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Repetitive transcranial magnetic stimulation in functional motor disorders: A systematic review of effects and targets.

OBJECTIVE: To evaluate the effectiveness, safety, and potential mechanistic implications of repetitive transcranial magnetic stimulation (rTMS) in adults with functional motor disorders (FMD), focusing on possible phenotype-specific responses and stimulation protocols. METHODS: Seven databases were searched from inception to July 2026. Randomised and non-randomised interventional studies were included. Risk of bias and evidence certainty were assessed using PEDro, RoB 2, JBI tools, and GRADE. Because of substantial clinical and methodological heterogeneity, findings were synthesised qualitatively. RESULTS: Fourteen studies were included. The primary motor cortex was targeted in 11 studies. Functional tremor showed the most consistent evidence with inhibitory stimulation: one small sham-controlled trial found a significant group-by-time effect on tremor severity (p = 0.007), while an uncontrolled prospective series reported 40 % reduction in postural tremor amplitude (p = 0.05). Evidence for functional weakness was conflicting: excitatory M1 stimulation increased objective strength by 25 % versus 10 % with sham (p = 0.004), whereas the largest inhibitory sham-controlled trial found no benefit (p = 0.80). No severe adverse events were reported, but safety reporting was incomplete. GRADE certainty was moderate for tremor and very low for all other outcomes. CONCLUSIONS: Current evidence is insufficient to establish the efficacy of rTMS in FMD or to recommend phenotype-specific protocols. Preliminary findings support further investigation of inhibitory stimulation for functional tremor, whereas evidence for excitatory stimulation in functional weakness remains uncertain. SIGNIFICANCE: The possible interaction between phenotype and stimulation direction is hypothesis-generating. rTMS should currently be considered an experimental, context-sensitive adjunct within multidisciplinary care, pending adequately powered phenotype-stratified sham-controlled trials. Prospero Registration Number: CRD420251250969.

Humans↗

Transcranial magnetic stimulation of the facial nerve: where is the actual excitation site?

The site where excitation on the facial nerve to transcranial magnetic stimulation occurs was studied by recording the muscle responses of 13 patients who had facial nerve lesions at different locations, and by comparing the latencies of muscle responses to transcranial magnetic and direct electrical stimulation of the facial nerve recorded in another 5 patients undergoing posterior fossa surgery. The results of both approaches of this study led independently to the conclusion that magnetic stimulation acts within the proximal part of the facial canal. It is suggested that the cerebrospinal fluid (CSF) conducts the magnetically induced stimulation currents into the labyrinthine segment of the facial canal, where the facial nerve is still surrounded by CSF for about 10 mm.

Action Potentials↗

Stimulus waveform influences the efficacy of repetitive transcranial magnetic stimulation.

BACKGROUND: Optimising stimulus parameters is important in maximising the efficacy of repetitive transcranial magnetic stimulation (rTMS) in treatment applications. RTMS over motor cortex has been reported as more effective in producing corticospinal inhibition when a monophasic rather than a biphasic stimulus waveform is used. However, non-optimal coil orientation and high intensities of monophasic rTMS may have influenced previous results. METHODS: In eight healthy subjects, we measured motor evoked potentials (MEPs) in a hand muscle after monophasic and biphasic rTMS (1 Hz for 15 min) over the motor cortex with the coil always in the optimal orientation. MEPs were evoked by both monophasic and biphasic stimuli. RESULTS: MEPs were initially significantly reduced after monophasic but not biphasic rTMS. However, a late reduction was seen after biphasic rTMS. LIMITATIONS: These motor cortical findings may not be directly applicable to prefrontal rTMS. CONCLUSIONS: This study confirms that low frequency rTMS with monophasic pulses produces more corticospinal inhibition than with biphasic pulses, even when the direction of current and intensity are as well-matched as possible.

Adult↗

Bridging the skull: electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) in psychiatry.

A brief account of repetitive transcranial magnetic stimulation (rTMS) with reference to electroconvulsive therapy (ECT) is given, identifying similarities and dissimilarities, and discussing their potential therapeutic roles. The insulating properties of the skull prevent specific, noninvasive stimulation of particular brain regions by direct electrical means. ECT allows electrical stimulation of the cortex, but its concomitant seizures and distributed electrical currents can have adverse effects on patients. By contrast, magnetic fields pass almost without attenuation through the skull, and can induce secondary electrical currents in localized areas of the brain. Subconvulsive rTMS does not require seizure or general anesthetic, and does not affect memory. Recent studies suggest that rTMS has therapeutic potential for mood disorders, for which ECT is well established. rTMS is a new technology with the potential to treat some mental disorders currently treated with ECT, with fewer side effects. ECT will almost certainly remain the treatment of choice in some situations, but ECT and rTMS may be alternatives for other patients. It is possible that rTMS will become established in some areas where ECT is not used. Further research will define these roles and evaluate the utility of rTMS.

Brain↗

New methods of minimally invasive brain modulation as therapies in psychiatry: TMS, MST, VNS and DBS.

Over the past 20 years, new methods have been developed that have allowed scientists to visualize the human brain in action. Initially positron emission tomography (PET) and now functional magnetic resonance imaging (fMRI) are causing a paradigm shift in psychiatry and the neurosciences. Psychiatry is abandoning the pharmacological model of 'brain as soup', used for much of the past 20 years. Instead, there is new realization that both normal and abnormal behavior arise from chemical processes that occur within parallel distributed networks in specific brain regions. Many of these pathological circuits are becoming well characterized, in disorders ranging from Parkinson's disease, to obsessive-compulsive disorder, to depression. Most recently, there has been an explosion of new techniques that allow for direct stimulation of these brain circuits, without the need for open craniotomy and neurosurgical ablation. The techniques include transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), vagus nerve stimulation (VNS), and deep brain stimulation (DBS). This review will describe these new tools, and overview their current and future potential for research and clinical neuropsychiatric use. The psychiatry of the future will be better grounded in a firm understanding of neuroanatomy and neurophysiology (as well as pharmacology). These brain stimulation tools, or their next iterations, will play an ever-larger role in clinical neuropsychiatric practice.

Brain↗

Associative plasticity in human motor cortex during voluntary muscle contraction.

TMS pulses over the hand area of motor cortex activate different subpopulations of synaptic connections if the direction of the induced current in the brain is reversed from posterior-anterior (PA) direction to anterior-posterior (AP). We tested whether this also made a difference to the after-effects of paired associative stimulation (PAS: ulnar nerve stimulation followed 25 ms later by a transcranial magnetic stimulation pulse). If 50 pairs of stimuli (0.1 Hz) were applied using conventional suprathreshold PA-PAS in resting subjects, there was no effect on motor-evoked potentials (MEPs) in the first dorsal interosseous muscle. In contrast if the same number of pulses were given while subjects made a small tonic (5% maximum) contraction, MEPs were facilitated and resting motor threshold reduced when AP but not PA pulses were used. Subsequent experiments employed subthreshold TMS (95% of the active motor threshold) during voluntary muscle contraction. MEP facilitation accompanied by reduced AP threshold occurred when PAS was given using AP pulses (AP-Sub-PAS), whereas PAS using PA pulses (PA-Sub-PAS) had no excitatory effect. There was no facilitation if the ulnar nerve stimulus was replaced by digital nerve stimulation. There was a tendency for short interval intracortical inhibition (SICI) to decrease and intracortical facilitation (ICF) to increase after AP-Sub-PAS. We propose that the increased effectiveness of AP-Sub-PAS over PA-Sub-PAS is due to the fact that AP TMS more readily activates I3 inputs to corticospinal neurons and hence that these are an important component of associative plasticity in the human motor cortex.

Adult↗

Coil design for real and sham transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) can be used to excite the human cortex noninvasively. TMS also activates scalp muscles and sensory receptors; additionally, the loud sound from the stimulating coil activates auditory pathways. These side effects complicate the interpretation of the results of TMS studies. For control experiments, we have designed a coil that can produce both real and sham stimulation without moving the coil. The sham TMS is similar to the real TMS, except for the different relative direction of the currents in the two loops of the figure-of-eight coil. While the real TMS elicited activation of hand muscles, sham TMS had no such effect; however, the auditory-evoked potentials were similar.

Electroencephalography↗

Motor evoked potentials from transcranial stimulation of the motor cortex in humans.

Electrical monitoring of the motor system offers the potential for the detection of injury, the diagnosis of disease, the evaluation of treatment, and the prediction of recovery from damage. Existing evoked potentials monitor one or another sensory modality, but no generally usable motor monitor exists. We have reported a motor evoked potential using direct stimulation of the spinal cord over the motor tracts in cats and in humans. To achieve a less invasive monitor, we used transcranial stimulation over the motor cortex in the cat, thus stimulating the motor cortex. We report here the initial application of this method to humans. A plate electrode over the motor cortex on the scalp and a second electrode on the palate direct a mild current through the motor cortex which will activate the motor pathways. This signal can be recorded over the spinal cord. It can elicit contralateral peripheral nerve and electromyographic signals in the limbs or movements when the appropriate stimulation parameters are used. In clinical use to date, this has been more reliable than the somatosensory evoked potential in predicting motor function in patients where the two tests differed. It offers a number of possibilities for the development of valuable brain and spinal cord monitoring techniques, but requires further animal studies and clinical experience. Studies to date have not demonstrated adverse effects, but evaluation is continuing.

Adult↗

Transcranial magnetic stimulation as a therapeutic tool in psychiatry: what do we know about the neurobiological mechanisms?

Potential therapeutic properties of repetitive transcranial magnetic stimulation (rTMS) have been suggested in several psychiatric disorders such as depression, mania, obsessive-compulsive disorder, posttraumatic stress disorder and schizophrenia. By inducing electric currents in brain tissue via a time-varying strong magnetic field, rTMS has the potential to either directly or trans-synaptically modulate neuronal circuits thought to be dysfunctional in these psychiatric disorders. However, in order to optimize rTMS for therapeutic use, it is necessary to understand the neurobiological mechanisms involved, particularly the nature of the changes induced and the brain regions affected. Compared to the growing number of clinical studies on its putative therapeutic properties, the studies on the basic mechanisms of rTMS are surprisingly scarce. rTMS currently still awaits clinical routine administration although,there is compelling evidence that it causes changes in neuronal circuits as reflected by behavioural changes and decreases in the activity of the hypothalamic-pituitary-adrenocortical system. Both alterations suggest regional changes in neurotransmitter/neuromodulator release, transsynaptic efficiency, signaling pathways and in gene transcription. Together, these changes are, in part, reminiscent of those accompanying antidepressant drugs.

Animals↗

The Ferrier Lecture 2004 what can transcranial magnetic stimulation tell us about how the brain works?

Transcranial magnetic stimulation (TMS) is a technique whereby parts of the cerebral cortex and underlying white matter can be excited by a brief electrical current induced by a similarly brief, rapidly fluctuating magnetic field which is itself produced by rapidly discharging a current through an insulated coil held against the scalp. When combined with magnetic resonance structural and functional images of the subject's brain, the stimulation can be directed at specific cortical areas. Over a period of only 15 years, TMS has revealed hitherto unsuspected aspects of brain function, such as the role of distant parts of the brain in recovery from stroke, and has helped to resolve several previously intractable disputes, such as the neuronal basis of conscious awareness. This article describes and discusses the origins and nature of TMS, its applications and limitations, and its especial usefulness in conjunction with other techniques of evaluating or imaging brain activity.

Awareness↗

Effects of coil orientation and magnetic field shield on transcranial magnetic stimulation in cats.

To obtain suitable stimulus conditions for transcranial magnetic stimulation, the evoked compound muscle action potential (ECMAP), evoked spinal cord potential (ESCP), and magnetic and electric fields were analyzed in cats with and without the use of a magnetic field shield. Cats were stimulated using a figure 8 magnetic coil placed on the cranium above the motor cortex. The maximum ECMAP amplitude was recorded when the electric current in the coil was in the mediolateral direction, regardless of whether a magnetic shield with a 5 x 5 cm window was used. ECMAP and ESCP thresholds were reduced when magnetic shielding was in place. Due to the edge effect, the strengths of the magnetic and electric fields were highest in the brainstem area, which is an inhomogeneous volume conductor of the cat's cranium. A large induced electric field directed caudally elicited ECMAP and ESCP responses effectively when a magnetic shield with a 5 x 5 cm window was in place.

Action Potentials↗

Polarization of the human motor cortex through the scalp.

Direct currents (DC) applied directly to central nervous system structures produce substantial and long-lasting effects in animal experiments. We tested the functional effects of very weak scalp DC (< 0.5 mA, 7 s) on the human motor cortex by assessing the changes in motor potentials evoked by transcranial magnetic brain stimulation. We performed four different experiments in 15 healthy volunteers. Our findings led to the conclusion that such weak (< 0.5 mA) anodal scalp DC, alternated with a cathodal DC, significantly depresses the excitability of the human motor cortex, providing evidence that a small electric field crosses the skull and influences the brain. A possible mechanism of action of scalp DC is the hyperpolarization of the superficial excitatory interneurones in the human motor cortex.

Adult↗

Intraoperative motor evoked potential monitoring: overview and update.

Amidst controversy about methodology and safety, intraoperative neurophysiology has entered a new era of increasingly routine transcranial and direct electrical brain stimulation for motor evoked potential (MEP) monitoring. Based on literature review and illustrative clinical experience, this tutorial aims to present a balanced overview for experienced practitioners, surgeons and anesthesiologists as well as those new to the field. It details the physiologic basis, indications and methodology of current MEP monitoring techniques, evaluates their safety, explores interpretive controversies and outlines some applications and results, including aortic aneurysm, intramedullary spinal cord tumor, spinal deformity, posterior fossa tumor, intracranial aneurysm and peri-rolandic brain surgeries. The many advances in motor system assessment achieved in the last two decades undoubtedly improve monitoring efficacy without unduly compromising safety. Future studies and experience will likely clarify existing controversies and bring further advances.

Animals↗

Comparison of descending volleys evoked by transcranial and epidural motor cortex stimulation in a conscious patient with bulbar pain.

OBJECTIVE: To compare the pattern of activation of motor cortex produced by transcranial magnetic stimulation and epidural electrical stimulation. METHODS: The spinal volleys evoked by transcranial magnetic stimulation and epidural electrical stimulation over the cerebral motor cortex were recorded from an electrode inserted into the cervical epidural space of one conscious subject who also had a cortical epidural electrode over the motor area. The volleys were termed D- and I-waves according to their latency. Magnetic stimulation was performed with a figure-of-eight coil and the induced current flowed either in a postero-anterior (PA) or in latero-medial (LM) direction. RESULTS: At active motor threshold intensity LM magnetic stimulation evoked a D wave whereas PA stimulation evoked an I(1) wave with later I waves being recruited at increasing stimulus intensities. Electrical epidural stimulation evoked both a D wave and I waves. However, the D wave evoked by electrical epidural stimulation had a longer latency than the LM D wave, suggesting either a more proximal site of activation of the pyramidal axon or activation of slightly faster conducting set of corticospinal fibres by LM stimulation. The I3 wave evoked by electrical epidural stimulation also had a longer latency than the PA I3-wave CONCLUSIONS: Epidural stimulation of the motor cortex can produce repetitive excitation of corticospinal neurones. The order of recruitment of the volleys, and the latency of the D and I3 waves may be slightly different to that seen after transcranial magnetic stimulation. SIGNIFICANCE: Our findings suggest that there may be subtle differences in the populations of neurones activated by the two forms of stimulation.

Consciousness↗

Neuroplasticity, learning and recovery after stroke: a critical evaluation of constraint-induced therapy.

Constraint-induced movement therapy (CIMT) has been hailed as a radical new approach to stroke rehabilitation. The guiding theory is that impairment of hand function is exacerbated by learned non-use and that this in turn leads to a loss of cortical representation of the upper limb. It is claimed that these processes can be reversed by two weeks of constraint of the unaffected limb combined with intensive practice in use of the paretic hand, and numerous small-scale studies have suggested that CIMT can lead to large improvements in function more than a year after stroke. However, the theory of learned non-use is open to question and there is uncertainty about the nature of the improvements induced by CIMT. The greatest effect seems to be increased spontaneous use of the hand, either through reduction of learned non-use or by overcoming the sense of effort during movement. There is also evidence of some improvement on dexterity tests but no studies have analysed in detail whether this reflects reduction of basic motor impairment or learning of compensatory movement strategies. The current weight of evidence is in favour of compensatory learning. Cortical changes detected by transcranial magnetic stimulation (TMS) or functional imaging may reflect this compensatory motor skill learning rather than restoration of representations lost due to the infarct or non-use of the limb. If future studies confirm this then the clinical implication is that direct teaching of unimanual or bimanual compensatory strategies might be a more productive approach than constraint.

Brain↗

A simple method for recording motor evoked potentials of lingual muscles to transcranial magnetic and peripheral electrical stimulation.

Motor evoked potentials were recorded from lingual muscles by means of clip electrodes applied on the lateral side of the tongue, following transcranial magnetic stimulation and peripheral electrical stimulation of the 12th cranial nerve at the mandible jaw. Using a circular coil, the stimulation of the cerebral cortex elicited a response of about 8 ms: its amplitude was higher in the right tongue placing the coil over the contralateral hemisphere, 4 cm from the vertex, with coil currents flowing counterclockwise. Coil position and current flow direction did not significantly modify the characteristics of responses recorded from the left side. The separate stimulation of either hemisphere was better obtained using an 8-shaped coil. The latency of the motor response measured 7.7-8.0 ms, the amplitude was greater on stimulation of the contralateral than the ipsilateral hemisphere and was larger recording from the right (3.3 +/- 1.1 mV) than from the left (1.2 +/- 0.7 mV) side. Positioning the circular coil over the parieto-occipital skull, a response of 4.1 +/- 0.3 ms was obtained, reflecting the intracranial activation of the hypoglossal nerve. The peripheral stimulation at the mandible elicited a response of 3.2 +/- 0.5 ms. The method described appears simple and reliable, potentially helpful in clinical practice.

Adolescent↗

Motor evoked potentials from masseter muscle induced by transcranial magnetic stimulation of the pyramidal tract: the importance of coil orientation.

BACKGROUND: Reliable recording of motor evoked potentials (MEPs) of the masseter muscle by transcranial magnetic stimulation (TMS) has proved more difficult than from facial or intrinsic hand muscles. Up to now it was unclear whether this difficulty was due to methodological and/or anatomical reasons. METHODS: The mechanism of pyramidal cell activation in masseter MEPs was investigated by using magnetic and electric transcranial stimulation. Analysing the effect of magnetic coil positioning and orientation over the scalp, and scrutinizing the masseter recording technique to avoid compound motor action potential (CMAP) contamination from facial muscles, an optimized method of masseter MEPs was developed. RESULTS: In particular, an antero-lateral inducing current orientation in the stimulating coil, approximately paralleling the central sulcus, proved clearly more effective for the masseter muscles than the postero-lateral orientation (P=0.005) found optimal for intrinsic hand muscles. The thus evoked masseter MEPs by transcranial magnetic stimulation (TMS) were found to be identical in shape, amplitude and latency as those evoked by transcranial electric stimulation (TES), evidencing a direct rather than trans-synaptic activation of the pyramidal cells. CONCLUSIONS: We conclude that in TMS evoked MEPs of masseter muscles, the direct stimulation of the pyramidal tract is more easily achieved than the trans-synaptic activation, which is in contrast to the intrinsic hand muscles. We hypothesize that the presynaptic projections to pyramidal cells of the masticatory muscles are less abundant than in hand muscles, and are therefore less accessible to trans-synaptic stimulation.

Action Potentials↗

Corticospinal volleys evoked by transcranial stimulation of the brain in conscious humans.

The direct recording in conscious humans of corticospinal volleys evoked by different magnetic and electric techniques of transcranial stimulation demonstrates that it is possible to activate neurones of the motor cortex in several different ways. Lateral electrical stimulation of the motor cortex preferentially activates the axons of corticospinal neurones in the subcortical white matter, and evokes a D-wave in pyramidal tract. The way of activation of corticospinal neurones using magnetic stimulation depends on the direction of the electrical current induced in the brain and on the shape of the coil. Monophasic magnetic stimulation with a focal figure-of-eight coil inducing posterior-anterior current in the brain activates corticospinal neurones trans-synaptically recruiting an 11-wave, with later I-waves appearing in sequence at higher intensities and a D-wave at very high intensities. If the induced current is rotated to the anterior-posterior direction late I-waves are preferentially recruited and when a D-wave is recruited, it has a later onset than the electrical D-wave, suggesting an activation nearer the cell body of the pyramidal neurones. A latero-medial induced current activates both corticospinal axons at the same point as electrical stimulation evoking a D wave and cortico-cortical axons evoking I-waves. A nonfocal large circular coil centered at the vertex is capable of activating pyramidal neurones both at the initial segment and trans-synaptically evoking a D wave with a longer latency than the electrical D-wave and I-waves. Using a biphasic magnetic stimulation, both phases of the biphasic pulse are capable of activating descending motor output and the pattern of recruitment of descending activity depends on the intensity of the stimulus and the relative threshold of each volley to each direction of current flow.

Consciousness↗