Effect of tDCS with an extracephalic reference electrode on cardio-respiratory and autonomic functions

Yves Vandermeeren, Jacques Jamart, Michel Ossemann, Yves Vandermeeren, Jacques Jamart, Michel Ossemann

Abstract

Background: Transcranial direct current stimulation (tDCS) is used in human physiological studies and for therapeutic trials in patients with abnormalities of cortical excitability. Its safety profile places tDCS in the pole-position for translating in real-world therapeutic application. However, an episode of transient respiratory depression in a subject receiving tDCS with an extracephalic electrode led to the suggestion that such an electrode montage could modulate the brainstem autonomic centres. We investigated whether tDCS applied over the midline frontal cortex in 30 healthy volunteers (sham n = 10, cathodal n = 10, anodal n = 10) with an extracephalic reference electrode would modulate brainstem activity as reflected by the monitoring and stringent analysis of vital parameters: heart rate (variability), respiratory rate, blood pressure and sympatho-vagal balance. We reasoned that this study could lead to two opposite but equally interesting outcomes: 1) If tDCS with an extracephalic electrode modulated vital parameters, it could be used as a new tool to explore the autonomic nervous system and, even, to modulate its activity for therapeutic purposes. 2) On the opposite, if applying tDCS with an extracephalic electrode had no effect, it could thus be used safely in healthy human subjects. This outcome would significantly impact the field of non-invasive brain stimulation with tDCS. Indeed, on the one hand, using an extracephalic electrode as a genuine neutral reference (as opposed to the classical "bi-cephalic" tDCS montages which deliver bi-polar stimulation of the brain) would help to comfort the conclusions of several modern studies regarding the spatial location and polarity of tDCS. On the other hand, using an extracephalic reference electrode may impact differently on a given cortical target due to the change of direct current flow direction; this may enlarge the potential interventions with tDCS.

Results: Whereas the respiratory frequency decreased mildly over time and the blood pressure increased steadily, there was no differential impact of real (anodal or cathodal) versus sham tDCS. The heart rate remained stable during the monitoring period. The parameters reflecting the sympathovagal balance suggested a progressive shift over time favouring the sympathetic tone, again without differential impact of real versus sham tDCS.

Conclusions: Applying tDCS with an extracephalic reference electrode in healthy volunteers did not significantly modulate the activity of the brainstem autonomic centres. Therefore, using an extracephalic reference electrode for tDCS appears safe in healthy volunteers, at least under similar experimental conditions.

Figures

Figure 1
Figure 1
Temporal evolution of the RF for each group (sham, cathodal, anodal). Mean +/- 1 SD of the RF by bins of 5 minutes over the monitoring period (3 epochs: baseline, tDCS, post-tDCS).
Figure 2
Figure 2
Temporal evolution of the sBP and HR for each group (sham, cathodal, anodal). Mean +/- 1 SD of the RF by bins of 5 minutes over the monitoring period (3 epochs: baseline, tDCS, post-tDCS).

References

    1. Hallett M. Transcranial magnetic stimulation: a primer. Neuron. 2007;55(2):187–199. doi: 10.1016/j.neuron.2007.06.026.
    1. Chen R. Studies of human motor physiology with transcranial magnetic stimulation. Muscle Nerve Suppl. 2000;9:S26–32. doi: 10.1002/1097-4598(2000)999:9<::AID-MUS6>;2-I.
    1. Fregni F, Pascual-Leone A. Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nat Clin Pract Neurol. 2007;3(7):383–393. doi: 10.1038/ncpneuro0530.
    1. Ridding MC, Rothwell JC. Is there a future for therapeutic use of transcranial magnetic stimulation? Nat Rev Neurosci. 2007;8(7):559–567. doi: 10.1038/nrn2169.
    1. Hummel FC, Cohen LG. Drivers of brain plasticity. Curr Opin Neurol. 2005;18(6):667–674. doi: 10.1097/01.wco.0000189876.37475.42.
    1. Priori A. Brain polarization in humans: a reappraisal of an old tool for prolonged non-invasive modulation of brain excitability. Clin Neurophysiol. 2003;114(4):589–595. doi: 10.1016/S1388-2457(02)00437-6.
    1. Manola L, Holsheimer J, Veltink P, Buitenweg JR. Anodal vs cathodal stimulation of motor cortex: a modeling study. Clin Neurophysiol. 2007;118(2):464–474. doi: 10.1016/j.clinph.2006.09.012.
    1. Bikson M, Bulow P, Stiller JW, Datta A, Battaglia F, Karnup SV, Postolache TT. Transcranial direct current stimulation for major depression: a general system for quantifying transcranial electrotherapy dosage. Curr Treat Options Neurol. 2008;10(5):377–385. doi: 10.1007/s11940-008-0040-y.
    1. Datta A, Elwassif M, Battaglia F, Bikson M. Transcranial current stimulation focality using disc and ring electrode configurations: FEM analysis. J Neural Eng. 2008;5(2):163–174. doi: 10.1088/1741-2560/5/2/007.
    1. Miranda PC, Faria P, Hallett M. What does the ratio of injected current to electrode area tell us about current density in the brain during tDCS? Clin Neurophysiol. 2009;120(6):1183–1187. doi: 10.1016/j.clinph.2009.03.023.
    1. Miranda PC, Lomarev M, Hallett M. Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol. 2006;117(7):1623–1629. doi: 10.1016/j.clinph.2006.04.009.
    1. Wagner T, Fregni F, Fecteau S, Grodzinsky A, Zahn M, Pascual-Leone A. Transcranial direct current stimulation: a computer-based human model study. Neuroimage. 2007;35(3):1113–1124. doi: 10.1016/j.neuroimage.2007.01.027.
    1. Holdefer RN, Sadleir R, Russell MJ. Predicted current densities in the brain during transcranial electrical stimulation. Clin Neurophysiol. 2006;117(6):1388–1397. doi: 10.1016/j.clinph.2006.02.020.
    1. Lippold OC, Redfearn JW. Mental Changes Resulting from the Passage of Small Direct Currents through the Human Brain. Br J Psychiatry. 1964;110:768–772. doi: 10.1192/bjp.110.469.768.
    1. Redfearn JW, Lippold OC, Costain R. A Preliminary Account of the Clinical Effects of Polarizing the Brain in Certain Psychiatric Disorders. Br J Psychiatry. 1964;110:773–785. doi: 10.1192/bjp.110.469.773.
    1. Priori A, Berardelli A, Inghilleri M, Pedace F, Giovannelli M, Manfredi M. Electrical stimulation over muscle tendons in humans. Evidence favouring presynaptic inhibition of Ia fibres due to the activation of group III tendon afferents. Brain. 1998;121(Pt 2):373–380. doi: 10.1093/brain/121.2.373.
    1. Priori A, Berardelli A, Rona S, Accornero N, Manfredi M. Polarization of the human motor cortex through the scalp. Neuroreport. 1998;9(10):2257–2260. doi: 10.1097/00001756-199807130-00020.
    1. Cogiamanian F, Brunoni AR, Boggio PS, Fregni F, Ciocca M, Priori A. Non-invasive brain stimulation for the management of arterial hypertension. Med Hypotheses. 2010;74(2):332–336. doi: 10.1016/j.mehy.2009.08.037.
    1. Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000;527(Pt 3):633–639. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x.
    1. Accornero N, Li Voti P, La Riccia M, Gregori B. Visual evoked potentials modulation during direct current cortical polarization. Exp Brain Res. 2007;178(2):261–266. doi: 10.1007/s00221-006-0733-y.
    1. Accolla E, Caputo E, Cogiamanian F, Tamma F, Mrakic-Sposta S, Marceglia S, Egidi M, Rampini P, Locatelli M, Priori A. Gender differences in patients with Parkinson's disease treated with subthalamic deep brain stimulation. Mov Disord. 2007;22(8):1150–1156. doi: 10.1002/mds.21520.
    1. Monti A, Cogiamanian F, Marceglia S, Ferrucci R, Mameli F, Mrakic-Sposta S, Vergari M, Zago S, Priori A. Improved naming after transcranial direct current stimulation in aphasia. J Neurol Neurosurg Psychiatry. 2008;79(4):451–453. doi: 10.1136/jnnp.2007.135277.
    1. Koenigs M, Ukueberuwa D, Campion P, Grafman J, Wassermann E. Bilateral frontal transcranial direct current stimulation: Failure to replicate classic findings in healthy subjects. Clin Neurophysiol. 2009;120(1):80–84. doi: 10.1016/j.clinph.2008.10.010.
    1. Ferrucci R, Mameli F, Guidi I, Mrakic-Sposta S, Vergari M, Marceglia S, Cogiamanian F, Barbieri S, Scarpini E, Priori A. Transcranial direct current stimulation improves recognition memory in Alzheimer disease. Neurology. 2008;71(7):493–498. doi: 10.1212/01.wnl.0000317060.43722.a3.
    1. Vaseghi M, Shivkumar K. The role of the autonomic nervous system in sudden cardiac death. Prog Cardiovasc Dis. 2008;50(6):404–419. doi: 10.1016/j.pcad.2008.01.003.
    1. Mironov S. Respiratory circuits: function, mechanisms, topology, and pathology. Neuroscientist. 2009;15(2):194–208. doi: 10.1177/1073858408329510.
    1. Malliani A, Pagani M, Furlan R, Guzzetti S, Lucini D, Montano N, Cerutti S, Mela GS. Individual recognition by heart rate variability of two different autonomic profiles related to posture. Circulation. 1997;96(12):4143–4145.
    1. Montano N, Porta A, Cogliati C, Costantino G, Tobaldini E, Casali KR, Iellamo F. Heart rate variability explored in the frequency domain: a tool to investigate the link between heart and behavior. Neurosci Biobehav Rev. 2009;33(2):71–80. doi: 10.1016/j.neubiorev.2008.07.006.
    1. Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981;213(4504):220–222. doi: 10.1126/science.6166045.
    1. Baillard C, Goncalves P, Mangin L, Swynghedauw B, Mansier P. Use of time frequency analysis to follow transitory modulation of the cardiac autonomic system in clinical studies. Auton Neurosci. 2001;90(1-2):24–28. doi: 10.1016/S1566-0702(01)00263-6.
    1. Zhang R, Iwasaki K, Zuckerman JH, Behbehani K, Crandall CG, Levine BD. Mechanism of blood pressure and R-R variability: insights from ganglion blockade in humans. J Physiol. 2002;543(Pt 1):337–348. doi: 10.1113/jphysiol.2001.013398.
    1. Eckberg DL. Sympathovagal balance: a critical appraisal. Circulation. 1997;96(9):3224–3232.
    1. Liang K-Y, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika. 1986;73(1):13–22. doi: 10.1093/biomet/73.1.13.
    1. Priori A, Mameli F, Cogiamanian F, Marceglia S, Tiriticco M, Mrakic-Sposta S, Ferrucci R, Zago S, Polezzi D, Sartori G. Lie-specific involvement of dorsolateral prefrontal cortex in deception. Cereb Cortex. 2008;18(2):451–455. doi: 10.1093/cercor/bhm088.
    1. Ferrucci R, Marceglia S, Vergari M, Cogiamanian F, Mrakic-Sposta S, Mameli F, Zago S, Barbieri S, Priori A. Cerebellar transcranial direct current stimulation impairs the practice-dependent proficiency increase in working memory. J Cogn Neurosci. 2008;20(9):1687–1697. doi: 10.1162/jocn.2008.20112.
    1. Grassi G, Arenare F, Pieruzzi F, Brambilla G, Mancia G. Sympathetic activation in cardiovascular and renal disease. J Nephrol. 2009;22(2):190–195.
    1. Nogues MA, Roncoroni AJ, Benarroch E. Breathing control in neurological diseases. Clin Auton Res. 2002;12(6):440–449. doi: 10.1007/s10286-002-0067-1.
    1. Olshansky B, Sabbah HN, Hauptman PJ, Colucci WS. Parasympathetic nervous system and heart failure: pathophysiology and potential implications for therapy. Circulation. 2008;118(8):863–871. doi: 10.1161/CIRCULATIONAHA.107.760405.
    1. Baranchuk A, Nault MA, Morillo CA. The central nervous system and sudden cardiac death: what should we know? Cardiol J. 2009;16(2):105–112.
    1. Bernardi L, Wdowczyk-Szulc J, Valenti C, Castoldi S, Passino C, Spadacini G, Sleight P. Effects of controlled breathing, mental activity and mental stress with or without verbalization on heart rate variability. J Am Coll Cardiol. 2000;35(6):1462–1469. doi: 10.1016/S0735-1097(00)00595-7.
    1. Goldberger JJ. Sympathovagal balance: how should we measure it? Am J Physiol. 1999;276(4 Pt 2):H1273–1280.
    1. Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006;117(4):845–850. doi: 10.1016/j.clinph.2005.12.003.
    1. Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular effects of human insular cortex stimulation. Neurology. 1992;42(9):1727–1732.
    1. Foster PS, Drago V, Ferguson BJ, Harrison DW. Cerebral moderation of cardiovascular functioning: a functional cerebral systems perspective. Clin Neurophysiol. 2008;119(12):2846–2854. doi: 10.1016/j.clinph.2008.08.021.
    1. Oppenheimer S. Cerebrogenic cardiac arrhythmias: cortical lateralization and clinical significance. Clin Auton Res. 2006;16(1):6–11. doi: 10.1007/s10286-006-0276-0.
    1. Abboud H, Berroir S, Labreuche J, Orjuela K, Amarenco P. Insular involvement in brain infarction increases risk for cardiac arrhythmia and death. Ann Neurol. 2006;59(4):691–699. doi: 10.1002/ana.20806.
    1. Rincon F, Dhamoon M, Moon Y, Paik MC, Boden-Albala B, Homma S, Di Tullio MR, Sacco RL, Elkind MS. Stroke location and association with fatal cardiac outcomes: Northern Manhattan Study (NOMAS) Stroke. 2008;39(9):2425–2431. doi: 10.1161/STROKEAHA.107.506055.
    1. Ardolino G, Bossi B, Barbieri S, Priori A. Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain. J Physiol. 2005;568(Pt 2):653–663. doi: 10.1113/jphysiol.2005.088310.
    1. Milby AH, Halpern CH, Baltuch GH. Vagus nerve stimulation for epilepsy and depression. Neurotherapeutics. 2008;5(1):75–85. doi: 10.1016/j.nurt.2007.10.071.
    1. McGregor A, Wheless J, Baumgartner J, Bettis D. Right-sided vagus nerve stimulation as a treatment for refractory epilepsy in humans. Epilepsia. 2005;46(1):91–96. doi: 10.1111/j.0013-9580.2005.16404.x.
    1. Xu WD, Gu YD, Lu JB, Yu C, Zhang CG, Xu JG. Pulmonary function after complete unilateral phrenic nerve transection. J Neurosurg. 2005;103(3):464–467. doi: 10.3171/jns.2005.103.3.0464.
    1. Tripp HF, Bolton JW. Phrenic nerve injury following cardiac surgery: a review. J Card Surg. 1998;13(3):218–223.
    1. Nitsche MA, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W. Modulation of cortical excitability by weak direct current stimulation--technical, safety and functional aspects. Suppl Clin Neurophysiol. 2003;56:255–276. full_text.
    1. Nitsche MA, Doemkes S, Karakose T, Antal A, Liebetanz D, Lang N, Tergau F, Paulus W. Shaping the effects of transcranial direct current stimulation of the human motor cortex. J Neurophysiol. 2007;97(4):3109–3117. doi: 10.1152/jn.01312.2006.

Source: PubMed

3
Sottoscrivi