Erzeugung und Modulation von Neuroplastizität durch transkranielle Gleichstromstimulation beim Menschen

Zusammenfassung

Die Erzeugung zerebraler Erregbarkeitsveränderungen mittels schwacher Gleichstromstimulation geht auf tierexperimentelle Untersuchungen der 50er- und 60er-Jahre des letzten Jahrhunderts zurück. Grundlegender Wirkungsmechanismus ist eine unterschwellige Ruhemembranpotenzialverschiebung, je nach Stimulationspolarität in hyper- oder depolarisierender Richtung, die zu Veränderungen der Exzitabilität kortikaler Neurone führt. Analoge Erregbarkeitsveränderungen können auch nicht invasiv durch transkranielle Gleichstromstimulation (tDCS) im menschlichen Kortex erzeugt werden. In Abhängigkeit von der Stimulationspolarität kann die kortikale Exzitabilität erhöht oder vermindert werden, bei ausreichender Stimulationsdauer halten diese Veränderungen nach Beendigung der Stimulation an. Die Dauer der Nacheffekte lässt sich durch die Wahl adäquater Stimulationsdauer und -intensität steuern. Neuere Studien zeigen, dass die Nacheffekte NMDA-Rezeptor-abhängig sind. Des Weiteren konnte belegt werden, dass tDCS sowohl im motorischen, als auch im präfrontalen, visuellen und somatosensorischen Kortex effektiv ist. Hierbei eignet sich tDCS nicht nur zur Erzeugung, sondern auch zur Modulation neuroplastischer Vorgänge. Erste funktionelle Studien belegen die Effektivität der Stimulation zur Modulation übungsabhängiger Neuroplastizität, visuomotorischer Koordination sowie motorischen und semantischen Lernens. Die transkranielle Gleichstromstimulation stellt somit ein viel versprechendes neues Verfahren zur Induktion und Beeinflussung von Neuroplastizität beim Menschen dar; es ermöglicht die fokale, selektive, reversible, schmerzfreie und noninvasive Induktion kortikaler Erregbarkeitsveränderungen. Mögliche zukünftige therapeutische Optionen werden diskutiert.

Abstract

In the past, weak direct currents were used for the induction of cerebral excitability modifications primarily in animal experiments. These excitability shifts are accomplished by a sub-threshold modulation of neuronal resting membrane potentials, and thus a polarity-dependent de- or hyperpolarisation of cortical neurons. Similar effects are achieved by the non-invasive transcranial direct current stimulation (tDCS) in humans. Here cathodal stimulation diminishes, while anodal tDCS enhances excitability. Given a sufficient stimulation duration and strength, after-effects are induced, which are NMDA receptor-dependent. As shown, tDCS is not only effective in the primary motor cortex, but also in prefrontal, visual and somatosensory areas. In this case the technique has been demonstrated not only to induce, but also to modulate neuroplastic mechanisms, as shown for use-dependent neuroplasticity, visuo-motor coordination, motor and semantic learning. Altogether, tDCS is a promising new tool to induce and modulate neuroplasticity in humans. It enables a focal, selective, prolonged, reversible, painless and non-invasive modification of cortical excitability. Possible future clinical applications are discussed.

Key words

Transcranial direct current stimulation - transcranial magnetic stimulation - polarization - brain - neuroplasticity

Literatur

• 1 Bindman L J, Lippold O CJ, Redfearn J WT. 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.  J Physiol. 1964;  172 369-382
• 2 Creutzfeldt O D, Fromm G H, Kapp H. Influence of transcortical d-c currents on cortical neuronal activity.  Exp Neurol. 1962;  5 436-452
• 3 Gartside I B. Mechanisms of sustained increases of firing rate of neurones in the rat cerebral cortex after polarization: reverberating circuits or modification of synaptic conductance?.  Nature. 1968;  220 382-383
• 4 Purpura D P, McMurtry J G. Intracellular activities and evoked potential changes during polarization of motor cortex.  J Neurophysiol. 1965;  28 166-185
• 5 Terzuolo C A, Bullock T H. Measurement of imposed voltage gradient adequate to modulate neuronal firing.  Proc Natl Ac Sci. 1956;  42 687-694
• 6 Nitsche M A, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W. Modulation of cortical excitability by weak direct current stimulation - technical, safety and functional aspects. In: Paulus W, Tergau F, Nitsche MA, Rothwell JC, Ziemann U, Hallett M (eds).  Clin Neurophysiol Suppl. 2003a;  56 255-276
• 7 Frégnac Y, Smith D, Friedlander M J. Postsynaptic membrane potential regulates synaptic potentiation and depression in visual cortical neurons.  Society for Neuroscience Abstracts. 1990;  16 798
• 8 Hattori Y, Moriwaki A, Hori Y. Biphasic effects of polarizing current on adenosine-sensitive generation of cyclic AMP in rat cerebral cortex.  Neurosci Lett. 1990;  116 320-324
• 9 Islam N, Aftabuddin M, Moriwaki A, Hattori Y, Hori Y. Increase in the calcium level following anodal polarization in the rat brain.  Brain Res. 1995;  684 206-208
• 10 Moriwaki A. Polarizing currents increase noradrenaline-elicited accumulation of cyclic AMP in rat cerebral cortex.  Brain Res. 1991;  544 248-252
• 11 Rush S, Driscoll D A. Current distribution in the brain from surface electrodes.  Anaest Analg Curr Res. 1968;  47 717-723
• 12 Dymond A M, Coger R W, Serafetinides E A. Intracerebral current levels in man during electrosleep therapy.  Biol Psychiatry. 1975;  10 101-104
• 13 Lolas F. Brain polarization: behavioral and therapeutic effects.  Biol Psychiatry. 1977;  12 37-47
• 14 Nitsche M A, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.  J Physiol. 2000;  527 633-639
• 15 Baudewig J, Nitsche M A, Fahm J, Paulus W. Regional modulation of BOLD MRI responses to human sensorimotor activation by transcranial direct current stimulation.  Magn Reson Med. 2001;  45 196-201
• 16 Nitsche M A, Paulus W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans.  Neurology. 2001;  57 1899-1901
• 17 Nitsche M A, Nitsche M S, Klein C C, Tergau F, Rothwell J C, Paulus W. Level of action of cathodal DC polarisation induced inhibition of the human motor cortex.  Clin Neurophysiol. 2003b;  114 600-604
• 18 Liebetanz D, Nitsche M A, Tergau F, Paulus W. Pharmacological approach to synaptic and membrane mechanisms of DC-induced neuroplasticity in man.  Brain. 2002;  125 2238-2247
• 19 Nitsche M A, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, Henning S, Tergau F, Paulus W. Pharmacological modulation of cortical excitability shifts induced by transcranial DC stimulation.  J Physiol. 2003c;  553 293-301
• 20 Nitsche M A, Grundey J, Liebetanz D, Lang N, Tergau F, Paulus W. Catecholaminergic consolidation of motor cortex plasticity in humans. Cereb Cortex in press
• 21 Antal A, Kincses T Z, Nitsche M A, Bartfai O, Paulus W. Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence.  Invest Ophthalmol Vis Sci. 2004;  45 702-707
• 22 Antal A, Kincses T Z, Nitsche M A, Paulus W. Manipulation of phosphene thresholds by transcranial direct current stimulation in man.  Exp Brain Res. 2003;  150 375-378
• 23 Antal A, Varga E T, Kinsces T Z, Nitsche M A, Paulus W. Oscillatory brain activity and transcranial direct current stimulation in humans. Neuroreport in press a
• 24 Matsunaga K, Nitsche M A, Tsuji S, Rothwell J. Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked potentials in humans.  Clin Neurophysiol. 2004;  115 456-460
• 25 Morrel F, Naitoh P. Effect of cortical polarization on a conditioned avoidance response.  Exp Neurol. 1962;  6 507-523
• 26 Proctor F, Pinto-Hamuy T, Kupferman I. Cortical stimulation during learning in rabbits.  Neuropsychologia. 1964;  2 305-310
• 27 Albert D J. The effects of polarizing currents on the consolidation of learning.  Neuropsychologia. 1966;  4 65-77
• 28 Rosen S C, Stamm J S. Transcortical polarization: facilitation of delayed response performance by monkeys.  Exp Neurology. 1972;  35 282-289
• 29 Rioult-Pedotti M S, Friedman D, Hess G, Donoghue J P. Strengthening of horizontal cortical connections following skill learning.  Nat Neurosci. 1998;  1 230-234
• 30 Siebner H R, Lang N, Rizzo V, Nitsche M A, Paulus W, Lemon R N, Rothwell J C. Pre-conditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial DC stimulation: evidence for homeostatic plasticity in human motor cortex.  J Neurosci. 2004;  24 3379-3385
• 31 Rosenkranz K, Nitsche M A, Tergau F, Paulus W. Diminution of training-induced transient motor cortex plasticity by weak transcranial direct current stimulation in the human.  Neuroscience Letters. 2000;  296 61-63
• 32 Antal A, Nitsche M A, Paulus W. External modulation of visual perception in humans.  Neuroreport. 2001;  12 3553-3555
• 33 Antal A, Nitsche M A, Kruse W, Hoffmann K-P, Paulus W. Visuomotor coordination is improved by transcranial direct current stimulation of the human visual cortex. J Cog Neurosci in press b
• 34 Elbert T, Lutzenberger W, Rockstroh B, Birbaumer N. The influence of low-level transcortical DC-currents on response speed in humans.  Int J Neurosci. 1981;  14 101-114
• 35 Jaeger D ET, Lutzenberger W, Birbaumer N. The effects of externally applied transcephalic weak direct currents on lateralization in choice reaction tasks.  Journal of Psychophysiology. 1987;  1 127-133
• 36 Nitsche M A, Schauenburg A, Lang N, Liebetanz D, Exner C, Paulus W, Tergau F. Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human.  J Cog Neurosci. 2003d;  15 619-626
• 37 Nissen M J, Bullemer P. Attentional requirements of learning: evidence from performance measures.  Cogn Psychol. 1987;  19 1-32
• 38 Antal A, Nitsche M A, Kinsces T Z, Kruse W, Hoffmann K-P, Paulus W. Facilitation of visuo-motor learning by transcranial direct current stimulation of the motor and extrastriate visual areas in humans. Eur J Neurosci in press c
• 39 Kincses T Z, Antal A, Nitsche M A, Bártfai O, Paulus W. Facilitation of probabilistic classification learning by transcranial direct current stimulation of the prefrontal cortex in the human.  Neuropsychologia. 2003;  42 113-117
• 40 Lang N, Nitsche M A, Sommer M, Tergau F, Paulus W. Modulation of motor cortex consolidation by external DC stimulation. In: Paulus W, Tergau F, Nitsche MA, Rothwell JC, Ziemann U, Hallett M (eds).  Clin Neurophysiol Suppl. 2003;  56 277-281
• 41 Durand D M, Bikson M. Suppression and control of epileptiform activity by electrical stimulation: a review.  Proceedings of the IEEE. 2001;  89 1065-1082