Distance-adjusted motor threshold for transcranial magnetic stimulation.

OBJECTIVE: To examine the relationship between coil-cortex distance and effective cortical stimulation using transcranial magnetic stimulation (TMS) in the left and right motor cortex. We also compare the effect of coil-cortex distance using 50 and 70 mm figure-eight stimulating coils. METHODS: Coil-cortex distance was manipulated within each participant using 5 and 10 mm acrylic separators placed between the coil and scalp surface. The effect of cortical stimulation was indexed by resting motor threshold (MT). RESULTS: Increasing distance between the coil and underlying cortex was associated with a steep linear increase in MT. For each additional millimetre separating the stimulating coil from the scalp surface, an additional approximately 2.8% of absolute stimulator output (approximately 0.062 T) was required to reach MT. The gradient of the observed distance effect did not differ between hemispheres, and no differences were observed between the 50 and 70 mm TMS coils. CONCLUSIONS: Coil-cortex distance directly influences the magnitude of cortical stimulation in TMS. The relationship between TMS efficacy and coil-cortex distance is well characterised by a linear function, providing a simple and effective method for scaling stimulator output to a distance adjusted MT. SIGNIFICANCE: MT measured at the scalp-surface is dependent on the underlying scalp-cortex distance, and therefore does not provide an accurate index of cortical excitability. Distance-adjusted MT provides a more accurate index of cortical excitability, and improves the safety and efficacy of MT-calibrated TMS.     

The use of transcranial magnetic stimulation for monitoring descending spinal cord motor function.

This report describes our initial clinical experience using transcranial magnetic stimulation for monitoring spinal cord motor function during surgical procedures. Motor evoked potentials were elicited using a cap shaped coil placed on the scalp of 27 patients while recording peripheral motor responses (compound muscle action potentials--CMAPs) from the upper (N = 1) or lower limbs (N = 26). Wherever possible, cortical somatosensory responses (SEPs) were also monitored by electrically stimulating the left and right posterior tibial nerve (N = 25) or the median nerve (N = 1). The judicious choice of anesthetic regimens resulted in successfully obtaining motor evoked responses (MEPs) in 21 of 27 patients and SEPs in 26 of 27 patients. Single pulse TMS resulted in peripheral muscle responses having large variability, whereas, the variability of SEPs was much less. Criteria based on response variability for assessing clinically significant changes in both MEPs and SEPs resulted in two false negative predictions for SEPs and none for MEPs when evaluating postoperative motor function. We recommend monitoring both sensory and motor pathways during procedures where placing the spinal cord at risk of damage.     

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     

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.     

Repetitive transcranial magnetic stimulation to improve mood and motor function in Parkinson's disease

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can produce lasting changes in excitability and activity in cortical regions underneath the stimulation coil (local effect), but also within functionally connected cortical or subcortical regions (remote effects). Since the clinical presentation of Parkinson's disease (PD) is related to abnormal neuronal activity within the basal ganglia and cortical regions, including the primary motor cortex, the premotor cortex and the prefrontal cortex, several studies have used rTMS to improve brain function in PD. Here, we review the studies that have investigated the possible therapeutic effects of rTMS on mood and motor function in PD patients. We highlight some methodological inconsistencies and problems, including the difficulty to define the most effective protocol for rTMS or to establish an appropriate placebo condition. We finally propose future directions of research that may help to improve the therapeutic efficacy of rTMS in PD.     

Effects of low-frequency transcranial magnetic stimulation on motor excitability and basic motor behavior.

OBJECTIVE: To explore effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) on motor excitability and basic motor behavior in humans.Design and METHODS: Seven normal volunteers underwent 1 Hz rTMS of the hand representation of the right M1 for 15 min at an intensity of 115% of the individual resting motor threshold. The effects of rTMS on motor excitability were assessed by monitoring changes in individual resting motor threshold and input-output curves of motor evoked potentials (MEPs) in the flexor pollicis brevis, first dorsal interosseus, abductor digiti minimi and biceps brachii muscles. Changes in basic motor behavior were studied by measuring maximal and mean peak force and peak accelerations of thumb flexions and abductions of the fifth finger before and after rTMS. RESULTS: rTMS produced a significant increase in resting motor threshold and a significant suppression of MEP input-output curves that persisted for 30 min. The suppressing effect was restricted to the hand motor representation which was the prime target of the stimulation procedure, and there were no significant effects on the biceps representation. Peak force and peak acceleration were not affected while the motor representations of muscles involved in the behavioral measurements were significantly suppressed by rTMS. CONCLUSIONS: Low-frequency rTMS of M1 transiently depresses motor excitability but this does not affect basic motor behavior. This is relevant for the therapeutic use of low-frequency rTMS in disorders with abnormal cortical excitability.     

Interhemispheric reorganization of motor hand function to the primary motor cortex predicted with functional magnetic resonance imaging and transcranial magnetic stimulation

The objective of this study was presurgical assessment of reorganization of motor hand function in an 11-year-old girl with intractable epilepsy and a right-sided hemiplegia resulting from an extensive perinatal left hemispheric stroke. Prior to a left functional hemispherectomy, functional magnetic resonance imaging (MRI) showed that both nonparetic and paretic motor hand function predominantly activated the right primary motor cortex, whereas no activation was found in the left hemisphere. Transcranial magnetic stimulation of the right central area yielded responses in both the nonparetic and the paretic hand, whereas no responses were obtained after stimulation of the affected hemisphere. Both techniques indicated that motor function was mediated by corticospinal fibers originating from the undamaged (primary) motor cortex and predicted no further loss of motor hand function after surgery. Indeed, subsequent functional hemispherectomy induced no new sensorimotor deficits. Functional MRI was repeated 22 months after surgery and matched preoperative sensorimotor functional MRI findings, confirming reorganization of the primary motor cortex. No additional reorganization was introduced by surgery.     

Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson''s disease patients

Cortical excitability of the primary motor cortex is altered in patients with Parkinson's disease (PD). Therefore, modulation of cortical excitability by high frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex might result in beneficial effects on motor functions in PD. The present study aims to evaluate the effect of rTMS of the motor cortex on motor functions in patients with PD. Thirty-six unmedicated PD patients were included consecutively in this study. The patients were assigned in a randomized pattern to one of two groups, one group receiving real-rTMS (suprathreshold 5-Hz, 2000 pulses once a day for 10 consecutive days) and the second group receiving sham-rTMS using closed envelopes. Total motor section of Unified Parkinson's Disease Rating Scale (UPDRS), walking speed, and self-assessment scale were performed for each patient before rTMS and after the first, fifth, 10th sessions, and then after 1 month. Evaluation of these measures was performed blindly without knowing the type of rTMS. anova for repeated measurements revealed a significant time effect for the total motor UPDRS, walking speed and self-assessment scale during the course of the study in the group of patients receiving real-rTMS (P = 0.0001, 0.001, and 0.002), while no significant changes were observed in the group receiving sham-rTMS except in self-assessment scale (P = 0.019). A 10-day course of real-rTMS resulted in statistically significant long-term improvement of the motor functions in comparison with the sham-rTMS. The rTMS could have a therapeutic role of for PD patients.     

Cerebral function revealed by transcranial magnetic stimulation

Although transcranial magnetic stimulation (TMS) has been introduced only recently, it is safe and provides a painless, inexpensive noninvasive method for the evaluation of brain function. Determining central motor conduction time (CMCT) permits assessment of the corticospinal pathways. Mapping the central representation of muscles provides a method for investigating the cortical reorganization that follows training, amputation and injury to the central nervous system. Such studies of human plasticity may have important implications for neurorehabilitation. TMS also provides a method whereby cortical excitability can be noninvasively evaluated, which is likely to have important implications in the study of epilepsy, movement disorders and related conditions. TMS is useful in tracking the flow of information from one brain region to another and in investigations of cognition and functional localization, thereby complementing information obtained using functional imaging techniques, which have superior spatial but inferior temporal resolution. Finally, TMS is currently being investigated as a method for establishing cerebral dominance and as a therapeutic tool in the treatment of depression. Investigations for treatment of other neurologic and psychiatric conditions are likely to be undertaken.     

Modifying the cortical processing for motor preparation by repetitive transcranial magnetic stimulation

To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on the central processing of motor preparation, we had subjects perform a precued-choice reaction time (RT) task. They had to press one of two buttons as quickly as possible after a go signal specifying both the hand to be used and the button to press. A precue preceding this signal conveyed full, partial, or no advance information (hand and/or button), such that RT shortened with increasing amount of information. We applied 1200 to 2400 pulses of 1-Hz rTMS over various cortical areas and compared the subjects' performances at various times before and after this intervention. rTMS delayed RT at two distinct phases after stimulation, one within 10 min and another with a peak at 20 to 30 min and lasting for 60 to 90 min, with no significant effects on error rates or movement time. The effect was significantly larger on left- than on right-hand responses. RT was prominently delayed over the premotor and motor cortices with similar effects across different conditions of advance information, suggesting that preparatory processes relatively close to the formation of motor output were influenced by rTMS. In contrast, the effect of rTMS over the supplementary motor area and the anterior parietal cortex varied with the amount of advance information, indicating specific roles played by these areas in integrating target and effector information. The primary motor area, especially of the left hemisphere, may take over this processing, implementing motor output based on the information processed in other areas.     

Worry facilitates corticospinal motor response to transcranial magnetic stimulation

Like other forms of emotion, anxiety has been theoretically linked to preparation for action. Worry is a type of anticipatory anxiety and the hallmark of generalized anxiety disorder. Research has shown that worry is associated with vigilance to threat cues and increased muscle tension, which may in part be explained by motor facilitation that accompanies preparation for action. This study assessed corticospinal motor responses during worry using transcranial magnetic stimulation (TMS). Participants received TMS during a worry induction, during motor imagery, and during mental arithmetic, while electromyography and force were measured. TMS over the primary motor cortex elicited larger corticospinal motor responses during worry than mental arithmetic and smaller responses than motor imagery of maximum voluntary contraction of targeted muscles. These findings suggest that the association between worry and motor preparation cannot be explained by high cognitive load and provide further support for theoretical accounts emphasizing the role of action preparation in anxiety.     

Iron-core coils for transcranial magnetic stimulation.

Transcranial magnetic stimulation requires a great deal of power, which mandates bulky power supplies and produces rapid coil heating. The authors describe the construction, modeling, and testing of an iron-core TMS coil that reduces power requirements and heat generation substantially, while improving the penetration of the magnetic field. Experimental measurements and numeric boundary element analysis show that the iron-core stimulation coil induces much stronger electrical fields, allows greater charge recovery, and generates less heat than air-core counterparts when excited on a constant-energy basis. These advantages are magnified in constant-effect comparisons. Examples are given in which the iron-core coil allows more effective operation in research and clinical applications.     

Reliability of motor cortex transcranial magnetic stimulation in four muscle representations.

OBJECTIVE: Motor cortex plasticity may underlie motor recovery after stroke. Numerous studies have used transcranial magnetic stimulation (TMS) to investigate motor system plasticity. However, research on the reliability of TMS measures of motor cortex organization and excitability is limited. We sought to test the reliability of these TMS measurements. METHODS: Twenty healthy volunteers were tested twice over a two-week period using TMS to determine motor threshold, map topography, and stimulus-response curves for first dorsal interosseous (FDI), abductor pollicis brevis (APB), extensor digitorum communis (EDC), and flexor carpi radialis (FCR) muscles. RESULTS: We found moderate to good test-retest reliability TMS measurements of motor threshold (ICC=0.90-0.97), map area (ICC=0.63-0.86) and location (ICC=0.69-0.86), and stimulus-response curves (ICC=0.60-0.83). CONCLUSIONS: TMS assessments of motor representation size, location, and excitability are generally reliable measures, although their reliability may vary according to the muscle under investigation. SIGNIFICANCE: These results suggest that TMS measurements of motor cortex function are reliable enough to be potentially useful in investigation of motor system plasticity.     

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.     

Repetitive transcranial magnetic stimulation effects on language function depend on the stimulation parameters.

In previous studies it has been shown that picture-naming latencies can be facilitated with both suprathreshold single and repetitive transcranial magnetic stimulation (TMS/rTMS) over Wernicke's area. The aim of this study was to investigate whether low-frequency rTMS (1 Hz) or high-frequency rTMS (20 Hz) at subthreshold intensities is also capable of influencing picture naming. In 16 healthy right-hand male subjects, trains of 1 Hz or 20 Hz were applied over either Wernicke's area, Broca's area, or the primary visual cortex. The subjects had to name 20 black-and-white line drawings, which were shown immediately after rTMS and again 2 minutes later. Naming latency could be facilitated only immediately after Wernicke's area stimulation at a frequency of 20 Hz and at an intensity of 55% of the maximal stimulator output, which was more than the motor threshold. All other stimulation procedures failed to influence naming latencies. These results indicate that language functions can be facilitated in healthy subjects only by high-frequency rTMS with intensities at or above the motor threshold.