Department of Clinical Neurophysiology

Georg-August University Goettingen

Combining tDCS and fMRI

Andrea Antal

OHMB Teaching Course, Hamburg

June 8, 2014

Classical „Biomarkers“ for measuring

human neuroplasticity

TMS – Motor evoked potential

Behavioral tests (RTs, accuracy)

EEG

fMRI?

Previous studies: Interleaved TMS - fMRI

Problems:

- The magnetic field of the MR scanner causes strong

mechanical forces on the TMS coil

- Stimulator induces noise that can decrease image

quality

-TMS pulses given directly during image acquisition

severely deteriorate the images

tDCS: experimental designs

Baudewig et al., 2001: 57% decrease of activated pixels in the

SMA after cathodal tDCS, but no change in the hand area of the

M1. Anodal tDCS yielded a nonsignificant 5% increase of activated

pixels with no regional differences.

Jang et al., 2009: The activation underlying primary sensorimotor

cortex was significantly increased in the anodal group and

significantly decreased in the sham group.

Stagg et al., 2009: anodal tDCS led to short-lived activation

increases in the M1 and the SMA within the stimulated hemisphere.

Cathodal tDCS led to an increase in activation in the contralateral

M1 and PMd, as well as an increase in functional connectivity.

Consecutive tDCS-fMRI measurements

Combining tDCS with fMRI

MR compatible resistors of 5.6 kOhm in each wire to avoid

sudden temperature increases due to induction voltages from

radio frequency pulses.

Concurrent tDCS & fMRI: Aims - Investigation of local and remote tDCS-effects non-

invasively

- Direct visualization of the stimulation-induced

changes in brain activity with high spatial resolution

and the possibility to chart how tDCS modifies ongoing

brain activations

Pitfalls

• Susceptibility Artefacts

• Decreased SNR

• Induced Currents

Artefacts

Kwon et al., 2008

Interleaved

tDCS – fMRI

resting–tDCS–tDCS–tDCS–tDCS

(21 sec each)

4th tDCS

Antal et al., 2011

Signal-to-noise ratio

T2*-weighted

EPI raw images

SNR

Antal et al., 2011

Courtesy of Klaus Schellhorn, NeuroConn

Intensity of stimulation during MR imaging

- 20 right handed subjects

- 3 Tesla (Siemens TIM Trio)

- 8 Channel Head Coil

- EPI: TR : 2000 ms, TE: 36 ms, 22 sections, 2x2x4 mm3

- 20 sec stimulation, 20 sec rest (x 8)

- Electrodes placed over:

Left M1 Hand / Right Orbita OTP junction

1. Anodal tDCS 6. Anodal / Cathodal tDCS

2. Cathodal tDCS 7. FT

3. Finger Tapping (FT) 8. FT + Anodal / Cathodal tDCS

4. FT + Anodal tDCS

5. FT + Cathodal tDCS

Effects of tDCS during rest and motor activity

Antal et al., 2011

peak TAL x=-6,y=-13,z=53; t(12)=4.1, p=0.0015

Sham - anodal

Antal et al., 2011

Antal et al., 2011

Antal et al., 2007

Decreased BOLD during cathodal tDCS:

Possible explanation

Artefacts or real signal?

Antal et al., 2012

Antal et al. 2012

fMRI

Modelling

Online - effects of tDCS:

is CBF measurement more sensitive

than BOLD?

Questions: - How specific?

- Regional / global CBF increases by anodal /

decreases by cathodal?

Method: ASL: usesmagnetically labeled arterial blood water as

an endogenous tracer

Smaller number of

inhibitory synapses?

Zheng et al., 2011

Zheng et al., 2011

CBF changes in a network of brain regions for

the anodal condition. Averaged distribution of

CBF response across the entire brain space

correlated with the timecourse obtained from

the VOI under the electrode for the anodal

condition.

Voxel-wisewhole-brain analysis of ON vs OFF for

the anodal condition.

Zheng et al., 2011

Stimulation intensity dependence

- L-DLPFC

- Aftereffects

- Functional connectivity

Similar results:

Stagg et al., 2013

Stagg et al., 2013

Anodal stimulation –

Anodal baseline

(Anodal stimulation –

Anodal baseline) – (Cathodal

stimulation –

Cathodal baseline)

Cathodal stimulation –

Cathodal baseline

Brain perfusion changes

Stagg et al., 2013

Anodal

Functional connectivity changes

Cathodal

After anodal stimulation

Stimulation of the R - mPFC

- 60 subjects: sham, anodal,

cathodal over Fp2-Fpz

- 20 min stimulation, before

and during 6 min ASL

Antal et al., 2014

Nodal connectivity degree in

the left PCC area and in the

right DLPFC significantly

increased after anodal tDCS

Polania et al., 2011

Seed-based and independent component analyses ICA

ROI analyses probing the coherence of inter-hemispheric activity in

major nodes within the motor network

Other approaches to evaluate the effect of tDCS

in the resting brain

Amadi et al., 2014

Cathodal tDCS

increased the inter-

hemispheric

coherence of resting

fMRI signal and

functional connectivity

within the ICA-

generated motor and

default mode

networks.

Cathodal tDCS increased the strength

of the default mode network.

Amadi et al., 2014

Summary

- Concurrent tDCS & fMRI at 3 T is feasible

- Potential safety and technical problems with wires and electrodes:

These issues and design considerations are very similar

to those for EEG within the MRI. Undesired coupling of

the wires to the transmit coil could produce currents

capable of burning the subject and distorting flip angles

and receive sensitivity near the wire.

- Task specific: Anodal / Cathodal tDCS alone has/has no effect on

BOLD fMRI

- Polarity specific?

- Method specific: BOLD, rCBF, resting state (what really happens at

the neuronal or synaptic level?)

- Other tES methods: tACS, tRNS - no data

Suggested reading material: Amadi et al. (2013). Polarity-specific effects of motor transcranial direct current stimulation on fMRI resting state

networks. Neuroimage, 88C, 155-161

Antal et al. (2014). Imaging artifacts induced by electrical stimulation during conventional fMRI of the brain.

Neuroimage, 85 Pt 3, 1040-1047.

Antal et al. (2012). Cathodal stimulation of human MT+ leads to elevated fMRI signal: a tDCS-fMRI study. Restor

Neurol Neurosci, 30(3), 255-263.

Antal et al. (2011). Transcranial direct current stimulation over the primary motor cortex during fMRI. Neuroimage,

55(2), 590-596.

Hampstead et al. (2014). Transcranial direct current stimulation modulates activation and effective connectivity

during spatial navigation. Brain Stimul, 7(2), 314-324.

Holland et al. (2011). Speech facilitation by left inferior frontal cortex stimulation. Curr Biol, 21(16), 1403-1407.

Keeser et al. (2011). Prefrontal transcranial direct current stimulation changes connectivity of resting-state networks

during fMRI. J Neurosci, 31(43), 15284-15293

Polania et al. (2012a). Modulating cortico-striatal and thalamo-cortical functional connectivity with transcranial direct

current stimulation. Hum Brain Mapp, 33(10), 2499-2508.

Polania et al. (2012b). Reorganizing the intrinsic functional architecture of the human primary motor cortex during

rest with non-invasive cortical stimulation. PLoS One, 7(1), e30971.

Saiote et al. (2013) High-frequency TRNS reduces BOLD activity during visuomotor learning. PLoSOne, 8, e59669.

Weber et al. (2014). Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and

subcortical reward systems: A tDCS-fMRI study. Hum Brain Mapp. In press