Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee

Abstract

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

Keywords: Clinical neurophysiology; Excitability threshold; Human cortex; Non-invasive stimulation; TMS measures; Transcranial magnetic stimulation.

Fig. 1

The pyramidal tract waves (from Kernell and Chien-Ping, 1967 – with permission). The records of Fig. 1 are from two different baboons (A and B, respectively), and they were obtained with an electrode resting on the dorsolateral surface of the cervical spinal cord. Weak stimuli are seen to elicit only a brief single ‘wave’ which has an initial positive and a more prominent negative phase (D-wave). At higher stimulus strengths the D wave attains a greater amplitude, and it is then succeeded by a series of rapidly recurring, smaller, and predominantly negative-going waves (I-waves). The interval between the various waves is of the order of 1–2 ms. The various I waves were numbered according to their latency at strong cortical stimuli, and they are referred to as the I1 (arrow marked “x”), I2, I3 and 14 waves, respectively.

Fig. 2

Illustration of direction of current flows in a magnetic coil and the induced current in the brain (from Hallett, 2007 – with permission). In magnetic stimulation, a brief, high-current pulse is produced in a coil of wire, called the magnetic coil. A magnetic field is produced with lines of flux perpendicular to the plane of the coil, which ordinarily is placed tangential to the scalp. The magnetic field can be up to about 2 T and typically lasts for about 100 μs. An electric field is induced perpendicularly to the magnetic field. The voltage of the field itself may excite neurons, but the induced currents are likely to be more important. In a homogeneous medium, spatial change of the electric field will cause current to flow in loops parallel to the plane of the coil, which will be predominantly tangential in the brain. The loops with the strongest current will be near the circumference of the coil itself. The current loops become weak near the center of the coil, and there is no current at the center itself. Neural elements are activated by the induced electric field by two mechanisms. If the field is parallel to the neural element, then the field will be most effective where the intensity changes as a function of distance. If the field is not completely parallel, activation will occur at bends in the neural element.

Fig. 3

Magnetic coil shape determines the pattern of the electric field (from Hallett, 2007 – with permission). Two magnetic coils with different shapes (A and B) and their resultant electric fields (C and D).

Fig. 4

Coil placement for MT determination of an intrinsic hand muscle (from Groppa et al., 2012 – with permission). In this and in the following figure the current flowing in the brain has an opposite direction to that flowing in the coil. Optimal coil orientation refers to monophasic pulse or the second phase of a biphasic pulse. Current direction in the coil can differ across commercially available stimulators.

Fig. 5

Coil placement for MT determination of a leg muscle (from Groppa et al., 2012 – with permission).

Fig. 6

A representative case of a linear pattern of increase of the CSP duration (right and left hemisphere, recordings from left and right FDI, respectively) as a function of transcranial stimulation intensity which was increased by about 20% from motor threshold (from Cicinelli et al., 2000 – with permission). The values of the CSP duration interhemispheric asymmetry (ms) are shown. The bottom part of the figure shows the peripheral SP recorded from FDI muscles following supramaximal electrical stimulation of the ulnar nerve at the wrist.

Fig. 7

Schematic representation of the calculation of central motor conduction time (CMCT) (from Kobayashi and Pascual-Leone, 2003 – with permission). Motor evoked potential induced by TMS. (b) MEP after cervical spinal root stimulation. (c) F-waves after ulnar nerve electric stimulation. CMCT is estimated by onset latency of T1 minus onset latency of T2. By use of F-wave latency CMCT can be estimated more precisely as T1–(F + M − 1)2. T1 = onset latency of MEP elicited by TMS; T2 = onset latency of MEP elicited by the coil placed on the back of cervical spine. M = onset latency of M-wave by electrical ulnar nerve stimulation. F = onset latency of F-wave by electrical ulnar nerve stimulation.

Fig. 8

Age effects on absolute latencies and ‘latency jump’ between “relaxed” and “contracted” motor evoked potentials (from Caramia et al., 1993 – with permission). Magnetic brain stimulation was carried out in children from 2 to 12 years. The latency of MEPs recorded during voluntary contraction increased in a linear fashion with age and body size. The latency of MEPs recorded when relaxed had a much slower “maturation,” and gained the adult value at about 10–12 years of age. The same effect is observed with TES.

Fig. 9

Central motor conduction studies using magnetic stimulation in humans. (A) CMCT for upper limbs, (B) CMCT for lower limbs. For upper limbs, cortical-brainstem conduction time (C–BST CT) and brainstem-cervical root conduction time (BST–R CT) can be measured as well as CMCT. For motor cortex and motor root stimulation, a round coil is usually used, whereas for brainstem stimulation, a double cone coil is required. For lower limbs, cortical-brainstem conduction time (C-BST CT) and brainstem-lumbar root conduction time (BST–R CT) also can be measured. Furthermore, cortico-conus motor conduction time (CCCT) and cauda equina conduction time (CECT) can be measured. For cortical stimulation, a round coil or double cone coil is used, whereas for motor root stimulation, a round coil or MATS coil is used. For conus stimulation, the MATS coil is required.

Fig. 10

TMS mapping of upper extremity muscles in right and left sides of one normal subject after stimulation of the contralateral M1s (from Wassermann et al., 1992 – with permission). Note that hand muscles are represented more laterally than proximal arm muscles. CZ, vertex.

Fig. 11

Cortical mapping procedure. (A) Threshold defined on the “hot spot” of the “target muscle”. (B) 4–8 stimuli for each position at intensity of MT +10%. (C) Create MEP amplitude maps and calculate the center of gravity.

Fig. 12

EMG responses to TMS in relaxed first dorsal interosseous muscle are inhibited by a prior, subthreshold, magnetic conditioning stimulus (from Kujirai et al., 1993 –with permission). (A) Shows examples of EMG data from a single subject. The top trace shows absence of any responses to the conditioning stimulus given alone. The lower two records have two superimposed traces, the response to the test stimulus given alone, and the response to the test stimulus when given 3 ms (middle traces) or 2 ms (lower traces) after a conditioning stimulus. The larger of the two traces (dotted line) is the response to the test stimulus alone. It is dramatically suppressed at these two interstimulus intervals. Note the shorter latency of the conditioned response at an ISI = 3 ms. Each trace is the average of 10 sweeps. (B) Shows the mean (+SEM) time course of suppression in 10 subjects. At each interstimulus interval, the size of the conditioned responses is expressed as a percentage of the size of the control response. In both (A) and (B), the conditioning and test stimuli were given through the same figure-of-eight coil oriented so that electric current in the junction region flowed from anterior to posterior over the lateral part of the motor cortex.

Fig. 13

TMS–EEG co-registration (Bonato et al., 2006 – with permission). (A) Grand average of the electroencephalographic (EEG) responses from 100 ms pre to 300 ms post-transcranial magnetic stimulation (TMS) at all scalp locations recorded during real-TMS and Sham-TMS. This figure refers to stimulation of the left primary motor cortex (MI) performed with the coil oriented 45° away from the midline and with the handle pointing backwards and laterally. The grey point indicates the site of stimulation (between F3 and C3), while the arrow indicates the orientation of the coil in respect to the stimulation site (45° to the sagittal plane). The electrode montage used for the experiment is shown at the bottom. Polarity of the waveforms is plotted with negative values upward in this and subsequent figures. The two Sham-TMS conditions (Sham 1-TMS and Sham 2-TMS) have been averaged. (B) Grand average of the EEG responses recorded at the vertex (Cz) during the real-TMS (thick solid line) and the Sham-TMS (thin solid line) conditions of the left MI performed with the coil oriented 45° away the midline and with the handle pointing backwards and laterally. Standard deviation of real TMS is also shown (dashed line). The onset of the TMS stimulus (at 0 ms) is labelled. Main features are marked in these sample waveforms for orientation. The two Sham-TMS conditions (Sham 1-TMS and Sham 2-TMS) have been averaged.