Noninvasive Cortical Stimulation
Transcranial magnetic stimulation (TMS) (Table 19.1): TMS in a repetitive mode (rTMS) is a noninvasive technique with a benign side effect profile and is easy to administer (for an in-depth description, see ). Patients are awake, are alert, and sit in a comfortable chair during treatment sessions, which are roughly 20–30 min in duration. Cardiac or neural pacemakers, metal clips in the brain, and previous seizures are contraindications. Side effects are transient and include scalp discomfort, headache, sleepiness, dizziness, or an increase in pain. Earplugs are recommended to avoid hearing damage.
In most studies, the primary motor area (M1) has been the target of stimulation; less frequently the primary and secondary somatosensory areas (S1 and S2) have been stimulated. The target is located either with conventional techniques or neuronavigation and may be confirmed by neurophysiological means (i.e., the ability to elicit motor-evoked potentials—assessed by electromyography and/or observation of twitches—in a muscle group corresponding to the affected body region). The classic somatotopic rule has also been questioned by some rTMS studies.
Puzzlingly, and without any real explanation, investigators based the final stimulation intensity on the motor threshold of the hand area of the unaffected hemisphere for pains affecting any body area; final intensity varied between 80 and 120% of the calculated motor threshold without any rationale.
Effects can be immediate or build up over several sessions over a few days. Aftereffects are highly variable, either being absent or lasting up to 2 weeks; they are unassociated with entrainment of specific frequencies.
A handheld machine might expand the use of rTMS to the patient’s home.
Transcranial direct current stimulation (tDCS) (Table 19.2): tDCS is even easier to administer (for an in-depth description, see ). It was introduced more than two centuries ago and was reintroduced for use toward the end of the 1990s. Patients are awake, are alert, and sit in a comfortable chair during treatment sessions. The power supply is 10 mA delivered via two surface conductive electrodes covered with saline- or gel-soaked sponges to reduce impedance. The size is 5 × 7 cm (but can be larger or smaller). The anode carries the positive charge and is considered excitatory, while the cathode conveys the negative charge and is considered inhibitory. Various parameters of stimulation in different settings have been used, with intensities up to 5 mA (generally 2 mA), in single to repeated sessions on consecutive days, and a duration of 5′–30′. The safe current density delivered is 0.029–0.08 mA/cm2. The target is located by using the EEG 10–20 system (M1: C3/4); the reference is placed on the contralateral supraorbital area or shoulder. However, given the large electrodes used, tDCS is expected to engage both M1 and S1. A more focal high-definition tDCS is under study. Side effects include redness under the electrode, tingling, light-headedness, headache, fatigue, insomnia, anxiety, confusion, and nausea, among others: these are generally transient. Exclusion criteria include prior head trauma, pregnancy, and epilepsy. The so-called Reduced Impedance Noninvasive Cortical Stimulation (RINCE) is a variant of tDCS.
Transcranial random noise stimulation (tRNS): tRNS uses alternating current with randomly varying frequencies, resulting in a “white noise” waveform. 10 min of 1 mA tRNS with 100–640 Hz random noise increases M1 excitability for 1 h or more. In contrast to tDCS, both electrodes have an activating effect. It appears safe, but the mechanism of action remains speculative: one possibility is alternating electrical fields repeatedly opening and closing voltage-gated channels. tRNS is well suited for blinded studies since the stimulation goes generally unnoticed, the threshold for cutaneous sensation being higher than for tDCS. Dizziness and headache can follow. Treatment is delivered from a battery-driven stimulator with saline-soaked sponge electrodes (6 × 4 cm), one overlying contralateral-to-pain M1 (hand area), another overlying ipsilateral M1 (face area), a third contralateral-to-pain M1 (face area). Full stimulation consists of 10′ of high-frequency bipolar Gaussian random noise (100–600 Hz) at 1.5 mA with 10″ of fade in/out. Stimulation is not as focal as TMS. It is insensitive to the orientation of neurons.
Cranial electrotherapy (CES): This uses a much small microcurrent than tDCS with electrodes over the ear lobules. It can reach deeper brain structures with intensity unchanged from the cortex to brainstem. Stimulation varies from 20′ to 1 h.
Transcranial low-intensity focused ultrasound (T-LIFU) or subablative sonication: As known since 1929, ultrasound can modulate the activity of excitable tissues, including neural tissues. The bone is no obstacle for ultrasound and may actually lens it. Pulsed 0.5 MHz T-LIFU (pulse duration: 360 μs repeated at 1 KHz for 500 ms; transducer diameter: 3 cm; focal length: 3 cm, perpendicular to the skull) centered on, e.g., S1 can modulate it—possibly by increasing local cortical inhibitory power—with a spatial resolution of <1 cm (S1 depth 2 cm). Initial studies in patients with chronic pain are promising, but no experience has accrued for CP ( and references herein).
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