Differences between the effects of three plasticity inducing protocols on the organization of the human motor cortex

Several experimental protocols induce lasting changes in the excitability of motor cortex. Some involve direct cortical stimulation, others activate the somatosensory system and some combine motor and sensory stimulation. The effects usually are measured as changes in amplitude of the motor-evoked-potential (MEP) or short-interval intracortical inhibition (SICI) elicited by a single or paired pulses of transcranial magnetic stimulation (TMS). Recent work has also tested sensorimotor organization within the motor cortex by recording MEPs and SICI during short periods of vibration applied to single intrinsic hand muscles. Here sensorimotor organization is focal: MEPs increase and SICI decreases in the vibrated muscle, whilst the opposite occurs in neighbouring muscles. In six volunteers we compared the after effects of three protocols that lead to lasting changes in cortical excitability: (i) paired associative stimulation (PAS) between a TMS pulse and an electrical stimulus to the median nerve; (ii) motor practice of rapid thumb abduction; and (iii) sensory input produced by semicontinuous muscle vibration, on MEPs and SICI at rest and on the sensorimotor organization. PAS increased MEP amplitudes, whereas vibration changed sensorimotor organization. Motor practice had a dual effect and increased MEPs as well as affecting sensorimotor organization. The implication is that different protocols target different sets of cortical circuits. We speculate that protocols that involve repeated activation of motor cortical output lead to lasting changes in efficacy of synaptic connections in output circuits, whereas protocols that emphasize sensory inputs affect the strength of sensory inputs to motor circuits.     

Prolonged peripheral nerve stimulation induces persistent changes in excitability of human motor cortex

This study sought to determine whether prolonged peripheral nerve stimulation was effective in inducing persistent "plastic" changes in the excitability of the human motor cortex. The amplitude of the electromyographic response evoked in resting intrinsic hand muscles by focal transcranial magnetic stimulation (TMS) was taken as an index of motor cortical excitability. Twelve subjects were stimulated with each of three protocols, one of which was given on each of three separate occasions. The protocols consisted of various schedules of electrical stimulation of the radial and ulnar nerves or the motor point of the first dorsal interosseous muscle (FDI), or stimulation of FDI motor point paired with low-frequency TMS. Amplitudes of TMS-elicited motor evoked potentials (MEPs) were measured before peripheral stimulation and for 2 h after stimulation. The data from one subject were unusable. In every other subject, all three protocols induced a prolonged, significant facilitation of MEPs in at least some of the three intrinsic hand muscles used. In some instances, MEPs were not enlarged and occasionally were significantly depressed. Different protocols based on peripheral afferent stimulation can induce plastic changes in the organisation of the motor cortex that persist for at least 2 h.     

Origin of facilitation in repetitive, 1.5ms interval, paired pulse transcranial magnetic stimulation (rPPS) of the human motor cortex.

OBJECTIVE: Repetitive paired-pulse TMS (rPPS) given at an interstimulus interval (ISI) of 1.5 ms has been reported to induce a lasting motor evoked potential (MEP) facilitation. This after-effect was considered to be a cortical event because F-waves were not affected by the same rPPS. To confirm its cortical facilitation, we compared the after-effects of rPPS on MEPs to single pulse TMS over the motor cortex (motor cortical MEPs) with those to brainstem stimulation (brainstem MEPs). METHODS: Subjects were 10 healthy volunteers. Suprathreshold paired-pulse TMS at an ISI of 1.5 ms was applied to the motor cortex for 30 min at a rate of 0.2 Hz. After intervention, we measured motor cortical MEPs for 30 min. We also studied brainstem MEPs in five subjects. RESULTS: Motor cortical MEPs were facilitated to about 190% of baseline (p<0.001) for 10 min post rPPS intervention and returned to the baseline at 10-15 min post intervention. Brainstem MEPs were not affected by the intervention. CONCLUSIONS: The facilitation of MEPs after rPPS at an interval of 1.5 ms occurs at the motor cortex. SIGNIFICANCE: rPPS at an interval of 1.5 ms is an effective method for increasing motor cortical excitability.     

Focal enhancement of motor cortex excitability during motor imagery: a transcranial magnetic stimulation study

OBJECTIVES: In order to learn more about the physiology of the motor cortex during motor imagery, we evaluated the changes in excitability of two different hand muscle representations in the primary motor cortex (M1) of both hemispheres during two imagery conditions. MATERIALS AND METHODS: We applied focal transcranial magnetic stimulation (TMS) over each M1, recording motor evoked potentials (MEPs) from the contralateral abductor pollicis brevis (APB) and first dorsal interosseus (FDI) muscles during rest, imagery of contralateral thumb abduction (C-APB), and imagery of ipsilateral thumb abduction (I-APB). We obtained measures of motor threshold (MT), MEP recruitment curve (MEP-rc) and F waves. RESULTS: Motor imagery compared with rest significantly decreased the MT and increased MEPs amplitude at stimulation intensities clearly above MT in condition C-APB, but not in condition I-APB. These effects were not significantly different between right and left hemisphere. MEPs simultaneously recorded from the FDI, which was not involved in the task, did not show facilitatory effects. There were no significant changes in F wave amplitude during motor imagery compared with rest. CONCLUSIONS: Imagery of unilateral simple movements is associated with increased excitability only of a highly specific representation in the contralateral M1 and does not differ between hemispheres.     

Decreased input to the motor cortex increases motor cortical excitability.

OBJECTIVE: To investigate whether a short-duration reduction of input to the motor cortex affects excitability in the hand region of the motor cortex. METHODS: Subjects (n=10) received sets of transcranial magnetic stimulation of the motor cortex (TMS) and peripheral ulnar nerve stimulation. Stimuli were delivered before and after 20 min of inactivity of the test hand. The evoked compound muscle action potentials were recorded in two relaxed intrinsic hand muscles using surface EMG. RESULTS: Motor evoked potential size (MEP; expressed relative to the maximal M-wave) increased by approximately 30-40 in both hand muscles (P=0.012) following inactivity. The enlarged MEP was not associated with changes in F-wave size, a marker of motoneurone excitability, or changes in intracortical inhibition and facilitation measured with paired-pulse TMS. CONCLUSIONS: MEP growth most likely reflects an increase in motor cortical excitability. The increased excitability appears to be more associated with reduced voluntary drive to and from the motor cortex rather than reduced afferent input from the periphery. SIGNIFICANCE: These results have important implications for any investigation of motor cortical excitability in relaxed subjects. The outcome of an experimental intervention is the net result of the intervention itself and alterations in cortical excitability produced by the subjects' inactivity.     

Inter- and intra-individual variability of paired-pulse curves with transcranial magnetic stimulation (TMS).

OBJECTIVES: Previous studies have evaluated the variability of motor thresholds (MTs) and amplitude of motor-evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) within and across individuals. Here we evaluate the reproducibility and inter-hemispheric variability of measures of cortical excitability using the 'conventional' paired-pulse (PP) TMS technique. METHODS: We studied PP curves of the left and right hemisphere in 10 healthy subjects on two separate days 2 weeks apart. The inter-stimulus intervals studied were 1, 3, 6, 8, 10 and 12 ms with the conditioning stimulus being 80% of the resting MT, and a single test stimulus producing MEPs of approximately 0.8 mV peak-to-peak amplitude. RESULTS: As a group, the PP curves of the left and right hemispheres, and of Day 1 and Day 2 were not significantly different. The intracortical inhibition (ICI), but not the intracortical facilitation, showed a good correlation across days within the individuals. CONCLUSIONS: Cortical excitability, particularly ICI, measured by PP TMS shows no inter-hemispheric asymmetry and is reproducible within individuals.     

Trigeminal sensory input elicited by electric or magnetic stimulation interferes with the central motor drive to the intrinsic hand muscles.

In 6 normal subjects, unilateral supraorbital magnetic or electric stimulation resulted in a consistent symmetrical inhibition of the motor evoked potentials (MEPs) of the relaxed and preactivated first dorsal interosseus (FDI) muscle. A supraorbital stimulus caused a significant reduction in amplitude when the trigeminal CS was given 30 to 65 ms before transcranial magnetic stimulation (TMS). In addition, supraorbital magnetic stimulation induced a bilateral EMG suppression of the isometrically contracting FDI muscles, starting about 40 to 50 ms after the magnetic stimulus. In 4 subjects, MEPs evoked by transcranial electric stimulation or by TMS during slight muscle contraction showed a comparable trigeminomotor inhibition. These findings demonstrate that electromagnetic stimulation of trigeminal afferents interferes with the motor output to the intrinsic hand muscles inducing a bilateral inhibition which is probably mediated by a multisynaptic subcortical network. In all 6 subjects, TMS over the motor hand area or the cerebellum elicited a reproducible blink reflex. Since the blink reflex is a sensitive indicator of trigeminal excitation, one has to assume that TMS is associated with a significant excitation of trigeminal afferents. Therefore, trigeminomotor inhibition has to be considered in all TMS studies that use a conditioning-test design.     

The effects of prolonged cathodal direct current stimulation on the excitatory and inhibitory circuits of the ipsilateral and contralateral motor cortex

Weak cathodal transcranial direct current stimulation (tDCS) of the human hand area modulates corticospinal excitability with a suppression of motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS). The changes in excitability persist beyond the time of stimulation if tDCS is given for several minutes and can remain stable for an hour or more. The aim of present study was to evaluate whether a long-lasting suppression of cortical excitability could be induced by prolonged cathodal tDCS (20?min of stimulation). We also explored the impact of brain-derived neurotrophic factor (BDNF) gene polymorphisms, on tDCS after-effects. Cortical excitability to single and paired-pulse TMS was evaluated both for the stimulated and contralateral hemisphere, before and up to 24?h after 20?min of cathodal tDCS. We evaluated threshold and amplitude of MEPs, short interval intracortical inhibition (SICI), and intracortical facilitation (ICF). tDCS produced a pronounced suppression of MEP amplitude that was still significant at 3?h after the end of stimulation. The BDNF genotype had not influence on tDCS after-effects. Thresholds for MEPs, SICI and ICF were not affected. No significant effect was observed in the contralateral hemisphere. Twenty minutes of cathodal tDCS is capable of inducing a long-lasting suppression of the excitability of the human motor cortex.     

Time-related changes of excitability of the human motor system contingent upon immobilisation of the ring and little fingers.

OBJECTIVES: To examine possible changes of excitability of the human motor system contingent upon immobilisation of two hand fingers. METHODS: Two series of 5 transcranial magnetic stimulation (TMS) sessions were carried out on different days (1, 2, 3, 4, and 7). In one series (fingers immobilised, FI), subjects wore for 4 days a device that kept immobilised the left fourth and fifth finger. In the other series (fingers free, FF), no constraining device was used. Focal TMS was applied over the right motor cortex and motor evoked potentials (MEPs) were recorded from left abductor digiti minimi (immobilised) and first dorsal interosseus (non-immobilised) muscles. Intensities of 10, 30, and 50% above the resting motor threshold (rMT), were used. RESULTS: In FI series, rMT for both muscles showed significant increase on days 3, 4, and 7 with respect to day 1. At high stimulation intensity a clear decrease of MEPs amplitude was observed on days 3 and 4 for both muscles. Since no time-related changes of peripheral (M-wave) and spinal (F-wave) excitability were noted, MEPs and rMT changes are likely to have a cortical origin. In FF series, no changes of excitability were detected. CONCLUSIONS: Sensorimotor restriction of two fingers induces an early decrease of excitability, possibly at cortical level, which involves not only the immobilised muscle but also muscles with purportedly overlapping neural representations.     

Changes in motor cortex excitability during ipsilateral hand muscle activation in humans.

OBJECTIVES: To test whether unilateral hand muscle activation involves changes in ipsilateral primary motor cortex (M1) excitability. METHODS: Single- and paired-pulse transcranial magnetic stimulation (TMS) of the right hemisphere was used to evoke motor evoked potentials (MEPs) from the resting left abductor pollicis brevis (APB) in 9 normal volunteers. We monitored changes in motor threshold (MT), MEP recruitment, intracortical inhibition (ICI) and intracortical facilitation (ICF) while the ipsilateral right APB was either at rest or voluntarily activated. Spinal motoneuron excitability was assessed using F-wave recording procedures. RESULTS: Voluntary muscle activation of the ipsilateral APB significantly facilitated the MEPs and F-waves recorded from the contralateral APB. Facilitation was observed with muscle activation >50% of the maximum voluntary force and with stimulus intensities >20% above the individual resting motor threshold. Intracortical inhibition significantly decreased in the ipsilateral M , while there was no significant change in intracortical facilitation during this maneuver. CONCLUSIONS: Unilateral hand muscle activation changes the excitability of homotopic hand muscle representations in both the ipsilateral M1 and the contralateral spinal cord. While the large proportion of MEP facilitation most likely occurred at a spinal level, involvement of the ipsilateral hemisphere may have contributed to the enlargement of magnetic responses.     

Bidirectional modulation of sensory cortical excitability by quadripulse transcranial magnetic stimulation (QPS) in humans

ObjectiveQuadripulse transcranial magnetic stimulation (QPS) is a newly designed patterned repetitive transcranial magnetic stimulation (TMS). Previous studies of QPS showed bidirectional effects on the primary motor cortex (M1), which depended on its inter-stimulus interval (ISI): motor evoked potentials (MEPs) were potentiated at short ISIs and depressed at long ISIs (homotopic effects). These physiological characters were compatible with synaptic plasticity. In this research, we studied effects of QPS on the primary sensory cortex (S1).MethodsOne burst consisted of four monophasic TMS pulses at an intensity of 90% active motor threshold. The ISI of four pulses was set at 5 ms (QPS-5) or at 50 ms (QPS-50). Same bursts were given every 5 s for 30 min. QPS-5 and QPS-50 were performed over three areas (M1, S1 and dorsal premotor cortex (dPMC)). One sham stimulation session was also performed. Excitability changes of S1 were evaluated by timeline of somatosensory evoked potentials (SEPs).ResultsQPS-5 over M1 or dPMC enhanced the P25–N33 component of SEP, and QPS-50 over M1 depressed it. By contrast, QPSs over S1 had no effects on SEPs.ConclusionsQPSs over motor cortices modulated the S1 cortical excitability (heterotopic effects). Mutual connections between dPMC or M1 and S1 might be responsible for these modulations.SignificanceQPSs induced heterotopic LTP or LTD-like cortical excitability changes.     

Corticospinal excitability is specifically modulated by motor imagery: a magnetic stimulation study

Transcranial magnetic stimulation (TMS) was used to investigate whether the excitability of the corticospinal system is selectively affected by motor imagery. To this purpose, we performed two experiments. In the first one we recorded motor evoked potentials from right hand and arm muscles during mental simulation of flexion/extension movements of both distal and proximal joints. In the second experiment we applied magnetic stimulation to the right and the left motor cortex of subjects while they were imagining opening or closing their right or their left hand. Motor evoked potentials (MEPs) were recorded from a hand muscle contralateral to the stimulated cortex. The results demonstrated that the excitability pattern during motor imagery dynamically mimics that occurring during movement execution. In addition, while magnetic stimulation of the left motor cortex revealed increased corticospinal excitability when subjects imagined ipsilateral as well as contralateral hand movements, the stimulation of the right motor cortex revealed a facilitatory effect induced by imagery of contralateral hand movements only. In conclusion, motor imagery is a high level process, which, however, manifests itself in the activation of those same cortical circuits that are normally involved in movement execution.     

Does the recruitment of excitation and inhibition in the motor cortex differ?

The level of excitability within the motor cortex can be described as a balance between excitation and inhibition, but it is unknown how well both processes correlate. To address this question, the authors measured motor cortical excitability and inhibition in healthy human subjects, comparing the recruitment of motor evoked potentials (MEPs) and the duration of the cortical silent period (CSP) after transcranial magnetic stimulation (TMS). Single-pulse "focal" TMS was applied at intensities varying between 90% and 200% of motor thresholds to the right motor cortex of 15 healthy volunteers. The peak-to peak size of MEP responses and the duration of the CSP were measured in small hand muscles. Stimulus-response (S-R) curves were constructed by plotting the MEP size and CSP duration against stimulus intensities. The absolute duration of CSP and the size MEPs correlated significantly and to a similar extent with stimulus intensity (r = 0.60 and 0.53, respectively). The slope of the MEP-S-R was steeper compared with CSP-S-R, particularly at low stimulation intensities. CSP duration saturated earlier and CSP-S-Rs were shifted upwards at a given stimulus intensity compared with MEP-S-Rs. The findings suggest that recruitment of inhibition and excitation within the sensorimotor cortex correlate. However, inhibitory effects are recruited at lower intensities and saturate earlier than excitation.     

Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability.

OBJECTIVE: Low-frequency repetitive transcranial magnetic stimulation (rTMS) can reduce cortical excitability. Here we examined whether inhibitory after effects of low-frequency rTMS are influenced by stimulus intensity, the type of TMS coil and re-afferent sensory stimulation. METHODS: In fifteen healthy volunteers, we applied 900 biphasic pulses of 1Hz rTMS to the left primary motor cortex (M1) at an intensity that was 10% below or 15% above resting motor threshold. For rTMS, we used two different figure-of-eight shaped coils (Magstim or Medtronic coil) attached to the same stimulator. We recorded motor evoked potentials (MEPs) evoked with the same set-up used for rTMS (MEP-rTMS) before and twice after rTMS. Using a different TMS setup, we also applied monophasic pulses to the M1 in order to assess the effects of rTMS on corticospinal excitability, intracortical paired-pulse excitability and the duration of the cortical silent period (CSP). In a control experiment, the same measurements were performed after 15min of 1Hz repetitive electrical nerve stimulation (rENS) of the right ulnar nerve. RESULTS: Analysis of variance revealed an interaction between intensity, coil and time of measurement (p<0.035), indicating that the effect of 1Hz rTMS on MEP-rTMS amplitude depended on the intensity and the type of coil used for rTMS. Suppression of corticospinal excitability was strongest after suprathreshold 1Hz rTMS with the Medtronic coil (p<0.01 for both post-rTMS measurements relative to pre-intervention baseline). Regardless of the type of coil, suprathreshold but not subthreshold rTMS transiently prolonged the CSP and attenuated paired-pulse facilitation. Suprathreshold 1Hz rENS also induced a short-lasting inhibition of MEP-rTMS. CONCLUSIONS: Both the stimulation intensity and the type of TMS coil have an impact on the after effects of 1Hz rTMS. Re-afferent feedback activation may at least in part account for the stronger suppression of corticospinal excitability by suprathreshold 1Hz rTMS. SIGNIFICANCE: These data should be considered when rTMS is used as a therapeutic means.     

Modulation of motor cortex excitability by different levels of whole-hand afferent electrical stimulation

Objective

In a previous transcranial magnetic stimulation (TMS) study we demonstrated that suprathreshold mesh-glove (MG) whole-hand stimulation elicits lasting changes in motor cortical excitability. Currently, there is no consensus with regard to the optimal parameters for the induction of sensorimotor cortical plasticity using peripheral electrical stimulation. Thus, in the present study we explore the modulatory effects of MG stimulation at different stimulus intensities and different frequencies in order to identify an optimal stimulation protocol.

Methods

MG stimulation was performed on 12 healthy subjects in separate sessions at different stimulation levels: sub-sensory at 50 Hz, sensory at 50 Hz and motor at 2 Hz. To verify if stimulation at lower frequencies is less effective, an additional experiment at sensory level with 2 Hz was performed. TMS was used to assess motor threshold (MT), motor evoked potentials (MEPs) recruitment curve (RC), short latency intracortical inhibition (SICI) and intracortical facilitation (ICF) to paired-pulse TMS at baseline (T0), immediately after (T1) and 1 h (T2) after 30 min of MG stimulation. F-wave studies were performed to assess spinal motoneuron excitability.

Results

MG stimulation at sub-sensory/50 Hz and sensory/2 Hz level determines no significant cortical excitability changes; at sensory/50 Hz level and at motor/2 Hz level we found decreased MT, increased MEP RC as well as reduced SICI and increased ICF at T1 and T2.

Conclusions

MG stimulation at sensory/50 Hz and motor/2 Hz level induces similar long-lasting modulatory effects on motor cortical excitability. Both the strength of the corticospinal projections and the intracortical networks are influenced to the same extend.

Significance

The study provides further evidence that stimulation intensity and frequency can independently modulate motor cortical plasticity. The selection of optimal stimulation parameters has potentially important implications for the neurorehabilitation of patients after brain damage (e.g. stroke, traumatic brain injury) with hand motor deficits.     

Distinct differences in cortical reactivity of motor and prefrontal cortices to magnetic stimulation.

OBJECTIVE: The stimulus intensity of prefrontal transcranial magnetic stimulation (TMS) is usually determined with respect to the motor threshold (MT). However, the association between the excitability of the prefrontal and motor cortices is unknown. METHODS: Magnetic pulses to the left motor and prefrontal cortices were delivered at the MT of the right abductor digiti minimi muscle for 9 subjects and at 4 different stimulus intensities (60, 80, 100, and 120% of MT) for two subjects. Simultaneously, EEG was recorded with 60 scalp electrodes. RESULTS: Global mean field amplitudes of the TMS-evoked responses were significantly (32%) smaller after prefrontal than after motor cortex TMS, but they correlated positively. CONCLUSIONS: The reactivity to TMS is different between the motor and prefrontal cortices. However, an association between these reactivities suggests that MT may be used for determining the stimulus intensity of prefrontal TMS.     

Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses?

OBJECTIVES: To investigate the mechanisms responsible for suppressing the amplitude of electromyogram (EMG) responses to a standard transcranial magnetic stimulus (TMS) after prior conditioning of the motor cortex with repetitive subthreshold TMS (rTMS) at a frequency of 1 Hz. METHODS: EMG responses from the first dorsal interosseous, abductor pollicis brevis and flexor carpi radialis (FCR) muscles were recorded after suprathreshold TMS of the motor cortex. In some experiments, H-reflexes were also obtained in the FCR. The amplitude of these responses was compared before and after applying from 150 to 1500 rTMS pulses to motor cortex at an intensity of 95% resting motor threshold through the same figure-of-8 coil. RESULTS: When tested with subjects relaxed, rTMS conditioning reduced the amplitude of motor evoked potentials (MEPs) to approximately 60% of pre-conditioning values for 2-10 min after the end of the conditioning train, depending on the number of pulses in the train. There was more suppression with 1500 rTMS pulses than with 150 pulses. There was no effect on H-reflexes. There was no effect on MEPs if the test stimuli were given during active contraction of the target muscle. CONCLUSIONS: The findings confirm previous observations that low-frequency, low-intensity rTMS to motor cortex can produce transient depression of MEP excitability. Since there was no effect on spinal H-reflexes, this is consistent with the idea that some of the suppression occurs because of an effect on the motor cortex itself. The lack of any conditioning effect on MEPs evoked in actively contracting muscle is not readily consistent with the idea that rTMS depresses transmission in synaptic connections to pyramidal cells activated by the test TMS pulse. An alternative explanation is that rTMS reduces the excitability of cortical neurones in relaxed subjects, so that responses to a given input are smaller than before conditioning. Voluntary contraction normalises excitability levels so that the effect is no longer seen.     

Role of intracortical mechanisms in the late part of the silent period to transcranial stimulation of the human motor cortex

Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the human motor cortex produce a silent period (SP) following motor evoked potentials (MEPs). The early part of the SP can be explained by decreased alpha motor neuron excitability, whereas the late part is presumably due to suprasegmental mechanisms. In order to determine the level of the suprasegmental contribution to the generation of SPs, we recorded excitatory and inhibitory responses to TMS, TES, and percutaneous electrical brainstem stimulation (PBS) in the voluntarily activated first dorsal interosseous muscle of the hand. Stimulus intensities were set so that PBS and TES induced MEPs with areas equal to or larger than those of MEPs obtained with TMS. This procedure revealed that SPs were 49% and 83% shorter with TES and PBS, respectively, than with TMS. As TMS is more effective than TES or PBS in activating cortical interneurons, these findings support the idea that a significant component of the SP arises from intracortical mechanisms.     

Theta burst stimulation does not reliably depress all regions of the human motor cortex

OBJECTIVE: The excitability of the human motor cortex projecting to hand muscles can be reduced by theta burst transcranial magnetic repetitive stimulation (TBS). This study compared the magnitude and variability of changes evoked by TBS for a distal and proximal arm muscle. METHODS: Eight subjects participated in three studies. In each study, electromyographic responses (MEPs) to single-pulse transcranial magnetic stimulation assessed cortical excitability before and after 40s of TBS. In the first two studies, TBS (intensity, 80% active motor threshold) was delivered to the optimal locations for biceps or first dorsal interosseous (FDI). In the final study, weaker intensity TBS was delivered over the biceps representation. RESULTS: TBS targeting biceps produced highly variable results among subjects. For the group, MEPs were not significantly depressed. Repeat studies in individual subjects highlighted the variability of responses. For FDI, MEPs were significantly depressed 5min after TBS and remained depressed for >30min (p<0.05). No significant changes in biceps MEPs occurred with weaker TBS. CONCLUSIONS: The magnitude and reliability of TBS depends on the region of the cortex targeted. SIGNIFICANCE: Results obtained for the hand should not be considered indicative of changes that will occur in other regions of the motor cortex or the brain.     

Nonspecific facilitation of responses to transcranial magnetic stimulation.

We examined the effect of facial muscle contraction and eye movements on motor evoked potentials (MEPs) from the abductor pollicis brevis muscle (APB) evoked by transcranial magnetic stimulation (TMS). The hypothesis was that activity of large cortical regions (face) influences the excitability of spinal motoneurons via cortical or subcortical pathways. MEPs were recorded in 12 healthy subjects during the following conditions: (1) rest; (2) facial muscle contraction; (3) eye movements; (4) 10% precontraction of the target muscle; and (5) simultaneous target muscle precontraction and facial muscle contraction. In 9 subjects, spinal motoneuron excitability was assessed by measurements of F waves during the same facilitation maneuvers. Activation of eye and facial muscles clearly facilitated MEPs from the APB. The facilitation of MEP size during nonspecific maneuvers was almost similar to that obtained by target muscle precontraction, whereas shortening of latencies was significantly smaller. The occurrence and amplitude of F waves increased in parallel with MEP size during specific and nonspecific facilitation, pointing to spinal motoneuronal threshold changes as a potential facilitatory mechanism by facial and eye muscle activation. The different MEP latencies during specific and nonspecific facilitation were not explained by different spinal motoneuron excitability, but raise the possibility that supraspinal mechanisms contributed to nonspecific facilitation.