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Y Combining tCS and EEG P O C T O N O D Emiliano - - PowerPoint PPT Presentation

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

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Combining tCS and EEG

Emiliano Santarnecchi

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

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

  • Center for Complex System study, Engineering and Mathematics Department, University of Siena, Italy

esantarn@bidmc.harvard.edu Boston, 23rd February 2017

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

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  • Measuring tCS effects without EEG

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

  • Basics of EEG

Ø EEG signal: features and opportunities Ø Analysis (ERP, Microstates, Source analysis, ...) Ø Examples of EEG-tCS combination

  • Beyond EEG

Ø TMS-EEG recording

Outline

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

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Questions? Comments? Ideas? Feedback?

  • Kirsten Building - KS-450
  • esantarn@bidmc.harvard.edu
  • emilianosantarnecchi@gmail.com

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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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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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 effect on Subcortical Structures?

Modeling based on tractography, structural MRI, CT scans….

Rossi, Santarnecchi 2016, Philos. Trans A

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 measuments (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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Open questions..

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

(connectivity) à 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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Electroencephalography

1934: Fisher and Lowenback first demonstration of epileptiform spikes. Hans Berger

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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Gamma: selective attention Alpha: visual perception Ѳ: working /long-term memory Beta: movement Alpha: automatic movements Θ: spatial orienting

Dominant Oscillations for Different brain regions

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

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  • Why are oscillatory pattern so important ?

Cyclic Excitability Changes

Rhythmic fluctuations in the local field potential (LFP), synchronous transmembrane currents in populations of neurons and thus represent cyclic changes in the excitability of local neuronal populations.

Ongoing oscillatory phase significantly modulates the probability of perceiving a near-threshold visual stimulus.

  • 1. Pulse processing

2 . Hierarchical information processing Multiplexing / Cross- frequency coupling

  • Various aspects of the stimulus are

encoded in different oscillations simultaneously, but at different frequencies.

  • Efficient coding scheme relying on

the hierarchical organization of

  • scillations.

Oscillatory pattern in the brain

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

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  • Why are oscillatory patterns so important?
  • 3. “Communication-through-coherence” Theory
  • Communication being facilitated when two
  • scillatory populations are aligned to their high

excitability phases.

  • Effective communication relies on spikes from the

sending population reaching the receiving population at a phase of high excitability.

  • Changes in synchronization between distant brain

areas (possibly reflecting communication) are systematically related to task performance.

Oscillatory pattern and periodicity in behaviour

Canolty, Science 2005

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).

– Fp prefrontal – F frontal – C central – T temporal – P parietal – O Occipital

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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Well known Evoked Response Potential (ERP )(P300, N100, ..)

  • 2. EVOCKED

EEG recording

  • 1. SPONTENEOUS
  • Meaningful data with ~5’ of recording
  • Eyes open/closed

TMS-EEG

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 vs Frequency Analysis

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

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Event-Related Potentials (ERPs)

Example of auditory evoked potentials EEG response to visual stimuli

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

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Event-Related Potentials and Source Analysis Attempt to localize cortical/subcortical Sources responsible for the EEG topography of interest.

Algorithm-threshold-model dependent results….

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

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EEG Connectivity analysis

Extract signal for all the electrodes Correlation / coherence / etc Zhavoronkova et al., 2013 Traumatic Brain Injury

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

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EEG Microstates

Sequence of spatially defined Topographies Khanna et al. 2014

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

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EEG Microstates

Four major Microstates (explain ~75% variance)

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

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EEG Microstates

EEG Microstates and fMRI Resting-state networks Synthax analysis

1 2 3 4

Significant differences in Alzheimer, Schizophrenia, ADHD

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

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EEG Microstates and Cognition

Santarnecchi et al., under revision Microstate Frequency correlates with Abstract Reasoning Microstate Topography changes with Cognitive Training

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: Stimulation Parameters (Frequency, phase,etc.)

Frequency

Individual Alpha frequency

Zahele et al., 2012

  • tACS on the occipital cortex at individual alpha frequency
  • Resting EEG à 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 not 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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P L E A S E D O N O T C O P Y

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Closed-Loop Studies in Animal Tremor suppression using EEG features from the motor cortex?

  • 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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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 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 à 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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Even better than EEG…? 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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Even better than EEG…? TMS-EEG

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

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Even better than EEG…? 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 à unclear OFFLINE tDCS à 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
  • f interest (!).
  • Notch filter 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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fMRI-based Multifocal tACS

Ruffini et al. 2013 fMRI activation map tCS solution with 2 electrodes Multifocal tCS solution with 8 electrodes

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

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fMRI-EEG based Multifocal tACS

Meta-analysis map of fMRI activation map during Executive functions tasks Targets for Fronto-parietal desynchronization

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

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In Summary

  • 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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esantarn@bidmc.harvard.edu

Thank you for your attention

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