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Page 1: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Lorella Battelli, PhD

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Page 2: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

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Page 3: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

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Page 4: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

TMS over M1

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Page 5: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Plasticity over 1 session:

- MEP amplitude after tRNS over M1

Terney et al., Journal of Neuroscience, 2008

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Page 6: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

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Page 7: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

a-tDCS

-Active Stimulation20 minutes @1mAanode EVA(OZ), cathode (CZ)

-Sham Stimulation

hf-tRNS

-Active Stimulation20 minutes @1mABilateral EVA (O2, O1)

-Sham Stimulation

n=12

n=12

Measuring Cortical excitability

Florian Heprich

Federica Contò

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Page 8: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Phosphene threshold

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Page 9: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

tRNS tDCS Sham

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Page 10: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

** ** ** ** ** ** **

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Page 11: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Herpich et al., in prep

** ** ** ** ** ** **

Terney et al., 2008

tRNS = 1 mA – 20 min – bilateral stimulation tRNS = 1 mA – 10 min – unilateral stimulation

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Page 12: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

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Page 13: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Perceptual Learning

Process by which training leads to improvement in abilities to detect, discriminate and identify sensory stimuli

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Page 14: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Single cell recordings revealed that visual experience modifies neuronal connections in early life.

Wiesel and Hubel, 1963

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Page 15: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

•  Traditionally, brain plasticity has been thought to occur only during infancy and early development

•  Although plasticity effects are strongest during childhood, the last two decades of research demonstrated that the adult brain is plastic

ConclusionsConclusions

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Page 16: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Coherent Motion Detection in Noise

Post Training

15% 50% 100%

Weak Signal Moderate Signal Strong Signal

Perf

orm

ance

Signal Strength

Pre Training

Threshold

0%

100%

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Page 17: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Time

Learning Threshold

SimpleSensory Input

Stimulus Presentation

Effic

acy

Optimization of Sensory Input

Attention Reinforcement (Reward - Punishment)

Non-Invasive Brain Stimulation

Conclusions

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Page 18: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Anodal

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Page 20: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

•  Visuo-perceptual functions can be trained both in healthy adults (Hang et al.,

2014) and in the neurological population (Huxlin et al., 2009; Das et al., 2014)

•  Can we use tRNS to boost PL processes to improve visual function in healthy subjects? (Miniussi et al., 2011)

•  Can we use tRNS to boost PL in stroke patients?

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Page 21: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Pre-Training Baseline

6 Months Follow Up

N = 45 220 Mins. @ 1mA.

Fixation

500 ms

ttES

1000 ms

Florian Heprich

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Page 22: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Stimulation Protocol

a-tDCS tRNS Parietal tRNS

Sham Behavioral

n = 9 n = 9 n = 9 n = 9 n = 9

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Page 23: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

0

10

20

30

40

50

60

70

1 2 4 6 8 103 5 7 9Session

Per

cent

impr

ovem

ent a-tDCS

ControltRNS

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Page 24: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

0

20

40

60

a-tDCSControltRNS

Post-test 6-month follow-up

Am

ount

of l

earn

ing

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Page 25: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Can tES promote recovery in stroke patients?

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Page 26: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

•  Damage to V1 in one hemisphere

•  Blindness in the opposite hemifield

•  Spontaneous recovery limited to the first weeks

hMT+

hMT+

OS/OD

-20

-10

0

10

20

Deg.

visua

l an

gle

Subjects with unilateral V1 damage

-30 -20 -10 0 10 20 30Deg. visual angle

hMT+N=25

Age: 59+14 yrs(6 >70 yrs)

Time sincedamage:

39+62 mths Hemianopic patients

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Page 27: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

•  No established validated clinical therapies exist for the restoration of visual field deficits

•  But the CB retain residual visual processing abilities (“Blindsight”, Weiskrantz 1974)

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Page 28: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Huxlin et al., Journal of Neuroscience, 2009

•  Stroke patients with V1 damage

•  Trained on global direction discrimination in cortically blind field

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Page 29: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Huxlin et al., Journal of Neuroscience, 2009

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Page 30: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Pre-Training Baseline

Baseline Visual Perimetry

Fixation1000 ms

Procedure

Visual Perimetry

Visual Perimetry

500 mss

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Page 31: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

tRNS

Sham

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Page 32: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

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Page 33: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

R2 =.601 R2 =.057

IntroductionNeuroplasticity Materials &

MethodsExperimentsResults

Materials & MethodsExperimentResults Results

ExperimentsMaterials & Methods

Perceptual LearningNIBS

Conclusions

r =.23 r =.78

tRNS Sham

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Page 34: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

tRNS Visual Perimetry

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Page 35: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Sham Visual Perimetry

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Page 36: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Plasticity over multiple sessions:

- Perceptual learning during tRNS over Parietal Cortex

Cappelletti et al., Journal of Neuroscience, 2013

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Page 37: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

• Can we promote learning with tRNS and make it more efficient? (Cappelletti et al., 2013)

• Short-training paradigm?

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Page 38: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Research report

Functional connectivity of parietal cortex duringtemporal selective attention

Sarah C. Tyler a,b,*, Samhita Dasgupta a, Sara Agosta b, Lorella Battelli b,c

and Emily D. Grossman a

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Page 39: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

The ‘When network’

•  Temporal Attention: ability to perceive the order and structure of events

•  Control of temporal attention, the ‘When Network’

Crucial role of the Parietal lobe

HypothesistRNS modulates parietal cortical activity and consequently improves

temporal attention

(Battelli et al., 2007; Tyler et al., 2015)

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Page 40: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Federica Contò

Sarah Tyler

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Page 41: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

     

   

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Page 42: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

BehavhMT+ParietalSham

Tyler et al., JoCN, in press1 Session

Blocks

Average performance Improvement by condition

Behavioral Improvement in One Session

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Page 43: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Dual-task Training

Optimize Training + Stimulation

•  Extend the effect in time multi-session stimulation

•  Efficiency of training paradigm double-training (Szpiro et al.,

2014)

Neurophysiological effect

•  Detecting changes in functional connectivity

•  Is the effect local or wide-spread across the attention network?

Grace Edwards

Federica Contò

Sarah Tyler

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Page 44: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Orientation Discrimination

+

Time1000 ms

Time1000 ms

+

+

SOAs

+

Temporal Order Judgment

Training on two tasks

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Page 45: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Experimental Procedure

Dual-taskPre-Test

Dual-taskPost-Test

Dual-task training + tRNS

MRI Stimulation MRI

t

Multi-Session Between Subjects Design

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Page 46: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Task Design

Orientation Discrimination (OD)

Temporal Order Judgment

(TOJ)

Conditions:Parietal (N = 10)hMT+ (N = 10)Sham (N = 10)

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Page 47: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

0

10

20

30

40

50

60

70

80

90

Day 1 Day 6

Per

cent

Cor

rect

hMT (n=10)

Sham (n=10)

Parietal (n=10)

**

Orientation Discrimination

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Page 48: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Functional Connectivity

Computed FC between these nodes of the attentional network

Individual ROIs

R,L FEF

R,L IPS

RL, TPJ

R,L hMT

FEF

MT

IPS

TPJ

F

T

IPS

TPJ

PSF

FEF

IPS

TPJ

hMT

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Page 49: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

FEF

IPS

TPJ

hMT

Day 6 vs Day 1

Parietal difference between session 1 and session 2

IPSR

IPSL

hMTR

hMTL

FEFR

FEFL

TPJR

TPJL

IPSR

IPSL

hMTR

hMTL

FEFR

FEFL

TPJR

TPJL

-1

-0.5

0

0.5

1

hMT difference between session 1 and session 2

IPSR

IPSL

hMTR

hMTL

FEFR

FEFL

TPJR

TPJL

IPSR

IPSL

hMTR

hMTL

FEFR

FEFL

TPJR

TPJL

-1

-0.5

0

0.5

1

Parietal Day6 vs Day1

hMT Day6 vs Day1

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Page 50: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Transcranial Direct Current StimulationFacilitates Associative Learning and AltersFunctional Connectivity in the Primate BrainMatthew R. Krause,1 Theodoros P. Zanos,2 Bennett A. Csorba,1 Praveen K. Pilly,3,5,* Jaehoon Choe,3

Matthew E. Phillips,3 Abhishek Datta,4 and Christopher C. Pack1,*

Current Biology

Article

B

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Page 51: DO class slides/024.pdf · 2017-11-16 · Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain Matthew

Conclusions

•  tRNS over the Parietal Lobe promotes and speeds up learning within few training sessions

 Neural processes sufficiently stimulated while in a sensitized state Double training coupled with tRNS can maximize learning

•  tRNS may be changing functional connectivity among critical nodes of the attention networks

•  Potential clinical applications

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