Abstract
Non-invasive brain stimulation started in the antiquity by treating headache with electric fishes (∼ 1 A, ∼ 700 V). Transcranial direct current stimulation dominated research in the 19 th century after the invention of the voltaic pile (∼ 1 mA, ∼10 V). At present the main applications involve either weak electric stimulation of many different types (transcranial direct, alternating, random noise or combinations) of currents or high energy pulsed stimulations (∼8 kA, ∼ 10 µs) mediated by transcranial magnetic energy transfer (transcranial magnetic stimulation: TMS). Inhibitory or excitatory after-effects are guided by stimulus intensity, duration and intervals (cf. theta burst, quadripulse and others). In general, lower intensities lead to inhibition and higher intensities to excitation. There is no linear correlation between the duration of stimulation and the size of the after-effects, prolongation of stimulus duration may lead to an oscillating pattern of inhibition or excitation. Missing the right windows in time or in amplitude may lead to no or opposite results explaining the variability and conflicting data in the field. Intracellular calcium increase may be a key leader for deciding between LTD- or LTP-like after-effects. Uncontrolled consumption of nicotine and caffeine increase variability further. Co-application of drugs may guide after-effects in terms of selectivity and duration of after-effects. Current developments encompass new physical techniques such as varying TMS pulse widths, multi-electrode stimulation, interference fields, ultrasound or near infrared stimulation, hypothesis driven protocols based on neurophysiological features of cortical neurons, optimized techniques on realistic individual head models for targeting current flow to predefined areas and others. Clinical applications targeting cortical excitability increases (e.g. depression, pain) or decreases (e.g. epilepsy, migraine) seem to be more rewarding than those requiring structural repair (e.g. stroke).
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