F. Balestrieri

Modulation of interhemispheric inhibition by volitional motor activity: an ipsilateral silent period study

Brief interruption of voluntary EMG in a hand muscle by focal transcranial magnetic stimulation (TMS) of the ipsilateral primary motor cortex (M1), the so‐called ipsilateral silent period (ISP), is a measure of interhemispheric motor inhibition. However, little is known about how volitional motor activity would modulate the ISP. Here we tested in 30 healthy adults to what extent and under what conditions voluntary activation of the stimulated right M1 by moving the left hand strengthens interhemispheric inhibition as indexed by an enhancement of the ISP area in the maximally contracting right first dorsal interosseous (FDI). Left index finger abduction, already at low levels of contraction, significantly enhanced the ISP compared to left hand at rest. Even imagination of left index finger movement enhanced the ISP compared to rest or mental calculation. This enhancement occurred in the absence of motor‐evoked potential amplitude modulation in the left FDI, thus excluding a non‐specific contribution from an increase in right M1 corticospinal excitability. Contraction of the left extensor indicis, but not contraction of more proximal left upper limb or left or right lower limb muscles also enhanced the ISP. A reaction time experiment showed that the ISP enhancement developed at a late stage of movement preparation just before or at movement onset. Interhemispheric inhibition of the motor‐evoked potential as tested by a bifocal paired‐pulse TMS protocol and thought to be mediated via a neuronal circuit different to the ISP was not enhanced when tested under identical motor task conditions. Finally, ISP enhancement by contraction of the left FDI correlated inversely with EMG mirror activity in the right FDI during phasic abductions of the left index finger. Our findings strongly suggest that voluntary M1 activation by real or imagined movement of the contralateral hand increases interhemispheric motor inhibition of the opposite M1. This phenomenon shows substantial topographical, temporal and neuronal circuit specificity, and has functional significance as it probably plays a pivotal role in suppressing mirror activity.

Suprathreshold 0.3 Hz repetitive TMS prolongs the cortical silent period: potential implications for therapeutic trials in epilepsy.

OBJECTIVE To investigate the after-effects of 0.3 Hz repetitive transcranial magnetic stimulation (rTMS) on excitatory and inhibitory mechanisms at the primary motor cortex level, as tested by single-pulse TMS variables. METHODS In 9 healthy subjects, we studied a wide set of neurophysiological and behavioral variables from the first dorsal interosseous before (Baseline), immediately after (Post 1), and 90 min after (Post 2) the end of a 30 min long train of 0.3 Hz rTMS delivered at an intensity of 115% resting motor threshold (RMT). Variables under investigation were: maximal M wave, F wave, and peripheral silent period after ulnar nerve stimulation; RMT, amplitude and stimulus-response curve of the motor evoked potential (MEP), and cortical silent period (CSP) following TMS; finger-tapping speed. RESULTS The CSP was consistently lengthened at both Post 1 and Post 2 compared with Baseline. The other variables did not change significantly. CONCLUSIONS These findings suggest that suprathreshold 0.3 Hz rTMS produces a relatively long-lasting enhancement of the inhibitory mechanisms responsible for the CSP. These effects differ from those, previously reported, of 0.9-1 Hz rTMS, which reduces the excitability of the circuits underlying the MEP and does not affect the CSP. This provides rationale for sham-controlled trials aiming to assess the therapeutic potential of 0.3 Hz rTMS in epilepsy.

Mechanisms underlying mirror movements in Parkinson's disease: A transcranial magnetic stimulation study

The neural mechanisms underlying unintended mirror movements (MMs) of one hand during unimanual movements of the other hand in patients with Parkinsons disease (PD) are largely unexplored. Here we used surface electromyographic (EMG) analysis and focal transcranial magnetic stimulation (TMS) to investigate the pathophysiological substrate of MMs in four PD patients. Surface EMG was recorded from both abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles. Cross‐correlation EMG analysis revealed no common motor drive to the two APBs during intended unimanual tasks. Focal TMS of either primary motor cortex (M1) elicited normal motor‐evoked potentials (MEPs) in the contralateral APB, whereas MEPs were not seen in the ipsilateral hand. During either mirror or voluntary APB contraction, focal TMS of the contralateral M1 produced a long‐lasting silent period (SP), whereas stimulation of the ipsilateral M1 produced a short‐lasting SP. During either mirror or voluntary finger tapping, 5 Hz repetitive TMS (rTMS) of the contralateral M1 disrupted EMG activity in the target FDI, whereas the effects of rTMS of the ipsilateral M1 were by far slighter. During either mirror or voluntary APB contraction, paired‐pulse TMS showed a reduction of short‐interval intracortical inhibition in the contralateral M1. These findings provide converging evidence that, in PD, MMs do not depend on unmasking of ipsilateral projections but are explained by motor output along the crossed corticospinal projection from the mirror M1.

Involvement of the human dorsal premotor cortex in unimanual motor control: an interference approach using transcranial magnetic stimulation

Unilateral movements are enabled through a distributed network of motor cortical areas but the relative contribution from the parts of this network is largely unknown. Failure of this network potentially results in mirror activation of the primary motor cortex (M1) ipsilateral to the intended movement. Here we tested the role of the right dorsal premotor cortex (dPMC) in 11 healthy subjects by disrupting its activity with 20 Hz repetitive transcranial magnetic stimulation (rTMS) whilst the subjects exerted a unilateral contraction of the left first dorsal interosseous (FDI). We found that disruption of right dPMC enhanced mirror activation of the ipsilateral left M1, as probed by motor evoked potential (MEP) amplitude to the right FDI. This was not the case with sham rTMS, when rTMS was directed to the right M1, or with rTMS of the right dPMC but without contraction of the left FDI. Findings suggest that activity in the dPMC contributes to the suppression of mirror movements during intended unilateral movements.

Role of the right dorsal premotor cortex in “physiological” mirror EMG activity

A distributed cortical network enables the lateralization of intended unimanual movements, i.e., the transformation from a default mirror movement to a unimanual movement. Little is known about the exact functional organization of this “non-mirror transformation” network. Involvement of the right dorsal premotor cortex (dPMC) was suggested because its virtual lesion by high-frequency repetitive transcranial magnetic stimulation (rTMS) increased the excitability of the left primary motor cortex (M1) during unilateral isometric contraction of a left hand muscle (Cincotta et al., Neurosci Lett 367: 189–93, 2004). However, no behavioural effects were observed in that experimental protocol. Here we tested behaviourally twelve healthy volunteers to find out whether focal disruption of the right dPMC by “off-line” One Hz rTMS (900 pulses, 115% of resting motor threshold) enhances “physiological” mirroring.This was measured by an established protocol (Mayston et al., Ann Neurol 45: 583–94, 1999) that quantifies the mirror increase in the electromyographic (EMG) level in the isometrically contracting abductor pollicis brevis (APB) muscle of one hand during brief phasic contractions performed with the APB of the other hand. Mirroring in the right APB significantly increased after real rTMS of the right dPMC. In contrast, no change in mirroring was seen with sham rTMS of the right dPMC, real rTMS of the right M1, or real rTMS of the left dPMC. These findings strongly support the hypothesis that the right dPMC is part of the non-mirror transformation cortical network.

Optically tracked neuronavigation increases the stability of hand-held focal coil positioning: Evidence from “transcranial” magnetic stimulation-induced electrical field measurements

The stability of hand-held coil positioning with neuronavigated versus conventional transcranial magnetic stimulation (TMS) is still underinvestigated. Eleven operators naïve for neuronavigation were asked to position and maintain a figure-of-eight-shaped coil over a dipole probe placed within of a polystyrene reproduction of the human head and scalp, in correspondence of the right primary motor cortex. Ten monophasic magnetic pulses were delivered at 46% maximal stimulator output (MSO) in two different experimental conditions: (1) assisted by an optically tracked neuronavigational system; and (2) without neuronavigation. With neuronavigated stimulation, both standard deviation and coefficient of variation of the voltages induced in the dipole probe were significantly lower than without neuronavigation. Results were confirmed in four operators performing a longer-lasting experiment using 50 magnetic pulses in each condition, at an intensity of at 40% MSO. Findings show that optically tracked neuronavigation improves the stability of focal coil positioning.

Surface electromyography shows increased mirroring in Parkinson's disease patients without overt mirror movements

Patients with Parkinsons disease (PD) may present mirror movements (MM). Transcranial magnetic stimulation data indicate that these movements reflect an abnormal enhancement of the “physiological mirroring” that can be observed in healthy adults during complex and effortful tasks. It was hypothesized that, in PD, enhanced mirroring is caused by a failure of basal ganglia output to support the cortical network that is responsible for the execution of strictly unimanual movements. If so, it is likely that subtle alterations of voluntary unimanual motor control are also present in PD patients without overt MM. We tested this hypothesis by using surface electromyographic (EMG) techniques in 12 mildly to moderately affected PD patients without overt MM, and in 2 control groups (12 age‐matched and 10 young healthy volunteers). Subjects performed unilateral phasic thumb abduction during a sustained tonic contraction of the opposite abductor pollicis brevis. All patients were tested on dopaminergic therapy. On a separate day, 7 of 12 patients were re‐tested after withdrawal of medication. During this task, involuntary mirror‐like increase in surface EMG of the tonically abducting thumb was significantly larger in PD patients than in age‐matched or young healthy volunteers. Off therapy, mirroring was slightly greater than on medication, although this difference was not significant. Our findings suggest that dysfunction of unimanual motor control is a general feature of PD. It is likely that this deficient movement lateralization contributes to an impairment of nonsymmetrical bimanual movements in PD.

FC40.2 Interhemispheric inhibition by voluntary motor cortex activation measured by enhancement of the ipsilateral silent period

Background: Repetitive transcranial magnetic stimulation (rTMS) represents an important therapeutic tool and it has been suggested that some of these therapeutic effects are mediated through enhanced cortical inhibition (CI). Therefore, this study endeavored to explore the effects of several different rTMS stimulus conditions on inhibition and excitability in the human motor cortex. Methods: Twelve healthy control subjects participated in this study. Subjects were randomly assigned to receive either 1, 10 or 20 Hz rTMS for a total of 900 stimulations or priming rTMS (10 subjects) (i.e., 600 6 Hz stimuli followed by 600 1 Hz stimuli) all separated by 1 week. CI was indexed using single pulse and paired TMS paradigms including short interval cortical inhibition (SICI) and cortical silent period (CSP), respectively. Cortical excitability was indexed using the rest EMG during the rTMS stimulus train and motor threshold and motor evoked potential (MEP) size after the stimulus train. Results: Across all stimulus conditions there was a significant increase in the CSP. There was also a significant increase in SICI, particularly in those subjects with reduced baseline SICI. There was no significant difference in the extent of inhibition (i.e., CSP, SICI) induced by different stimulus conditions. There was also a strong correlation between rest EMG activity and stimulation frequency during the stimulus train but no significant change in measures of excitability (e.g., MT and MEP size) after the stimulus train. Conclusions: These findings suggest that rTMS increases inhibition following an rTMS course and that higher rTMS frequency stimulation results in greater cortical excitability during the stimulus train but not afterward. Future studies designed to replicate these initial findings as well as assessing the effects of repeated administration of rTMS courses on CI are warranted to elucidate potential novel therapeutic mechanisms involved in this exciting new treatment.

P20-22 Modulation of interhemispheric inhibition by volitional motor activity: an ipsilateral silent period study

Objective: Brief interruption of voluntary EMG in hand muscles by focal transcranial magnetic stimulation (TMS) of the ipsilateral primary motor cortex (M1), the so-called ipsilateral silent period (ISP), is a measure of interhemispheric motor inhibition. However, little is known about how volitional motor activity would modulate the ISP. Here we tested in 30 healthy adults to what extent and under what conditions voluntary activation of the stimulated right M1 by moving the left hand strengthens interhemispheric inhibition as indexed by an enhancement of the ISP area in the maximally contracting right first dorsal interosseous (FDI). Methods and Results: Left index finger abduction significantly enhanced the ISP compared to left hand at rest. Even imagination of left index finger movement enhanced the ISP compared to rest or mental calculation. This enhancement occurred in absence of motor-evoked potential amplitude modulation in the left FDI, excluding a non-specific contribution from increased right M1 corticospinal excitability. Contraction of the left extensor indicis, but not contraction of more proximal left upper limb or lower limb muscles also enhanced the ISP. A reaction time experiment showed that the ISP enhancement developed at a late stage of movement preparation. Interhemispheric inhibition of the motor-evoked potential as tested by a bifocal paired-pulse TMS protocol and thought to be mediated via a neuronal circuit different to the ISP was not enhanced when tested under identical motor task conditions. Finally, ISP enhancement by contraction of the left FDI correlated inversely with EMG mirror activity in the right FDI during phasic abductions of the left index finger. Conclusions: Findings strongly suggest that voluntary M1 activation by real or imagined movement of the contralateral hand increases interhemispheric inhibition of the opposite M1. This phenomenon shows substantial topographical, temporal and neuronal circuit specificity, and likely plays a pivotal role in suppressing mirror activity.

FC8.2 Modulatory effects of high-frequency repetitive transcranial magnetic stimulation on the ipsilateral silent period

athy were included in this study (aged 4–11 years). HDsEMG was recorded using an electrode grid with densely packed electrodes (inter-electrode distance of 5 or 3 mm) in a monopolar fashion (with a far way reference). Two distal and two proximal muscles, both in arm and leg, were examined. All muscles were tested at three different force levels: light, moderate, and maximal. A subset of the signals was used to determine muscle fibre conduction velocity (MFCV), root mean square amplitude, monopolar and bipolar (RMS), and the so-called level of interference (LOI). Results: All children tolerated the protocol well. In the patient group the MFCV and the monopolar RMS showed significantly lower values compared to the control group. The LOI was expected to be higher but was, to our surprise, significantly lower in the patients. The bipolar RMS amplitude did not differ between groups. Conclusion: Clearly, children would benefit the most of a non-invasive clinical neurophysiological technique. This study shows that it is well possible to examine young children using HD-sEMG with the current protocol. The LOI helps to identify patients, but the result is still difficult to interpret. More research is required. Amplitude should be recorded in a monopolar montage. Furthermore, MFCV, that does not become available with standard needle EMG, might become a sensitive variable for diagnostic purposes in myopathies.