A standardized motor threshold estimation procedure for transcranial magnetic stimulation research

OBJECTIVES: To introduce and to test a simple standardized motor threshold (MT) estimation procedure for transcranial magnetic stimulation (TMS) research. METHODS: A 5-step MT estimation procedure was introduced, and interestimator reliability was tested by comparing MTs as determined by an experienced and a trainee TMS researcher in a double-blind design. RESULTS: The parametric Pearson correlation between the MTs of the experienced and the MTs of the trainee TMS researcher was 0.95 (P < 0.001). CONCLUSIONS: The currently proposed estimation procedure may be helpful in obtaining reliable MT values in experimental and clinical settings.     

Elevated motor threshold in drug-free, cocaine-dependent patients assessed with transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) provides a noninvasive method of examining cortical inhibitory and excitatory processes and cortical excitability in awake subjects. There is evidence from clinical and electroencephalographic (EEG) data that cortical excitability may be abnormal in some psychiatric populations. Chronic cocaine abuse influences a number of neurotransmitters that are involved in the excitatory/inhibitory balance of the cerebral cortex. This pilot study was conducted to ascertain the possible utility of TMS in examining cortical excitability in a population of chronic cocaine abusers. METHODS: The right and left motor thresholds of ten cocaine-dependent subjects, according to DSM-IV, and ten normal control subjects were examined using single pulse TMS. RESULTS: The resting motor thresholds resulting from stimulation of the right or the left motor cortical regions were significantly elevated in cocaine-dependent subjects compared with matched control subjects. CONCLUSIONS: These pilot data suggest that chronic cocaine use significantly alters cortical excitability in the direction of increased inhibition or decreased excitability. We hypothesize that this observation reflects adaptation to those effects of cocaine intoxication that promote cortical excitability and seizures.     

Laterality of motor cortical function measured by transcranial magnetic stimulation threshold tracking

Introduction: Threshold tracking paired‐pulse transcranial magnetic stimulation (TTTMS) examines cortical function and is useful for diagnosis of motor neuron disorders. Differences in cortical function have been identified between dominant and non‐dominant limbs using constant stimulus methods, but they remain unclear, potentially due to methodological differences. In this study we aimed to clarify differences in cortical function between dominant and non‐dominant limbs using TTTMS. Methods: Single‐pulse TMS, TTTMS, and nerve conduction studies were performed in 25 healthy, right‐handed participants by recording from the abductor pollicis brevis muscle. Results: There were no side‐to‐side differences observed in resting motor threshold, motor evoked potential (MEP) amplitude, MEP latency, central motor conduction time, cortical silent period, short‐interval intracortical inhibition and facilitation, compound muscle action potential (CMAP) amplitude, CMAP latency, F‐wave latency, or neurophysiological index. Conclusions: These findings suggest that, when using TTTMS, there are no differences in cortical function between dominant and non‐dominant hemispheres. Muscle Nerve 55 : 424–427, 2017     

Excitation threshold of the motor cortex estimated with transcranial magnetic stimulation electroencephalography

The excitation threshold of the human motor cortex was estimated on the basis of electroencephalographic responses evoked by transcranial magnetic stimulation. The hand area of the primary motor cortex was stimulated at 10 intensities, for seven healthy individuals. The four dominant peaks of the overall brain response could be reliably determined when stimulation was intense enough to induce a cortical electric field of approximately 33-44 mV/mm. This may be estimated as the threshold for evoking measurable brain activity by motor-cortex transcranial magnetic stimulation. The remarkably low threshold reflects the excellent sensitivity of the combination of transcranial magnetic stimulation and electroencephalography for the study of neuronal function of the cortex.     

Increased transcranial magnetic motor threshold after ECT

Electroconvulsive therapy (ECT) is a powerful antidepressive treatment, but its mechanism of action remains poorly understood. To clarify the influence of ECT on corticospinal tract excitability we tested the motor threshold, the motor evoked potential (MEP) input/output curve, and the intracortical excitability using transcranial magnetic stimulation in a depressed patient before and after successful treatment with ECT. Resting motor thresholds were increased bilaterally after treatment, and the input/output curve less steep. These results point to a decreased excitability of the corticospinal motor tract after successful ECT.     

Probing interhemispheric dorsal premotor-primary motor cortex interactions with threshold hunting transcranial magnetic stimulation

ObjectiveTo characterise the effect of altering transcranial magnetic stimulation parameters on the magnitude of interhemispheric inhibition (IHI) from dorsal premotor (PMd) to primary motor cortex (M1).MethodWe used a fully automated adaptive threshold hunting paradigm to quantify PMd-M1 IHI across a range of conditioning stimulus (CS) intensities (90%, 110%, 130% of resting motor threshold, rMT) and interstimulus intervals (ISIs) (8, 10, 40 ms). M1-M1 IHI was examined with CS intensities of 110%, 120%, and 130% rMT and ISIs of 10 and 40 ms. Two test coil orientations (inducing posterior-anterior or anterior-posterior current) were used.ResultsPMd-M1 IHI was obtained consistently with posterior-anterior (but not anterior-posterior) test stimuli and increased with CS intensity. M1-M1 IHI was expressed across all conditions and increased with CS intensity when posterior-anterior but not anterior-posterior induced current was used.ConclusionsThe expression of PMd-M1 IHI is contingent on test coil orientation (requiring posterior-anterior induced current) and increases as a function of CS intensity. The expression of M1-M1 IHI is not dependent on test coil orientation.SignificanceWe defined a range of parameters that elicit reliable PMd-M1 IHI. This (threshold hunting) methodology may provide a means to quantify premotor-motor pathology and reveal novel quantitative biomarkers.     

Reliability of the 'observation of movement' method for determining motor threshold using transcranial magnetic stimulation

The aim of this study was to establish the reliability of the observation of movement (OM) method for obtaining motor threshold (MT) in transcranial magnetic stimulation (TMS). MTs were obtained on separate days, following separate hunting procedures, for both left and right motor cortex (M1), with one or multiple estimates obtained from the same hemisphere within a single session. MTs obtained using the OM method were highly reliable and reproducible on different days (left M1: r = .98, p < .0001; right M1: r = .97, p < .0001). MTs were not influenced by the order of acquisition when two hemispheres were stimulated in the same session [F(1,22) = .12, p = .73] or by the collection of additional MTs as part of the distance-adjusted procedure [F(1,23) = .74, p = .40]. The results verify the reliability of the OM method and confirm its viability for the safe and efficient application of TMS to the left and right M1. The OM method is a reliable technique for obtaining MT and is relatively simple and quick to run. It therefore provides an effective procedure for research and clinical applications.     

Optimization of facilitation related to threshold in transcranial magnetic stimulation.

OBJECTIVES: To attain the standardized procedure for optimal facilitation, we analyzed motor-evoked potential (MEP) responses to the degree of voluntary contraction and stimulus intensity. METHODS: Fifteen normal subjects were included. MEPs were elicited at thenar muscles during rest and at gradual voluntary contraction (MVC), using 10, 30, and 50% of MVC. During rest and each contraction, the excitability threshold at rest (RET) and at contraction (CET) were determined. Consecutive stimuli were applied, with the intensity of ratio increments (110-150% of ET). RESULTS: The RET showed a remarkable decrease after contraction. Shortening of latency reached a saturation level at 10% of MVC. Amplitude reached a saturation level at 30% of MVC with 62.7+/-8.5% of the maximum output, which is equal to 140% intensity of CET, and 110% of RET. The MEP amplitudes at rest and at 10% MVC were influenced by their ETs, but those measured above 30% of MVC were not related. CONCLUSIONS: The procedure recommended for optimal facilitation is as follows: to achieve minimal latency of MEPs, a minimal contraction (10% of MVC) with RET intensity is sufficient and for maximal amplitude, a moderate contraction (30% of MVC) with 110% of RET intensity is adequate.     

Optimal transcranial magnetic stimulation sites for the assessment of motor function.

The optimal placement sites for eliciting motor evoked potentials from the abductor digiti minimi and abductor hallucis muscles by means of transcranial magnetic stimulation were determined using a commercially available circular coli. Fifty volunteers were used for the study. The ability to elicit responses was found to be strongly dependent upon the scalp placement of the stimulator coil. The effects of altering the direction of current flow in the coil were tested on two different sets of volunteers: clockwise in one and counterclockwise in the other. It influenced only the locations of the sites which were optimal for eliciting responses from the abductor hallucis muscles and not those which were optimal for eliciting responses from the abductor digiti minimi muscles. Response latencies were found to be significantly dependent only upon volunteers' heights and not on their sex, age, or weight or the stimulus intensities used to elicit responses. No previous studies have defined the optimal scalp placements for eliciting responses from the lower extremities. This information may have clinical importance for making reliable assessments of patients with significantly impaired motor function.     

Determination of motor threshold using visual observation overestimates transcranial magnetic stimulation dosage: Safety implications

ObjectiveWhile the standard has been to define motor threshold (MT) using EMG to measure motor cortex response to transcranial magnetic stimulation (TMS), another method of determining MT using visual observation of muscle twitch (OM-MT) has emerged in clinical and research use. We compared these two methods for determining MT.MethodsLeft motor cortex MTs were found in 20 healthy subjects. Employing the commonly-used relative frequency procedure and beginning from a clearly suprathreshold intensity, two raters used motor evoked potentials and finger movements respectively to determine EMG-MT and OM-MT.ResultsOM-MT was 11.3% higher than EMG-MT (p < 0.001), ranging from 0% to 27.8%. In eight subjects, OM-MT was more than 10% higher than EMG-MT, with two greater than 25%.ConclusionsThese findings suggest using OM yields significantly higher MTs than EMG, and may lead to unsafe TMS in some individuals. In more than half of the subjects in the present study, use of their OM-MT for typical rTMS treatment of depression would have resulted in stimulation beyond safety limits.SignificanceFor applications that involve stimulation near established safety limits and in the presence of factors that could elevate risk such as concomitant medications, EMG–MT is advisable, given that safety guidelines for TMS parameters were based on EMG-MT.     

Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation.

OBJECTIVE: To investigate the effect of high frequency rTMS (25 Hz at 90-100% of resting motor threshold) on the excitability of the motor cortex of healthy human subjects. METHODS: Resting and active motor threshold, MEP recruitment curve (I/O curve), short interval intracortical inhibition (SICI) and facilitation (ICF), and the duration of the silent period (SP) were tested in the right first dorsal interosseous muscle (FDI) before and twice after the end of 1500 pulses in 16 normal young adult male volunteers. RESULTS: Twenty-five Hertz rTMS decreased motor thresholds, reduced the duration of the silent period and had a tendency to increase the slope of the I/O curve. Most of these effects lasted for the duration of the two post-testing sessions (at least 30 min) and had returned to normal by 2h. There were no significant effects on SICI/ICF. CONCLUSION: Twenty-five Hertz rTMS can produce a long lasting increase in cortical excitability in healthy subjects. SIGNIFICANCE: This method may prove useful for the study of normal human physiology and for therapeutic manipulation of brain plasticity.     

Navigated transcranial magnetic stimulation and computed electric field strength reduce stimulator-dependent differences in the motor threshold

The motor threshold (MT) is a fundamental parameter for evaluating cortical excitability in transcranial magnetic stimulation (TMS) despite remarkable variation, both within, and between subjects. We intended to test whether the variation could be reduced by targeting the stimulation on-line and modeling the TMS-induced electric field on individual MR images. Navigated TMS was used to map the primary motor cortex for the representation area of the thenar muscles (abductor pollicis brevis) and to determine the MT. Thirteen healthy subjects participated in the study. To determine the between-subject variation, the MTs of nine subjects were measured with two different stimulators (comparison study). To study the individual variation, the MT measurement was repeated 20 times in four subjects always using the same stimulator (longitudinal study). In the comparison study, the MTs differed significantly between the two stimulators over all subjects (p<0.001), whereas the electric field strengths did not exhibit significant difference between the stimulators. Both, the MTs, and the electric field strengths showed similar variations, which were greater between subjects (comparison study) than within subjects (longitudinal study). In the comparison study, the distance between the locations of the two different coils on the scalp was significantly greater than the distance between the induced electric field maxima in the brain (p<0.001). We conclude that on-line navigation can be used to reduce the variation caused by different stimulator types and individual subject anatomy. In addition, cortical excitability can be evaluated by using computed electric field strength as well as stimulator-dependent MT.     

Resting motor threshold changes and clinical response to prefrontal repetitive transcranial magnetic stimulation in depressed patients

Aims: Several variables are able to influence the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS), particularly the intensity of stimulation, which is generally expressed according to the resting motor threshold (RMT). The aim of our study was to investigate whether or not RMT changes during the treatment of resistant depression by rTMS and whether these fluctuations could alter treatment outcome. Methods: Seventy‐five inpatients suffering from unipolar or bipolar treatment‐resistant depression and who had been antidepressant‐free or taking a stable antidepressant drug and a daily dose of benzodiazepine for at least a month received a left prefrontal rTMS session once a day for 10 days at 10 Hz and 95% RMT. Results: For the whole group, no significant fluctuation of RMT was observed between the first and the second week of rTMS treatment. However, RMT increased, decreased or remained constant throughout treatment depending on the patient. These RMT changes influenced the outcome of the 10 sessions concerning the severity of depressive and anxiety symptoms, measured by the Beck Depression Inventory and State Trait Anxiety, respectively. Conclusions: Our results justify calculating RMT regularly, and suggest that its variations play a role in treatment outcome.     

Age-dependent changes in physiological threshold asymmetries for the motor evoked potential and silent period following transcranial magnetic stimulation

OBJECTIVE: To study the effect of age on the physiological threshold asymmetries for the motor evoked potential (MEP) and silent period (SP) following transcranial magnetic stimulation. METHODS: We studied 63 right-handed subjects and 13 young left-handed subjects (19-39 years). The right-handers were classified into three age groups; 22 young (20-38 years), 20 middle-aged (40-58 years) and 21 old (61-82 years) subjects. We measured the MEP thresholds at rest and during voluntary contraction (VC), and the SP thresholds from the right and left abductor pollicis brevis (APB) muscles. We also measured the side to side differences of the F wave persistency and the F wave/M wave amplitude ratio from the same muscles. RESULTS: Among young subjects, all of the MEP and SP thresholds for the right APB were significantly lower than those for the left APB in the right-handers, and the reverse was true in the left-handers. The results in the middle-aged right-handers were similar to those in the young right-handers, but in the old right-handers, none of the thresholds were different between the two sides. We did not find any asymmetries of the F wave in the subjects of any age group. CONCLUSION: We speculate that the age-dependent threshold asymmetries are preferentially related to functional asymmetries at the cortical level.