Anodal Transcranial Direct Current Stimulation (tDCS) Over the Motor Cortex Increases Sympathetic Nerve Activity

BACKGROUND Transcranial direct current stimulation (tDCS) is currently being investigated as a non-invasive neuromodulation therapy for a range of conditions including stroke rehabilitation. tDCS affects not only the area underlying the electrodes but also other areas of the cortex and subcortical structures. This could lead to unintended alteration in brain functions such as autonomic control. OBJECTIVE We investigated the potential effects of tDCS on cardiovascular autonomic function in healthy volunteers. METHODS Anodal (n = 14) or cathodal (n = 8) tDCS at 1 mA was applied over the primary motor cortex with the second electrode placed on the contralateral supraorbital region. Subjects visited the department twice and received active or sham tDCS for 15 min. Heart rate, blood pressure and respiration were recorded at baseline, during tDCS and after stimulation. Heart rate variability (HRV) was calculated using spectral analysis of beat-to-beat intervals derived from ECG data. Microneurography was also used to record muscle sympathetic nerve activity (MSNA; n = 5). RESULTS Anodal tDCS caused a significant shift in HRV toward sympathetic predominance (P = 0.017), whereas there was no significant change in the cathodal or sham groups. Microneurography results also showed a significant increase in MSNA during anodal tDCS that continued post-stimulation. CONCLUSIONS Anodal tDCS of the motor cortex shifts autonomic nervous system balance toward sympathetic dominance due at least in part to an increase in sympathetic output. These results suggest further investigation is warranted on tDCS use in patient groups with potential autonomic dysfunction, such as stroke patients.

[1]  D. Purpura,et al.  INTRACELLULAR ACTIVITIES AND EVOKED POTENTIAL CHANGES DURING POLARIZATION OF MOTOR CORTEX. , 1965, Journal of neurophysiology.

[2]  N. Owens,et al.  Medial prefrontal cortex depressor response: role of the solitary tract nucleus in the rat , 1999, Neuroscience.

[3]  G. Breithardt,et al.  Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. , 1996 .

[4]  A. Verberne,et al.  Cortical Modulation of theCardiovascular System , 1998, Progress in Neurobiology.

[5]  B. Wallin,et al.  Sex, ageing and resting blood pressure: gaining insights from the integrated balance of neural and haemodynamic factors , 2012, The Journal of physiology.

[6]  J. Brasil-Neto,et al.  Lack of clinically detectable acute changes on autonomic or thermoregulatory functions in healthy subjects after transcranial direct current stimulation (tDCS) , 2012, Brain Stimulation.

[7]  A Krogh,et al.  The regulation of respiration and circulation during the initial stages of muscular work , 1913, The Journal of physiology.

[8]  M. Nitsche,et al.  Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans , 2001, Neurology.

[9]  R. Cohen,et al.  Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. , 1981, Science.

[10]  L. Bindman,et al.  The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long‐lasting after‐effects , 1964, The Journal of physiology.

[11]  M. Nitsche,et al.  Safety criteria for transcranial direct current stimulation (tDCS) in humans , 2003, Clinical Neurophysiology.

[12]  C. Gerloff,et al.  Non-invasive brain stimulation in neurological diseases , 2013, Neuropharmacology.

[13]  A. Verberne,et al.  Cortical modulation of the cardiovascular system. , 1998, Progress in neurobiology.

[14]  R. Dampney,et al.  Functional organization of central pathways regulating the cardiovascular system. , 1994, Physiological reviews.

[15]  Vladimir Hachinski,et al.  Cardiovascular and neurological causes of sudden death after ischaemic stroke , 2012, The Lancet Neurology.

[16]  J P Greenwood,et al.  Single-unit sympathetic discharge : quantitative assessment in human hypertensive disease. , 1999, Circulation.

[17]  Delgado Jm.  Circulatory effects of cortical stimulation. , 1960 .

[18]  M. Nitsche,et al.  Physiological Basis of Transcranial Direct Current Stimulation , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[19]  Mark S. George,et al.  Feasibility, safety, and effectiveness of transcranial direct current stimulation for decreasing post-ERCP pain: a randomized, sham-controlled, pilot study. , 2011, Gastrointestinal endoscopy.

[20]  M. Chapleau,et al.  Methods of assessing vagus nerve activity and reflexes , 2011, Heart Failure Reviews.

[21]  Yves Vandermeeren,et al.  Effect of tDCS with an extracephalic reference electrode on cardio-respiratory and autonomic functions , 2010, BMC Neuroscience.

[22]  F. Fregni,et al.  The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. , 2013, JAMA psychiatry.

[23]  Richard S. J. Frackowiak,et al.  How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain? , 2005, The European journal of neuroscience.

[24]  Paul Leonard Gabbott,et al.  Prefrontal cortex in the rat: Projections to subcortical autonomic, motor, and limbic centers , 2005, The Journal of comparative neurology.

[25]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[26]  M. Nitsche,et al.  Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation , 2000, The Journal of physiology.

[27]  Alberto Malliani,et al.  Heart rate variability: from bench to bedside. , 2005, European journal of internal medicine.

[28]  O. Lippold,et al.  A Preliminary Account of the Clinical Effects of Polarizing the Brain in Certain Psychiatric Disorders , 1964, British Journal of Psychiatry.

[29]  Ravi S. Menon,et al.  Cortical regions associated with autonomic cardiovascular regulation during lower body negative pressure in humans , 2005, The Journal of physiology.

[30]  O. Creutzfeldt,et al.  Influence of transcortical d-c currents on cortical neuronal activity. , 1962, Experimental neurology.

[31]  N. Charkoudian,et al.  Sympathetic neural mechanisms in human cardiovascular health and disease. , 2009, Mayo Clinic proceedings.

[32]  Carles Falcón,et al.  Modulation of verbal fluency networks by transcranial direct current stimulation (tDCS) in Parkinson’s disease , 2013, Brain Stimulation.

[33]  O. Lippold,et al.  Mental Changes Resulting from the Passage of Small Direct Currents Through the Human Brain , 1964, British Journal of Psychiatry.

[34]  A. D. Smith,et al.  A monosynaptic pathway from an identified vasomotor centre in the medial prefrontal cortex to an autonomic area in the thoracic spinal cord , 1993, Neuroscience.

[35]  Gian Domenico Pinna,et al.  Baroreflex Sensitivity: Measurement and Clinical Implications , 2008, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[36]  C. Im,et al.  Evaluation of local electric fields generated by transcranial direct current stimulation with an extracephalic reference electrode based on realistic 3D body modeling , 2012, Physics in Medicine and Biology.

[37]  Henrique Sequeira,et al.  Motor cortical control of cardiovascular bulbar neurones projecting to spinal autonomic areas , 2003, Journal of neuroscience research.

[38]  A B Vallbo,et al.  The discharge behaviour of single vasoconstrictor motoneurones in human muscle nerves. , 1994, The Journal of physiology.

[39]  P. Schlindwein,et al.  Sympathetic activity at rest and motor brain areas: FDG–PET study , 2008, Autonomic Neuroscience.

[40]  Henrique Sequeira,et al.  Cortical control of somato-cardiovascular integration: neuroanatomical studies , 2000, Brain Research Bulletin.

[41]  Ravi S. Menon,et al.  Ventral medial prefrontal cortex and cardiovagal control in conscious humans , 2007, NeuroImage.

[42]  P. Soares,et al.  ranscranial direct current stimulation influences the cardiac autonomic ervous control afael , 2011 .

[43]  Neri Accornero,et al.  Visual evoked potentials modulation during direct current cortical polarization , 2007, Experimental Brain Research.

[44]  J. Deuchars,et al.  Tonic GABAergic Inhibition of Sympathetic Preganglionic Neurons: A Novel Substrate for Sympathetic Control , 2008, The Journal of Neuroscience.