Weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex. These plastic excitability changes are selectively controlled by the polarity, duration and current strength of stimulation. To reveal the underlying mechanisms of direct current (DC)‐induced neuroplasticity, we combined tDCS of the motor cortex with the application of Na⁺‐channel‐blocking carbamazepine (CBZ) and the N‐methyl‐d‐aspartate (NMDA)‐receptor antagonist dextromethorphan (DMO). Monitored by transcranial magnetic stimulation (TMS), motor cortical excitability changes of up to 40% were achieved in the drug‐free condition. Increase of cortical excitability could be selected by anodal stimulation, and decrease by cathodal stimulation. Both types of excitability change lasted several minutes after cessation of current stimulation. DMO suppressed the post‐stimulation effects of both anodal and cathodal DC stimulation, strongly suggesting the involvement of NMDA receptors in both types of DC‐induced neuroplasticity. In contrast, CBZ selectively eliminated anodal effects. Since CBZ stabilizes the membrane potential voltage‐dependently, the results reveal that after‐effects of anodal tDCS require a depolarization of membrane potentials. Similar to the induction of established types of short‐ or long‐term neuroplasticity, a combination of glutamatergic and membrane mechanisms is necessary to induce the after‐effects of tDCS. On the basis of these results, we suggest that polarity‐driven alterations of resting membrane potentials represent the crucial mechanisms of the DC‐induced after‐effects, leading to both an alteration of spontaneous discharge rates and to a change in NMDA‐receptor activation.

Weak transcranial direct current stimulation (tDCS) with a homogenous DC field at intensities of around 1 mA induces long-lasting changes in the brain. tDCS can be used to manipulate brain excitability via membrane polarisation: cathodal stimulation hyperpolarises, while anodal stimulation depolarises the resting membrane potential, whereby the induced after-effects depend on polarity, duration and intensity of the stimulation. A variety of other parameters influence tDCS effects; co-application of neuropharmacologically active drugs may most impressively prolong or even reverse stimulation effects. Transcranial alternating stimulation (tACS) and random noise stimulation (tRNS) are used to interfere with ongoing neuronal oscillations and also finally produce neuroplastic effects if applied with appropriate parameters.

Transcranial alternating current stimulation (tACS) seems likely to open a new era of the field of noninvasive electrical stimulation of the human brain by directly interfering with cortical rhythms. It is expected to synchronize (by one single resonance frequency) or desynchronize (e.g., by the application of several frequencies) cortical oscillations. If applied long enough it may cause neuroplastic effects. In the theta range it may improve cognition when applied in phase. Alpha rhythms could improve motor performance, whereas beta intrusion may deteriorate them. TACS with both alpha and beta frequencies has a high likelihood to induce retinal phosphenes. Gamma intrusion can possibly interfere with attention. Stimulation in the “ripple” range induces intensity dependent inhibition or excitation in the motor cortex (M1) most likely by entrainment of neuronal networks, whereas stimulation in the low kHz range induces excitation by neuronal membrane interference. TACS in the 200 kHz range may have a potential in oncology.

The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504-32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer's disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentato-thalamo-motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity.

The medical treatment of patients with chronic primary headache syndromes (chronic migraine, chronic tension-type headache, chronic cluster headache, hemicrania continua) is challenging as serious side effects frequently complicate the course of medical treatment and some patients may be even medically intractable. When a definitive lack of responsiveness to conservative treatments is ascertained and medication overuse headache is excluded, neuromodulation options can be considered in selected cases.