Andrea Antal Department of Clinical Neurophysiology Georg-August University Goettingen Combining tdcs and fmri 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
Consecutive tdcs-fmri measurements 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.
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 noninvasively - 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
Interleaved tdcs fmri resting tdcs tdcs tdcs tdcs (21 sec each) 4th tdcs Kwon et al., 2008
Antal et al., 2011
Signal-to-noise ratio SNR T2*-weighted EPI raw images Antal et al., 2011
Intensity of stimulation during MR imaging Courtesy of Klaus Schellhorn, NeuroConn
Effects of tdcs during rest and motor activity - 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
Antal et al., 2011
Sham - anodal peak TAL x=-6,y=-13,z=53; t(12)=4.1, p=0.0015 Antal et al., 2011
Antal et al., 2011
Decreased BOLD during cathodal tdcs: Possible explanation Antal et al., 2007
Artefacts or real signal?
Antal et al., 2012
fmri Modelling Antal et al. 2012
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
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 Zheng et al., 2011
Similar results: - L-DLPFC - Aftereffects - Functional connectivity Stagg et al., 2013
Brain perfusion changes Anodal stimulation Anodal baseline Cathodal stimulation Cathodal baseline (Anodal stimulation Anodal baseline) (Cathodal stimulation Cathodal baseline) Stagg et al., 2013
Functional connectivity changes Anodal Cathodal After anodal stimulation Stagg et al., 2013
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
ther approaches to evaluate the effect of tdcs in the resting brain Seed-based and independent component analyses ICA ROI analyses probing the coherence of inter-hemispheric activity in major nodes within the motor network Cathodal tdcs increased the interhemispheric coherence of resting fmri signal and functional connectivity within the ICAgenerated motor and default mode networks. Amadi et al., 2014
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