Transcranial Magnetic Transcranial Magnetic Stimulation - - PowerPoint PPT Presentation

Transcranial Magnetic Transcranial Magnetic Stimulation Stimulation

Alvaro Pascual Alvaro Pascual-

• Leone, M.D., Ph.D.

Leone, M.D., Ph.D.

Michael Faraday (1831) Michael Faraday (1831)

d d’ ’Arsonval Arsonval

A.T. Barker A.T. Barker 1984 1984

TMS TMS

TMS Terminology TMS Terminology

• Single pulse TMS

Single pulse TMS

• single stimulus every 5

single stimulus every 5-

• 10 sec

10 sec

• Paired pulse TMS

Paired pulse TMS

• subthreshold

subthreshold stim

• stim. then

. then suprathreshold suprathreshold stim stim. .

• stimuli separated by 1

stimuli separated by 1-

• 20

20 msec msec

• Repetitive TMS (rTMS)

Repetitive TMS (rTMS)

• trains of stimuli to one brain area

trains of stimuli to one brain area

• slow = low frequency

slow = low frequency

• fast (high freq) > 1 Hz

fast (high freq) > 1 Hz

Equipment Equipment Repetitive Stimulators Repetitive Stimulators

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Stimulation Coils Stimulation Coils

Induced Current Induced Current

• Depends of coil geometry

Depends of coil geometry

• Decay with square of distance

Decay with square of distance

Mechanism of action Mechanism of action

Mechanisms of action: Mechanisms of action:

Interaction between induced current and axons Interaction between induced current and axons

Mechanism of action: Mechanism of action:

Interindividual Interindividual variability variability

∂% in MEP area pre/post rTMS

• 100
• 50

50 100 150 200

1Hz 10Hz 15Hz 20Hz

• 20
• 10

10 20 30 40

rTMS condition

Modulation of Cortical Excitability Modulation of Cortical Excitability

• Inter

Inter-

• individual variability

individual variability

• Dependency on baseline cortical excitability

Dependency on baseline cortical excitability

Maeda et al, 2000 Maeda et al, 2000

rTMS: 240 stimuli at 90% of motor threshold

1Hz 10Hz 15Hz 20Hz rTMS condition

rTMS: 240 stimuli at 90% of motor threshold ∂% in MEP area pre/post rTMS

BEWARE OF INTER BEWARE OF INTER-

• INDIVIDUAL VARIABILITY

INDIVIDUAL VARIABILITY

• ? different subject populations

? different subject populations ( (Gangitano Gangitano et al) et al)

• ? genetics

? genetics

• 30
• 20
• 10

10 20 30 40

1 Hz 10 Hz 20 Hz rTMS conditions Day1 Day2 ∂% in MEP area pre/post rTMS

Reproducibility of Reproducibility of Modulatory Modulatory Effects of rTMS Effects of rTMS

IS REPEATED APPLICATION IS REPEATED APPLICATION SAFE? SAFE?

• Ethics of studies in normal subjects

Ethics of studies in normal subjects

• Is primed

Is primed-

• 1 Hz or theta burst pattern

1 Hz or theta burst pattern stimulation ethical? stimulation ethical?

Different brain areas Different brain areas

Robertson et al. Robertson et al. J. Cog.

• J. Cog. Neurosci

Neurosci 2003 2003

DO WE NEED MOTOR DO WE NEED MOTOR THRESHOLD? THRESHOLD?

• Safety guidelines need rewriting

Safety guidelines need rewriting

• Setting intensity by:

Setting intensity by:

– – Output of the device? Output of the device? – – Induced current density? Induced current density? – – Behavioral marker? Behavioral marker?

Scalp to Brain Relation Scalp to Brain Relation

Scalp Scalp ≠ ≠ Brain Brain

Pascual Pascual-

• Leone et al.,

Leone et al., Trans. R. Phil. Soc.

• Trans. R. Phil. Soc. 1999

1999

Frameless Frameless Stereotaxy Stereotaxy

Brainsight Brainsight

• Rogue Research Inc.

Rogue Research Inc.

Topographic Precision Topographic Precision

Scalp markers Scalp markers

Gugino Gugino et al. et al. Clin Clin Neurophysiol Neurophysiol 2000 2000

Stereotaxy Stereotaxy

FRAMELESS STEREOTAXY FRAMELESS STEREOTAXY

• What about the value of functional

What about the value of functional resolution? resolution?

• Is projection of main vector good

Is projection of main vector good enough? enough?

– – BEWARE OF BEWARE OF ‘ ‘PRETTY PICTURES PRETTY PICTURES’ ’

Magnitude of Induced Current Magnitude of Induced Current

Wagner et al., Wagner et al., Neurosci Neurosci Lett Lett 2003 2003 Humans: Humans: measured 12 measured 12µ µA/cm A/cm2

2

1 cm from coil 1 cm from coil 7% of max. output intensity 7% of max. output intensity

A More Realistic Head Model

• MRI Guided CAD Design
• Included: Skin, Skull, CSF,

Gray Matter, and White Matter

• Distinct Electrical Properties

Assigned to Each Tissue

Induced Current Density

Evaluating the effect of pathologies

• To account for the

effects of a cortical stroke a cut was made in the gray matter and replaced with CSF

Induced Current Density

5kHz104ε Solution- Normalized to Gray Matter

Induced Current Density

5kHz104ε Solution- Normalized to Gray Matter

Tissue Boundary Effects

Stroke Case vs. Healthy Model

Stroke Healthy

Stroke Case- Tissue Boundaries

Stroke Modeling

Focus Here Stimulate Here

Summary

• Tissues clearly have an influence in the current distribution

– TMS is not the same as stimulation in a surgical environment with the cortex exposed

• Strokes

– Near centimeter perturbation – CSF shunts current

• Alterations in the cortical geometry and/or electrical

characteristics can alter the predicted site of stimulation

– Ignored by current tracking systems

• Integration of field

solver with frameless stereotaxic system

• Validation of theories in

animal models

– Cat studies

Where to Go From Here?

TMS non TMS

20 Hz 1 Hz

DSI Guided TMS

• Effects of TMS represent an interaction between the characteristics of

the applied TMS pulse and those of the tissue stimulated.

• Brain tissue is not homogeneous.
• Enhanced knowledge about the characteristics of the tissue affected by

TMS will allow to adjust the TMS parameters in order to maximize spatial resolution.

• Diffusion spectrum imaging (DSI) can provide the required

information and be used to guide TMS for optimized spatial resolution.

Diffusion MRI - Diffusion Spectrum Imaging Cerebral Neurography -Tractography

Diffusion MRI - Diffusion Spectrum Imaging Mapping Cortical Cytoarchitectonics

DSI-Guided TMS

Computed TMS interaction with cerebral white matter

• circular 10 cm TMS coil over

vertex

• DTI of cerebral white matter
• rientation, coronal slab
• induced axonal

EMF’s computed with “ antenna ” model: d< E,s>/ ds red +, blue -

EFFECTS OF TMS ARISE EFFECTS OF TMS ARISE FROM THE INTERACTION OF FROM THE INTERACTION OF A NON A NON-

• PHYSIOLOGIC

PHYSIOLOGIC STIMULUS WITH THE TISSUE STIMULUS WITH THE TISSUE (AND ITS ONGOING (AND ITS ONGOING ACTIVITY) ACTIVITY)

Topographic precision Topographic precision

Siebner Siebner et al. 2001 et al. 2001

Topographic resolution Topographic resolution

TURN TOPOGRAPHIC TURN TOPOGRAPHIC RESOLUTION INTO AN RESOLUTION INTO AN EXPERIMENTAL QUESTION EXPERIMENTAL QUESTION

Temporal resolution Temporal resolution

TURN TEMPORAL TURN TEMPORAL RESOLUTION INTO AN RESOLUTION INTO AN EXPERIMENTAL QUESTION EXPERIMENTAL QUESTION

Neurophysiologic Effects of Neurophysiologic Effects of 1 Hz off 1 Hz off-

• line

line rTMS rTMS

Waechter Waechter, Ashe, Pascual , Ashe, Pascual-

• Leone

Leone

Before rTMS After 1 Hz rTMS

Mechanism of action: Mechanism of action:

Studying the effects of TMS on neuronal Studying the effects of TMS on neuronal activity in the visual cortex of cats activity in the visual cortex of cats

Moliadze Moliadze et al. et al. J.

• J. Physiol

Physiol. . 2003 2003

Effects of TMS on spontaneous Effects of TMS on spontaneous neuronal activity neuronal activity

TMS alone Visual + TMS (late) Visual + TMS (early)

Effect of TMS on neuronal activity Effect of TMS on neuronal activity modulated by visual stimuli modulated by visual stimuli

rTMS rTMS: : Lasting Modulation of Cortical Activity Lasting Modulation of Cortical Activity

Sham Sham TMS TMS

TMS

1 Hz 1 Hz TMS TMS 20 Hz 20 Hz TMS TMS

Valero et al. 2002 Valero et al. 2002

Splenial visual area Area 19 Area 17

*

PUL LPl LPi L G N M G N M G N L G N

Superior Colliculus Lateral Post. Complex

*

EFFECTS OF TMS ARISE EFFECTS OF TMS ARISE FROM THE INTERACTION FROM THE INTERACTION WITH THE ACTIVITY IN A WITH THE ACTIVITY IN A DISTRIBUTED NETWORK DISTRIBUTED NETWORK

Repetitive TMS: Online Repetitive TMS: Online

1 Hz 5 Hz 1 20 10 10 Hz 20 Hz

0.5 mV 1 mV 1 mV 1 mV 20 ms TMS

TMS train 10 pulses, 20 Hz, 150% 1 20 10 ms 100 µV 0.2 Hz, 90% 1 20 40 21 41 60

Repetitive TMS: Offline Repetitive TMS: Offline

Modulation of Cortical Modulation of Cortical Excitability Excitability

Pascual Pascual-

• Leone et al, 1998

Leone et al, 1998

High frequency High frequency rTMS increases rTMS increases CBF CBF Low frequency Low frequency rTMS decreases rTMS decreases CBF CBF

Distant Effects of rTMS Distant Effects of rTMS

Ilmoniemi Ilmoniemi et al. et al. Paus Paus et al. et al.

TMS in Neuroscience TMS in Neuroscience Functional Brain Connectivity Functional Brain Connectivity

Before Before

rTMS rTMS to M1; to M1; subthreshold subthreshold intensity; 1600 stimuli intensity; 1600 stimuli

After After Sham Sham rTMS rTMS 1 Hz 1 Hz rTMS rTMS 10 Hz 10 Hz rTMS rTMS

Adaptation and Reaction Adaptation and Reaction Not Lesion but Compensation Not Lesion but Compensation

Mottaghy Mottaghy et al. et al. Neurosci Neurosci Lett Lett 2000 2000

70 75 80 85 90 % correc Condition 2back 2back+F3rTM 2back+F4rTMS 2back+FzrTMS

Significant decreases during Significant decreases during Left Left

• r
• r Right

Right DLPFC rTMS DLPFC rTMS

EFFECTS OF TMS REFLECT EFFECTS OF TMS REFLECT THE CAPACITY OF THE THE CAPACITY OF THE REST OF THE BRAIN TO REST OF THE BRAIN TO SUSTAIN BEHAVIOR SUSTAIN BEHAVIOR

Potential Adverse Effects Potential Adverse Effects

• Seizure induction

Seizure induction

• Effects on Cognition

Effects on Cognition

• Effects on Mood

Effects on Mood

• Endocrine effects

Endocrine effects

• Transient auditory threshold

Transient auditory threshold shift shift

• Local pain and headache

Local pain and headache

• Burns from scalp electrodes

Burns from scalp electrodes

Safety Guidelines Safety Guidelines Monitoring Monitoring

• Study cortical excitability

Study cortical excitability

– – Single Pulse Single Pulse – – Paired Pulse Paired Pulse

• Study brain

Study brain-

• behavior relation

behavior relation

– – Causality Causality – – Chronometry Chronometry – – Functional Connectivity Functional Connectivity

• Lasting modulation

Lasting modulation

• f excitability
• f excitability

– – Therapeutic application Therapeutic application

TMS: Study and Modulate TMS: Study and Modulate Cortical Excitability Cortical Excitability

Spinal root Stimulation (b) Ulnar nerve Stimulation (c) MEP from FDI

10 ms 1 mV 0.1 mV 1 mV

TMS (a) (a) (b) (c)

T1 T2 M F

Central Conduction Time Central Conduction Time

Erb Wrist 1 2 3 4 Erb Wrist Brain Erb Wrist Brain Erb’s stim. Erb’s stim. Wrist stim. Wrist stim. Wrist stim. Brain stim. Brain stim. TST control curve TST test curve (normal) TST test curve (corticospinal tract lesion) 1 2 3 4 1 2 3 4

1 2 3 4 1 2 3 4

Erb’s stim.

1 2 3 4

Erb’s stim. * * * Muscle

Triple Triple Stimulation Stimulation Technique Technique Magistris Magistris

Percentage of control size

• 5

10 15 20 100 200 300 400

Interstimulus interval (ms)

1

Conditioning TMS

2

Test TMS 0.5 mV 25 ms

Control 2ms 12ms

Paired Paired-

• pulse TMS

pulse TMS

• ••• •
• 5

10 15 20 20 40 60 80 100 120

Percentage of control size Interstimulus interval (ms)

1 Conditioning TMS 2 Test TMS Control 8 ms

0.5 mV 25 ms

Paired Paired-

• pulse TMS

pulse TMS

Creating Virtual Patients Creating Virtual Patients

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Visual cortex activation in the blind

Causality: Causality: Striate Cortex for Striate Cortex for Tactile Braille Reading in Blind Tactile Braille Reading in Blind

Sadato Sadato et al. et al. Nature 1996 Nature 1996

0.05 0.1 0.15 0.2 0.25 0.3

Error rate

Early Blind Sighted Control S1 V1

Cohen et al. Cohen et al. Nature 1997 Nature 1997

Visual cortex activation in the blind

Visual cortex activation in the blind

Therapeutic Applications of Therapeutic Applications of rTMS rTMS

• Depression

Depression

• Acute Mania

Acute Mania

• Bipolar Disorder

Bipolar Disorder

• OCD

OCD

• PTSD

PTSD

• Schizophrenia

Schizophrenia

• Auditory

Auditory Hallucinoses Hallucinoses

• Pain

Pain

– – Visceral pain Visceral pain – – Atypical facial pain Atypical facial pain – – Phantom pain Phantom pain

• PD

PD

• Focal

Focal dystonia dystonia

• Epilepsy

Epilepsy

– – Myoclonic Myoclonic epilepsy epilepsy – – Focal status Focal status epilepticus epilepticus

• Stuttering

Stuttering

• Tics

Tics

• Neurorehabilitation

Neurorehabilitation

– – Neglect Neglect – – Aphasia Aphasia – – Hand weakness Hand weakness

Mesmer Mesmer Barker Barker Double-blind, sham stimulation (placebo) controlled trials