A. Borgheresi

Dissociation of the pathways mediating ipsilateral and contralateral motor‐evoked potentials in human hand and arm muscles

1 Growing evidence points toward involvement of the human motor cortex in the control of the ipsilateral hand. We used focal transcranial magnetic stimulation (TMS) to examine the pathways of these ipsilateral motor effects. 2 Ipsilateral motor‐evoked potentials (MEPs) were obtained in hand and arm muscles of all 10 healthy adult subjects tested. They occurred in the finger and wrist extensors and the biceps, but no response or inhibitory responses were observed in the opponens pollicis, finger and wrist flexors and the triceps. 3 The production of ipsilateral MEPs required contraction of the target muscle. The threshold TMS intensity for ipsilateral MEPs was on average 1.8 times higher, and the onset was 5.7 ms later (in the wrist extensor muscles) compared with size‐matched contralateral MEPs. 4 The corticofugal pathways of ipsilateral and contralateral MEPs could be dissociated through differences in cortical map location and preferred stimulating current direction. 5 Both ipsi‐ and contralateral MEPs in the wrist extensors increased with lateral head rotation toward, and decreased with head rotation away from, the side of the TMS, suggesting a privileged input of the asymmetrical tonic neck reflex to the pathway of the ipsilateral MEP. 6 Large ipsilateral MEPs were obtained in a patient with complete agenesis of the corpus callosum. 7 The dissociation of the pathways for ipsilateral and contralateral MEPs indicates that corticofugal motor fibres other than the fast‐conducting crossed corticomotoneuronal system can be activated by TMS. Our data suggest an ipsilateral oligosynaptic pathway, such as a corticoreticulospinal or a corticopropriospinal projection as the route for the ipsilateral MEP. Other pathways, such as branching of corticomotoneuronal axons, a transcallosal projection or a slow‐conducting monosynaptic ipsilateral pathway are very unlikely or can be excluded.

Slow Repetitive TMS for Drug-resistant Epilepsy: Clinical and EEG Findings of a Placebo-controlled Trial

Summary:  Purpose: To assess the effectiveness of slow repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for drug‐resistant epilepsy.

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.

Reorganization of the motor cortex in a patient with congenital hemiparesis and mirror movements

Article abstract Abnormal branching of corticospinal fibers from the unaffected motor cortex is responsible for mirror movements in patients with congenital hemiparesis, but it is unknown which mechanisms enable these patients to lateralize motor activity. Using multiunit electromyographic analysis and transcranial magnetic stimulation, the authors provide evidence for nonbranched crossed and uncrossed corticospinal projections and intracortical inhibition of the mirror hand. They propose that this remarkable reorganization of the unaffected motor cortex helps these patients to reduce mirror movements.

Interictal inhibitory mechanisms in patients with cryptogenic motor cortex epilepsy: a study of the silent period following transcranial magnetic stimulation

The silent period (SP) following transcranial magnetic stimulation (TMS) of the motor cortex is mainly due to cortical inhibitory mechanisms. The aim of the present study was to investigate these inhibitory phenomena in primary motor cortex epilepsy. We studied the TMS-induced SP in both the first dorsal interosseous (FDI) muscles in 8 patients who suffered from cryptogenic partial epilepsy with seizures starting with clonic movements of the right upper limb. All patients were on chronic medication with antiepileptic drugs. Therefore, besides contrasting the results with 16 age-matched normal controls, we also studied 10 patients receiving similar antiepileptic treatments who suffered from cryptogenic partial epilepsy with seizures characterised by the absence of clonic manifestations. The duration of the SP was bilaterally increased in the patients with clonic seizures when compared with the two other groups of subjects. The SP was longer in the left FDI muscle (contralateral to the side of the clonic manifestation in all the patients). Our findings likely indicate enhanced interictal inhibitory mechanisms in patients with partial epilepsy involving the primary motor cortex. The resulting inhibitory effect could be greater in the intact hemisphere rather than in the affected one, in which the hyperexcitability of the epileptic focus had to be counterbalanced.

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.

Separate ipsilateral and contralateral corticospinal projections in congenital mirror movements: Neurophysiological evidence and significance for motor rehabilitation†

The neurophysiological hallmark of congenital mirror movements (MM) are fast‐conducting corticospinal projections from the hand area of one primary motor cortex to both sides of the spinal cord. It is still unclear whether the abnormal ipsilateral projection originates through branching fibres from the normal contralateral projection or constitutes a separate ipsilateral projection. To clarify this question, we used focal paired‐pulse transcranial magnetic stimulation to test task‐related modulation of short‐interval intracortical inhibition (SICI) in the abductor pollicis brevis (APB) muscles of a 15‐year‐old girl (Patient 1) and a 40‐year‐old woman (Patient 2) with congenital MM. In both patients, during intended unilateral APB contraction, SICI decreased markedly in the “task” APB but remained unchanged in the “mirror” APB when compared to muscle rest. In contrast, spinal excitability as tested with H reflexes increased similarly in the task and mirror flexor carpi radialis muscles. This dissociation of task‐related SICI modulation strongly supports the existence of a separate ipsilateral fast‐conducting corticospinal projection. In Patient 1, we tested the functional significance of this separate ipsilateral projection during 7 months of motor rehabilitation training, which was designed to facilitate unilateral finger movements. A marked reduction of MM was observed after training, suggesting that unwanted mirror activity in the ipsilateral pathway can be suppressed by learning.

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.

Bilateral motor cortex output with intended unimanual contraction in congenital mirror movements

Abstract—In congenital mirror movements (MM), it is unclear whether the “mirror” motor cortex (M1) produces output during intended unimanual movements. In two patients with MM, the cortical silent period (CSP) was abnormally short after focal transcranial magnetic stimulation (TMS) of either M1, but simultaneous bilateral TMS led to significant CSP lengthening. Thus, it is likely that the shortened CSP after unilateral TMS is caused by output from the nonstimulated M1, suggesting that both M1 produce output with intended unimanual movements in patients with MM.