Immediate and after effects of transcranial direct-current stimulation in the mouse primary somatosensory cortex (original) (raw)

Abstract

Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique consisting in the application of weak electric currents on the scalp. Although previous studies have demonstrated the clinical value of tDCS for modulating sensory, motor, and cognitive functions, there are still huge gaps in the knowledge of the underlying physiological mechanisms. To define the immediate impact as well as the after effects of tDCS on sensory processing, we first performed electrophysiological recordings in primary somatosensory cortex (S1) of alert mice during and after administration of S1-tDCS, and followed up with immunohistochemical analysis of the stimulated brain regions. During the application of cathodal and anodal transcranial currents we observed polarity-specific bidirectional changes in the N1 component of the sensory-evoked potentials (SEPs) and associated gamma oscillations. On the other hand, 20 min of cathodal stimulation produced significant aftereffects including a decreased SEP amplitude for up to 30 min, a power reduction in the 20-80 Hz range and a decrease in gamma event related synchronization (ERS). In contrast, no significant changes in SEP amplitude or power analysis were observed after anodal stimulation except for a significant increase in gamma ERS after tDCS cessation. The polarity-specific differences of these after effects were corroborated by immunohistochemical analysis, which revealed an unbalance of GAD 65-67 immunoreactivity between the stimulated versus non-stimulated S1 region only after cathodal tDCS. These results highlight the differences between immediate and after effects of tDCS, as well as the asymmetric after effects induced by anodal and cathodal stimulation. Transcranial direct-current stimulation (tDCS) is a safe and well tolerated neuromodulatory technique 1-4 that relies on the application of constant weak electrical currents on the scalp during several minutes through strategically positioned electrodes 5,6. Most studies using tDCS deliver a low-current intensity (from conventional 1-2 mA up to currents of 4 mA) between two rubber electrodes (25-35 cm 2) placed on the scalp for 10-20 min 1,3,7. Given its ability to modulate neuronal excitability, tDCS has attracted the attention of basic and clinical neuroscientists that have investigated its potential to modulate brain function 8 and treat a variety of neurological conditions such as epilepsy 9 , attention deficit hyperactivity disorder (ADHD) 10 or ataxia 11 among others (for a review see 12-14). From a mechanistic point of view, the effects of tDCS on cortical excitability can be separated into immediate and after effects. Immediate effects, appearing at the very moment of electric field application, are related to changes in membrane polarization caused by redistribution of charges in the cells in presence of the externally applied electric field 15,16. On the other hand, after effects observed following current cessation require several minutes of stimulation to develop and involve plasticity mechanisms 17. Recently, in vitro models have been successfully used to show that different neuronal features such as the orientation of the somatodendritic axis with

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References (79)

  1. Vol:.(1234567890) Scientific Reports | (2021) 11:3123 | https://doi.org/10.1038/s41598-021-82364-4
  2. Khadka, N. et al. Adaptive current tDCS up to 4 mA. Brain Stimul. 13, 69-79 (2020).
  3. Jackson, M. P., Bikson, M., Liebetanz, D. & Nitsche, M. Toward comprehensive tDCS safety standards. Brain. Behav. Immun. 66, 413 (2017).
  4. Aparício, L. V. M. et al. A systematic review on the acceptability and tolerability of transcranial direct current stimulation treatment in neuropsychiatry trials. Brain Stimul. 9, 671-681 (2016).
  5. Paneri, B. et al. Tolerability of repeated application of transcranial electrical stimulation with limited outputs to healthy subjects. Brain Stimul. 9, 740-754 (2016).
  6. Nitsche, M. & Paulus, W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J. Physiol. 527, 633-639 (2000).
  7. Woods, A. J. et al. A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin. Neurophysiol. 127, 1031-1048 (2016).
  8. Stagg, C. J. & Nitsche, M. A. Physiological basis of transcranial direct current stimulation. Neuroscientist 17, 37-53 (2011).
  9. Nitsche, M. A. et al. Transcranial direct current stimulation: state of the art 2008. Brain Stimul. 1, 206-223 (2008).
  10. Regner, G. G. et al. Preclinical to clinical translation of studies of transcranial direct-current stimulation in the treatment of epilepsy: a systematic review. Front. Neurosci. 12, 189 (2018).
  11. Salehinejad, M. A., Wischnewski, M., Nejati, V., Vicario, C. M. & Nitsche, M. A. Transcranial direct current stimulation in attention- deficit hyperactivity disorder: a meta-analysis of neuropsychological deficits. PLoS ONE 14, 1-26 (2019).
  12. Grimaldi, G. et al. Non-invasive cerebellar stimulation-a consensus paper. Cerebellum 13, 121-138 (2014).
  13. Brunoni, A. et al. Clinical research with tDCS: challenges and future directions. Brain stimul. 5, 175-195 (2012).
  14. Stagg, C. J., Antal, A. & Nitsche, M. A. Physiology of transcranial direct current stimulation. J. ECT 34, 144-152 (2018).
  15. Miterko, L. N. et al. Consensus paper: experimental neurostimulation of the cerebellum. Cerebellum 18(6), 1064-1097 (2019).
  16. Chan, C., Hounsgaard, J. & Nicholson, C. Effects of electric fuelds on transmembrane potential and excitability of turtle cerebellar purkinje cells in vitro. Physiology 402, 751-771 (1988).
  17. Bikson, M., Paulus, W., Esmaeilpour, Z., Kronberg, G. & Nitsche, M. A. Mechanisms of acute and after effects of transcranial direct current stimulation. In Practical Guide to Transcranial Direct Current Stimulation (2019). https ://doi.org/10.1007/978-3-319-95948 -1
  18. Huang, Y. Z. et al. Plasticity induced by non-invasive transcranial brain stimulation: a position paper. Clin. Neurophysiol. 128, 2318-2329 (2017).
  19. Bikson, M. et al. Effect of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro. J. Physiol. 557, 175-190 (2004).
  20. Radman, T., Ramos, R., Brumberg, J. & Bikson, M. Role of cortical cell type and morphology in sub-and suprathreshold uniform electric field stimulation. Brain Stimul. 2, 215-228 (2009).
  21. Vol:.(1234567890) Scientific Reports | (2021) 11:3123 | https://doi.org/10.1038/s41598-021-82364-4 www.nature.com/scientificreports/
  22. Kabakov, A. Y., Muller, P. A., Pascual-Leone, A., Jensen, F. E. & Rotenberg, A. Contribution of axonal orientation to pathway- dependent modulation of excitatory transmission by direct current stimulation in isolated rat hippocampus. J. Neurophysiol. 107, 1881-1889 (2012).
  23. Liu, A. et al. Immediate neurophysiological effects of transcranial electrical stimulation. Nat. Commun. 9, 5092 (2018).
  24. Stagg, C. J. et al. Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation. J. Neurosci. 29, 5202-5206 (2009).
  25. Bachtiar, V. et al. Modulating regional motor cortical excitability with noninvasive brain stimulation results in neurochemical changes in bilateral motor cortices. J. Neurosci. 38, 7327-7336 (2018).
  26. Patel, H. J. et al. Proton Magnetic Resonance Spectroscopy of the motor cortex reveals long term GABA change following anodal Transcranial Direct Current Stimulation. Sci. Rep. 9, 1-8 (2019).
  27. Monai, H. et al. Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain. Nat. Commun. 7, 1-10 (2016).
  28. Ranieri, F. et al. Modulation of LTP at rat hippocampal CA3-CA1 synapses by direct current stimulation. J. Neurophysiol. 107, 1868-1880 (2012).
  29. Fritsch, B. et al. Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learn- ing. Neuron 66, 198-204 (2010).
  30. Sun, Y. et al. current stimulation induces mGluR5-dependent neocortical plasticity. Ann. Neurol. 80, 233-246 (2016).
  31. Stafford, J., Brownlow, M. L., Qualley, A. & Jankord, R. AMPA receptor translocation and phosphorylation are induced by tran- scranial direct current stimulation in rats. Neurobiol. Learn. Mem. 150, 36-41 (2018).
  32. Martins, C. W., de Melo Rodrigues, L. C., Nitsche, M. A. & Nakamura-Palacios, E. M. AMPA receptors are involved in prefrontal direct current stimulation effects on long-term working memory and GAP-43 expression. Behav. Brain Res. 362, 208-212 (2019).
  33. Márquez-Ruiz, J. et al. Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits. Proc. Natl. Acad. Sci. 109, 6710-6715 (2012).
  34. Antal, A., Varga, E. T., Kincses, T. Z., Nitsche, M. A. & Paulus, W. Oscillatory brain activity and transcranial direct current stimula- tion in humans. NeuroReport 15, 1307-1310 (2004).
  35. Reinhart, R. M. G., Zhu, J., Park, S. & Woodman, G. F. Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain. Proc. Natl. Acad. Sci. 112, 9448-9453 (2015).
  36. Wiesman, A. I. et al. Polarity-dependent modulation of multi-spectral neuronal activity by transcranial direct current stimulation. Cortex 108, 222-233 (2018).
  37. Matsunaga, K., Nitsche, M. A., Tsuji, S. & Rothwell, J. C. Effect of transcranial DC sensorimotor cortex stimulation on somatosen- sory evoked potentials in humans. Clin. Neurophysiol. 115, 456-460 (2004).
  38. Dieckhöfer, A. et al. Transcranial direct current stimulation applied over the somatosensory cortex-differential effect on low and high frequency SEPs. Clin. Neurophysiol. 117, 2221-2227 (2006).
  39. Woodman, G. F. A brief introduction to the use of Event-Related Potentials (ERPs) in studies of perception and attention. Atten. Percept. Psychophys. 72, 1-29 (2010).
  40. Sugawara, K. et al. The effect of anodal transcranial direct current stimulation over the primary motor or somatosensory cortices on somatosensory evoked magnetic fields. Clin. Neurophysiol. 126, 60-67 (2015).
  41. Vaseghi, B., Zoghi, M. & Jaberzadeh, S. Differential effects of cathodal transcranial direct current stimulation of prefrontal, motor and somatosensory cortices on cortical excitability and pain perception-a double-blind randomised sham-controlled study. Eur. J. Neurosci. 42, 2426-2437 (2015).
  42. Castro-Alamancos, M. A. & Bezdudnaya, T. Modulation of artificial whisking related signals in barrel cortex. J. Neurophysiol. 113, 1287-1301 (2015).
  43. Modi, M. E. & Sahin, M. Translational use of event-related potentials to assess circuit integrity in ASD. Nat. Rev. Neurol. 13, 160-170 (2017).
  44. Sánchez-León, C. A., Ammann, C., Medina, J. F. & Márquez-Ruiz, J. Using animal models to improve the design and application of transcranial electrical stimulation in humans. Curr. Behav. Neurosci. Rep. 5, 125-135 (2018).
  45. Sun, Y. et al. Drug-responsive inhomogeneous cortical modulation by direct current stimulation. Ann. Neurol. 88, 489-502 (2020).
  46. Paxinos, G. & Franklin, K. B. J. The Mouse Brain in Stereotaxic Coordinates 4th ed (Academic Press, San Diego, 2013).
  47. Feuerstein, D., Parker, K. H. & Boutelle, M. G. Practical methods for noise removal: applications to spikes, nonstationary quasi- periodic noise, and baseline drift. Anal. Chem. 81, 4987-4994 (2009).
  48. Tallon-Baudry, C. & Bertrand, O. Oscillatory gamma activity in humans and its role in object representation. Trends Cogn. Sci. 3, 151-162 (1999).
  49. Bastiaansen, M. & Hagoort, P. Event-induced theta responses as a window on the dynamics of memory. Cortex 39, 967-992 (2003).
  50. Makeig, S. Auditory Event-Related Dynamics of the EEG Spectrum and Effects of Exposure to Tones. Electroencephalogr. Clin. Neurophysiol. 86, 283-293 (1993).
  51. Makeig, S. et al. Dynamic brain sources of visual evoked responses. Science 295, 690-694 (2002).
  52. Opitz, A. et al. Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in humans and nonhuman primates. Sci. Rep. 6, 1-11 (2016).
  53. Chhatbar, P. Y. et al. Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo. Brain Stimul. 11, 727-733 (2018).
  54. Ozen, S. et al. Transcranial electric stimulation entrains cortical neuronal populations in rats. J. Neurosci. 30, 11476-11485 (2010).
  55. Vöröslakos, M. et al. Direct effects of transcranial electric stimulation on brain circuits in rats and humans. Nat. Commun. 9, 483 (2018).
  56. Chakraborty, D., Truong, D. Q., Bikson, M. & Kaphzan, H. Neuromodulation of axon terminals. Cereb. Cortex 28(8), 2786-2794 (2018).
  57. Herculano-Houzel, S. The human brain in numbers: a linearly scaled-up primate brain. Front. Hum. Neurosci. 3, 1-11 (2009).
  58. Reato, D., Rahman, A., Bikson, M. & Parra, L. C. Low-intensity electrical stimulation affects network dynamics by modulating population rate and spike timing. J. Neurosci. 30, 15067-15079 (2010).
  59. Fröhlich, F. & McCormick, D. A. Endogenous electric fields may guide neocortical network activity. Neuron 67, 129-143 (2010).
  60. Márquez-Ruiz, J. et al. Synthetic tactile perception induced by transcranial alternating-current stimulation can substitute for natural sensory stimulus in behaving rabbits. Sci. Rep. 6, 1-12 (2016).
  61. Cambiaghi, M. et al. Brain transcranial direct current stimulation modulates motor excitability in mice. Eur. J. Neurosci. 31, 704-709 (2010).
  62. Cambiaghi, M. et al. Flash visual evoked potentials in mice can be modulated by transcranial direct current stimulation. Neurosci- ence 185, 161-165 (2011).
  63. Rogalewski, A., Breitenstein, C., Nitsche, M. A., Paulus, W. & Knecht, S. SHORT COMMUNICATION Transcranial direct current stimulation disrupts tactile perception. Eur. J. Neurosci. 20, 2001-2004 (2004).
  64. Ragert, P., Vandermeeren, Y., Camus, M. & Cohen, L. G. Improvement of spatial tactile acuity by transcranial direct current stimulation. Clin. Neurophysiol. 119, 805-811 (2008).
  65. Ammann, C., Spampinato, D. & Márquez-Ruiz, J. Modulating motor learning through transcranial direct-current stimulation: an integrative view. Front. Psychol. 7, 1981 (2016).
  66. McDermott, T. J. et al. tDCS modulates behavioral performance and the neural oscillatory dynamics serving visual selective atten- tion. Hum. Brain Mapp. 40(3), 729-740 (2019).
  67. Gray, C. M., Engel, A. K., König, P. & Singer, W. Stimulus-dependent neuronal oscillations in cat visual cortex: receptive field properties and feature dependence. Eur. J. Neurosci. 2, 607-619 (1990).
  68. Engel, A. K. & Singer, W. Temporal binding and the neural correlates of sensory awareness. Trends Cogn. Sci. 5, 16-25 (2001).
  69. Herrmann, C. S., Senkowski, D. & Röttger, S. Phase-locking and amplitude modulations of EEG alpha: two measures reflect dif- ferent cognitive processes in a working memory task. Exp. Psychol. 51, 311-318 (2004).
  70. Kahana, M. J. The cognitive correlates of human brain oscillations. J. Neurosci. 26, 1669-1672 (2006).
  71. Siegle, J. H., Pritchett, D. L. & Moore, C. I. Gamma-range synchronization of fast-spiking interneurons can enhance detection of tactile stimuli. Nat. Neurosci. 17, 1371-1379 (2014).
  72. Berryhill, M. E. & Martin, D. Cognitive effects of transcranial direct current stimulation in healthy and clinical populations: an overview. J. ECT 34, e25-e35 (2018).
  73. Krause, B., Márquez-Ruiz, J. & Kadosh, R. C. The effect of transcranial direct current stimulation: a role for cortical excitation/ inhibition balance?. Front. Hum. Neurosci. 7, 1-4 (2013).
  74. Jackson, M. P. et al. Animal models of transcranial direct current stimulation: methods and mechanisms. Clin. Neurophysiol. 127, 3425-3454 (2016).
  75. Cirillo, G. et al. Neurobiological after-effects of non-invasive brain stimulation. Brain Stimul. 10, 1-18 (2017).
  76. Bikson, M. et al. Transcranial electrical stimulation nomenclature. Brain Stimul. 12(6), 1349-1366 (2019).
  77. Khadka, N., Truong, D. Q., Williams, P., Martin, J. H. & Bikson, M. The quasi-uniform assumption for spinal cord stimulation translational research. J. Neurosci. Methods 328, 108446 (2019).
  78. Krause, M. R., Vieira, P. G., Csorba, B. A., Pilly, P. K. & Pack, C. C. Transcranial alternating current stimulation entrains single- neuron activity in the primate brain. Proc. Natl. Acad. Sci. USA 116, 5747-5755 (2019).
  79. Krause, M. R. et al. Transcranial direct current stimulation facilitates associative learning and alters functional connectivity in the primate brain. Curr. Biol. 27, 3086-3096.e3 (2017).