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Techniques in Cognitive Neuroscience Transcranial Magnetic Stimulation (TMS) Dr. Roger Newport.

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Presentation on theme: "Techniques in Cognitive Neuroscience Transcranial Magnetic Stimulation (TMS) Dr. Roger Newport."— 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 sudies Direct cortical stimulation Imaging TMS Design Considerations TMS safety Contraindications Acceptable risks Ethics Coil shape Depth and spatial resolution of stimulation Coil Localisation Control conditions Stimulation techniques and effects

3 dArsonval (1896/1911) Magnusson & Stevens, 1911 Thompson, 1910 History of TMS and obligatory funny pictures Merton &Morton (1980). Successful Transcranial Electrical Stimulation

4 Barker, 1984 Transcranial Magnetic Stimulation allows the Safe, Non-invasive and Painless Stimulation of the Human Brain Cortex. Cadwell DantecMagstim Common rTMS machines

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 sudies Direct cortical stimulation Imaging TMS

7 Lesion Studies –Dependence of serendipity of nature or experimental models in animals –Single or few case studies –might be more than a single lesion –lesion may be larger than the brain area under study –Cognitive abilities may be globally impaired –Lesion can only be accurately defined post mortem –The damaged region cannot be reinstated to obtain control measures that bracket the lesion-induced effect –Comparisons must be made to healthy controls; internal double dissociations are not possible –Given brain plasticity, connections might be modified following lesions Other Brain-Behavior Techniques

8 Cortical Stimulation –Invasive –Limited to the study of patients with brain pathologies requiring neurosurgical interventions –Stressful situation in the OR and medications might condition subjects performance –Time constraints limit the experimental paradigms –Retesting is not possible Other Brain-Behavior Techniques

9 Neuroimaging (Brain Mapping) –Non-invasive identification of the brain injury correlated with a given behavior –Association of brain activity with behavior - cannot rule out epiphenomenon –Cannot demonstrate the necessity of given region to function –Neuroimaging 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 substrates Acute studies minimize the possibility of plastic reorganization of brain function Repeated studies in the same subject Study multiple subjects with the same experimental paradigm Study the time course of network interactions When 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 Real lesion Blue = sighted; Red = E blind Cohen et al., Occipital TMS disrupts braille reading in early blind, but not control subjects Hamilton et al., Reported case of blind woman who lost ability to read braille following bilateral occipital lesions Advantages of TMS: Virtual Patients causal link between brain activity and behaviour TMS lesion Braille Alexia

12 Advantages of TMS: Chronometry Role of visual cortex in tactile information processing in early blind subjects Hamilton and Pascual- Leone, 1998 Chronometry: timing the contribution of focal brain activity to behavior

13 Paus et al. TMS/PET TMS to FEF - correlation between TMS and CBF at i) stimulation site ii) distal regions consistent with known anatomical connectivity of monkey FEF Functional connectivity- relate behaviour to the interaction between elements of a neural network

14 Mapping and modulation of neural plasticity - rapid changes Serial Reaction Time Task 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. Rapid plasticity - map changes in cortical excitability using TMS/MEPs during a learning task (Pacual-Leone et al.)

15 Other uses for TMS Clinical - test speed, or existence of, of corticospinal connections (MS/stroke) Therapy -rTMD has long term effects on depression 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. Measure changes in motor excitability in neurologic disorders (e.g. PD, HD) Mapping and modulation of neural plasticity - slow changes Amputee cortical excitability

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 network Map 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 sudies Direct cortical stimulation Imaging TMS Design Considerations TMS safety Contraindications Acceptable risks Ethics Coil shape Depth and spatial resolution of stimulation Coil Localisation Control conditions Stimulation techniques and effects

18 Safety Seizure 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 W Engineering 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 dont put your tea on it.

19 Safety Scalp 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 time Local 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 + minimum inter-train interval e.g. at T leave >5s inter train Frequency (Hz)Max. duration (s) Maximum safe duration of single rTMS train at 110% MT Follow published safety guidelines for rTMS Caution: Guidelines not perfect Safety

21 Safety -Contraindications Metallic hardware near coil –Pacemakers –implantable medical pumps –ventriculo-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 relative Medicines which reduce seizure threshold Subjects who are pregnant (case studies have not shown complications) History of serious head trauma History of substance abuse Stroke Status after Brain Surgery Other medical/neurologic conditions either associated with epilepsy or in whom a seizure would be particularly hazardous (e.g. increased intracranial pressure)

22 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, surgical clips, 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? Safety TMS Adult Safety Screen

23 Levels of Risk Class I - Direct clinical benefit is expected, e.g. depression. Level of acceptable risk (i.e. sz) is moderate Class 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. Ethics Guidelines Informed Consent - disclosure of all significant risks, both those known and those suspected possible Potential Benefit must outweigh risk Equal distribution of risk - Particularly vulnerable patient populations should be avoided

24 The geometry of the coil determines the focality of the magnetic field and of the induced current - hence also of the targeted brain area. T Practical considerations Coil shape

25 25mm 15mm 20mm 70x60 55x45 40x30 0 5mm Practical Considerations - stimulation depth Cannot stimulate medial or sub-cortical areas

26 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 measure It is possible that differences in brain anatomy may lead to inter- individual differences in the substrates of TMS effects The presumed intensity of TMS is usually based on motor threshold But this assumes a uniform and constant threshold throughout cortex Caution! All the figures quoted on the previous page are estimated. Temporal effects depend on recovery rate of neural area

27 Further Caution! Spread of activation and the path of least resistance

28 Find anatomical landmark inion/nasion-ear/ear vertex EEG 10/20 system Coil localisation - hitting the right spot Move a set distance along and across (e.g. FEF = 2-4 cm anterior and 2-4 cm lateral to hand area) Find functional effect M1 - hand twitch (MEP) V5 - moving phosphenes

29 But: not all brains are the same Functional and structural scan e.g. eye movement test from functional and map onto structural, then co-reg v. expensive and laborious MRI co-registration Coil localisation - hitting the right spot Frameless Stereotactic System Paus et al.

30 Stimulation techniques and possible effects Single pulse rTMS (low/high fr.) Paired pulse Paradoxical effectsConnected effects Expected effect

31 Real Sham Control Conditions Different hemisphere Different site Different effect or no effect Or interleave TMS with no TMS trials

32 Major limitations summary Only regions on cortical surface can be stimulated Can be unpleasant for subjects Risks to subjects and esp. patients Stringent ethics required (cant be used by some institutions) Localisation uncertainty Stimulation level uncertainty Major advantages summary Reversible lesions without plasticity changes Repeatable High spatial and temporal resolution Can establish causal link between brain activation and behaviour Can measure cortical plasticity Can modulate cortical plasticity Therapeutic benefits

33 Suggested Readings Walsh 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, 180–183 Pascual-Leone, Walsh and Rothwell. (2000) Transcranial magnetic stimulation in cognitive neuroscience – virtual lesion, chronometry, and functional connectivity Current Opinion in Neurobiology 2000, 10:232–237 Hamilton et al., (2000).. Alexia for Braille following bilateral occipital stroke in an early blind woman. Neuroreport 11: , 2000 Hamilton and Pascual-Leone (1998). Cortical plasticity associated with Braille learning, Trends in Cognitive Sciences, Volume 2, Issue 5, 1 May 1998, Pages Eric 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


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