tCS and EEG

1

Faranak Farzan, PhD

Assistant Professor, Simon Fraser University

Chair in Technology Innovations for Youth Addiction Recovery and Mental Health

Email: ffarzan@sfu.ca

Why & How

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Guess Game: Maximum Voltage a Torpedo Fish Can Generate?

http://www.painbytes.com/images/History/Electroanalgesia/EAFig.png

8 to 220 volts

Where Did It All Begin?

46 AD

Torpedo Fish

3

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Galvanism

Charles Le Roy

Treating blind with

electricity

1755

Luigi Galvani

Late 18th century

founder of

bioelectromagnetics

famous for his animal

experiments

46 AD Late 1700s

Galvani

Le Roy

4

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Aldini’s Showmanship

DC current stimulation mostly ignored in scientific community

Giovanni Aldini

1804: First report of electricity for

treating psychosis and melancholia

46 AD Late 1700s

Galvani

Le Roy

Galvanism

5

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6

1934

ECT

1980

TES

1985

TMS

2000

tDCS

46 AD Late 1700s

Galvani

Le Roy

1800s

Faraday

D’Arsonval

1900s

Thompson

Kolin

1982

Anthony Barker

Reza Jalinous

Ian Freeston

MST

2000

Today…

2008

tACs

Nitsche

Paulus

Antal

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tCS Application

• Basic & Cognitive Neuroscience

• Intervene with a function to examine causality

• Clinical Application• Depression

• Pain

• Addiction

• ADHD Do Not

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Mechanism of Action?

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tCS Outcome?

20 ms

1 m

V

Latency

Peak-to-Peak

AmplitudeMotor Evoked

Potentials

Nitsche & Paulus, 2000: Changes in cortical excitability in humans demonstrated using TMS Motor-Evoked Potentials (MEP)s as a metric

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tCS Outcome?Nitsche et al, 2003: After 5 or 7 minutes of stimulation MEP amplitudes

return to baseline within a few minutes. After 9 minutes, effects last for at least 60 minutes.

20 ms

1 m

V

Latency

Peak-to-Peak

AmplitudeMotor Evoked

Potentials

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Kuo et al, 2012: 4x1 ring tDCS stimulates a

smaller area, but the

resulting change in cortical

excitability is dramatically

different

20 ms

1 m

V

Latency

Peak-to-Peak

AmplitudeMotor Evoked

Potentials

tCS Outcome?

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tCS Outcome Depends on Many Factors

• Stimulation Parameters

• Duration of stimulation

• Number of electrodes

• Electrode size and shape

• Electrode positions

• Current intensity

• Brain State Do Not

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Bergmann et al., 2016

Where, When and How Matters …

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We know relatively little about the neurophysiologicalmechanisms in humans; little we know about local effect, andmuch less about the network effect; Difficulty tailoring itsparameters for desired impact.

Brain Recording to Rescue?

tCS-Induced Outcomes?

20 ms

1 m

V

Latency

Peak-to-Peak

AmplitudeMotor Evoked

Potentials

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Brain Recording? EEG, fMR, PET, DTI, …

EPSP + IPSP generated bysynchronous activity ofneurons. Interplay betweenexcitatory pyramidal neuronsand inhibitory interneurons.

http://www.nature.com/scitable/content/ion-channels-14615258

A change in membranepotential, release ofneurotransmitters, change inconcentration of ions channelsmay change the state ofmembrane channels and giverise to an oscillatory activity.

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Added Value of tCS+EEG

1- Detailed understanding of the tCS-induced effect on neural activityo To not fall for the “circular experimental results/conclusions”o Examine both local and network effects in humans, non-invasively

2- Monitor brain stateo Brain state influences the tCS effecto Improve tCS protocols considering brain state dynamicso By monitoring dynamical state, design closed-loop systems

3- Guide the tCS input parameters o An infinite number of stimulation parameters to choose fromo Guide the Location, Stimulation Parameters, Time of Delivery

EEG may tell us about: Excitability of cortical tissue; excitation/inhibition balance; brain state; the integrity of local

and distributed networks.

More efficacious treatmentsBetter understanding of brain-behavior relationship

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TCS + EEG

Retrieved from: http://3.bp.blogspot.com/_-sFohRgxOBI/RiH4NDo37zI/AAAAAAAAAG8/ZwS5CBfB3qI/

s320/Married+couple+fighting.jpg

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System Diagram for Designing tCS+EEG Studies

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tCS+EEG Approaches

• Offline

• Online

• EEG-Guided (Online or Offline)

Record EEG(Rest/+Event)

Stop EEGApply tCS

Stop tCSRecord EEG

(Rest/+Event)

Record EEG(Rest/+Event)

Record EEG&

Apply tCS

Stop tCSRecord EEG

(Rest/+Event)

Record EEG(Rest/+Event)

Apply tCSguided by

EEG

Stop tCSRecord EEG

(Rest/+Event)

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EEG Signal Processing

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EEG: History

EEG in humans introduced by Hans Berger in 1920s

Berger’s Waves

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EEG: Language

Alpha (8-12Hz)

Delta (1-3Hz)

Theta (4-7Hz)

Beta (12-28Hz)

Gamma (30Hz+)

F

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EEG language

Amplitude (or Power)

Frequency

Phase

# of Cycles/Second (Hz)

Strength

(µV or µV2)

10Hz

20Hz

π0

(Radians)

F

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Time vs. Frequency Domain

F

Frequency Domain

imag

realPhase

Xi (f)

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When/How to Record EEG?

• Anesthesia, • Sleep• Resting (eyes open/closed)

• Sensory, motor, cognitive processing

Continuous Recording (No Event)

Trial 1

Trial 2

Trial 100

Event/Stimulus

Time: Event Related Potential or Evoked potentialsFrequency: Event Related Spectral Perturbation

Phase

Relative to An Event/Stimulation

• Electrical stimulation

F

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EEG Features

(2) Connectivity

(1) Local

Response

12

3

1 2 3

Θ

(3) Global Dynamic

Adapted from Khanna A, Pascual-

Leone A, Farzan F, 2014

Adapted from Shafi et al., 2012

26

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System Diagram for Designing tCS+EEG Studies

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tCS Outcomes: Local Effects

Continuous EEG Recording (No Event)

Jacobson et al., 2012Montage: Anodal rIFG, cathodal lOFC tDCsResting EEG: Selective decrease of theta band

Zaehle., 2012 (EEG-guided)Montage: Posterior tACs at individual alpha oscillationsResting EEG: Increase in alpha in parieto-central electrodes

Change in PowerP

ow

er

Frequency (Hz)

10 20 30 40 50

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EEG + Event

50 ms

20

µV

Change in ERP

Change in ERSP or ERD/ERS

Keeser et al., 2011 • Montage: Anodal tDCS on LDLPFC, cathode on contralateral supraorbital region • EEG Rest: Reduced left frontal delta, source analysis localized this to ACC and orbitofrontal regions• EEG+ Working Memory: Increased P2 and P3 ERP amplitudes• Performance: Reduced error rates in working memory

tCS Outcomes: Local Effects

Matsumoto et al., 2010• Montage: Anodal/cathodal tDCS on MC• EEG+ Motor Imagery: Mu rhythms ERD increased after anodal tDCS

Zaehle., 2011• Montage: anodal or cathodal left DLPFC tDCS• EEG+ Working Memory: Enhanced performance and amplified oscillatory power in the theta and alpha bands after anodal tDCS

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tCS Outcomes: Network Effects

Polania et al, Human Brain Mapping 2011• M1 anodal + contralateral frontopolar cathodal stimulation

• shifted brain network connectivity at rest and especially during task performance

Sham (before vs after)Sham vs active

Real (before vs after)

Gamma during voluntary hand movementDo N

ot Cop

y

tCS Outcomes: Network Effects

Polania et al, Human Brain Mapping 2011• M1 anodal + contralateral frontopolar cathodal stimulation shifted brain

network connectivity at rest and especially during task performance

Beta

Pre

Post

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50 ms

20 µ

V

5 ms

20 µ

V

20 ms

1

mV

Cortical

Evoked

Potentials

Descending

Volleys

Motor Evoked

Potentials

I1 I4D

P30

N100

Latency

Peak-to-Peak

Amplitude

TMS Pulse

Magnetic

Field

32

TMS-EEG

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Inhibition, Connectivity, Plasticity, …

Farzan et al., 2013, NeuroImage

Neural inhibition

Neural inhibition

Motor DLPF

C

Farzan et al., 2009, Neuropsychopharmacology

Voineskos*, Farzan *et al., 2010. Biological Psychiatry

Interhemispheric connectivity

Inhibition mediated modulation

of oscillations

Daskalakis, Farzan et al., 2008, Neuropsychopharmacology

M1 DLPFCMarkersLICIMC

LICIDLPFC

MarkersISPMC

ISPDLPFC

MarkersLICIMCδ

,LICIDLPFCδLICIMCΘ

,LICIDLPFCΘLICIMCα

,LICIDLPFCαLICIMCβ

,LICIDLPFCβLICIMC

,LICIDLPFC

MarkersTEPAmp

TEPDur

TEPPeaks

TEPPower

GMFAAMP

GMFADur

GMFAPeaks

GMFAPower33

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34Farzan F et al., Frontiers in Neural Circuits , 2016

TMS-EEG in extracting Markers of Health

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tCS Outcomes: TMS-EEG

Bai, 2017

Differential changes in tDCS-induced

cortical excitability in MCS and VS.

50 ms

20 µ

V

Cortical

Evoked

Potentials

P30

N100

Magnetic

Field

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tCS Outcomes: TMS-EEG

Hill, 2017

HD tDCS induced changes in P60.

50 ms

20 µ

V

Cortical

Evoked

Potentials

P30

N100

Magnetic

Field

P60

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Designing tCS+EEG StudiesEEG to Guide

Stimulation

Parameters

When/Where/How Do Not

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EEG-Guided Input Location

Faria 2012EEG evaluation of a patient

with continuous spike-wave

discharges during slow-wave

sleep allowed identification of

a spike focus.

Cathodal tDCS over the spike

focus resulted in a significant

decrease in interictal spikes

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EEG-Guided Frequency of tACs

Zaehle., 2012Montage: Posterior tACs at individual alpha oscillationsResting EEG: Increase in alpha in parieto-central electrodes

EEG-Guided

Po

we

r

Frequency (Hz)

10 20 30 40 50

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EEG-Guided Input Time

Polania et al., 2012 Protocol: 6Hz tACs at 0 or 180 phase difference to frontal and parietal regions during taskResult: Exogenously induced fronto-parietal theta synchronization (0 degrees) significantly improved visual memory-matching reaction times. Desyncronization (180 degree) deteriorated performance. Brain-Behavior Relationship: Evidence of causality of theta phase-coupling of distant cortical areas for cognitive performance in healthy humans

Fronto-Parietal Theta-Phase coupling during a delayed letter discrimination task

F3

P3

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Cancelli et al, 2016Simple ad hoc approaches achieved reasonable targeting for the case of a cortical

dipole. Only 2–8 electrodes and no need for a model of the head

Verified directly only for a theoretically localized source, but may be

potentially applied to an arbitrary EEG topography. Can be applied to static (tDCS),

time-variant (e.g., tACS, tRNS, tPCS), or closed-loop tES

EEG-Guided tCS

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EEG-Guided tCS

Dmochowski, 2017

Optimal use of EEG for targeting tCS (e.g., determine montage)

without making assumptions about the underlying source

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Designing tCS+EEG Studies

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Closed-Loop Studies in Animal

Berenyi et al, 2012: In a rodent model of generalized epilepsy, detection of

interictal spikes triggers TES, and aborts the spike-wave discharge bursts

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Technical Issues

Challenges:

o Placement of EEG and tCS Electrodes

o Current may be shunted through EEG electrodes

o Stimulation artifact

• tDCS: A DC drift and maybe rhythmic frequencies

• tACs: Rhythmic frequencies that coincide with the frequency of cortical oscillations

Record EEG(Rest/+Event)

Stop EEGApply tES Stop tES

Record EEG (Rest/+Event)Record EEG

&Apply tES

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Previous Online Studies

tDCS:• Same kind of sintered AgCl electrodes for DC stimulation as for EEG recording• Current delivered through Phoresor 850 current source• 3 Anodes (Fp1, FpZ, FP1 electrodes shorted)• 1 Cathode (CP5 electrodes)

F

Faria et al., 2012

EEG: • 24 Electrodes • Ground and reference electrodes placed contralateral to the stimulation site on the mastoid area

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Online Studies

Record EEGRecord EEG

&Apply tCS

Faria et al., 2012

Artifact correction can significantly remove the noise

Artifact Correction• Software package developed for removing gradient artifacts in the MRI environment• Independent component analysis (ICA)

Artifact• High frequency artifact in the neighborhood of cathode • Small AC component with a 12Hz multiple• period characteristics of the Phoresor 850

functioning

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Sehm et al., 2013

Online Studies

• SEPs were recorded in the bore of the tDCS ring electrode. • no tDCS-induced artifacts could be observed after the application of a standard EEG filter.

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Online Studies

Sehm et al., 2013Noisy and Filtered Sensory Evoked Potentials

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online studies

Witkowski, 2016: tACs + MEG

- Amplitude-modulated tACs using a carrier frequency well beyond the frequencies of

interest (e.g. 220 Hz) and modulates the amplitude of the carrier frequency at the

frequency of interest (e.g., 23 Hz).

- Amplitude-modulated high-frequency tACs may enable the artefact-free assessment of the lower frequency of interest

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TMS-EEG Signal Processing

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http://fc01.deviantart.net/fs70/f/2012/015/a/7/an

gry_eye_by_sawsa-d4meu5q.jpg

http://sci-ence.org/wp-content/uploads/2011/07/Sensory-

Homunculus1.jpg

Problems Solutions

AmplifierSaturation

• Pin-and-Hold• High Sensitivity, Operational

Range • DC-Coupling, High Sampling

Rate

Electrode Heating• Small Pellet Electrodes

• Plastic interface

Eddy Current • Sensor placement

Capacitor Recharge

• Proper Setting in Biphasic

Movement • Sensor-wire Arrangement

Capacitance Built up, Slow Decay

• Algorithmically

Auditory Evoked Potentials

• Ear plugs, • Play Noise

• Sham•Algorithmically**

Blinks •Algorithmically**

Muscle • Algorithmically

SEP • Subthreshold Control

Somatosensory • Spatial topographies http://www.staceyreid.com/news/wp-

content/uploads/2011/09/Muscles.png52

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Matthew Frehlich

Masters of

Engineering

University of

Toronto

Sravya Atluri

PhD

Biomedical

Engineering

University of

Toronto

TMS-EEG Software Development

Frank Mei

Postdoc

Electrical

Engineering

Luis G. Dominguez

Postdoc

Physics53

Atluri et al., 2016, Frontiers in Neural

Circuits

Nigel Rogasch, PhD

Monash University, Australia

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TMS-EEG Software TMSEEG App

Matthew Frehlich

Masters of Engineering

University of Toronto

Sravya Atluri

PhD

Biomedical

Engineering

University of

TorontoFrank Mei

Postdoc

Electrical

Engineering

Luis G. Dominguez

Postdoc

Physics54

Atluri et al., 2016, Frontiers in Neural

Circuits

Nigel Rogasch, PhD

School of Psychological Sciences

and Monash Biomedical Imaging

Monash University, Australia

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TCS + EEG

Retrieved from: http://3.bp.blogspot.com/_-sFohRgxOBI/RiH4NDo37zI/AAAAAAAAAG8/ZwS5CBfB3qI/

s320/Married+couple+fighting.jpg

RECAP

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Added Value of tCS+EEG

1- Detailed understanding of the tCS-induced effect on neural activityo To not fall for the “circular experimental results/conclusions”o Examine both local and network effects in humans, non-invasively

2- Monitor brain stateo Brain state influences the tCS effecto Improve tCS protocols considering brain state dynamicso By monitoring dynamical state, design closed-loop systems

3- Guide the tCS input parameters o An infinite number of stimulation parameters to choose fromo Guide the Location, Stimulation Parameters, Time of Delivery

EEG may tell us about: Excitability of cortical tissue; excitation/inhibition balance; brain state; the integrity of local

and distributed networks.

More efficacious treatmentsBetter understanding of brain-behavior relationship

Do Not

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Summary

• EEG Added Value

• Different Approaches (Online, Offline, Guided)

• Online Approach is Becoming Possible (Easier for tDCS than tACS)

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