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Facilitation of A[delta]-fiber-mediated acute pain by repetitive transcranial magnetic stimulation.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex modulates acute and chronic pain perception. The authors previously showed that rTMS over the primary motor cortex (M1) inhibited capsaicin-induced acute pain ascending through C-fibers. OBJECTIVE: To investigate the effects of 1-Hz rTMS over M1 on acute experimentally induced pain mediated by Adelta-fibers (i.e., another type of acute pain). METHODS: The authors examined whether rTMS over M1 affected laser evoked potentials (LEPs) in 13 normal subjects using thulium: yttrium-aluminum-garnet laser stimulation. Subjective pain-rating scores and LEPs obtained under three different conditions--rTMS, realistic sham stimulation, and a control condition with no stimulation--were compared. RESULTS: The authors found that 1-Hz rTMS over M1 significantly aggravated the subjective pain and enhanced the N2-P2 amplitudes compared with the sham or control sessions. Because the pain-rating scores and the N2-P2 amplitudes correlated positively, the N2-P2 amplitudes in the present study can be regarded as the cortical correlate of subjective pain. CONCLUSIONS: Together with the authors' previous study on C-fiber pain, this facilitatory effect of repetitive transcranial magnetic stimulation on Adelta-fiber-mediated further strengthens the notion of a relationship between repetitive transcranial magnetic stimulation over M1 and pain perception.

Acute Disease↗

Post-stroke reorganization of hand motor area: a 1-year prospective follow-up with focal transcranial magnetic stimulation.

OBJECTIVE: Focal transcranial magnetic stimulation was used to test prospectively corticospinal excitability changes and reorganization of first dorsal interosseous (FDI) motor cortical representation in 31 patients who experienced a first ischemic stroke in the middle cerebral artery territory. All had severe hand palsy at onset. METHODS: Patients were assessed clinically with the Medical Research Council, Rankin, the National Institutes of Health stroke scales and Barthel Index at days 1, 8, 30, 90, 180 and 360 after stroke. The following parameters of FDI motor evoked potential (MEPS) to focal transcranial magnetic stimulation were measured at the same delays: motor threshold, MEP amplitude, excitable cortical area, hot spot and center of gravity of FDI motor maps on affected and unaffected hemispheres. Correlations were sought between clinical and electrophysiological parameters. RESULTS: In patients whose affected motor cortex remained excitable at day 1, motor thresholds were not significantly different between sides and were similar to those of controls. Persistence of MEP on the affected side at day 1 was a strong predictor of good recovery. If present at day 1, MEPs recorded in affected FDI were significantly smaller than of the opposite side or in normals and progressively recovered up to day 360. In these patients, area of excitable cortex remained stable throughout the entire study. At day 1, amplitudes of MEPs obtained in unaffected FDI were significantly larger than later. Between days 1 and 360, we observed a significant displacement of center of gravity of motor maps towards more frontal regions on the affected side while no change was noted on the unaffected side. CONCLUSIONS: Our data confirm the early prognosis value of transcranial magnetic stimulation in stroke. They indicate that the brain insult induces a transient hyperexcitability of the unaffected motor cortex. The evolution of FDI motor maps along the course of recovery mostly reflect corticospinal excitability changes but might also reveal some degree of brain plasticity. Most modifications observed occurred within 3 months of stroke onset.

Adult↗

Brain-derived neurotrophic factor serum concentrations in depressive patients during vagus nerve stimulation and repetitive transcranial magnetic stimulation.

BACKGROUND: Vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex are brain stimulation techniques used as therapeutic interventions in major depression. METHODS: In this study, we report the impact of these stimulation techniques on serum concentrations of brain-derived neurotrophic factor (BDNF) in treatment-resistant patients with a diagnosis of major depression. RESULTS: We found no changes of BDNF serum concentrations and no association of neurotrophin concentrations in serum with clinical parameters in our sample. CONCLUSION: Our preliminary results suggest that brain stimulation techniques-in contrast to several antidepressant medications-do not change BDNF serum concentrations.

Adult↗

Spatial differences in the sites of direct and indirect activation of corticospinal neurones by magnetic stimulation.

Transcranial magnetic stimulation (TMS) over the human motor cortex evokes multiple descending volleys possibly through activation of different elements within the brain. We have investigated whether such elements can be distinguished spatially. Using a figure of eight coil, TMS was delivered over multiple scalp sites during a low level voluntary contraction of the left first dorsal interosseous muscle. At near-threshold intensity, early or late surface electromyograph (EMG) components (relative to anodal response latency) could be preferentially evoked with the coil aligned in a medio-lateral (ML), antero-posterior (AP), or postero-anterior (PA) orientation. The optimal location of the earliest component with ML coil orientation was 8 mm medial and 5 mm anterior compared to a later component with AP orientation. The optimal location for the same latency EMG component mapped using two different coil orientations (AP and ML) was not significantly different. The optimal location of two different late components, one obtained with AP and the other with PA coil orientations, was similar. It is argued that the earliest TMS-evoked component results from direct activation of corticospinal cell axons while later components result from activation of these cells trans-synaptically (indirectly), and that consequently there is a substantial spatial separation between these activation sites.

Adult↗

Subjective reactions of children to single-pulse transcranial magnetic stimulation.

Single-pulse transcranial magnetic stimulation is a useful tool to investigate cortical function in childhood neuropsychiatric disorders. Magnetic stimulation is associated with a shock-like sensation that is considered painless in adults. Little is known about how children perceive the procedure. We used a self-report questionnaire to assess children's subjective experience with transcranial magnetic stimulation. Normal children and children with attention-deficit hyperactivity disorder (ADHD) underwent transcranial magnetic stimulation in a study of cortical function in ADHD. Subjects were asked to rate transcranial magnetic stimulation on a 1 to 10 scale (most disagreeable = 1, most enjoyable = 10) and to rank it among common childhood events. Thirty-eight subjects completed transcranial magnetic stimulation; 34 said that they would repeat it. The overall rating for transcranial magnetic stimulation was 6.13, and transcranial magnetic stimulation was ranked fourth highest among the common childhood events. These results suggest that although a few children find transcranial magnetic stimulation uncomfortable, most consider transcranial magnetic stimulation painless. Further studies are necessary to confirm these findings.

Adolescent↗

Changes in visual responses in the feline dLGN: selective thalamic suppression induced by transcranial magnetic stimulation of V1.

Transcranial magnetic stimulation (TMS) of the cortex can modify activity noninvasively and produce either excitatory or inhibitory effects, depending on stimulus parameters. Here we demonstrate controlled inhibitory effects on the large corticogeniculate feedback pathway from primary visual cortex to cells of the dorsal lateral geniculate nucleus (dLGN) that are focal and reversible-induced by either single pulses or trains of pulses of TMS. These effects selectively suppress the sustained component of responses to flashed spots or moving grating stimuli and are the result of loss of spikes fired in tonic mode, whereas the number of spikes fired in bursts remain the same. We conclude that acute inactivation of the corticogeniculate downflow selectively affects the tonic mode. We found no evidence to suggest that cortical inactivation increased burst frequency.

Action Potentials↗

Locating the motor cortex on the MRI with transcranial magnetic stimulation and PET.

Transcranial magnetic stimulation with a focal coil was used to map the cortical representation of a hand muscle in four healthy subjects. In each subject, the three-dimensional locations of the magnetic stimulation positions and about 400 positions on the surface of the head were digitized. The amplitude-weighted center of gravity of each subject's map was found, and a line perpendicular to the local head surface was projected inward. The digitized heads were registered with the subjects' MRIs using the scalp contours. The coordinate transformations yielded by this process were used to map the stimulation positions and the perpendicular line into the MRIs. Brain areas imaged with positron emission tomography (PET) and 15O-labeled water, activated by movement of the same muscle, were registered with the MRIs using the brain contours. In all cases, the magnetic stimulation lines encountered the surface of the brain at the anterior lip of the central sulcus and ran along the precentral gyrus a few millimeters anterior to the central sulcus, coming within 5-22 mm of all the PET activation maxima. This technique demonstrates the accuracy of transcranial magnetic stimulation for locating the primary motor area.

Adult↗

Transcranial magnetic stimulation in clinical practice.

Transcranial magnetic stimulation allows a non-invasive and painless stimulation of the human brain and cranial nerves. The method is in use since 1985. Transcranial magnetic stimulation can use single stimuli, pairs of stimuli separated by different intervals (to the same or to several brain areas), or trains of repetitive stimuli at various frequencies. Single stimuli give rise to motor evoked potentials that have clinical use and serve diagnostic and prognostic purposes. Repetitive transcranial magnetic stimulation can modify excitability of cerebral cortex. Repetitive transcranial magnetic stimulation has opened a new field of investigation of the neural circuitry, and is developing into a therapeutic tool. This general review considers basic principles of transcranial magnetic stimulation, discusses methodological aspects and techniques, and analyses their utility in clinical practice.

Brain↗

Prefrontal cortex modulation of mood and emotionally induced facial expressions: a transcranial magnetic stimulation study.

Repetitive transcranial magnetic stimulation (rTMS) can serve as a tool to experimentally test hypotheses of prefrontal cortex (PFC) modulation of emotions. The present study used rTMS to test whether self-rated mood and emotionally induced facial expressions are hemispherically lateralized depending on their valence, as indicated by previous studies. Healthy volunteers underwent mood self-rating and computerized analysis of emotionally induced facial expressions before and after rTMS of left or right PFC. Facial expression analysis revealed lateralized changes of facial expressions after rTMS, whereas changes of subjective mood ratings did not show a hemispheric lateralization. On the basis of this study, the authors propose to combine rTMS and facial expression analysis for further studies of the cortical modulation of emotions in humans.

Adult↗

Predominant activation of I1-waves from the leg motor area by transcranial magnetic stimulation.

We performed transcranial magnetic stimulation (TMS) to elucidate the D- and I-wave components comprising the motor evoked potentials (MEPs) elicited from the leg motor area, especially at near-threshold intensity. Recordings were made from the tibialis anterior muscle using needle electrodes. A figure-of-eight coil was placed so as to induce current in the brain in eight different directions, starting from the posterior-to-anterior direction and rotating it in 45 degrees steps. The latencies were compared with those evoked by transcranial electrical stimulation (TES) and TMS using a double cone coil. Although the latencies of MEPs ranged from D to I3 waves, the most prominent component evoked by TMS at near-threshold intensity represented the I1 wave. With the double cone coil, the elicited peaks always represented I1 waves, and D waves were evoked only at very high stimulus intensities, suggesting a high effectiveness of this coil in inducing I1 waves. Using the figure-of-eight coil, current flowing anteriorly or toward the hemisphere contralateral to the recorded muscle was more effective in eliciting large responses than current flowing posteriorly or toward the ipsilateral hemisphere. The effective directions induced I1 waves with the lowest threshold, whereas the less effective directions elicited I1 and I2 waves with a similar frequency. Higher stimulus intensities resulted in concomitant activation of D through I3 waves with increasing amount of D waves, but still the predominance of I1 waves was apparent. The amount of I waves, especially of I1 waves, was greater than predicted by the hypothesis that TMS over the leg motor area activates the output cells directly, but rather suggests predominant transsynaptic activation. The results accord with those of recent human epidural recordings.

Electric Stimulation↗

Effects of diazepam, baclofen and thiopental on the silent period evoked by transcranial magnetic stimulation in humans.

The cortical silent period evoked by magnetic transcranial stimulation and the peripheral silent period were studied in healthy subjects after intravenous injection of diazepam, baclofen or thiopental. None of the drugs tested changed the peripheral silent period. But, unexpectedly, diazepam significantly shortened the cortical silent period, the inhibitory effect lasting about 30 min. In experiments using paired transcranial stimuli, the conditioning shock inhibited the test response to a similar extent with and without diazepam. Although baclofen did not change the cortical silent period, it reduced the size of the H reflex in the forearm muscles. Thiopental also left the duration of the cortical silent period unchanged. These findings show that the cortical silent period can be modified pharmacologically. Diazepam possibly shortens the silent period by modulating GABA A receptors at a subcortical site.

Adult↗

Intra- and interindividual variability of motor responses to repetitive transcranial magnetic stimulation.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) can modify cortical excitability and is widely used for clinical and research purposes. We sought to determine the intra- and interindividual variability of its effects on motor cortex excitability, and whether repeated paired-pulses yield less variability than repeated single-pulses. METHODS: We investigated rTMS over the left motor cortex of 6 healthy subjects and recorded motor evoked potentials (MEPs) from the right abductor digiti minimi muscle. Eighty single suprathreshold stimuli or conditioning-test pairs of stimuli were delivered at 2Hz frequency. The pairs consisted of a subthreshold pulse followed by a suprathreshold pulse after 2, 5 or 10ms. In each subject we studied all types of rTMS 5 times on separate days. Single suprathreshold pulses at 0.17Hz preceded rTMS for baseline determination. RESULTS: The day-to-day variability of MEPs during either type of rTMS was small compared to the subject-to-subject variability. MEPs increased during all types of rTMS except for interstimulus interval (ISI) 2ms. Paired-pulses yielded less variability than single-pulse rTMS. CONCLUSIONS: Motor responses to rTMS show a high interindividual, but a low intraindividual variability. Repeated paired-pulses yield less variability than repeated single-pulses.

Adult↗

Deconvolution of transcranial magnetic stimulation (TMS) maps.

Transcranial magnetic stimulation (TMS) is a noninvasive method for local stimulation of cerebral cortex using a small coil's pulsed magnetic field. TMS response maps consist of measured responses to stimulations at points on a scalp-referenced grid and are used to study the topography of the brain's inhibitory and excitatory response. Because the magnetic field distributions of stimulation coils are 1-2 centimeters wide and 2-3 centimeters long, and the induced electric fields are even broader, the resolution of TMS maps is limited and the actual region of cortical stimulation is poorly defined. To better characterize the activation pattern, a practical mathematical procedure was developed for deconvolving a spherical model approximation of the coil's induced electric field distribution (here measured in a phantom) from the TMS response maps. This procedure offers an integrated, internally consistent method for processing TMS response maps to estimate the spatial distribution of motor cortex activations and inhibitions.

Algorithms↗

Spatial neglect in near and far space investigated by repetitive transcranial magnetic stimulation.

Localized repetitive transcranial magnetic stimulation was used to disrupt visuospatial perception in the near and far space of six healthy volunteer subjects. In addition to the baseline condition, they were stimulated over the right posterior parietal cortex, the right or left dorsal occipital cortex or the right ventral occipital cortex, during the brief presentation of a transected horizontal line. Subjects had to indicate whether the part of the line to the left or right of the transection appeared longer. The stimulus display was back-projected on a screen at a viewing distance of either 50 or 150 cm ("near" and "far" space, respectively). Reaction times and choices were measured. In a forced-choice paradigm, subjects showed "pseudoneglect", the natural tendency of neurologically intact subjects to perceive the left side of a centrally transected line as slightly longer than the right. These errors occurred more for lines in near space than for lines in far space. Magnetic stimulation of the right posterior parietal cortex or the right ventral occipital lobe selectively induced a significant shift to the right in the perceived midpoint for near- and far-space lines, respectively. The results reproduced in normal subjects the dissociation between neglect in near and far space that has been described in patients with different right-hemisphere lesions. This dissociation supports the contention that there is a dorsal/near space-ventral/far space segregation of processing in the visual system which reflects the behavioural goals of the two putative visual streams.

Adult↗

Effect of spatial attention on human sensorimotor integration studied by transcranial magnetic stimulation.

OBJECTIVE: Recent transcranial magnetic stimulation (TMS) studies showed that the sensory input can decrease the motor cortex excitability (afferent inhibition). To clarify the effect of attention on sensorimotor integration, we investigated the effect of spatial attention on afferent inhibition. METHODS: Right median nerve electrical stimulation followed, at variable delays (10-300 ms), by TMS over the left motor cortex was applied to 9 subjects, during 3 conditions; spatial attention to the right and left hand, and control (no attention) tasks. RESULTS: Inhibition of the motor evoked potential occurred at inter-stimulus interval of 20 and 100 ms, which was more was marked during spatial attention to the right than to the left hand. CONCLUSIONS: Enhancement of the afferent inhibition induced by spatial attention to the stimulated side is likely to reflect the interaction between attention and sensorimotor integration. SIGNIFICANCE: The spatial attention may modulate the sensorimotor integration studied by afferent inhibition of the MEP.

Adult↗

General principles for clinical use of repetitive transcranial magnetic stimulation (rTMS).

Repetitive transcranial magnetic stimulation (rTMS), a non-invasive technique allowing stimulating neurons in the cerebral cortex, is able to modify durably local as well as distant neuronal activity. Results obtained by stimulation of the primary motor cortex and measurements of induced muscle responses suggest that effects on cortical excitability depend on stimulation frequency and intensity, as well as of pulse-train duration. Such data, as well as results of animal studies have brought a physiological basis for the use of rTMS for treatment of various neurological and psychiatric disorders, and particularly depression. Nevertheless, as long as large randomized studies have not been conducted, rTMS should not replace other existing and validated therapies.

Depression↗

Significance of coil orientation for motor evoked potentials from nasalis muscle elicited by transcranial magnetic stimulation.

OBJECTIVE: In transcranial magnetic stimulation (TMS) of the motor cortex, the optimal orientation of the coil on the scalp is dependent on the muscle under investigation, but not yet known for facial muscles. METHODS: Using a figure-of-eight coil, we compared TMS induced motor evoked potentials (MEPs) from eight different coil orientations when recording from ipsi- and contralateral nasalis muscle. RESULTS: The MEPs from nasalis muscle revealed three components: The major ipsi- and contra-lateral middle latency responses of approximately 10 ms onset latency proved entirely dependent on voluntary pre-innervation. They were most easily obtained from a coil orientation with posterior inducing current direction, and in this respect resembled the intrinsic hand rather than the masseter muscles. Early short duration responses of around 6 ms onset latency were best elicited with an antero-lateral current direction and not pre-innervation dependent, and therefore most probably due to stimulation of the nerve roots. Late responses (>18 ms) could inconsistently be elicited with posterior coil orientations in pre-innervated condition. CONCLUSIONS: By using the appropriate coil orientation and both conditions relaxed and pre-innervated, cortically evoked MEP responses from nasalis muscle can reliably be separated from peripheral and reflex components and also from cross talk of masseter muscle activation.

Adult↗

Effects of chronic levodopa and pergolide treatment on cortical excitability in patients with Parkinson's disease: a transcranial magnetic stimulation study.

OBJECTIVES: Transcranial magnetic stimulation was used to assess the effects of chronic levodopa and pergolide treatment on motor cortex excitability in Parkinson disease (PD). METHODS: Motor thresholds, intracortical inhibition and facilitation were studied at baseline and after 6 and 12 months of therapy in 10 PD patients and compared to 7 age-matched controls. RESULTS: At baseline, there was significantly less intracortical inhibition with only a slight reduction of intracortical facilitation in PD as compared to controls. Relative to pretreatment condition, levodopa restored intracortical inhibition for 12 months while pergolide did not. Intracortical facilitation was always within the normal range. Motor thresholds were unchanged in both groups of patients over 12 months. Clinically, levodopa and pergolide improved motor Unified Parkinson's disease rating scale (UPDRS) scores at 6 months but only levodopa maintained benefit at 12 months as compared to baseline. CONCLUSIONS: Levodopa and pergolide differentially affected cortical inhibitory circuits at 12 months. The progressive deterioration of restored intracortical inhibition with pergolide may be due to the development of tolerance and down-regulation of dopamine receptors.

Aged↗