Quantitative assessment of pain threshold induced by a single-pulse transcranial magnetic stimulation

AbstractObjectiveTranscranial magnetic stimulation (TMS) is commonly used in basic research to evaluate human brain function. Although scalp pain is a side effect, no studies have quantitatively assessed the TMS intensity threshold for inducing pain and whether sensitivity to TMS-induced pain differs between sexes.MethodsWe measured pain thresholds when single-pulse TMS was applied over either Broca’s area (BA) or left primary motor cortex (M1). We compared these thresholds with motor threshold for inducing motor evoked potential (MEP) through M1 stimulation. We also compared pain thresholds for BA and M1 between males and females.ResultsPain thresholds for both sites were significantly lower than motor threshold. Further, the pain threshold for BA was much lower than that for M1. No significant difference was observed between sexes.ConclusionThe results suggest that TMS at an intensity equivalent to motor thresholds, which is often used in experimental or clinical studies, causes slight scalp pain.SignificanceExperimental designs using TMS to evaluate functional relationships between brain and behaviors should consider scalp pain and reduce its likelihood as much as possible.HighlightsWe investigated pain thresholds induced by a single-pulse TMS over the head.Pain thresholds for TMS over Broca’s area (BA) and primary motor cortex (M1) were much lower than motor threshold.No significant differences in the pain thresholds were observed between sexes.

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Cerebral Blood-Flow Changes Induced by Paired-Pulse Transcranial Magnetic Stimulation of the Primary Motor Cortex

Journal of Neurophysiology ◽

10.1152/jn.2001.85.6.2624 ◽

2001 ◽

Vol 85 (6) ◽

pp. 2624-2629 ◽

Cited By ~ 81

Author(s):

A. P. Strafella ◽

T. Paus

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Transcranial Magnetic Stimulation ◽

Motor Cortex ◽

Magnetic Stimulation ◽

Primary Motor Cortex ◽

Premotor Cortex ◽

Single Pulse ◽

Paired Pulse ◽

Positive Correlation

Positron emission tomography (PET) was used to assess changes in regional cerebral blood flow (CBF) induced by paired-pulse transcranial magnetic stimulation (TMS) of primary motor cortex (M1). The study was performed in eight normal volunteers using two Magstim-200 stimulators linked with a Bistim module. A circular TMS coil was held in the scanner by a mechanical arm and located over the left M1. Surface electrodes were used to record motor evoked potentials (MEPs) from the contralateral first dorsal interosseous muscle (FDI). Cortical excitability was evaluated in the relaxed FDI using a paired conditioning-test stimulus paradigm with two interstimulus intervals (ISIs): 3 and 12 ms. The subjects were scanned three times during each of the following four conditions: 1) baseline with no TMS (BASE); 2) single-pulse TMS (TMSsing); 3) 3-ms paired-pulse TMS (TMS3); and 4) 12-ms paired-pulse TMS (TMS12). CBF and peak-to-peak MEP amplitudes were measured over each 60-s scanning period. To assess TMS-induced changes in CBF, a t-statistic map was generated by first subtracting the single-pulse TMS condition from the 3- and 12-ms paired-pulse TMS conditions and then correlating the CBF differences, respectively, with the amount of suppression and facilitation of the EMG responses. A significant positive correlation was observed between the CBF difference (TMS3-TMSsing) and the amount of suppression of EMG response, as well as between the CBF difference (TMS12-TMSsing) and the amount of facilitation of EMG response. This positive correlation was observed in the left M1, left lateral premotor cortex, and right M1 in the case of 3-ms paired-pulse TMS, but only in the left M1 in the case of 12-ms paired-pulse TMS. The above pattern of CBF response to paired-pulse TMS supports the possibility that suppression and facilitation of the EMG response are mediated by different populations of cortical interneurons.

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Hand perceptions induced by single pulse transcranial magnetic stimulation over the primary motor cortex

Brain Stimulation ◽

10.1016/j.brs.2018.12.972 ◽

2019 ◽

Vol 12 (3) ◽

pp. 693-701 ◽

Cited By ~ 2

Author(s):

Matteo Franza ◽

Giuliana Sorrentino ◽

Matteo Vissani ◽

Andrea Serino ◽

Olaf Blanke ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Motor Cortex ◽

Magnetic Stimulation ◽

Primary Motor Cortex ◽

Single Pulse

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Dosimetry Analysis in Non-brain Tissues During TMS Exposure of Broca’s and M1 Areas

Frontiers in Neuroscience ◽

10.3389/fnins.2021.644951 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jose Gomez-Tames ◽

Keisuke Tani ◽

Kazuya Hayashi ◽

Satoshi Tanaka ◽

Shoogo Ueno ◽

...

Keyword(s):

Electric Field ◽

Magnetic Stimulation ◽

Primary Motor Cortex ◽

International Standards ◽

Head Model ◽

Internal Electric Field ◽

Broca’S Area ◽

Broca's Area ◽

Pain Thresholds ◽

Main Adverse Effect

For human protection, the internal electric field is used as a dosimetric quantity for electromagnetic fields lower than 5–10 MHz. According to international standards, in this frequency range, electrostimulation is the main adverse effect against which protection is needed. One of the topics to be investigated is the quantification of the internal electric field threshold levels of perception and pain. Pain has been reported as a side effect during transcranial magnetic stimulation (TMS), especially during stimulation of the Broca’s (speech) area of the brain. In this study, we designed an experiment to conduct a dosimetry analysis to quantify the internal electric field corresponding to perception and pain thresholds when targeting the Broca’s and M1 areas from magnetic stimulator exposure. Dosimetry analysis was conducted using a multi-scale analysis in an individualized head model to investigate electrostimulation in an axonal model. The main finding is that the stimulation on the primary motor cortex has higher perception and pain thresholds when compared to Broca’s area. Also, TMS-induced electric field applied to Broca’s area exhibited dependence on the coil orientation at lower electric field threshold which was found to be related to the location and thickness of pain fibers. The derived dosimetry quantities provide a scientific rationale for the development of human protection guidelines and the estimation of possible side effects of magnetic stimulation in clinical applications.

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Time course and spatial distribution of fMRI signal changes during single-pulse transcranial magnetic stimulation to the primary motor cortex

NeuroImage ◽

10.1016/j.neuroimage.2011.03.011 ◽

2011 ◽

Vol 56 (3) ◽

pp. 1469-1479 ◽

Cited By ~ 22

Author(s):

H. Shitara ◽

T. Shinozaki ◽

K. Takagishi ◽

M. Honda ◽

T. Hanakawa

Keyword(s):

Spatial Distribution ◽

Transcranial Magnetic Stimulation ◽

Motor Cortex ◽

Magnetic Stimulation ◽

Time Course ◽

Primary Motor Cortex ◽

Single Pulse ◽

Fmri Signal ◽

Signal Changes

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Synchronization of Neuronal Activity in the Human Primary Motor Cortex by Transcranial Magnetic Stimulation: An EEG Study

Journal of Neurophysiology ◽

10.1152/jn.2001.86.4.1983 ◽

2001 ◽

Vol 86 (4) ◽

pp. 1983-1990 ◽

Cited By ~ 229

Author(s):

T. Paus ◽

P. K. Sipila ◽

A. P. Strafella

Keyword(s):

Transcranial Magnetic Stimulation ◽

Motor Cortex ◽

Cortical Neurons ◽

Magnetic Stimulation ◽

Primary Motor Cortex ◽

Temporal Dynamics ◽

Single Pulse ◽

Cortical Oscillations ◽

Cortical Rhythms ◽

Oscillatory Response

Using multichannel electroencephalography (EEG), we investigated temporal dynamics of the cortical response to transcranial magnetic stimulation (TMS). TMS was applied over the left primary motor cortex (M1) of healthy volunteers, intermixing single suprathreshold pulses with pairs of sub- and suprathreshold pulses and simultaneously recording EEG from 60 scalp electrodes. Averaging of EEG data time locked to the onset of TMS pulses yielded a waveform consisting of a positive peak (30 ms after the pulse P30), followed by two negative peaks [at 45 (N45) and 100 ms]. Peak-to-peak amplitude of the P30–N45 waveform was high, ranging from 12 to 70 μV; in most subjects, the N45 potential could be identified in single EEG traces. Spectral analysis revealed that single-pulse TMS induced a brief period of synchronized activity in the beta range (15–30 Hz) in the vicinity of the stimulation site; again, this oscillatory response was apparent not only in the EEG averages but also in single traces. Both the N45 and the oscillatory response were lower in amplitude in the 12-ms (but not 3-ms) paired-pulse trials, compared with the single-pulse trials. These findings are consistent with the possibility that TMS applied to M1 induces transient synchronization of spontaneous activity of cortical neurons within the 15- to 30-Hz frequency range. As such, they corroborate previous studies of cortical oscillations in the motor cortex and point to the potential of the combined TMS/EEG approach for further investigations of cortical rhythms in the human brain.

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Comparison of low frequency repetitive transcranial magnetic stimulation parameters on motor cortex excitability in normal subjects

International Journal of Epilepsy ◽

10.1016/j.ijep.2016.02.003 ◽

2016 ◽

Vol 03 (01) ◽

pp. 002-006

Author(s):

Lara Schrader ◽

Sima Sadeghinejad ◽

Jalleh Sadeghinejad ◽

Movses Kazanchyan ◽

Lisa Koski ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Motor Cortex ◽

Magnetic Stimulation ◽

Primary Motor Cortex ◽

Cortical Excitability ◽

Repetitive Transcranial Magnetic Stimulation ◽

Low Frequency ◽

Motor Threshold ◽

Motor Cortex Excitability ◽

Resting Motor Threshold

Abstract Background/objectives Optimal low frequency repetitive transcranial magnetic stimulation (LF-rTMS) parameters for treating epilepsy and other brain disorders are unknown. To address this question, a systematic study of the effects of LF-rTMS frequency and intensity on cortical excitability was performed. Methods Using a four-period crossover design, subjects were scheduled for four LF-rTMS sessions that were at least four weeks apart. LF-rTMS was delivered as 900 pulses directed at primary motor cortex using four protocols: 0.5 Hz at 90% resting motor threshold (RMT), 0.5 Hz at 110% RMT, 1 Hz at 90% RMT, and 1 Hz at 110% RMT. Motor evoked potential (MEP) amplitude, resting motor threshold (RMT), and cortical silent period (CSP) were measured before, immediately after, and 60 min after LF-rTMS. Each of the four protocols was analyzed separately to compare baseline measurements to those after LF-rTMS. Results None of the four LF-rTMS protocols produced a trend or significant change in MEP amplitude, RMT, or CSP. Conclusion The lack of significant effect from the four LF-rTMS protocols indicates that none produced evidence for alteration of cortical excitability. The direct comparison of four LF-rTMS protocols is distinct to this investigation, as most similar studies were exploratory and studied only one or two protocols. The negative result relates only to the methods used in this investigation and does not indicate that LF-rTMS does not alter cortical excitability with other parameters. These results may be useful when designing additional investigations into the effect of LF-rTMS on epilepsy, other disorders, and cortical excitability.

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Preconditioning Repetitive Transcranial Magnetic Stimulation of Premotor Cortex Can Reduce But Not Enhance Short-Term Facilitation of Primary Motor Cortex

Journal of Neurophysiology ◽

10.1152/jn.00753.2007 ◽

2008 ◽

Vol 99 (2) ◽

pp. 564-570 ◽

Cited By ~ 28

Author(s):

A. Suppa ◽

M. Bologna ◽

F. Gilio ◽

C. Lorenzano ◽

J. C. Rothwell ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Motor Cortex ◽

Magnetic Stimulation ◽

Primary Motor Cortex ◽

Repetitive Transcranial Magnetic Stimulation ◽

Premotor Cortex ◽

Single Pulse ◽

Short Term ◽

Hand Muscles ◽

Term Potentiation

Short trains of suprathreshold 5-Hz repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) evoke motor potentials (MEPs) in hand muscles that progressively increase in amplitude via a mechanism that is thought to be similar to short-term potentiation described in animal preparations. Long trains of subthreshold rTMS over dorsal premotor cortex (PMd) are known to affect the amplitude of single-pulse MEPs evoked from M1. We tested whether PMd-rTMS affects short-term facilitation in M1. We also explored the effect of PMd-rTMS on M1 responses evoked by single-pulse TMS of different polarities. We tested in 15 healthy subjects short-term facilitation in left M1 (10 suprathreshold TMS pulses at 5 Hz) after applying rTMS to left PMd (1,500 subthreshold pulses at 1 and 5 Hz). In a sample of subjects we delivered single-pulse TMS with different polarities and paired-pulse TMS at short intervals (SICI) after PMd-rTMS. Short-term facilitation in M1 was reduced after applying 1 Hz to PMd, but was unaffected after 5-Hz PMd-rTMS. PMd-rTMS with 1 Hz reduced the amplitude of MEPs evoked by monophasic posteroanterior (PA) or biphasic anteroposterior (AP)–PA but had little effect on MEPs by monophasic AP or biphasic PA–AP single-pulse TMS. PMd-rTMS left SICI unchanged. PMd-rTMS (1 Hz) reduces short-term facilitation in M1 induced by short 5-Hz trains. This effect is likely to be caused by reduced facilitation of I-wave inputs to corticospinal neurons.

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