Combining tCS and EEG Y P O C T O N O D Davide Cappon, PhD - - PowerPoint PPT Presentation

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Combining tCS and EEG Y P O C T O N O D Davide Cappon, PhD - - PowerPoint PPT Presentation

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Combining tCS and EEG Y P O C T O N O D Davide Cappon, PhD E S - Berenson-Allen Center for Non-invasive Brain Stimulation, Department of Cognitive Neurology | Beth Israel Deaconess Medical Center | Harvard Medical School | Boston, MA,

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Combining tCS and EEG

Davide Cappon, PhD

  • Berenson-Allen Center for Non-invasive Brain Stimulation, Department of Cognitive Neurology | Beth Israel Deaconess

Medical Center | Harvard Medical School | Boston, MA, USA

dcappon@bidmc.harvard.edu Boston, 23rd June 2019

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

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axies that can be seen today make up ju NASA

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

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Observable Universe

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

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Observable Universe Planet Earth

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

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  • Measuring tCS effects with EEG

➢ Measuring effects outside the motor cortex ➢ Measuring focality of tCS interventions

  • Basics of EEG

➢ EEG signal: features and opportunities ➢ Analysis (ERP,Power, ...) ➢ Experimental example of EEG-tCS combination

  • Beyond EEG

➢ TMS-EEG recording

Outline

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

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Corticospinal excitability as an index of Brain excitability Applied to tCS: limitation for online recording, only after effects

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

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Measuring tCS effects without EEG

First evidence of tDCS after effect from Nitsche and Paulus, 2000 Changes in cortical excitability assessed using TMS-EMG

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

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tDCS effect on corticospinal excitability:Online and Offline effects

Santarnecchi et al., 2014

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

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tDCS Effects on the motor cortex: pre/during/post

ONLINE (15’) PRE (15’) POST (30’) Anodal and Cathodal tDCS modulate (increase/decrease excitability) right after the stimulation respect to Sham. No significant effects During the stimulation.

Still limited to the motor cortex!

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

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Are we stimulating the motor cortex?

Montage, Timing, Stimulation site, Duration, Intensity, etc. suggest a complex scenario underlying tCS effects TMS-EMG is not enough Kuo et al., 2013 HD-tDCS

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

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Multifactorial model

…Brain… Brain state (electrophysiological recording - EEG) Individual trait (personality, cognitive profile) Behavioural performance Behavioural scores Electrophysiological responses – EEG/ERPs/etc.. Neuroimaging ($$$) Genetics (e.g. BDNF) Physiological measurements (EKG, EDR,..) EEG/ERPs/??? fMRI? BEFORE DURING AFTER

?

Neuroimaging ($$$)

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

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Targeting Optimization

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

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Open questions..

  • the effect of tCS on Non-Motor regions?
  • distant effects and changes in the interplay between regions

(connectivity)  Network effects?

  • the Online effects of tCS on brain activity other than

“excitability”? Useful information to define tCS parameters and increase efficacy of interventions

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

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1875: Richard Caton (1842-1926) measured currents in between the cortical surface and the skull, in dogs and monkeys 1929: Hans Berger (1873-1941) first EEG in humans (his young son), description of alpha and beta waves

  • 1950s. Grey Walter ( 1910 – 1977). Invention of topographic

EEG maps.

Electroencephalography

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

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Where does the signal come from?

  • Signals stem from synchronous activity of large (~1000s)

groups of neurons close to each other and exhibiting similar patterns of activity

  • Most of the signal generated by pyramidal neurons in the

cortex (parallel to each other, oriented perpendicular to the surface)

  • EEG measures synaptic currents, not action potentials

(currents flow in opposite directions and cancel out!)

Electroencephalography

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

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Primary intracellular currents give rise to volume currents and a magnetic field

Current Magnetic field Volume currents Magnetic field cortex skull scalp MEG pick-up coils Electrical potential difference (EEG) Volume currents yield potential differences on the scalp that can be measured by EEG

Electroencephalography

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

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Pros and cons of EEG

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

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EEG recording and analysis

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

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EEG recording

  • International 10-20 system
  • Left side: odd numbers
  • Right side: even numbers
  • Numbers increase from the hemispheric line towards the edges. Letter

indicates brain regions (lobes). High-Density EEG (64-256 Channels)

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

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  • EEG records potential differences at the scalp using a set of

active electrodes and a reference

  • The ground electrode is important to eliminate noise from the

amplifier circuit

  • Potential differences are then amplified
  • The representation of the EEG

channels is referred to as a montage – Unipolar/Referential ⇒ potential difference between electrode and designated reference – Bipolar ⇒ represents difference between adjacent electrodes (e.g. ECG, EOG)

EEG recording

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

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  • 1. SPONTANEOUS
  • Meaningful data with ~5’ of recording
  • Eyes open/closed
  • 2. EVOKED

EEG recording

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

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Time domain:

  • > when do things (amplitudes) happen?

EEG analysis

TIME

Frequency domain (spectral):

  • > magnitudes and frequencies of

waves- no time information.

Time-frequency (wavelet analysis):

  • > when do which frequencies occur?

From ERPs to Waveform

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

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EEG features

fMRI

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

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Time domain Analysis

Example of auditory evoked potentials

Event Relate Potentials ERPs

Advantages: computationally simple

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

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How to disentangle oscillations Jean Joseph Fourier (1768–1830): “An arbitrary function, continuous or with discontinuities, de

ned in a finite interval by an arbitrarily capricious graph can always be expressed as a sum of sinusoids”.

Frequency Domain Analysis (EEG)

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

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Time- Frequency Domain Analysis (EEG)

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

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Connectivity Analysis (EEG)

Connectivity based on… .Phase (eg. phase-slope index) .Power (eg. coherence) .Cross-frequency coupling

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

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Hipp et al., 2013

ambiguous audiovisual stimulus: two bars approached, briefly

  • verlapped while a click sound was played, and moved apart

from each other

Connectivity Analysis (EEG)

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

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Cohen et al., 2013

Connectivity Analysis (EEG)

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

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Advantages of tCS + EEG

  • Understanding the role of brain oscillations in both motor and non-

motor regions, in both the healthy and pathological brain

  • Measure both local and distant effects.
  • Guide tCS intervention on the basis of and online/offline monitoring
  • f brain states.

How can tCS + EEG be implemented?

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

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tCS + EEG approaches

Resting or Event related EEG

tCS (no EEG recording)

Resting or Event related EEG Resting or Event related EEG

EEG recording during tCS

Resting or Event related EEG Resting or Event related EEG

tCS guided by EEG recording Resting or Event related EEG

OFFLINE ONLINE

EEG-Guided, closed-loop system

? ?

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

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tCS and EEG: variables

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

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EEG-Guided tCS: Location

Faria et al., 2012 EEG evaluation of a patient with Continuous spike-wave discharges during slow-wave sleep allowed identification of an epileptogenic focus. Cathodal tDCS over the focus resulted in a significant decrease in interictal spikes.

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

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EEG-Guided tCS: Stimulation Parameters (Frequency, phase,etc.)

Frequency

Individual Alpha frequency

Zahele et al., 2012

  • tACS on the occipital cortex at individual alpha frequency
  • Resting EEG 

increase in alpha in parieto-central electrodes, no effects on surrounding frequencies

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

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EEG-Guided tCS: Stimulation Parameters (Frequency, phase,etc.)

Vossen et al., 2015

Frequency

Individual Alpha frequency

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

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EEG-Guided tCS: Stimulation Parameters (Frequency, phase,etc.)

Phase

Neuling et al., 2012

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

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

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State dependency: Eyes Open vs. Eyes Closed

Significant increase in alpha-power after individual-alpha frequency tACS when applied with Eyes open, but no with Eyes closed. Neuling et al., 2013

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

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State-Trait dependency

Variability in the response to tCS Neurotrasmitters balance Cortical “excitability” Fatigue, wakefulness, attention, habituation to stimuli  can Flip the effect Silvanto et al., 2007 Head-tissue morphology age Circadian rhythm Hormonal levels

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

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

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Closed-Loop Diagram

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

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Closed-Loop Studies in Animal

  • Rodent model of generalized

epilepsy.

  • Detection of interictal spikes

triggers tCS at 1Hz

Aborts the spike-wave discharge burst

Berenyi et al., 2012

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

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Closed-Loop Studies in human sleep

Clark et al., 2017

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

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TIME Amplitude

Closed-Loop Studies in human sleep

Enhancing slow waves improves memory

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

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Closed-Loop Studies in human sleep

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

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

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Output Measures: Power/Amplitude - Local effects

  • Anodal tDCS on right Inferior Frontal Gyrus, Cathode on OFC
  • Offline approach, tDCS + task, EEG before/after

Jacobson et al., 2012

Decrease in Theta power after tDCS

Theta Alpha Gamma Beta

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

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Output Measures: Power/Amplitude - Distant effect

  • Increased Theta and Alpha

power after Anodal tDCS

  • Decreased Alpha power

after Cathodal tDCS and v nd viceversa

Occipito-Parietal Electrodes…

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

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Output: Connectivity

  • 10’ of anodal tDCS over M1
  • Cathode on the contralateral Forehead
  • 62 Channels EEG recording Before & After, Resting & Task
  • Output 

Connectivity metrics (Synchronization Likelihood) in directed and undirected graphs, for each frequency band.

Polania et al., 2011 Task PRE – Task POST , High Gamma @ 60-90Hz tDCS Increases connectivity between motor, premotor and suppl. motor areas. Nose Nose R L

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

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Output: Connectivity

Polania et al., 2011

  • tDCS Increases connectivity between left motor, premotor and suppl. motor areas.
  • tDCS Decreases interhemispheric connectivity in High-Gamma during task.

!

ACTIVITY DURING MOTOR TASK

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

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Other multimodal approaches?

  • tCS + TMS-EMG
  • tCS + EEG (Resting – ERPs)
  • tCS + fMRI
  • tCS + NIRS
  • ….tCS + TMS-EEG ?

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

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TMS-EEG

TMS evoked potential (TEP)

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

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TMS-EEG

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

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TMS-EEG

Santarnecchi et al. 2016, SPJ

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

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TMS-EEG to investigate local and distant tDCS effects

  • 14 right-handed participants
  • 0.75mA for 15’ (anodal tDCS) + Sham
  • 60 Channels EEG
  • Masking Noise for TMS click

Romero Lauro et al., 2014 Output: TMS-Evoked Potentials (TEP) as a cortical activity/reactivity measure Global Excitability Index: Global Mean Field Power (GFMP) Local Excitability Index: Local Mean Field Power (LMFP) over 6 different clusters of electrodes, left/right Frontal-Temporal- Parietal. 3 Time windows: 0-50ms, 50-100ms, 100-150ms

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

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TMS-EEG to investigate local and distant tDCS effects

Global Mean Field Potential

0-50ms 50-100ms 100-150ms

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

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TMS-EEG to investigate local and distant tDCS effects

Local Mean Field Potential as an index of distant effects

Effects are (i) mostly in the 0-50ms window, which is expression of inter- regional monosynaptic connections; (ii) exclusively in the POST tDCS ONLINE tDCS  unclear OFFLINE tDCS  more specific, network-based effects

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

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Technical challenges

Resting or Event related EEG tCS guided by EEG recording Resting or Event related EEG EEG-Guided, closed-loop system Stimulation Artifact during EEG recording

tDCS

  • Relatively easier, Available tools

(algorithm) to “clean” the data from Drifts

tACS

  • Artifact is bigger and affects the EEG band of

interest (!).

  • Specific filtering can be applied (reduces the

available spectrum)

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

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EEG during tDCS

Sehm et al., 2013

SEP: somatosensory evoked potential 3rd order Butterworth filter (1-250Hz) to eliminate tDCS induced blurring of EEG response. POSTPROCESSING

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

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EEG during tACS

Helfrich at al.,2014 Moving Average + Principal Component Analysis to Capture and eliminate the artifact (?)

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

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Take home

  • Understand of Motor and non-Motor

tCS effects

  • Capture Distant effects other than cortical

excitability (e.g. Power, Coherence, Connectivity)

  • Guide tCS interventions (closed loop, etc.)
  • Interact with complex dynamics (e.g. CFC, phase-

related processing)

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

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Questions? Comments? Ideas? Feedback?

  • dcappon@bidmc.harvard.edu
  • davide.balos.cappon@gmail.com

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

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dcappon@bidmc.harvard.edu

Thank you for your attention

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