3Neurology of languageStrokes & DiseaseIntra-cortical mapping
4MRI studies of brain structure PET and MRI studies of brain function Non-invasive methodsMRI studies of brain structurePET and MRI studies of brain function
5Magnetic 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 ( )
8Induced electric field Induced tissue current How does it work?TMS coil current8kAMagnetic field pulse2.5TRate of change ofmagnetic field30kT/sThe 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 field500v/mInduced tissue current15mA/cm2
11Broca’s area re-visited Categorisation(man-made?)Semantic decision(Synonyms?)Sentencecompletion: MeaningMeaning preferentially engages anterior, ventral Broca’s area
12Broca’s area re-visited Phonological decision(Homophones?)SentenceCompletion: RhymesTwo syllables?Sounds of words (or sentences) preferentially engage posterior, dorsal parts of Broca’s area
13Common activationsSingle wordsWord pairsSentencesFor 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
14Two possibilities 1. Necessary processing quantitative difference Semantic Phonological1. Necessary processing quantitative difference2. Incidental processing qualitative differenceTheoretically 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.
15Subdividing 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 CaudalrTMSrTMSSemanticPhonologicalWe 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.NoneNonerTMSrTMSNoneNoneGough et al (2005). J Neuroscience
20Functional connectivity MEP magnitude in hand during reading+BeforeSeyal et al. (1999). Clin Neurophysiol, 110(3),
21Functional connectivity MEP magnitude in hand during readingAfterofficerBeforeSeyal et al. (1999). Clin Neurophysiol, 110(3),
22Implications Evolutionary link? Or inexplicable link between hand gestures and language(most refined in Italian speakers)?
23Actions and motor cortex He turned thekey.He kicked theball.He forgot thename.Buccino et al. (2005). Brain Res Cogn Brain Res, 24(3),
24Speech comprehensionSuggests 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),
25Somatotopy of speech Results D’Ausilio et al. (2009). Current Biology, 19,
26Disrupting speech perception TMS ResultsMeister et al. (2007). Current Biology, 17,
27Recovery from aphasia peri-lesional activation Contralateral L Rperi-lesionalactivationContralateralactivation
28Stimulating IFG in patients No effectThiel et al. (2006). Brain Lang. 98(1):
29Pre-morbid differences? Left RightLateralisation in 324 normal adults by fTCDKnecht et al. (2000). Brain, 123 ( Pt 1),
30Laterality affects susceptibility Knecht et al. (2002). Nat Neurosci, 5(7),
31Theraputic TMS?Naeser et al. (2005) Neurocase, 11(3), ; Naeser et al. (2005) Brain Lang, 93(1),
36Designing experiments for TMS What backgrounds people from?PsychologyPhysiologyNeurologyPsychiatryOther?36
37Design considerations Type of stimulationChoosing control conditionsTargeting stimulationChoosing parametersEthical considerations
38Design considerations Type of stimulationChoosing control conditionsTargeting stimulationChoosing parametersEthical considerations
39Choosing a type of TMSOn-line stimulation occurs while the subject performs a task and the effects last for approximately the duration of stimulation.Eg: Virtual lesionsChronometricsFunctional connectivityOff-line stimulation occurs without a task and the length of effect is typically measured in minutes.Eg: 1Hz stimulationTheta burstAdvantages of each (be sure to put in handout).
40Repetitive or chronometric? Repetitive stimulation typically involves trains of three or more pulses evenly spaced in timeEffect lasts approx. duration of stimulationDon’t need to know exactly when to stimulateLots of pulsesChronometric studies use either single or paired-pulses to examine the processing time course in a regionRequires far more trials!!!Subjects tolerate stimulation betterHow to best order trials?
42Ordering timing trials No TMSInter-sensory facilitation. Implicit waiting. Give example of rTMS of vOTC 3 pulses vs. 5 pulses.
43Design considerations Type of stimulationChoosing control conditionsControl sitesControl tasksControl stimuliSham stimulationTargeting stimulationChoosing parametersEthical considerations
44Control site: VertexIn 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.
45Choosing 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.
48Design considerations Type of stimulationChoosing control conditionsTargeting stimulationFunctional localizersAnatomically guided: MRI based stereotaxyHeuristicsChoosing parametersEthical considerations
49Area sensitive to reading words Functionally localize w/ fMRIArea sensitive to reading wordsVentral occipito-temporal cortex
54Design considerations Type of stimulationChoosing control conditionsTargeting stimulationChoosing parametersEthical considerations
55Choosing parameters Stimulation intensity / duration / rate Inter-stimulation intervalType of coilType of stimulation / stimulatorAccessibilityNumber of trials per condition?Number of subjects in a study?Analysis methods?
56Design considerations Type of stimulationChoosing control conditionsTargeting stimulationChoosing parametersEthical considerations
57Ethics of TMSAlthough the risk is small, it is always present, so there is an obligation on the experimenter to always consider the value of a given experimentHow 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?