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Simple metric for scaling motor threshold based on scalp-cortex distance: application to studies using transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a unique method in neuroscience used to stimulate focal regions of the human brain. As TMS gains popularity in experimental and clinical domains, techniques for controlling the extent of brain stimulation are becoming increasingly important. At present, TMS intensity is typically calibrated to the excitability of the human motor cortex, a measure referred to as motor threshold (MT). Although TMS is commonly applied to nonmotor regions, most applications do not consider the effect of changes in distance between the stimulating device and underlying neural tissue. Here we show that for every millimeter from the stimulating coil, an additional 3% of TMS output is required to induce an equivalent level of brain stimulation at the motor cortex. This abrupt spatial gradient will have crucial consequences when TMS is applied to nonmotor regions because of substantial variance in scalp-cortex distances over different regions of the head. Stimulation protocols that do not account for cortical distance therefore risk substantial under- or overstimulation. We describe a simple method for adjusting MT to account for variations in cortical distance, thus providing a more accurate calibration than unadjusted MT for the safe and effective application of TMS in clinical and experimental neuroscience.

Adolescent↗

Disability in multiple sclerosis. The role of transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) was used to measure intensity threshold, conduction of the central motor pathways (CMCT) and amplitude of the motor evoked potentials (MEPs) in 50 patients with definite form of multiple sclerosis (MS), 31 females and 19 males, aged 15 to 58 years (mean 31.9 +/- 9.8). Abnormalities in at least one parameter after TMS have been found in 76% of the cases. Interside CMCT asymmetries increased the diagnostic yield to 86% of the patients. Three MS individuals with normal clinical examination have prolonged CMCT (silent lesions). There was significant correlation between CMCT and evolution of the disease, and with the degree of pyramidal signs. CMCT correlated with cerebral motor pathway, pons, and cervical cord lesions in MRI study. TMS is an easy and reliable method to quantify pyramidal and cerebellar dysfunction in MS and monitoring the evolution of the disease.

Adolescent↗

Arm function after stroke: neurophysiological correlates and recovery mechanisms assessed by transcranial magnetic stimulation.

Transcranial Magnetic Stimulation has been used for over 20 years to investigate recovery of motor function in stroke patients. In particular, it has been used to quantify the extent of damage to the corticospinal output, reorganisation of the cortical representation of the affected body parts and excitability of intracortical and cortico-cortical circuitries in both hemispheres. In this review, we provide a detailed account of most of the published data with particular reference to methodological issues that affect their interpretation.

Arm↗

Masking visual stimuli by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) applied over the occipital pole can suppress visual perception. Since its first description in 1989 by Amassian et al., this technique has widely been used to investigate visual processing at the cortical level. This article presents a review of experiments masking visual stimuli by TMS. The psychophysical characterization of TMS masking, the dependence on stimulus onset asynchrony between visual stimulus and TMS pulse, and the topography of masking within the visual field are considered. The relation between visual masking and the generation of phosphenes is discussed as well as the underlying physiological mechanisms.

Evoked Potentials, Visual↗

Separation of contamination caused by coil clicks from responses elicited by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is accompanied with loud clicks that evoke auditory responses in the brain, confounding several types of TMS studies. We investigated the effects of these clicks with high-resolution EEG by applying TMS pulses at 3 magnitudes, with the coil placed either at 10 or 50 mm over the subjects' vertex and recording event-related potentials (ERPs). The clicks were found to elicit a positively displaced response at 150-250 ms post-TMS. Furthermore, clicks were found to interact with simultaneously presented auditory sinewave stimuli, resulting in an amplitude decrease in the auditory N1 response.

Adult↗

Suppressing the surface field during transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is used commonly as both a diagnostic tool and as an alternative to electric shock therapy for the treatment of clinical depression. Among the clinical issues encountered in its use is the mitigation of accompanying pain. The objective becomes one of minimizing the induced surface field while still achieving the target field objective. Three techniques discussed for realizing this end are 1) placing a conducting shield over a portion of the central target region, 2) using supplementary coils of opposite polarity in tandem with the primary field, and 3) opening the core angle to distribute the field. Option (3) shows the greatest promise for reducing the ratio of the maximum surface field to the induced target field.

Brain↗

Hemispheric asymmetry in visuospatial attention assessed with transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) was used to study visuospatial attention processing in ten healthy volunteers. In a forced choice recognition task the subjects were confronted with two symbols simultaneously presented during 120 ms at random positions, one in the left and the other in the right visual field. The subject had to identify the presented pattern out of four possible combinations and to press the corresponding response key within 2 s. Double-pulse TMS (dTMS) with a 100-ms interstimulus interval (ISI) and an intensity of 80% of the stimulator output (corresponding to 110-120% of the motor threshold) was applied by a non-focal coil over the right or left posterior parietal cortex (PPC, corresponding to P3/P4 of the international 10-20 system) at different time intervals after onset of the visual stimulus (starting at 120 ms, 270 ms and 520 ms). Double-pulse TMS over the right PPC starting at 270 ms led to a significant increase in percentage of errors in the contralateral, left visual field (median: 23% with TMS vs 13% without TMS, P=0.0025). TMS applied earlier or later showed no effect. Furthermore, no significant increase in contra- or ipsilateral percentage of errors was found when the left parietal cortex was stimulated with the same timing. These data indicate that: (1) parietal influence on visuospatial attention is mainly controlled by the right lobe since the same stimulation over the left parietal cortex had no significant effect, and (2) there is a vulnerable time window to disturb this cortical process, since dTMS had a significant effect on the percentage of errors in the contralateral visual hemifield only when applied 270 ms after visual stimulus presentation.

Adult↗

An investigation into asymmetrical cortical regulation of salivary S-IgA in conscious man using transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) can activate discrete areas of the cerebral cortex through the intact skull of healthy conscious volunteers. A magnetic coil generates a brief and focused magnetic field that penetrates the skull to activate the specific area of cerebral cortex beneath. This non-invasive procedure is painless, well tolerated by participants and now widely used to explore brain function. We used TMS to investigate asymmetrical cortical regulatory influences on one aspect of immune function: secretion of the antibody immunoglobulin A (S-IgA) into saliva. The right and left temporo-parietal-occipital cortex of 16 healthy, conscious subjects was stimulated on two different occasions, at least 1 week apart. There was an immediate increase in S-IgA concentration following both right and left stimulation. Saliva volume was reduced immediately post-right but not left stimulation. When secretion (microg/min) of S-IgA was calculated (controlling for changing saliva volume) an increase was apparent following left but not right hemisphere stimulation. Furthermore, a significant difference between the relationship between S-IgA concentration and volume of saliva post-left and right stimulation was observed. We conclude that TMS can be used as a tool to investigate cortical regulation of autonomic and immune function in healthy, conscious human subjects and that secretion of saliva and S-IgA is differentially affected by stimulation of the left and right cerebral cortex.

Analysis of Variance↗

The navigation of transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a new method for investigating cortical information processing and for investigating therapeutic applications in psychiatry and neurology. A common problem of most studies in this field regards the localization of the magnetic coil with respect to the cortex. This article reviews the currently used methods and proposes a neuronavigational approach. The method of neuronavigated TMS is described and discussed in detail. It is used to guide the magnetic coil on an individual basis to a structurally or functionally predetermined cortical area while monitoring the location of the coil in relation to the subject's head in real time. Possible applications of TMS in combination with functional neuroimaging in clinical research within a cognitive neuroscience framework are discussed. Future applications of TMS should take individual anatomy into account, and neuronavigation provides the means to do so.

Brain Mapping↗

Low level of intracortical inhibition in children shown by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to evaluate the integrity and maturation of the corticospinal tract. TMS was used in this study to compare intracortical inhibition (ICI) in children, adolescents, and adults. The paired-pulse technique of TMS with interstimulus intervals of 2 ms was used to determine the ratio of conditioned (cMEP) and unconditioned amplitudes (ucMEP) that measures ICI. In experiment 1 (Exp 1) stimulus intensity was adapted to motor threshold (50 healthy subjects; 24 male, 26 female, median age 13.5 years, range 6.3 - 34 years) and in experiment 2 (Exp 2) stimulus intensity was adapted to the ucMEP (200 - 400 microV). Children (quotient of cMEP and ucMEP: Exp. 1: 0.71 +/- 0.41, Exp. 2: 0.82 +/- 0.25) had significantly less ICI compared to adults (Exp. 1: 0.21 +/- 0.19, mean +/- STD, Exp. 2: 0.35 +/- 0.22, in both experiments p < 0.001). Recently, ICI has been linked to the regulating function of GABAergic cortical interneurons on practice-dependent neuronal plasticity. Therefore, the lower ICI in children points to maturation processes that may have implications for the greater capacity of practice-dependent neuronal plasticity in children.

Adolescent↗

Characteristics of the silent period after transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) of human cortex during voluntary muscle contraction produces a transient period of inhibition (i.e., silent period, SP) in the electromyographic (EMG) activity. The duration of the SP in relation to the level of muscle force (10%, 50% and 100% of maximum voluntary contraction) as well as possible cumulative effects of sequential TMS on the SP were studied. Methodologic problems were encountered in defining the SP and thus the duration of both an absolute (complete EMG silence) and relative (return of uninterrupted EMG activity) SP was measured. In all subjects, shortening of the SP duration occurred in relation to an increase in force when the criterion for absolute SP was used. Conversely, the relative SP duration suggested a trend toward prolongation with increasing force of contraction. No cumulative effects of TMS were observed on the absolute SP duration, whereas two subjects showed a cumulative effect of TMS on the relative SP. We conclude that the effect of muscle force and sequential TMS on the SP duration is dependent on the methods used to measure the SP. It is therefore essential to agree on methodology before SP measurements are clinically useful.

Adult↗

Study and modulation of human cortical excitability with transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) can be applied in different paradigms to obtain a measure of various aspects of cortical excitability. These different TMS paradigms provide information about different neurotransmitter systems, enhance our understanding about the pathophysiology of neuropsychiatric conditions, and in the future may be helpful as a guide for pharmacological interventions. In addition, repetitive TMS (rTMS) modulates cortical excitability beyond the duration of the rTMS trains themselves. Depending on rTMS parameters, a lasting inhibition or facilitation of cortical excitability can be induced. These effects can be demonstrated neurophysiologically or by combining rTMS with neuroimaging techniques. The effects do not remain limited to the cortical area directly targeted by rTMS, but affect a wider neural network transynaptically. Modulation of cortical excitability by rTMS may in the future be useful not only as a research tool but also as a therapeutic intervention in neurology, psychiatry, and neurorehabilitation.

Cerebral Cortex↗

[Transcranial magnetic stimulation].

Transcranial magnetic stimulation (TMS) allows non-invasive study and modulation of cortical excitability in humans. Changes in cortical excitability in physiological and pathological conditions can be tracked by measurements such as motor threshold, motor evoked potentials, recruitment curves, intracortical facilitation and inhibition. The central motor conduction time can estimate neural transmission in central motor pathways. Changes in areas of representation in sensorimotor cortex can be studied with cortical mapping. Modulation of cortical processing can be used to evaluate different brain functions. Therapeutic use in depression, Parkinson's disease and epilepsy has raised great interest over the past decade. Non-invasive cortical mapping may be achieved by combining TMS to other neurophysiological/ neuroimaging techniques. TMS has great potential both as an investigational and as a therapeutical tool in Neurology and Psychiatry.

Brain Diseases↗

Motor hand recovery after stroke. Prognostic yield of early transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) was performed in 20 patients within the first days after stroke. Motor evoked potentials (MEPs) were bilaterally recorded over thenar eminence muscles, and central motor conduction time (CMCT), amplitude of the MEPs (A%M) and threshold intensity compared between both sides. Six months later the patients were reexamined. Within the first days after stroke the obtention of MEPs at rest or during voluntary muscle activation have a favorable prognostic value. All patients with early response by TMS reached a good motor function in the following months. The follow-up showed that the electrophysiological improvement was closely related to clinical recovery of the hand function. However, even in cases with a good recovery, the CMCT and, mainly, the A%M, may be significantly different related to those in normal hand. TMS may be an early and valuable prognostic indicator of hand function recovery after stroke, and their prognostic yield is higher than clinical evaluation and CT study. TMS is a quantifiable method of motor disability and may have practical application in the management and rehabilitation therapy in stroke patients.

Adult↗

Functional reorganization after lesions of the human brain: studies with transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) can be used to map representations in brain, assess excitability and briefly deactivate brain regions. The study of brain plasticity in humans in a variety of circumstances has been supported by using TMS. TMS has been one of the tools used to demonstrate changes in motor map size, location and excitability in the setting of peripheral deafferentation, motor learning, and brain lesions such as stroke. In patients with hemispherectomy, recovery is mediated by enhanced activity in ipsilateral pathways, and this mechanism may also be operative after stroke, but the evidence is controversial. The best recovery after stroke is due to reorganization of the lesioned hemisphere. Rehabilitative strategies might well be able to enhance rehabilitative efforts.

Afferent Pathways↗

[Panic disorder and transcranial magnetic stimulation].

Transcranial magnetic stimulation (TMS) has been tried in some Anxiety Disorders (Obsessive-compulsive disorder and Posttraumatic Stress Disorder) with different results. We present a pilot study including three Panic Disorder patients. The subjects who were enrolled had a history of the disease for at least 1 year and they had unsuccessfully followed psychotherapy and pharmacological treatment. The patients received 10 sessions during two weeks; each session lasted 30 trains of 60 seconds at a frequency of 1 Hz, on the right dorsolateral prefrontal cortex, at 110% of the motor threshold. All three patients experienced a modest and partial symptom improvement that did not seemed to be clinically relevant. Two patients accepted to participate in a TMS second phase, where the previous stimulation parameters were alternated with an application of 30 trains of 20 Hz during 2 seconds on the left prefrontal cortex. This alternate application of high and low frequency TMS in each session was also well tolerated, but failed to produce additional improvement. In addition to presenting these three cases, we emphasize some features concerning the neurobiological basis of the anxiety disorders and we connect them to the previously described TMS neurophysiological actions in order to justify further investigation.

Adult↗

[Transcranial magnetic stimulation.].

Transcranial Magnetic Stimulation (TMS) is a new non-invasive method to investigate the central nervous system. Initially it was used to assess the functional integrity of the pyramidal pathways but more recently various other aspects of brain function have been studied including cortical excitability. By localised interference with brain function, it is possible to use TMS to assess the relationship between various brain regions and cognitive functions. The therapeutic effect of TMS has been explored in the treatment of neurological diseases and psychiatric disorders such as epilepsy, cerebellar ataxia and depressive illness.

English Abstract↗

[Assessment of motor cranial nerve functions using transcranial magnetic stimulation].

Transcranial magnetic stimulation applied over one cerebral hemisphere evokes bilateral responses in the muscles supplied by cranial nerves (masseter, mentalis, sternomastoid, genioglossus) (Tabl. 1). The relatively long latencies of these responses and the influence that preactivation of the muscle has on them, suggests that they are cortically evoked. Shorter latency and exclusively ipsilateral responses can be obtained if the position of the stimulating coil over the head is more lateral. These responses are uninfluenced by pre-activation of the muscle which suggests that they arise from stimulation of the peripheral nerve itself. By considering the conduction velocity of the nerve and the response latency such stimulation probably occurs in the proximal intracisternal segment (Fig. 2). The results obtained using magnetic stimulation of the cortex in patients with unilateral cerebral hemisphere lesions lend support to the idea of a bilateral projection from each cerebral hemisphere to the motor nuclei of the facial and hypoglossal nerves on both sides: stimulations over the intact hemisphere produces bilateral responses, whereas stimulations over the damaged hemisphere produce no responses (Fig. 1). In patients with idiopathic facial palsy no short latency responses were obtained on the affected side either during the acute (less than 10 days) or during the chronic phase (greater than 3 months) of the illness-despite clinical improvement during the chronic stage (Fig. 3, 4). However cortically evoked responses were obtainable in patients seen during the chronic phase indicating that facial motoneurones could be excited transsynaptically (Fig. 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Infarction↗