Transcranial Magnetic

Stimulation + EEG: Brain-based

biomarker detector, or sham?
Raaj Chatterjee – NEUR 800
Master’s Candidate at eBrain Lab SFU
Transcranial Magnetic Stimulation (TMS):
Induced Magnetic Field

TMS also generates:

- Loud “click” noise
- Somatosensory stimulation
of peripheral nerves

Figure 1. Induced currents in brain following TMS [1]

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 How to build a TMS Circuit

Switch 1
Current

+ +
Dis-
3000
- charge-
Volts!

Switch 2

Figure 1. Basic TMS circuit diagram [1]

Figure 2. TMS Current waveforms [1]

 Cellular Activation from TMS - Modeling
• Cellular mechanisms of TMS are not well understood!
• TMS in motor cortex is hypothesized to activate L2,L3,L5 pyramidal neurons in gyrus.
• Excitable areas depend strongly on coil orientation.
• This study posits that neuronal activation starts in the initial segment of axon (iseg)

Figure 1: Model of layer 5 cortical pyramidal cell, Figure 2: Model of Layer 3 cortical pyramidal cell,
Seo et. al, 2016, F1000 Research [2] Seo et. al, 2016, F1000 Research [2] 4
 Cellular Activation from TMS - Modeling
In contrast, this study says TMS activates the axon terminals.
The authors do not agree with the modeling approach in previous study shown.

Gyral Crown

Figure 1: TMS activates axonal terminations aligned to local Electric field in the crown of gyri [3],
Aberra et. al, 2019, Brain Stimulation 5
 Cellular Activation from TMS – Parietal
Single Neuron Recording in Macaque
Monkey• TMS is more focal than predicted in
models by an order of magnitude,
can change firing rate of neurons
within 4mm2
• Magnitude of stimulation and
orientation of coil changes
underlying activity (AP or PA)
• TMS may induce low frequency
oscillatory activity in spiking neurons
and neighbors
Figure 1. Excitatory vs. Inhibitory activity in neurons
Romero et. al, Nature Communications, 2019
• TMS influences a wide variety of cell
types and generates a response by
40ms and lasting 100ms post stim. 6
What is TMS-EEG?
• Transcranial Magnetic Stimulation + Electroencephalography
• Measures sum of neuronal activity
immediately after TMS pulse
• We can average the signal over many trials
to get transcranial evoked potentials (TEPs)
• We can measure functional connectivity
between electrodes in frequencies 1-50 Hz
TMS+EEG
• Features extracted from TMS-EEG signals
have good individual repeatability

Figure 1. TEPs from Prefrontal Cortex stimulation [1]

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The Problem: Variability of treatment
outcomes between individuals
• Treatment-resistant depression:
• ~60% of people do not respond to initial antidepressant treatments
• ~30% do not respond after subsequent treatments [5]
• Alternative Treatments:
• Transcranial magnetic stimulation (TMS) to dorsolateral prefrontal cortex
• Electro-convulsive therapy
• Cognitive behavioral therapy
• Trial-and-error approach is the status-quo
• What if we could measure the state of the brain to help diagnose the
condition and predict the response to a certain treatment?

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Using TMS-EEG features to map behavior and
evaluate interventions

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Figure 1. Schematic of translational value of TMS-EEG [6], Farzan et. al., 2016, Front. Neural Circuits
Controversy: Sham and Active TEPs may be
similar

TMS sham condition: Electrical

stimulation on scalp, loud click noise,
no transcranial stimulation
Conde et al. 2018 [7]
Criticism of Paper on Left, saying they did not
use appropriate stimulation parameters.
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Belardinelli et al. 2019 [8]
Where do we go from here?
• How much of TMS is truly transcranial? And how much of its effects can
we resolve with EEG?
• EEG suffers from volume conduction and source mixing
• Intracranial EEG with better temporal resolution (1-200 Hz) and source
localization may be a good approach to understand which TEPs are
coming from Auditory, Somatosensory, and Transcranial sources.

Left, EEG Volume conduction

Right, Electrocorticography

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References
1. Course Notes, MSE 491. Prepared by Dr. Faranak Farzan
2. Seo, Hyeon et al. “A multi-scale computational model of the effects of TMS on motor cortex.” F1000Research vol. 5 1945.
10 Aug. 2016, doi:10.12688/f1000research.9277.3
3. Simulation of transcranial magnetic stimulation in head model with morphologically-realistic cortical neuronsAberra, Aman
S. et al.Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, Volume 0, Issue 0
4. Romero, M.C., Davare, M., Armendariz, M. et al. Neural effects of transcranial magnetic stimulation at the single-cell level.
Nat Commun 10, 2642 (2019) doi:10.1038/s41467-019-10638-7
5. M. Fava, “Diagnosis and definition of treatment-resistant depression.,” Biol. Psychiatry, vol. 53, no. 8, pp. 649–659, Apr.
2003.
6. Farzan, Faranak et al. “Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined
with Electroencephalography.” Frontiers in neural circuits vol. 10 73. 22 Sep. 2016, doi:10.3389/fncir.2016.00073
7. Virginia Conde, Leo Tomasevic, Irina Akopian, Konrad Stanek, Guilherme B. Saturnino, Axel Thielscher, Til Ole Bergmann,
Hartwig Roman Siebner,The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies,
NeuroImage, Volume 185, 2019
8. Reproducibility in TMS–EEG studies: A call for data sharing, standard procedures and effective experimental control
Belardinelli, PaoloBiabani, ManaBlumberger, Daniel M.Bortoletto, MartaCasarotto, SilviaDavid, OlivierDesideri, DeboraEtkin,
AmitFerrarelli, FabioFitzgerald, Paul B.Fornito, AlexGordon, Pedro C.Gosseries, OliviaHarquel, SylvainJulkunen, PetroKeller,
Corey J.Kimiskidis, Vasilios K.Lioumis, PantelisMiniussi, CarloRosanova, MarioRossi, SimoneSarasso, SimoneWu, WeiZrenner,
ChristophDaskalakis, Zafiris J.Rogasch, Nigel C.Massimini, MarcelloZiemann, UlfIlmoniemi, Risto J. et al.
Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, Volume 12, Issue 3, 787 - 790 12
Thank you, any questions?
Raaj Chatterjee – NEUR 800
 TMS-iEEG Types of
Artifacts
Decay
• Ringing artifact from filtering
(present in active and sham) Ringing

• Decay artifact
(some active channels only)
• Motion, Step artifacts
Parietal stimulation Macaque Monkey
 Decay Artifact Investigation
Type of electrode, grid, depth, or surface?

Stimulation
Site

Strength of
Ventral artifact (uV)
Surface Depth

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