M. Inghilleri

Silent period evoked by transcranial stimulation of the human cortex and cervicomedullary junction.

1. The silent period evoked in the first dorsal interosseous (FDI) muscle after electrical and magnetic transcranial stimulation (TCS), electrical stimulation of the cervicomedullary junction and ulnar nerve stimulation was studied in ten healthy subjects. 2. With maximum‐intensity shocks, the average duration of the silent period was 200 ms after electrical TCS, 300 ms after magnetic TCS, 43 ms after stimulation at the cervicomedullary junction and 100 ms after peripheral nerve stimulation. 3. The duration of the silent period, the amplitude of the motor‐evoked potential, and the twitch force produced in the muscle were compared at increasing intensities of magnetic TCS. When the stimulus strength was increased from 30 to 70% of the stimulator output, the duration of the silent period lengthened as the amplitude of the motor potential and force of the muscle twitch increased. At 70 to 100% of the output, the amplitude of the motor potential and force of the muscle twitch saturated, whereas the duration of the silent period continued to increase. 4. Proximal arm muscle twitches induced by direct electrical stimulation of the biceps and extensor wrist muscles produced no inhibition of voluntary activity in the contracting FDI muscle. 5. The level of background activation had no effect on the duration of the silent period recorded in the FDI muscle after magnetic TCS. 6. Corticomotoneurone excitability after TCS was studied by means of a single magnetic conditioning shock and a test stimulus consisting either of one single magnetic shock or single and double electrical shocks (interstimulus interval 1.8 ms) in the relaxed muscle. A conditioning magnetic shock completely suppressed the response evoked by a second magnetic shock, reduced the size of the response evoked by a single electrical shock but did not affect the response evoked by double electrical shocks. Inhibition of the test magnetic shock was also present during muscle contraction. 7. Our findings indicate that the first 50 ms of the silent period after TCS are produced mainly by spinal mechanisms such as after‐hyperpolarization and recurrent inhibition of the spinal motoneurones. If descending inhibitory fibres contribute, their contribution is small. Changes in proprioceptive input probably have a minor influence. From 50 ms onwards the silent period is produced mainly by cortical inhibitory mechanisms.

Facilitation of muscle evoked responses after repetitive cortical stimulation in man

Abstract The technique of repetitive transcranial magnetic stimulation (rTMS) allows cortical motor areas to be activated by trains of magnetic stimuli at different frequencies and intensities. In this paper, we studied long-term neurophysiological effects of rTMS delivered to the motor cortex at 5 Hz with an intensity of 120% of motor threshold. Each stimulus of the train produced muscle-evoked potentials (MEPs) in hand and forearm muscles, which gradually increased in size from the first to the last shock. After the end of the train, the response to a single-test stimulus remained enhanced for 600–900 ms. In contrast, the train had no effect on the size of the MEPs evoked by transcranial electrical stimulation, while it suppressed H-reflexes in forearm muscles for 900 ms. We conclude that rTMS of these parameters increases the excitability of the motor cortex and that this effect outlasts the train for almost 1 s. At the spinal level, rTMS may increase presynaptic inhibition of Ia afferent fibers responsible for the H-reflex.

Effects of diazepam, baclofen and thiopental on the silent period evoked by transcranial magnetic stimulation in humans

The cortical silent period evoked by magnetic transcranial stimulation and the peripheral silent period were studied in healthy subjects after intravenous injection of diazepam, baclofen or thiopental. None of the drugs tested changed the peripheral silent period. But, unexpectedly, diazepam significantly shortened the cortical silent period, the inhibitory effect lasting about 30 min. In experiments using paired transcranial stimuli, the conditioning shock inhibited the test response to a similar extent with and without diazepam. Although baclofen did not change the cortical silent period, it reduced the size of the H reflex in the forearm muscles. Thiopental also left the duration of the cortical silent period unchanged. These findings show that the cortical silent period can be modified pharmacologically. Diazepam possibly shortens the silent period by modulating GABA A receptors at a subcortical site.

Transcranial magnetic stimulation techniques in clinical investigation

Transcranial magnetic stimulation (TMS) is a technique that can activate cortical motor areas and the corticospinal tract without causing the subject discomfort. Since TMS was introduced, numerous applications of the technique have been developed for the evaluation of neurologic diseases. Standard TMS applications (central motor conduction time, threshold and amplitude of motor evoked potentials) allow the evaluation of motor conduction in the CNS. Conduction studies provide specific information in neurologic conditions characterized by clinical and subclinical upper motor neuron involvement. In addition, they have proved useful in monitoring motor abnormalities and the recovery of motor function. TMS also gives information on the pathophysiology of the processes underlying the various clinical conditions. More complex TMS applications (paired-pulse stimulation, silent period, ipsilateral silent period, input-output curve, and evaluation of central fatigue) allow investigation into the mechanisms of diseases causing changes in the excitability of cortical motor areas. These techniques are also useful in monitoring the effects of neurotrophic drugs on cortical activity. TMS applications have an important place among the investigative tools to study patients with motor disorders.

Urodynamic and neurophysiological evaluation in Parkinson's disease and multiple system atrophy.

AIMS: To determine whether Parkinsons disease and multiple system atrophy each has a distinct pattern of micturition abnormalities and whether a urodynamic evaluation could be useful in the differential diagnosis between the two diseases. METHODS: Sixty two patients (30 with Parkinsons disease and 32 with multiple system atrophy) underwent a complete urodynamic evaluation and neurophysiological testing. RESULTS: Of the parkinsonian patients 36.6% had normal micturition findings with normal bladder sensitivity; 26.7% had delayed or incomplete pelvic floor relaxation; 26.7% had hyperreflexia with vesicosphincteric synergy; and 10% had hyperreflexia with vesicosphincteric synergy associated with incomplete pelvic floor relaxation. Parkinsonian patients with a normal urodynamic pattern had significantly less severe disease and a shorter duration of disease in years than those who had abnormal patterns. Patients with hyperreflexia had significantly higher severity of disease. All the patients with multiple system atrophy had hyperreflexia with synergy. Two urodynamic patterns were identified: hyperreflexia with vesicosphincteric synergy (90.6% of patients), and hyperreflexia with vesicosphincteric synergy and incomplete pelvic floor relaxation (in 9.4%). Hyperreflexia with synergy correlated neither with the severity nor with the duration of disease. Sphincter EMG analysis showed that all the parkinsonian patients had normal sphincter EMG whereas 24 of the 32 patients with multiple system atrophy had neurogenic signs. CONCLUSIONS: Urodynamic evaluation and sphincter EMG are both useful tests in the differential diagnosis between Parkinsons disease and multiple system atrophy. Urodynamic findings may be abnormal before patients with multiple system atrophy reach an advanced stage of the disease. Recordings of EMGs from perineal muscles become abnormal as the disease progresses in multiple system atrophy but not in Parkinsons disease.

Brain-computer interface boosts motor imagery practice during stroke recovery

Motor imagery (MI) is assumed to enhance poststroke motor recovery, yet its benefits are debatable. Brain–computer interfaces (BCIs) can provide instantaneous and quantitative measure of cerebral functions modulated by MI. The efficacy of BCI‐monitored MI practice as add‐on intervention to usual rehabilitation care was evaluated in a randomized controlled pilot study in subacute stroke patients.

Ovarian hormones and cortical excitability. An rTMS study in humans

OBJECTIVE Ovarian steroids influence neural excitability. Using repetitive transcranial magnetic stimulation (rTMS) we investigated changes in cortical excitability during the menstrual cycle. METHODS Eight women underwent rTMS on Days 1 and 14 of the menstrual cycle. As a control group, 8 age-matched men were also tested twice, with a 14-day interval between the two experimental sessions. Repetitive magnetic pulses were delivered in trains of 10 stimuli (5 Hz frequency and 120% of the motor threshold calculated at rest) to the left motor area of the first dorsal interosseous muscle. RESULTS In women, the motor evoked potential (MEP) size did not increase on Day 1, but it increased progressively during the train on Day 14. The duration of the silent period progressively lengthened during the train on both days. In men the MEP increased in size, and the silent period lengthened to a similar extent on both days. CONCLUSIONS In women, hormone changes related to the menstrual cycle alter cortical excitability. SIGNIFICANCE Low estrogen levels probably reduce cortical excitability because their diminished action on sodium channels reduces recruitment of excitatory interneurons during rTMS thus abolishing the MEP facilitation.

Silent period in upper limb muscles after noxious cutaneous stimulation in man

We studied the effect of electrical stimulation of the C5-C8 dermatomes on voluntary electromyographic activity (EMG) recorded from the ipsilateral first dorsal interosseus (FDI), abductor digiti minimi, flexor and extensor carpi, triceps brachii, biceps brachii, and orbicularis oculi muscles of healthy humans. Finger stimulation (C6-C8) produced an EMG inhibition (silent period, SP), which progressively decreased in duration from distal to proximal muscles; in the biceps it induced a slight facilitation and in the orbicularis oculi muscle, it had no effect. Stimulation of the C5 dermatome induced no response in either distal or proximal muscles. Only high-intensity stimuli evoked clear silent periods. The threshold for evoking an SP was almost double that required for sensory action potentials, 3.25 times the sensory threshold, and decidedly above the pain threshold. An indirect estimation of the conduction velocity of SP afferent fibres placed them in the A-delta group of myelinated fibres. In double-shock experiments, used to study the recovery cycle of the SP in the FDI muscle after finger stimulation, neither low- nor high-intensity conditioning stimuli delivered 100-500 ms before the test stimulus changed test SPs. Experiments designed to evaluate motoneuronal excitability showed that in relaxed FDI muscle, finger stimulation markedly reduced the F wave at the 50 ms time interval, the time when the SP normally occurs. Our findings demonstrate that the activation of A-delta afferents from the fingers inhibits the C7-T1 motoneurons postsynaptically, through an oligosynaptic spinal circuit. We propose that the strong inhibitory effect exerted by noxious cutaneous stimuli on all distal muscles may contribute to a defence action which is specific for the human upper limb.

The masseter inhibitory reflex is evoked by innocuous stimuli and mediated by A beta afferent fibres

SummaryMechanical or electrical stimulations in the area of the mouth evoke two phases of inhibition in the masseter muscle (early and late inhibitory reflex, also called masseter silent periods). The question whether the afferents of the human masseter inhibitory reflex are nociceptive or non-nociceptive has not yet been settled. We showed that an innocuous stimulus, such as a fine jet of saline directed to the lips of healthy humans, evokes an early and a late masseter inhibitory reflex, similar to those following electrical stimulation. We measured the efferent and afferent delay of the masseter early inhibitory reflex in patients submitted to intracranial stimulation of the motor and sensory trigeminal root, and found that the reflex afferents belong to the intermediately fast conducting fibre group.

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.