Transcranial magnetic stimulation of the brain

Abstract

Recognizing that electrically stimulating the motor cortex could relieve chronic pain sparked development of noninvasive technologies. In transcranial magnetic stimulation (TMS), electromagnetic coils held against the scalp influence underlying cortical firing. Multiday repetitive transcranial magnetic stimulation (rTMS) can induce long-lasting, potentially therapeutic brain plasticity. Nearby ferromagnetic or electronic implants are contraindications. Adverse effects are minimal, primarily headaches. Single provoked seizures are very rare. Transcranial magnetic stimulation devices are marketed for depression and migraine in the United States and for various indications elsewhere. Although multiple studies report that high-frequency rTMS of the motor cortex reduces neuropathic pain, their quality has been insufficient to support Food and Drug Administration application. Harvard's Radcliffe Institute therefore sponsored a workshop to solicit advice from experts in TMS, pain research, and clinical trials. They recommended that researchers standardize and document all TMS parameters and improve strategies for sham and double blinding. Subjects should have common well-characterized pain conditions amenable to motor cortex rTMS and studies should be adequately powered. They recommended standardized assessment tools (eg, NIH's PROMIS) plus validated condition-specific instruments and consensus-recommended metrics (eg, IMMPACT). Outcomes should include pain intensity and qualities, patient and clinician impression of change, and proportions achieving 30% and 50% pain relief. Secondary outcomes could include function, mood, sleep, and/or quality of life. Minimum required elements include sample sources, sizes, and demographics, recruitment methods, inclusion and exclusion criteria, baseline and posttreatment means and SD, adverse effects, safety concerns, discontinuations, and medication-usage records. Outcomes should be monitored for at least 3 months after initiation with prespecified statistical analyses. Multigroup collaborations or registry studies may be needed for pivotal trials.

Challenges of differential placebo effects in contemporary medicine: The example of brain stimulation

“…TMS’s robust placebo responses are not limited to studies of depression and have also been well characterized in other neuropsychiatric fields including schizophrenia 34 , obsessive-compulsive disorder 35 , Parkinson’s disease 36 and chronic pain. 37 Other areas of TMS research such as epilepsy 38 and motor learning 39 have reported more modest placebo responses.…”

“…Accordingly, a RCT investigating a treatment with a large embedded placebo effect will generally need more subjects to prove efficacy than a treatment with a smaller placebo effect. 3,37 This has almost certainly wreaked havoc on translational TMS research and may help explain a common trend in the field: very promising initial open-label, single arm studies and then mixed results from small (underpowered) RCTs. 28 Very few TMS clinical applications in neurology and psychiatry have been able to maneuver past this stage.…”

“…28 This is not surprising as the factors related to enhanced placebo devices are combined with a patient population known to be high placebo responders. 21,37 …”

New advances in prevention of migraine

“…The optimal dose of pulses and their frequency is still uncertain. The data showed that the use of TMS is effective and safe in the short-term use; however, there is still no evidence for its long-term safety 28. Similarly, transcutaneous electrical nerve stimulation is another noninvasive procedure that could have potential benefit for migraineurs.…”

“…Similarly, transcutaneous electrical nerve stimulation is another noninvasive procedure that could have potential benefit for migraineurs. A recent randomized clinical trial28 investigated the safety and efficacy of trigeminal supraorbital transcutaneous stimulation (STS) as a preventive therapy for migraine. It showed STS significantly decreasing mean number of migraine days.…”