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BOLD fMRI response to direct stimulation (transcranial magnetic stimulation) of the motor cortex shows no decline with age.

Previous studies using BOLD fMRI to examine age-related changes in cortical activation used tasks that relied on peripheral systems to activate the brain. They were unable to distinguish between alterations due to age-related changes in the periphery and actual changes in cortical physiology. Transcranial magnetic stimulation (TMS), which allows direct, noninvasive stimulation of cortical neurons, was interleaved with BOLD fMRI to study 6 young and 5 old subjects. Three different tasks were compared: direct stimulation by TMS, indirect active stimulation produced by a motor task, and indirect passive stimulation produced by hearing the TMS coil discharge. Direct neuronal stimulation by TMS produced similar fMRI signal increases in both groups, suggesting that cortical physiology itself may not necessarily decline with age.

Acoustic Stimulation↗

Effect of stimulus intensity and voluntary contraction on corticospinal potentials following transcranial magnetic stimulation.

Following magnetic transcranial stimulation, motor-evoked potentials (MEPs) from the abductor digiti minimi muscle, and evoked spinal cord potentials (ESCPs) from the cervical epidural space were recorded simultaneously in 9 subjects in the awake and anesthetized condition. In the awake condition, during voluntary contraction, one (n = 5) or two (n = 4) components of the ESCPs were elicited at the threshold stimulus intensity of the MEPs. As the stimulus intensity increased, an early response (n = 7) and multiple late components were recorded. The first component at high stimulus output (average 80%) preceded the small potentials elicited at threshold stimulus intensity. The latency of each component of the ESCPs during voluntary contraction was the same as that during the resting condition. In addition, the enhancement of amplitude of the ESCPs during voluntary contraction was not significant compared with that recorded at rest. During general anesthesia with volatile anesthetics, the first component of the ESCPs could be elicited at high stimulus intensity, but later components were markedly attenuated. In paired transcranial magnetic stimulation, the amplitude of this first potential following the test stimulus completely recovered within the 2 ms interstimulus interval. From these results, we hypothesized that the first component was generated non-synaptically (D-wave), but later components were generated transsynaptically (I-waves). Compound muscle action potentials (CMAPs) and F-waves also were recorded following supramaximal ulnar nerve stimulation at the wrist. Peripheral conduction time, which included synaptic delay in spinal motor neurons, was measured as follows (latency of CMAPs+ latency of F-wave + 1)/2 (ms). The central motor conduction time (CMCT) was measured by subtracting the peripheral conduction time from the onset latency of the MEP at high stimulus intensity in the awake state. During voluntary contraction, the calculated CMCT (4.9 +/- 1.0 ms) was the same as the onset latency of the second component of the ESCPs (I-wave, 4.3 +/- 0.2 ms) recorded from the C6-C6/7 epidural space. These results suggest that transcranial magnetic stimulation generates I-waves preferentially when the stimulus intensity was set at just the threshold level of the MEPs during voluntary contraction in the awake condition. At high stimulus intensity, transcranial magnetic stimulation can elicit both D- and I-waves, but most spinal cells require I-wave activation to fire. Facilitatory effects of voluntary contraction on the muscle response following transcranial magnetic stimulation mainly originates at a spinal level.

Adult↗

Inadequacy of transcranial magnetic stimulation in the neurophysiologic assessment of Bell's palsy.

Transcranial magnetic stimulation is a non-invasive procedure which to stimulate the brain cortex and the peripheral nerve pathways. A new technique was recently introduced to record the muscle action potential of facial muscles by means of transcranial magnetic stimulation of the facial nerve. The experimental data that was obtained indicate that this technique allows to stimulate the facial nerve above the stylomastoid foramen: a greater tract of the nerve can therefore be explored than what was possible with the traditional electrical stimulation at the mastoid. Until now no comparison data was available on the clinical usefulness of the two methods. We decided to study 14 normal controls and 26 patients suffering from unilateral idiopathic facial palsy (Bell's palsy) and to submit these two groups to magnetic transcranial stimulation and electrical stimulation of the facial nerve in the mastoid region, to the purpose of observing where the nerve is stimulated by the magnetic impulse and which of the two techniques can be of accurate prognostic value in the study of the evolution of the clinical lesion. The electromyographic responses were elicited by the electrical stimulation at the mastoid and by transcranial stimulation after positioning the coil on the parieto-occipital scalp. A recording was taken from the ipsilateral orhicularis oculi muscle utilising two cupped electrodes. The latency and the amplitude of the compound muscle action potential were measured bilaterally in order to compare the results obtained on both the affected and the healthy sides. The patients were scheduled to two neurophysiological and clinical evaluations at about 30 days interval one from the other: the first test was not carried out before 20 days from the onset of the deficit; further clinical examination was carried out only 6 months later. The analysis of the results obtained in the normal controls submitted to transcranial magnetic stimulation indicate that the nerve is activated at the point where it originates from the brainstem. The study carried out showed that transcranial magnetic stimulation of the facial nerve, does not provide data which can be correlated to the clinical situation observed at the time of the study; furthermore, transcranial magnetic stimulation does not supply any prognostic data on the clinical evolution of the lesion.

Action Potentials↗

Demonstration of facilitatory I wave interaction in the human motor cortex by paired transcranial magnetic stimulation.

1. Transcranial magnetic stimulation (TMS) of the human motor cortex results in multiple discharges (D and I waves) in the corticospinal tract. We tested whether these volleys can be explored non-invasively with paired TMS. The intensity of the first stimulus (S1) was set to produce a motor-evoked potential (MEP) of 1 mV in the resting contralateral abductor digiti minimi (ADM) muscle; the second stimulus (S2) was set to 90 % of the resting motor threshold. At interstimulus intervals of 1.1-1.5, 2.3-2.9 and 4.1-4.4 ms the MEP elicited by S1 plus S2 was larger than that produced by S1 alone. 2. Varying the S1 intensity between 70 and 130 % resting motor threshold with S2 held constant at 90 % resting motor threshold showed that the threshold for the first MEP peak was <= 70 % resting motor threshold. The second and third MEP peaks appeared only at higher S1 intensities. The latency of all peaks decreased with increasing S1 intensity. 3. Varying the S2 intensity with S1 held constant to produce a MEP of 1 mV on its own showed that the amplitude of all MEP peaks increased with S2 intensity, but that their timing remained unchanged. 4. Paired TMS in the active ADM (S1 clearly suprathreshold, S2 just above threshold; interstimulus interval, 1 ms) produced strong MEP facilitation. The onset of this facilitation occurred later by about 1.5 ms than the onset of the MEP evoked by S2 alone. No MEP facilitation was seen if the magnetic S2 was replaced by anodal or cathodal transcranial electrical stimulation. 5. It is concluded that the MEP facilitation after paired TMS, at least for the first MEP peak, is due to facilitatory interaction between I waves, and takes place in the motor cortex at or upstream from the corticospinal neurone.

Adult↗

Depressed mood, index finger force and motor cortex stimulation: a transcranial magnetic stimulation (TMS) study.

The present study utilized transcranial magnetic stimulation (TMS) of the motor cortex to understand basic motor processes associated with depressive symptoms independent of cognitive requirements or diagnostic category. To assess the integrity of the basic cortical-spinal-motor circuit associated with depressed mood, TMS to the motor cortex was used to initiate motor evoked potentials (MEPs) in forearm EMG and force production measured in the right (dominant) index finger. While at rest, a group with more depressive symptoms showed less force response in the index finger following stimulations compared with a group endorsing less depressive symptoms. A negative correlation between force response in the index finger at baseline (rest) following stimulation and the Beck depression inventory indicated that depressive mood symptom elevations were associated with less response to stimulations. The results argue for a greater importance placed on the relationship between depressive mood symptoms and basic motor processes.

Affect↗

Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex.

Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal excitability for at least 20 min. No changes in excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal excitability within a physiologically useful range.

Adult↗

Long-term effects of transcranial magnetic stimulation on hippocampal reactivity to afferent stimulation.

Transcranial magnetic stimulation (TMS) has become a promising treatment of affective disorders in humans, yet the neuronal basis of its long-lasting effects in the brain is still unknown. We studied acute and lasting effects of TMS on reactivity of the rat hippocampus to stimulation of the perforant path. Application of TMS to the brain of the anesthetized rat caused a dose-dependent transient increase in population spike (PS) response of the dentate gyrus to perforant path stimulation. In addition, TMS caused a marked decrease in inhibition and an increase in paired-pulse potentiation of reactivity to stimulation of the perforant path. Also, TMS suppressed the ability of fenfluramine (FFA), a serotonin releaser, to potentiate PS response to perforant path stimulation. Chronic TMS did not affect single population spikes but caused an increase in paired-pulse potentiation, which was still evident 3 weeks after the last of seven daily TMS treatments. After chronic TMS, FFA was ineffective in enhancing reactivity to perforant path stimulation, probably because it lost the ability to release serotonin. In addition, the beta adrenergic receptor agonist isoproterenol, which caused an increase in PS in the control rats, failed to do so in the TMS-treated rats. These results indicate that TMS produces a long-term reduction in efficacy of central modulatory systems.

Afferent Pathways↗

EEG modification induced by repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is a powerful, noninvasive tool for investigating cortical physiologic functions in the brain. However, EEG spectral analysis has not been investigated extensively in rTMS study. The authors investigated the influence of rTMS on the EEG power spectrum by stimulating the left frontal cortex in 32 healthy subjects. Stimulation parameters were a 10-Hz frequency, a 3-second duration, and a 100% motor threshold. The data showed that rTMS increased the peak frequency of EEG across the scalp within 2 minutes after stimulation, whereas the value decreased at 3 to 4 minutes. The mean absolute powers within 3 minutes after rTMS did not differ from those estimated before rTMS, but increased uniformly at 4 to 5 minutes. The spectra did not change after sham stimulation. These results indicate that rTMS can influence cortical activities significantly by increasing the frequency and amplitude of EEG, and is a useful tool for helping us understand brain functions.

Adult↗

Transcallosal inhibition and motor conduction studies in patients with schizophrenia using transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation of the motor cortex may not only elicit excitatory responses in hand muscles contralateral to the stimulated hemisphere, but may also suppress tonic voluntary electromyogram activity in muscles ipsilateral to the stimulation. This inhibition is mediated between the motor cortices via the corpus callosum. AIMS: To investigate motor excitability and interhemispheric (transcallosal) connections in patients with schizophrenia. METHOD: Transcallosal inhibition and motor conduction parameters were investigated in ten patients with schizophrenia and in ten age- and gender-matched healthy subjects. RESULTS: Transcallosal conduction time (TCT) and duration of the inhibition were significantly longer in patients with schizophrenia (mean (s.d.)): TCT, 12.4 (2.9) ms in normal subjects and 15.3 (2.6) ms in patients (P = 0.03); mean duration, 34.1 (4.9) ms in normal subjects and 51.9 (16.8) ms in patients (P = 0.01). CONCLUSIONS: Magnetic motor conduction parameters are unaltered in schizophrenia, but transcallosal inhibition is significantly delayed and prolonged. This may indicate abnormal function of the corpus callosum in these patients.

Adult↗

Information for assistants of repeated transcranial magnetic stimulation.

Repeated transcranial magnetic stimulation (rTMS) is an exciting new technology being used in psychiatric and neurological research in many centres around the world. rTMS has been accepted as a routine treatment of depression in Canada and Israel. To this point, it has been exclusively conducted by medical officers. As knowledge and experience grows, it is probable that professionals with other backgrounds will have the opportunity to play a role. The aim of this paper is to provide information that will be valuable to assistants. Electromagnetic principles are harnessed to deliver electric currents to localized regions of the cortex. rTMS does not involve anaesthesia or seizure. Side-effects appear to be few. Much remains uncertain, however, even including the most appropriate treatment parameters.

Clinical Competence↗

Treatment of bipolar mania with right prefrontal rapid transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) has been suggested for the treatment of a variety of CNS disorders including depression and mania. METHODS: Nine bipolar (I) in-patients diagnosed with mania were treated with right prefrontal rapid TMS in an open and prospective study. Eight of nine patients received TMS as add-on treatment to an insufficient or only partially effective drug therapy. RESULTS: During the 4 weeks of TMS treatment a sustained reduction of manic symptoms as measured by the Bech-Rafaelsen mania scale (BRMAS) was observed in all patients. LIMITATIONS: Due to the open and add-on design of the study, a clear causal relationship between TMS treatment and reduction of manic symptoms cannot be established. CONCLUSIONS: Our data suggest that right prefrontal rapid TMS is safe and efficacious in the add-on treatment of bipolar mania showing laterality opposed to the proposed effect of rapid TMS in depression.

Adult↗

Ipsi- and contralateral EEG reactions to transcranial magnetic stimulation.

OBJECTIVES: Transcranial magnetic stimulation (TMS) and high-resolution electroencephalography (EEG) were used to study the spreading of cortical activation in 6 healthy volunteers. METHODS: Five locations in the left sensorimotor cortex (within 3cm(2)) were stimulated magnetically, while EEG was recorded with 60 scalp electrodes. A frameless stereotactic method was applied to determine the anatomic locus of stimulation and to superimpose the results on magnetic resonance images. Scalp potential and cortical current-density distributions were derived from averaged electroencephalographic (EEG) data. RESULTS: The maxima of the ipsilateral activation were detected at the gyrus precentralis, gyrus supramarginalis, and lobulus parietalis superior, depending on the subject. Activation over the contralateral cortex was observed in all subjects, appearing at 22plus minus2ms (range 17--28); the maxima were located at the gyrus precentralis, gyrus frontalis superior, and the lobulus parietalis inferior. Contralateral EEG waveforms showed consistent changes when different sites were stimulated: stimulation of the two most medial points evoked the smallest responses fronto-parietally. CONCLUSIONS: With the combination of TMS, EEG, and magnetic resonance imaging, an adequate spatiotemporal resolution may be achieved for tracing the intra- and interhemispheric spread of activation in the cortex caused by a magnetic pulse.

Adult↗

Topiramate and cortical excitability in humans: a study with repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) delivered at 5 Hz frequency and suprathreshold intensity progressively increases the size of muscle evoked potentials (MEPs) and the duration of the cortical silent period (CSP) in normal subjects. The aim of this study was to evaluate the effects of topiramate (TPM) at different doses on cortical excitability variables tested with rTMS. We tested the facilitation of the MEP size and CSP duration evoked by focal rTMS in eight patients before and after treatment with TPM at different doses for chronic neuropathic pain. In each patient, rTMS (5 Hz frequency-120% resting motor threshold) was applied at baseline and during the TPM induction phase (drug intake schedule: week I 25 mg/day, week II 50 mg/day, week III 75 mg/day, week IV 100 mg/day) and total TPM plasma concentrations were measured. The effects on the MEP size of 5 Hz-rTMS delivered over repeated sessions were tested in eight control subjects. TPM had no effect on the resting motor threshold. Antiepileptic treatment at increasing doses abolished the normal rTMS-induced MEP facilitation. ANOVA showed that this was a dose-related effect. Accordingly, in patients receiving TPM at higher doses (75 and 100 mg) rTMS failed to elicit the MEP facilitation. TPM left the progressive lengthening of the CSP during the rTMS train unchanged. In control subjects, rTMS applied over repeated sessions elicited a constant increase in MEP size. Our results suggest that TPM modulates the excitatory intracortical interneurons probably by altering rTMS-induced synaptic potentiation. These drug-induced effects are related to TPM doses and plasma concentrations. In conclusion, rTMS may be useful for quantifying the effectiveness of antiepileptic drugs and for assessing individual responses to different drugs but acting through similar mechanisms, thus combining functional neurophysiological information and laboratory data.

Adult↗

Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation.

Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

Animals↗

[Transcranial magnetic stimulation].

INTRODUCTION: Transcranial magnetic stimulation (TMS) permits stimulation of the cerebral cortex in humans without requiring open access to the brain and is one of the newest tools available in neuroscience. There are two main types of application: single-pulse TMS and repetitive TMS. DEVELOPMENT: The magnetic stimulator is composed of a series of capacitors that store the voltage necessary to generate a stimulus of the sufficient intensity of generate an electric field in the stimulation coil. The safety of TMS is supported by the considerable experience derived from studies involving electrical stimulation of the cortex in animals and humans, and also specific studies on the safety of TMS in humans. CONCLUSIONS: In this article we review historical and technical aspects of TMS, describe its adverse effects and how to avoid them, summarize the applications of TMS in the investigation of different cerebral functions, and discuss the possibility of using TMS for the treatment of neuropsychiatric disorders.

Cerebral Cortex↗

Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) of human primary motor cortex (M1) changes cortical excitability at the site of stimulation and at distant sites without affecting simple motor performance. The aim of this study was to explore how rTMS changes regional excitability and how the motor system compensates for these changes. Using functional brain imaging, activation was mapped at rest and during freely selected finger movements after 30 min of 1 Hz rTMS. rTMS increased synaptic activity in the stimulated left M1 and induced widespread changes in activity throughout areas engaged by the task. In particular, movement-related activity in the premotor cortex of the nonstimulated hemisphere increased after 1 Hz rTMS. Analyses of effective connectivity confirmed that the stimulated part of M1 became less responsive to input from premotor and mesial motor areas. Conversely, after rTMS our results were consistent with increased coupling between an inferomedial portion of left M1 and anterior motor areas. These results are important for three reasons. First, they show changes in motor excitability to central inputs from other cortical areas (as opposed to peripheral or exogenous inputs used in previous studies). Second, they suggest that maintenance of task performance may involve activation of premotor areas contralateral to the site of rTMS, similar to that seen in stroke patients. Third, changes in motor activations at the site of rTMS suggest an rTMS-induced remodeling of motor representations during movement. This remapping may provide a neural substrate for acute compensatory plasticity of the motor system in response to focal lesions such as stroke.

Adult↗

Enhancement of human motor cortex inhibition by the dopamine receptor agonist pergolide: evidence from transcranial magnetic stimulation.

Focal transcranial magnetic stimulation was used to evaluate the effect a single oral dose (0.125 mg) of the dopamine agonist pergolide on the excitability of the motor cortex in five healthy subjects. Resting and active motor thresholds of the abductor digiti minimi muscle were unaffected. The mean duration of the cortical silent period was significantly lengthened by up to 22 ms. The cortico-cortical inhibition as studied by a paired conditioning-test stimulation (interstimulus intervals of 1-5 ms) was enhanced significantly while the cortico-cortical facilitation at longer intervals (6-15 ms) showed only an insignificant trend towards less facilitation. All effects peaked at 3 h after drug intake and were reversible after 24 h. Peripheral motor excitability as tested by the duration of the peripheral silent period and the size of the maximum M wave remained unchanged. The present data support the view that pergolide is capable of enhancing motor cortex inhibition which is known to be deficient in idiopathic Parkinson's disease.

Electromyography↗

Modulation of monoamine transporter expression and function by repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is a new tool for the treatment of neuropsychiatric disorders. However, the mechanisms underlying the effects of rTMS are still unclear. In this study, we analyzed mRNA expression changes of monoamine transporter (MAT) genes, which are targets for antidepressants and psychostimulants. Following a 20-day rTMS treatment, these genes were found to be differentially expressed in the mouse brain. Down-regulation of serotonin transporter (SERT) mRNA levels and the subsequent decrease in serotonin uptake and binding were observed after chronic rTMS. In contrast to the SERT changes, increased mRNA levels of dopamine transporter (DAT) and norepinephrine transporter (NET) were observed. For NET, but not DAT, there were accompanying changes in uptake and binding. Similar effect on NET was observed in PC12 cells stimulated by rTMS for 15 days. These results indicate that modulation of MATs by chronic rTMS may be one therapeutic mechanism for the treatment of neuropsychiatric disorders.

Animals↗