tCS and EEG Faranak Farzan, PhD Assistant Professor, Simon Fraser - - PowerPoint PPT Presentation

tCS and EEG

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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

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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

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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

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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

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Mechanism of Action?

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tCS Outcome?

20 ms 1 mV Latency Peak-to-Peak Amplitude

Motor 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 mV Latency Peak-to-Peak Amplitude

Motor 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 mV Latency Peak-to-Peak Amplitude

Motor 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

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Bergmann et al., 2016

Where, When and How Matters …

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We know relatively little about the neurophysiological mechanisms in humans; little we know about local effect, and much less about the network effect; Difficulty tailoring its parameters for desired impact.

Brain Recording to Rescue? tCS-Induced Outcomes?

20 ms 1 mV Latency Peak-to-Peak Amplitude

Motor Evoked Potentials

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Brain Recording?

EEG, fMR, PET, DTI, … EPSP + IPSP generated by synchronous activity

• f

neurons. Interplay between excitatory pyramidal neurons and inhibitory interneurons.

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

A change in membrane potential, release

• f

neurotransmitters, change in concentration of ions channels may change the state

• f

membrane channels and give rise to an oscillatory activity.

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Added Value of tCS+EEG

1- Detailed understanding of the tCS-induced effect on neural activity

• To not fall for the “circular experimental results/conclusions”
• Examine both local and network effects in humans, non-invasively

2- Monitor brain state

• Brain state influences the tCS effect
• Improve tCS protocols considering brain state dynamics
• By monitoring dynamical state, design closed-loop systems

3- Guide the tCS input parameters

• An infinite number of stimulation parameters to choose from
• 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 treatments Better 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 EEG Apply tCS Stop tCS Record EEG (Rest/+Event) Record EEG (Rest/+Event) Record EEG & Apply tCS Stop tCS Record EEG (Rest/+Event) Record EEG (Rest/+Event) Apply tCS guided by EEG Stop tCS Record 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+)

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EEG language

Amplitude (or Power) Frequency Phase # of Cycles/Second (Hz) Strength (µV or µV2) 10Hz 20Hz π (Radians)

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Time vs. Frequency Domain

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Frequency Domain

imag real

Phase

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 potentials Frequency: Event Related Spectral Perturbation Phase

Relative to An Event/Stimulation

• Electrical stimulation

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EEG Features

(2) Connectivity (1) Local Response

1 2 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., 2012

Montage: Anodal rIFG, cathodal lOFC tDCs Resting EEG: Selective decrease of theta band

Zaehle., 2012 (EEG-guided)

Montage: Posterior tACs at individual alpha oscillations Resting EEG: Increase in alpha in parieto-central electrodes

Change in Power

Power

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
• n 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 movement

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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

Beta Pre Post

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50 ms 20 µV 5 ms 20 µV 20 ms 1 mV

Cortical Evoked Potentials Descending Volleys Motor Evoked Potentials

I1 I4

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P30 N100

Latency Peak-to-Peak Amplitude

TMS Pulse

Magnetic Field

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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

• f oscillations

Daskalakis, Farzan et al., 2008, Neuropsychopharmacology

M1 DLPFC

Markers LICIMC LICIDLPFC Markers ISPMC ISPDLPFC Markers LICIMCδ,LICIDLPFCδ LICIMCΘ,LICIDLPFCΘ LICIMCα,LICIDLPFCα LICIMCβ,LICIDLPFCβ LICIMC,LICIDLPFC  Markers TEPAmp TEPDur TEPPeaks TEPPower GMFAAMP GMFADur GMFAPeaks GMFAPower

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Farzan 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 µV

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 µV

Cortical Evoked Potentials

P30 N100

Magnetic Field

P60

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Designing tCS+EEG Studies

EEG to Guide Stimulation Parameters When/Where/How

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EEG-Guided Input Location

Faria 2012

EEG 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., 2012

Montage: Posterior tACs at individual alpha oscillations Resting EEG: Increase in alpha in parieto-central electrodes EEG-Guided

Power

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 task Result: 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, 2016

Simple 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:

• Placement of EEG and tCS Electrodes
• Current may be shunted through EEG electrodes
• 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 EEG Apply 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)

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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 EEG Record 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., 2013 Noisy and Filtered Sensory Evoked Potentials

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• nline 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 Amplifier Saturation

• 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.png

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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 Physics

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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 Toronto Frank Mei Postdoc Electrical Engineering Luis G. Dominguez Postdoc Physics

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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 activity

• To not fall for the “circular experimental results/conclusions”
• Examine both local and network effects in humans, non-invasively

2- Monitor brain state

• Brain state influences the tCS effect
• Improve tCS protocols considering brain state dynamics
• By monitoring dynamical state, design closed-loop systems

3- Guide the tCS input parameters

• An infinite number of stimulation parameters to choose from
• 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 treatments Better understanding of brain-behavior relationship

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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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