Transcranial Alternating Current Stimulation at Beta Frequency: Lack of Immediate Effects on Excitation and Interhemispheric Inhibition of the Human Motor Cortex

Viola Rjosk, Elisabeth Kaminski, Maike Hoff, Christopher Gundlach, Arno Villringer, Bernhard Sehm, Patrick Ragert, Viola Rjosk, Elisabeth Kaminski, Maike Hoff, Christopher Gundlach, Arno Villringer, Bernhard Sehm, Patrick Ragert

Abstract

Transcranial alternating current stimulation (tACS) is a form of noninvasive brain stimulation and is capable of influencing brain oscillations and cortical networks. In humans, the endogenous oscillation frequency in sensorimotor areas peaks at 20 Hz. This beta-band typically occurs during maintenance of tonic motor output and seems to play a role in interhemispheric coordination of movements. Previous studies showed that tACS applied in specific frequency bands over primary motor cortex (M1) or the visual cortex modulates cortical excitability within the stimulated hemisphere. However, the particular impact remains controversial because effects of tACS were shown to be frequency, duration and location specific. Furthermore, the potential of tACS to modulate cortical interhemispheric processing, like interhemispheric inhibition (IHI), remains elusive. Transcranial magnetic stimulation (TMS) is a noninvasive and well-tolerated method of directly activating neurons in superficial areas of the human brain and thereby a useful tool for evaluating the functional state of motor pathways. The aim of the present study was to elucidate the immediate effect of 10 min tACS in the β-frequency band (20 Hz) over left M1 on IHI between M1s in 19 young, healthy, right-handed participants. A series of TMS measurements (motor evoked potential (MEP) size, resting motor threshold (RMT), IHI from left to right M1 and vice versa) was performed before and immediately after tACS or sham using a double-blinded, cross-over design. We did not find any significant tACS-induced modulations of intracortical excitation (as assessed by MEP size and RMT) and/or IHI. These results indicate that 10 min of 20 Hz tACS over left M1 seems incapable of modulating immediate brain activity or inhibition. Further studies are needed to elucidate potential aftereffects of 20 Hz tACS as well as frequency-specific effects of tACS on intracortical excitation and IHI.

Keywords: interhemispheric inhibition (IHI); motor cortical excitability; neuroplasticity; transcranial alternating current stimulation (tACS); transcranial magnetic stimulation (TMS).

Figures

Figure 1
Figure 1
Experimental procedures. Nineteen young and healthy participants took part in two experimental sessions in a cross-over design on 2 days separated by at least 48 h. At each experimental session, cortical excitability (motor evoked potential (MEP) size, resting motor threshold (RMT)) and interhemispheric inhibition (IHI) were measured by transcranial magnetic stimulation (TMS) single- and paired-pulse protocols over both primary motor cortex (M1) hand areas before and after transcranial alternating current stimulation (tACS; tACS session) or sham (sham session). IHI was investigated both from left M1 to right M1 (LIHI) and vice versa (RIHI) in a randomized order. MEPs of right and left first dorsal interosseus muscle (FDI) were recorded by electromyography (EMG). The experimental sessions only differed in the type of stimulation: 10 min of 20 Hz tACS vs. sham (30 s of 20 Hz tACS) stimulation with an intensity of 1 mA each. The active electrode was placed on the FDI hotspot of the left M1, the “reference” electrode was placed on Pz according to the International 10-20 EEG system. The order of stimulation was randomized between participants and the study was performed in a double-blinded manner. Throughout the experiment, participants were seated in a comfortable chair in a relaxed position and were asked to keep their eyes open. See also “Experimental Procedures” Section for a detailed description.
Figure 2
Figure 2
Interhemispheric inhibition. Depicted are the individual IHIs of each participant (slim gray lines) as well as the mean IHI (bold black lines) per session and direction of IHI measurement. IHI was assessed with paired-pulse TMS before (pre) and after (post) 10 min of 20 Hz tACS (tACS) or sham stimulation (sham). IHI from left to right M1 (LIHI) was obtained by delivering a conditioning stimulus (CS) to left M1 followed by a test stimulus (TS) delivered to right M1 with an interstimulus interval (ISI) of 10 ms. For RIHI, CS was applied to right M1 followed by TS applied to left M1. For LIHI_pre and RIHI_pre, the TS and CS intensity was adjusted to the minimum stimulus intensity to evoke 1 mV control MEPs. For LIHI_post and RIHI_post CS intensity was maintained, but TS intensity was adjusted, if necessary, to evoke 1 mV control MEPs after tACS or sham. (A,B) Depict LIHI and RIHI under sham stimulation and (C,D) depict LIHI and RIHI under 10 min of tACS. See “Interhemispheric Inhibition: Paired-Pulse TMS Protocols” and “IHI” Sections for details as well as Table 1.

References

    1. Alagapan S., Schmidt S. L., Lefebvre J., Hadar E., Shin H. W., Fröhlich F. (2016). Modulation of cortical oscillations by low-frequency direct cortical stimulation is state-dependent. PLoS Biol. 14:e1002424. 10.1371/journal.pbio.1002424
    1. Antal A., Boros K., Poreisz C., Chaieb L., Terney D., Paulus W. (2008). Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans. Brain Stimul. 1, 97–105. 10.1016/j.brs.2007.10.001
    1. Baker S. N. (2007). Oscillatory interactions between sensorimotor cortex and the periphery. Curr. Opin. Neurobiol. 17, 649–655. 10.1016/j.conb.2008.01.007
    1. Barker A. T. (1991). An introduction to the basic principles of magnetic nerve stimulation. J. Clin. Neurophysiol. 8, 26–37. 10.1097/00004691-199101000-00005
    1. Brittain J. S., Probert-Smith P., Aziz T. Z., Brown P. (2013). Tremor suppression by rhythmic transcranial current stimulation. Curr. Biol. 23, 436–440. 10.1016/j.cub.2013.01.068
    1. Cantello R., Gianelli M., Civardi C., Mutani R. (1992). Magnetic brain stimulation: the silent period after the motor evoked potential. Neurology 42, 1951–1959. 10.1212/WNL.42.10.1951
    1. Cappon D., D’Ostilio K., Garraux G., Rothwell J., Bisiacchi P. (2016). Effects of 10 Hz and 20 Hz transcranial alternating current stimulation on automatic motor control. Brain Stimul. 9, 518–524. 10.1016/j.brs.2016.01.001
    1. Chaieb L., Antal A., Paulus W. (2011). Transcranial alternating current stimulation in the low kHz range increases motor cortex excitability. Restor. Neurol. Neurosci. 29, 167–175. 10.3233/RNN-2011-0589
    1. Chen R., Yung D., Li J. Y. (2003). Organization of ipsilateral excitatory and inhibitory pathways in the human motor cortex. J. Neurophysiol. 89, 1256–1264. 10.1152/jn.00950.2002
    1. Di Lazzaro V., Oliviero A., Profice P., Insola A., Mazzone P., Tonali P., et al. . (1999). Direct demonstration of interhemispheric inhibition of the human motor cortex produced by transcranial magnetic stimulation. Exp. Brain Res. 124, 520–524. 10.1007/s002210050648
    1. Duque J., Murase N., Celnik P., Hummel F., Harris-Love M., Mazzocchio R., et al. . (2007). Intermanual Differences in movement-related interhemispheric inhibition. J. Cogn. Neurosci. 19, 204–213. 10.1162/jocn.2007.19.2.204
    1. Ferbert A., Priori A., Rothwell J. C., Day B. L., Colebatch J. G., Marsden C. D. (1992). Interhemispheric inhibition of the human motor cortex. J. Physiol. 453, 525–546. 10.1113/jphysiol.1992.sp019243
    1. Feurra M., Bianco G., Santarnecchi E., Del Testa M., Rossi A., Rossi S. (2011a). Frequency-dependent tuning of the human motor system induced by transcranial oscillatory potentials. J. Neurosci. 31, 12165–12170. 10.1523/JNEUROSCI.0978-11.2011
    1. Feurra M., Paulus W., Walsh V., Kanai R. (2011b). Frequency specific modulation of human somatosensory cortex. Front. Psychol. 2:13. 10.3389/fpsyg.2011.00013
    1. Feurra M., Pasqualetti P., Bianco G., Santarnecchi E., Rossi A., Rossi S. (2013). State-dependent effects of transcranial oscillatory currents on the motor system: what you think matters. J. Neurosci. 33, 17483–17489. 10.1523/JNEUROSCI.1414-13.2013
    1. Fitzgerald P. B., Brown T. L., Daskalakis Z. J. (2002a). The application of transcranial magnetic stimulation in psychiatry and neurosciences research. Acta Psychiatr. Scand. 105, 324–340. 10.1034/j.1600-0447.2002.1r179.x
    1. Fitzgerald P. B., Brown T. L., Daskalakis Z. J., Chen R., Kulkarni J. (2002b). Intensity-dependent effects of 1 Hz rTMS on human corticospinal excitability. Clin. Neurophysiol. 113, 1136–1141. 10.1016/s1388-2457(02)00145-1
    1. Fröhlich F., McCormick D. A. (2010). Endogenous electric fields may guide neocortical network activity. Neuron 67, 129–143. 10.1016/j.neuron.2010.06.005
    1. Hanajima R., Ugawa Y., Machii K., Mochizuki H., Terao Y., Enomoto H., et al. . (2001a). Interhemispheric facilitation of the hand motor area in humans. J. Physiol. 531, 849–859. 10.1111/j.1469-7793.2001.0849h.x
    1. Hanajima R., Ugawa Y., Okabe S., Yuasa K., Shiio Y., Iwata N. K., et al. . (2001b). Interhemispheric interaction between the hand motor areas in patients with cortical myoclonus. Clin. Neurophysiol. 112, 623–626. 10.1016/s1388-2457(01)00477-1
    1. Herrmann C. S., Rach S., Neuling T., Strüber D. (2013). Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front. Hum. Neurosci. 7:279. 10.3389/fnhum.2013.00279
    1. Houweling S., Beek P. J., Daffertshofer A. (2010). Spectral changes of interhemispheric crosstalk during movement instabilities. Cereb. Cortex 20, 2605–2613. 10.1093/cercor/bhq008
    1. Kanai R., Paulus W., Walsh V. (2010). Transcranial alternating current stimulation (tACS) modulates cortical excitability as assessed by TMS-induced phosphene thresholds. Clin. Neurophysiol. 121, 1551–1554. 10.1016/j.clinph.2010.03.022
    1. Kilavik B. E., Zaepffel M., Brovelli A., MacKay W. A., Riehle A. (2013). The ups and downs of β oscillations in sensorimotor cortex. Exp. Neurol. 245, 15–26. 10.1016/j.expneurol.2012.09.014
    1. Kobayashi M., Hutchinson S., Schlaug G., Pascual-Leone A. (2003). Ipsilateral motor cortex activation on functional magnetic resonance imaging during unilateral hand movements is related to interhemispheric interactions. Neuroimage 20, 2259–2270. 10.1016/s1053-8119(03)00220-9
    1. Kujirai T., Caramia M. D., Rothwell J. C., Day B. L., Thompson P. D., Ferbert A., et al. . (1993). Corticocortical inhibition in human motor cortex. J. Physiol. 471, 501–519. 10.1113/jphysiol.1993.sp019912
    1. Marshall L., Helgadóttir H., Mölle M., Born J. (2006). Boosting slow oscillations during sleep potentiates memory. Nature 444, 610–613. 10.1038/nature05278
    1. Miles J., Shevlin M. (2001). Applying Regression and Correlation : A Guide for Students and Researchers. London, Thousand Oaks, Calif: Sage Publications.
    1. Neuling T., Rach S., Herrmann C. S. (2013). Orchestrating neuronal networks: sustained after-effects of transcranial alternating current stimulation depend upon brain states. Front. Hum. Neurosci. 7:161. 10.3389/fnhum.2013.00161
    1. Niedermeyer E. (1999). “The normal EEG of the waking adult,” in Electroencephalography: Basic Principles, Clinical Applications and Related Fields, eds Niedermeyer E., Lopes da Silva F. (Baltimore: Lippincott, Williams and Wilkins; ), 149–173.
    1. Oldfield R. C. (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113. 10.1016/0028-3932(71)90067-4
    1. Ozen S., Sirota A., Belluscio M. A., Anastassiou C. A., Stark E., Koch C., et al. . (2010). Transcranial electric stimulation entrains cortical neuronal populations in rats. J. Neurosci. 30, 11476–11485. 10.1523/JNEUROSCI.5252-09.2010
    1. Pal P. K., Hanajima R., Gunraj C. A., Li J. Y., Wagle-Shukla A., Morgante F., et al. . (2005). Effect of low-frequency repetitive transcranial magnetic stimulation on interhemispheric inhibition. J. Neurophysiol. 94, 1668–1675. 10.1152/jn.01306.2004
    1. Pascual-Leone A., Tormos J. M., Keenan J., Tarazona F., Cañete C., Catalá M. D. (1998). Study and modulation of human cortical excitability with transcranial magnetic stimulation. J. Clin. Neurophysiol. 15, 333–343. 10.1097/00004691-199807000-00005
    1. Pogosyan A., Gaynor L. D., Eusebio A., Brown P. (2009). Boosting cortical activity at Beta-band frequencies slows movement in humans. Curr. Biol. 19, 1637–1641. 10.1016/j.cub.2009.07.074
    1. Polanía R., Nitsche M. A., Korman C., Batsikadze G., Paulus W. (2012). The importance of timing in segregated theta phase-coupling for cognitive performance. Curr. Biol. 22, 1314–1318. 10.1016/j.cub.2012.05.021
    1. Reato D., Rahman A., Bikson M., Parra L. C. (2013). Effects of weak transcranial alternating current stimulation on brain activity-a review of known mechanisms from animal studies. Front. Hum. Neurosci. 7:687. 10.3389/fnhum.2013.00687
    1. Rossi S., Hallett M., Rossini P. M., Pascual-Leone A., Safety of TMS Consensus Group . (2009). Safety, ethical considerations and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin. Neurophysiol. 120, 2008–2039. 10.1016/j.clinph.2009.08.016
    1. Rossini P. M., Berardelli A., Deuschl G., Hallett M., Maertens de Noordhout A. M., Paulus W., et al. . (1999). Applications of magnetic cortical stimulation. The international federation of clinical neurophysiology. Electroencephalogr. Clin. Neurophysiol. Suppl. 52, 171–185.
    1. Rossini P. M., Rossi S. (2007). Transcranial magnetic stimulation: diagnostic, therapeutic and research potential. Neurology 68, 484–488. 10.1212/01.WNL.0000250268.13789.b2
    1. Ruhnau P., Neuling T., Fuscá M., Herrmann C. S., Demarchi G., Weisz N. (2016). Eyes wide shut: transcranial alternating current stimulation drives alpha rhythm in a state dependent manner. Sci. Rep. 6:27138. 10.1038/srep27138
    1. Schutter D. J., Hortensius R. (2011). Brain oscillations and frequency-dependent modulation of cortical excitability. Brain Stimul. 4, 97–103. 10.1016/j.brs.2010.07.002
    1. Sela T., Kilim A., Lavidor M. (2012). Transcranial alternating current stimulation increases risk-taking behavior in the balloon analog risk task. Front. Neurosci. 6:22. 10.3389/fnins.2012.00022
    1. Shimizu T., Hosaki A., Hino T., Sato M., Komori T., Hirai S., et al. . (2002). Motor cortical disinhibition in the unaffected hemisphere after unilateral cortical stroke. Brain 125, 1896–1907. 10.1093/brain/awf183
    1. Stefan K., Wycislo M., Classen J. (2004). Modulation of associative human motor cortical plasticity by attention. J. Neurophysiol. 92, 66–72. 10.1152/jn.00383.2003
    1. Thut G., Miniussi C., Gross J. (2012). The functional importance of rhythmic activity in the brain. Curr. Biol. 22, R658–R663. 10.1016/j.cub.2012.06.061
    1. Valls-Solé J., Pascual-Leone A., Wassermann E. M., Hallett M. (1992). Human motor evoked responses to paired transcranial magnetic stimuli. Electroencephalogr. Clin. Neurophysiol. 85, 355–364. 10.1016/0168-5597(92)90048-g
    1. Wach C., Krause V., Moliadze V., Paulus W., Schnitzler A., Pollok B. (2013). Effects of 10 Hz and 20 Hz transcranial alternating current stimulation (tACS) on motor functions and motor cortical excitability. Behav. Brain Res. 241, 1–6. 10.1016/j.bbr.2012.11.038
    1. Wassermann E. M., Samii A., Mercuri B., Ikoma K., Oddo D., Grill S. E., et al. . (1996). Responses to paired transcranial magnetic stimuli in resting, active and recently activated muscles. Exp. Brain Res. 109, 158–163. 10.1007/bf00228638
    1. Wassermann E. M., Wedegaertner F. R., Ziemann U., George M. S., Chen R. (1998). Crossed reduction of human motor cortex excitability by 1-Hz transcranial magnetic stimulation. Neurosci. Lett. 250, 141–144. 10.1016/s0304-3940(98)00437-6
    1. Zaehle T., Rach S., Herrmann C. S. (2010). Transcranial alternating current stimulation enhances individual alpha activity in human EEG. PLoS One 5:e13766. 10.1371/journal.pone.0013766
    1. Zaghi S., Acar M., Hultgren B., Boggio P. S., Fregni F. (2010a). Noninvasive brain stimulation with low-intensity electrical currents: putative mechanisms of action for direct and alternating current stimulation. Neuroscientist 16, 285–307. 10.1177/1073858409336227
    1. Zaghi S., de Freitas Rezende L., de Oliveira L. M., El-Nazer R., Menning S., Tadini L., et al. . (2010b). Inhibition of motor cortex excitability with 15 Hz transcranial alternating current stimulation (tACS). Neurosci. Lett. 479, 211–214. 10.1016/j.neulet.2010.05.060

Source: PubMed

3
Tilaa