Y P O C T O N TMS physics: Quantitative aspects of O - PDF document

Y P O C T O N TMS physics: Quantitative aspects of O targeting and dosing Intensive Course in Transcranial Magnetic Stimulation Oct 26, 2015 D Berenson-Allen Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center E S Aapo Nummenmaa, PhD A TMS core director E Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston L P

Y P O C T O N O Introduction D E S A E L P

Y P O The TMS Setup C Operator Subject T Stimulator O Coil Creates large N currents. Creates magnetic and O electric fields. D E Electrodes S EMG records A muscle activity. E L From Barker et al. 1991 Journal of Clinical Neurophysiology P

Y P O TMS variables: Recap C Variables that depend on “coil settings”: T � Coil type (circular, figure-of-eight, other) O � Coil location N � Coil orientation and tilt O Variables that depend on “stimulator settings”: D � Pulse waveform (monophasic, biphasic) � Sequence (single, double, rTMS, patterned) E � Pulse direction (clockwise/counter; forward/backward) S � Intensity and dose A E Subject (variability across individuals, subject state) L P

Y P O Concepts of TMS quantification C � How to stimulate a desired brain location? T � This is called “targeting”. O � How to stimulate with a desired strength? N � This called “dosing”. O � Depends on pulse strength, stimulus pattern, duration etc. � Computational methods exist for quantifying spatial D pattern and amplitude of the TMS stimuli. E � This is the main topic of this talk. S � The effect of stimulus pattern (rTMS, theta burst) and A duration is more challenging to model. E � TMS+imaging is typically needed for quantification. L P

Y P O Introductory example to targeting & dosing C � Let us assume that you have selected a position and T orientation for your TMS coil. O � Question: How strongly will you stimulate at different N locations in the brain “X”? O D ? ? ? ? E S A E L P

Y P Computational modeling approach to O targeting and dosing C � The electric field distribution can be estimated using T computational methods presented in detail later. O � It looks like the maximum field intensity is just under coil. N � What is the value added in a more quantitative approach? O Simulated double coil Maximum E-field = 68 V/m D E S c current A E L P

Y P O Effect of coil location on TMS strength C � Let’s assume that stimulator output intensity is fixed. T � Then, we move the coil between two locations. O � Coil orientation is fixed Anterior-Posterior. N � Question: Is the E-field intensity the same in the brain? O D E S Move coil A E L P

Y P Effect of coil location on TMS strength O (cont.) C Location #1 Location #2 T O Max(E)= Max(E)= N 59 V/m 68 V/m O D E S A E � The difference in E-field amplitude is over 10%. L � Is 100% Motor Threshold (MT) same as 110% MT? P

Y P O Effect of coil orientation: Rotation C � Let us assume that the coil is rotated 90 degrees T while keeping the location fixed: O N Max(E)=60 V/m Max(E)=59 V/m O D E S A E L The amplitude remains same but shape and direction change! P

Y P O Effect of coil orientation: Tilt C � Assume location is fixed but coil is tilted in the left- T right direction by 20 degrees. O N O D E Tilt coil S A E L P

Y P O Effect of coil orientation: Tilt C Case#1: NO TILT Case#2: WITH TILT T O Max(E)=69 V/m Max(E)=74 V/m N O D E S A E � Tilting the coil changes the maximum amplitude and mplitude and L the shape of the electric field as well! P

Y P O Introductory example conclusions C The shape and strength of the TMS T electric field pattern in the brain O varies when the coil is moved -> Even if the stimulator output N intensity is fixed! O The E-field distribution depends on: D -coil POSITION and ORIENTATION -coil GEOMETRY E -DISTANCE to the brain location S -CONDUCTIVITIES of tissue compartments A -SHAPES of tissue compartments E L P

Y P O C T O N O TMS physics background D E S A E L P

Y P O Electromagnetic fields and forces C Magnetic force on a charge Electric force on a charge +q T F E = q E F M = q v × B O N F M O E [Volt/meter] B [Tesla] D +q Velocity +q F E E v S • E-field is parallel to the • B-field is perpendicular to A force. the force. E • E will accelerate charge • B will only turn the direction L if initially at rest! of a moving charge! P

Y P O Static charges generate static E-fields C Earth surface has an Voltage source electric field of 100 V/m! T O N OUT IN O D E E S A E L How large are TMS E-fields? Conducting plates P Should we feel more stimulated?

Y P O The Earth’s electric field around you C The human body is a relatively good conductor -> T you tend to make an isopotential surface (also with ground). O N O D E S A E L From “ Feynman Lectures on Physics, Vol. 2” P

Y P O Stimulation with static E-field? C In a static case, the E-field What about tDCS then? inside a perfect conductor is T zero. O N IN OUT OUT IN O D E S A • Physical contact between • Human head is a relatively head and electrodes needed! E good conductor. • The potential at the contacts • External static E-fields do not L is forced to be different! P penetrate to brain (much)!

Y P O Static currents generate static B-fields C Does static B-field stimulate the brain? DC source: T O N OUT IN O D E Wire S loop A E A 3T scanner at MGH Martinos Center B L Currents flow in superconducting medium! P (3 Tesla >10 5 times earth’s B-field)

Y P O Time-varying B-fields create E-fields! C Case 1: current constant & coil moves Case 2: current changes & coil fixed T O CHANGE OUT IN M N OU OU OUT IN N N O O V D E E S A E Current meter L Time-varying B-field induces E-field that drives current in the loop! P

Y P O Volume conductors C � To get charges going, we must have a current source. T � What happens if a battery gets into a glass of salt water? O � Ionic currents in the water flow to “close the circuit”. N O EEG D E Primary c current S A E V Volume L currents P

Y P O Ohm’s law C The volume currents are Battery in a glass: determined by Ohm’s law: T J = σ E O N “ J ” is current density [Ampere / m 2 ] “ σ “ is conductivity [Siemens / m] O “ E ” is the electric field [Volt / m] D Values of conductivity “ σ ” at E temperature of 20 � : S Conductivity “ σ “ is zero Copper: 5.96 × 10 7 S/m A outside the glass -> Current Sea water: 4.8 S/m must be zero too! E Air: 3 × 10 − 15 to 8 × 10 − 15 S/m L This sets boundary conditions (From Wikipedia) P for E-field created by the battery.

Y P O Conductivity boundaries: Simple example C T O N O D E S A Haus, Hermann A., and James R. Melcher, Electromagnetic Fields and E Energy. (Massachusetts Institute of Technology: MIT OpenCourseWare). L http://ocw.mit.edu (accessed Monday, July 16, 2012 4:56 PM). License: Creative Commons Attribution-NonCommercial-Share Alike. P

Y P Conductivity boundaries: Simple example O (cont) C In the quasi-static (low-frequency) approximation: T Electric current density must be continuous across O boundary. σ a > σ b N σ a < σ b O D σ b E S A σ a E L The conductive object alters the path of the current! P

Y P Conductivity boundaries: Simple example O (cont) C Tangential component of E-field is continuous across boundary. T Normal component of E-field is in general discontinuous! O σ a >> σ b σ a << σ b N O D E S A E E-field HIGHER inside region R inside re Charge accumulation at boundary L of LOWER conductivity! creates secondary E-fields. P

Y P O C T O N O The effects of a TMS pulse: D Physics and physiology E S A E L P

Y P Current sources and volume conductors in O TMS C T The stimulator and the coil O OUT IN are the current source. N O The subject’s head is the volume D conductor. E S Since the TMS E-field is created by eated by A induction, contactless operation E possible! L P

Y P O Pulse waveforms C � Monophasic � Bi-phasic T Large effect on neuronal membrane potentials! O N O D E S Note: the E-field ~ dB/dt A -> never fully “mono-phasic” E L From Wassermann, Eric M. et al, Oxford Handbook of Transcranial Stimulation, 1st Edition P

Y P O Bi-phasic TMS pulse: A closer look C T O N O D E S � Peak current amplitude ~ kA (kiloAmpere) A � Peak magnetic field ~ T (Tesla) E � Electric field strength in brain ~ 100 V/m (Volts/meter) L � Pulse frequency ~ kHz (kiloHertz) P

Y P O Basic TMS coils C Circular / Single Figure-of-eight / Double T (diffuse stimulation) (focal stimulation) O N O D E S A E L P