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Stimulating language: Insights from TMS
Joseph T. Devlin
MSc Neuroscience, Language &Communication
16 November 2011
Lack of animal models
“I say, is that a banana?”
Neurology of language
Intra-cortical mappingStrokes & Disease
MRI studies of brain structure
PET and MRI studies of brain function
Non-invasive methods
Magnusson & Stevens (1911-1912)
Magnetic stimulation elicited phosphenes
Magnetic stimulation
Magnetic stimulation
Barker, Jalinous & Freeston (1985). Lancet, 11, 1106-7.
Transcranial magnetic stimulation
TMS coil current
8kA
Magnetic field pulse2.5T
Rate of change of magnetic field
30kT/s
Induced tissue current
15mA/cm2
Induced electric field
500v/m
How does it work?
It’s fun -- really!
Speech arrest with TMS
Semantic decision(Synonyms?)
Sentencecompletion: Meaning
Categorisation(man-made?)
Meaning preferentially engages anterior, ventral Broca’s area
Broca’s area re-visited
Broca’s area re-visited
Phonological decision(Homophones?)
SentenceCompletion: Rhymes
Two syllables?
Sounds of words (or sentences) preferentially engage posterior, dorsal parts of Broca’s area
Common activations
BUT… both sound and meaning engage all of Broca’s area relative to low level baselines
Word pairs SentencesSingle words
Two possibilities
1. Necessary processing
quantitative difference
2. Incidental processing
qualitative difference
Semantic Phonological
rTMSNone
Rostral Caudal
Semantic
Phonological
Gough et al (2005). J Neuroscience
rTMSNone
rTMSNone
rTMSNone
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?
TMS Results
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
MNI coordinates Relative to C-T line
Anatomic localisation
*
Single pulse TMS
Devlin et al (2003). J of Cognitive Neuroscience
NoTMS
Motor evoked potentials
Functional connectivity
Seyal et al. (1999). Clin Neurophysiol, 110(3), 424-429.
MEP magnitude in hand during reading
Before
+
Functional connectivity
Seyal et al. (1999). Clin Neurophysiol, 110(3), 424-429.
MEP magnitude in hand during reading
Before After
officer
Implications
Evolutionary link?
Or inexplicable link between hand gestures and language(most refined in Italian speakers)?
Actions and motor cortex
Buccino et al. (2005). Brain Res Cogn Brain Res, 24(3), 355-363.
He turned the key.
He kicked theball.
He forgot thename.
Speech comprehension
Watkins et al. (2003). Neuropsychologia, 41(8), 989-994.
Somatotopy of speech
Results
D’Ausilio et al. (2009). Current Biology, 19, 381-5.
Disrupting speech perception
Meister et al. (2007). Current Biology, 17, 1692-6.
TMS Results
Recovery from aphasia
L R
peri-lesionalactivation
Contralateral activation
Stimulating IFG in patients
Thiel et al. (2006). Brain Lang. 98(1): 57-65.
No effect
Pre-morbid differences?
Knecht et al. (2000). Brain, 123 ( Pt 1), 74-81.
Lateralisation in 324 normal adults by fTCD
Left Right
Laterality affects susceptibility
Knecht et al. (2002). Nat Neurosci, 5(7), 695-699.
Theraputic TMS?
Naeser et al. (2005) Neurocase, 11(3), 182-193; Naeser et al. (2005) Brain Lang, 93(1), 95-105
Long term enhancement
Relation to other methods
Walsh and Cowey (2000). Nat Revs Neurosci.
PET and TMS
Paus et al. (1997). J Neurosci.
EEG and TMS
Ilmoniemi et al. (1997). NeuroReport
Designing experiments for TMS
Design considerations
1. Type of stimulation
2. Choosing control conditions
3. Targeting stimulation
4. Choosing parameters
5. Ethical considerations
Design considerations
1. Type of stimulation
2. Choosing control conditions
3. Targeting stimulation
4. Choosing parameters
5. Ethical considerations
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 lesionsChronometricsFunctional connectivity
Off-line stimulation occurs without a task and the length of effect is typically measured in minutes.
Eg: 1Hz stimulationTheta burst
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?
Single pulse TMS
NoTMS
Ordering timing trials
No TMS
Design considerations
1. Type of stimulation
2. Choosing control conditions• Control sites• Control tasks• Control stimuli• Sham stimulation
3. Targeting stimulation
4. Choosing parameters
5. Ethical considerations
Control site: Vertex
Choosing another control site
Control task(s)
Sham TMS…
…is a sham
Design considerations
1. Type of stimulation
2. Choosing control conditions
3. Targeting stimulation• Functional localizers• Anatomically guided: MRI based stereotaxy• Heuristics
4. Choosing parameters
5. Ethical considerations
Ventral occipito-temporal cortex
Area sensitive to reading words
Functionally localize w/ fMRI
Rostral siteTask: Same category?
potato+
turnip
Caudal siteTask: Rhyme?
vein+
pane
41 ms* 52 ms*
Functionally localize w/ TMS
Identifying corresponding positions on the subject and subject’s MRI scan for registration
Frameless stereotaxy
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
MNI coordinates Relative to C-T line
Scalp coordinates
International 10-20 system
Design considerations
1. Type of stimulation
2. Choosing control conditions
3. Targeting stimulation
4. Choosing parameters
5. Ethical considerations
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?
Design considerations
1. Type of stimulation
2. Choosing control conditions
3. Targeting stimulation
4. Choosing parameters
5. Ethical considerations
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?