morbid differences?
Left Right
Lateralisation in 324 normal adults by fTCD
Knecht et al. (2000). Brain, 123 ( Pt 1),

30. Laterality affects susceptibility
Knecht et al. (2002). Nat Neurosci, 5(7),

31. Theraputic TMS?
Naeser et al. (2005) Neurocase, 11(3), ; Naeser et al. (2005) Brain Lang, 93(1),

32. Long term enhancement

33. Relation to other methods
Walsh and Cowey (2000). Nat Revs Neurosci.

34. PET and TMS
Paus et al. (1997). J Neurosci.

35. EEG and TMS
Ilmoniemi et al. (1997). NeuroReport

36. Designing experiments for TMS
What backgrounds people from?
Psychology
Physiology
Neurology
Psychiatry
Other? 36

37. Design considerations
Type of stimulation
Choosing control conditions
Targeting stimulation
Choosing parameters
Ethical considerations

38. Design considerations
Type of stimulation
Choosing control conditions
Targeting stimulation
Choosing parameters
Ethical considerations

39. Choosing a type of TMS
On-line stimulation occurs while the subject performs a task and the effects last for approximately the duration of stimulation.
Eg: Virtual lesions
Chronometrics
Functional connectivity
Off-line stimulation occurs without a task and the length of effect is typically measured in minutes.
Eg: 1Hz stimulation
Theta burst
Advantages of each (be sure to put in handout).

40. Repetitive or chronometric?
Repetitive stimulation typically involves trains of three or more pulses evenly spaced in time
Effect lasts approx. duration of stimulation
Don’t need to know exactly when to stimulate
Lots of pulses
Chronometric studies use either single or paired-pulses to examine the processing time course in a region
Requires far more trials!!!
Subjects tolerate stimulation better
How to best order trials?

41. Single pulse TMS No
TMS

42. Ordering timing trials
No TMS
Inter-sensory facilitation. Implicit waiting. Give example of rTMS of vOTC 3 pulses vs. 5 pulses.

43. Design considerations
Type of stimulation
Choosing control conditions
Control sites
Control tasks
Control stimuli
Sham stimulation
Targeting stimulation
Choosing parameters
Ethical considerations

44. Control site: Vertex
In this experiment, authors used TMS to stimulate vOTC in an attempt to interfere with reading single words. Multiple stimuli conditions including consonant letter strings, pronounceable pseudowords, and also low and high frequency words. Main effect of TMS could be anything and a main effect of Site is equally problematic (ie Vertex -- constant speed up). Interaction reveals TMS-specific effects.

45. Choosing another control site
Sensation / experience of vertex TMS tends to be different than most other sites. Might want to control the phenomonological experience more closely. In this case, comparing vOTC to lateral OTC -- areas separated by roughly 2cm. Subject’s can’t tell them apart from the sensation of TMS but big difference in the effects of TMS on words. Note again there is an extra control condition: pseudowords are another stimulus and again the interaction is the strongest effect.

46. Control task(s)

47. Sham TMS…
…is a sham

48. Design considerations
Type of stimulation
Choosing control conditions
Targeting stimulation
Functional localizers
Anatomically guided: MRI based stereotaxy
Heuristics
Choosing parameters
Ethical considerations

49. Area sensitive to reading words
Functionally localize w/ fMRI
Area sensitive to reading words
Ventral occipito-
temporal cortex

50. Functionally localize w/ TMS
Rostral site
Task: Same category?
potato +
turnip
Caudal site
Task: Rhyme?
vein +
pane
41 ms*
52 ms*

51. Frameless stereotaxy
Identifying corresponding positions on the subject and subject’s
MRI scan for registration

52. Scalp coordinates Rostral: -52, 35, -7 4 × 6cm
MNI coordinates
Relative to C-T line
Rostral: -52, 35, -7 4 × 6cm
Caudal: -52, 15, 8 2 × 3cm
 Mean distance in cortex of 2.3cm apart
 Sites on scalp separated by 3.5cm, on average

53. International 10-20 system

54. Design considerations
Type of stimulation
Choosing control conditions
Targeting stimulation
Choosing parameters
Ethical considerations

55. Choosing parameters Stimulation intensity / duration / rate
Inter-stimulation interval
Type of coil
Type of stimulation / stimulator
Accessibility
Number of trials per condition?
Number of subjects in a study?
Analysis methods?

56. Design considerations
Type of stimulation
Choosing control conditions
Targeting stimulation
Choosing parameters
Ethical considerations

57. Ethics of TMS
Although the risk is small, it is always present, so there is an obligation on the experimenter to always consider the value of a given experiment
How can you minimize risk & discomfort?
What is the minimal stimulation necessary?
Is the TMS information clear and consent informed?
Are subjects always screened?
Are the experimenters safety trained?
Are emergency procedures clear & in place?
Would YOU do this experiment?