Presentation on theme: "Techniques in Cognitive Neuroscience"— Presentation transcript:
1 Techniques in Cognitive Neuroscience Transcranial Magnetic Stimulation (TMS)Dr. Roger Newport
2 Lecture Overview Brief history of TMS and how it works What can TMS add to Cognitive Neuroscience ?What advantages are there for TMS over other brain-behavior techniques?Lesion sudiesDirect cortical stimulationImagingTMSDesign ConsiderationsTMS safetyContraindicationsAcceptable risksEthicsCoil shapeDepth and spatial resolution of stimulationCoil LocalisationControl conditionsStimulation techniques and effects
3 History of TMS and obligatory funny pictures Merton &Morton (1980). Successful Transcranial Electrical Stimulationd’Arsonval (1896/1911)Magnusson &Stevens, 1911Thompson, 1910
4 Barker, 1984Common rTMS machinesMagstimDantecTranscranial Magnetic Stimulation allows the Safe, Non-invasive and Painless Stimulation of the Human Brain Cortex.Cadwell
5 Electromagnetic Induction Introduces disorder into a normally ordered system
6 Lecture Overview Brief history of TMS and how it works What can TMS add to Cognitive Neuroscience ?What advantages are there for TMS over other brain-behavior techniques?Lesion sudiesDirect cortical stimulationImagingTMS
7 Other Brain-Behavior Techniques Lesion StudiesDependence of serendipity of nature or experimental models in animalsSingle or few case studiesmight be more than a single lesionlesion may be larger than the brain area under studyCognitive abilities may be globally impairedLesion can only be accurately defined post mortemThe damaged region cannot be reinstated to obtain control measures that bracket the lesion-induced effectComparisons must be made to healthy controls; internal double dissociations are not possibleGiven brain plasticity, connections might be modified following lesions
8 Other Brain-Behavior Techniques Cortical StimulationInvasiveLimited to the study of patients with brain pathologies requiring neurosurgical interventionsStressful situation in the OR and medications might condition subject’s performanceTime constraints limit the experimental paradigmsRetesting is not possible
9 Other Brain-Behavior Techniques Neuroimaging (Brain Mapping)Non-invasive identification of the brain injury correlated with a given behaviorAssociation of brain activity with behavior - cannot rule out epiphenomenonCannot demonstrate the necessity of given region to functionNeuroimaging techniques are usually only good either temporally or spatially, not both (e.g. Pet & fMRI lack temporal resolution, EEG lacks spatial resolution)
10 Advantages of TMS in the Study of Brain-Behavior Relations Study of normal subjects eliminates the potential confounds of additional brain lesions and pathological brain substratesAcute studies minimize the possibility of plastic reorganization of brain functionRepeated studies in the same subjectStudy multiple subjects with the same experimental paradigmStudy the time course of network interactionsWhen combined with PET or fMRI, can build a picture of not only which areas of brain are active in a task, but also the time at which each one contributes to the task performance.Study internal double dissociations and network interactions by targeting different brain structures during single a task and disrupting the same cortical area during different related tasks
11 Advantages of TMS: Virtual Patients causal link between brain activity and behaviourBraille AlexiaReal lesionTMS lesionCohen et al., Occipital TMS disrupts braille reading in early blind, but not control subjectsHamilton et al., Reported case of blind woman who lost ability to read braille following bilateral occipital lesionsBlue = sighted; Red = E blind
12 Advantages of TMS: Chronometry “Chronometry”: timing the contribution of focal brain activity to behaviorRole of “visual” cortex in tactile information processing in early blind subjectsHamilton and Pascual-Leone, 1998
13 Functional connectivity- relate behaviour to the interaction between elements of a neural network TMSTMS to FEF - correlation between TMS and CBF ati) stimulation siteii) distal regions consistent with known anatomical connectivity of monkey FEFPaus et al.TMS/PET
14 Mapping and modulation of neural plasticity - rapid changes Rapid plasticity - map changes in cortical excitability using TMS/MEPs during a learning task (Pacual-Leone et al.)Cohen and colleagues.Modulation of cortical excitability in “deafferentation” studies.TMS of plastic hemisphere increases neural response,TMS of non-plastic hemisphere downgrades neural response of plastic hemisphere.Serial Reaction Time Task
15 Mapping and modulation of neural plasticity - slow changes Braille reader took 10-day holiday from reading. Size of finger representation shrank dramatically until she returned to work — even time off over the weekend quantitatively reduced finger representation.Other uses for TMSClinical - test speed, or existence of, of corticospinal connections (MS/stroke)Therapy -rTMD has long term effects on depressionAmputee cortical excitabilityMeasure changes in motor excitability in neurologic disorders (e.g. PD, HD)
16 Summary: What can TMS add to Cognitive Neuroscience ? “Virtual Patients”: causal link between brain activity and behavior“Chronometry”: timing the contribution of focal brain activity to behavior“Functional connectivity”: relate behavior to the interaction between elements of a neural networkMap and modulate neural plasticity
17 Lecture Overview Brief history of TMS and how it works What can TMS add to Cognitive Neuroscience ?What advantages are there for TMS over other brain-behavior techniques?Lesion sudiesDirect cortical stimulationImagingTMSDesign ConsiderationsTMS safetyContraindicationsAcceptable risksEthicsCoil shapeDepth and spatial resolution of stimulationCoil LocalisationControl conditionsStimulation techniques and effects
18 SafetySeizure induction - Caused by spread of excitation. Single-pulse TMS has produced seizures in patients, but not in normal subjects. rTMS has caused seizures in patients and in normal volunteers. Visual and/or EMG monitoring for afterdischarges as well as spreading excitation may reduce risk.Hearing loss - TMS produces loud click ( dB) in the most sensitive frequency range (2–7 kHz). rTMS = more sustained noise. Reduced considerably with earplugs.Heating of the brain - Theoretical power dissipation from TMS is few milliwatts at 1 Hz, while the brain's metabolic power is 13 WEngineering safety - TMS equipment operates at lethal voltages of up to 4 kV. The maximum energy in the capacitor is about 500 J, equal to dropping 100 kg from 50 cm on your feet. So don’t put your tea on it.
19 SafetyScalp burns from EEG electrodes - Mild scalp burns in subjects with scalp electrodes can be easily avoided using, e.g., small low-conductivity Ag/AgCl-pellet electrodes.Effect on cognition - Slight trend toward better verbal memory, improved delayed recall and better motor reaction timeLocal neck pain and headaches - Related to stimulation of local muscles and nerves, site and intensity dependant. Particularly uncomfortable over fronto-temporal regions.Effect on Mood in normals - Subtle changes in mood are site and frequency dependant. High frequency rTMS of left frontal cortex worsens mood. High frequency rTMS of right frontal cortex may improve mood.
20 Safety Follow published safety guidelines for rTMS Maximum safe duration of single rTMS train at 110% MTFrequency (Hz)Max. duration (s)11800+510201.625.84+ minimum inter-train intervale.g. at T leave >5s inter trainCaution: Guidelines not perfect
21 Safety -Contraindications Metallic hardware near coilPacemakersimplantable medical pumpsventriculo-peritoneal shunts(case studies with implanted brain stimulators and abdominal devices have not shown complications)History of seizures or history of epilepsy in first degree relativeMedicines which reduce seizure thresholdSubjects who are pregnant(case studies have not shown complications)History of serious head traumaHistory of substance abuseStrokeStatus after Brain SurgeryOther medical/neurologic conditions either associated with epilepsy or in whom a seizure would be particularly hazardous (e.g. increased intracranial pressure)
22 Safety TMS Adult Safety Screen Have you ever: had an adverse reaction to TMS?Had a seizure?Had an EEG?Had a stroke?Had a head injury(include neurosurgery)?Do you have any metal in your head (outside of the mouth,) such as shrapnel, surgicalclips, or fragments from welding or metalwork? (Metal can be moved or heated by TMS)Do you have any implanted devices such as cardiac pacemakers, medical pumps, or intracardiac lines? (TMS may interfere with electronics and those with heart conditions are at greater risk in event of seizure)Do you suffer from frequent or severe headaches?Have you ever had any other brain-related condition?Have you ever had any illness that caused brain injury?Are you taking any medications? (e.g. Tricyclic anti-depressants, neuroleptic agents, and other drugs that lower the seizure threshold)If you are a woman of childbearing age, are you sexually active, and if so, are you not using a reliable method of birth control?Does anyone in your family have epilepsy?Do you need further explanation of TMS and its associated risks?
23 Ethics Guidelines Levels of Risk Informed Consent - disclosure of all significant risks, both those known and those suspected possiblePotential Benefit must outweigh riskEqual distribution of risk - Particularly vulnerable patient populations should be avoidedLevels of RiskClass I - Direct clinical benefit is expected, e.g. depression. Level of acceptable risk (i.e. sz) is moderateClass II - Potential, but unproven benefit, e.g. PD. Level of acceptable risk is low.Class III - No expected benefit. Will advance general understanding. Requires stringent safety guidelines.
24 Practical considerations Coil shapeTThe geometry of the coil determines the focality of the magnetic field and of the induced current - hence also of the targeted brain area.
25 Practical Considerations - stimulation depth 70x605mm55x4515mm40x3020mm25mmCannot stimulate medial or sub-cortical areas
26 Caution!All the figures quoted on the previous page are estimated.Knowledge of the magnetic field induced by the coil is not sufficient to know the induced current in the brain - and that is very difficult to measureThe presumed intensity of TMS is usually based on motor thresholdBut this assumes a uniform and constant threshold throughout cortexIt is possible that differences in brain anatomy may lead to inter-individual differences in the substrates of TMS effectsTemporal effects depend on recovery rate of neural area
27 Further Caution! Spread of activation and the path of least resistance
28 Coil localisation - hitting the right spot Find functional effectM1 - hand twitch (MEP)V5 - moving phosphenesFind anatomical landmarkinion/nasion-ear/ear vertexEEG 10/20 systemMove a set distance along and across (e.g. FEF = 2-4 cm anterior and 2-4 cm lateral to hand area)
29 Frameless Stereotactic System Coil localisation - hitting the right spotBut: not all brains are the samePaus et al.MRI co-registrationFunctional and structural scanFrameless Stereotactic Systeme.g. eye movement test from functional and map onto structural, then co-regv. expensive and laborious
30 - - Stimulation techniques and possible effects + Expected effect Connected effectsParadoxical effectsSingle pulserTMS (low/high fr.)Paired pulsePaired pulse
31 Control Conditions Real Different hemisphere Different effect or no effectShamDifferent siteOr interleave TMS with no TMS trials
32 Major advantages summary Reversible lesions without plasticity changesRepeatableHigh spatial and temporal resolutionCan establish causal link between brain activation and behaviourCan measure cortical plasticityCan modulate cortical plasticityTherapeutic benefitsMajor limitations summaryOnly regions on cortical surface can be stimulatedCan be unpleasant for subjectsRisks to subjects and esp. patientsStringent ethics required (can’t be used by some institutions)Localisation uncertaintyStimulation level uncertainty
33 Suggested ReadingsWalsh and Cowey (1998) Magnetic stimulation studies of visual cognition. Trends in Cognitive Sciences 2(3),Vincent Walsh and Matthew Rushworth (1999) A primer of magnetic stimulation as a tool for neuropsychology. Neuropsychologia 37,Paus (1999) Imaging the brain before, during and after transcranial magnetic stimulation. Neuropsychologia 37.Paus et al. (1997) Transcranial magnetic stimulation during positron emission tomography: a new method for studying connectivity of the human cerebral cortex. Journal of Neuroscience 17,Cohen, L.G. et al. (1997) Functional relevance of cross-modal plasticity in blind humans Nature 389, 180–183Pascual-Leone, Walsh and Rothwell. (2000) Transcranial magnetic stimulation in cognitiveneuroscience – virtual lesion, chronometry, and functionalconnectivity Current Opinion in Neurobiology 2000, 10:232–237Hamilton et al., (2000).. Alexia for Braille following bilateral occipital stroke in an early blind woman. Neuroreport 11: , 2000Hamilton and Pascual-Leone (1998). Cortical plasticity associated with Braille learning, Trends in Cognitive Sciences, Volume 2, Issue 5, 1 May 1998, PagesEric M. Wassermann. (1998). Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996 Electroencephalography and clinical Neurophysiology 108 (1998) 1–16