A. Maertens De Noordhout

Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee

P.M. Rossini (Chairman) (Rome, Baly), A.T. Barker (Sheffield, UK), A. Berardelli (Rome, Italy), M.D. Caramia (Rome, Italy), G. Caruso (Naples, Italy), R.Q. Cracco (Brooklyn, NY;, USA), M.R. Dimitrijevid (Houston, TX, USA), M. Hallett ( Bethesda, MD, USA), Y. Katayama (Tokyo, Japan), C.H. Liicking ( Freiburg, Germany), A.L. Maertens de Noordhout (Liege, Belgium), C.D. Marsden (London, UK), N.M.F. Murray (London, UK), J.C. Rothwell (London, UK), M. Swash (London, UK) and C. Tomberg (Brussels, Belgium)

Electric and magnetic stimulation of human motor cortex: surface EMG and single motor unit responses.

1. The effects of different forms of brain stimulation on the discharge pattern of single motor units were examined using the post‐stimulus time histogram (PSTH) technique and by recording the compound surface electromyographic (EMG) responses in the first dorsal interosseous (FDI) muscle. Electrical and magnetic methods were used to stimulate the brain through the intact scalp of seven normal subjects. Electrical stimuli were applied either with the anode over the lateral central scalp and the cathode at the vertex (anodal stimulation) or with the anode at the vertex and the cathode lateral (cathodal stimulation). Magnetic stimulation used a 9 cm diameter coil centred at the vertex; current in the coil flowed either clockwise or anticlockwise when viewed from above. 2. Supramotor threshold stimuli produced one or more narrow (less than 2 ms) peaks of increased firing in the PSTH of all thirty‐two units studied. Anodal stimulation always produced an early peak. The latencies of the peaks produced by other forms of stimulation, or by high intensities of anodal stimulation, were grouped into four time bands relative to this early peak, at intervals of ‐0.5 to 0.5, 1‐2, 2.5‐3.5 and 4‐5.5 ms later. Peaks occurring within these intervals are referred to as P0 (the earliest anodal), P1, P2 and P3 respectively. 3. At threshold, anodal stimulation evoked only the P0 peak; at higher intensities, the P2 or more commonly the P3 peak also was recruited. The size of the P0 peak appeared to saturate at high intensities. 4. In five of six subjects, cathodal stimulation behaved like anodal stimulation, except that there was a lower threshold for recruitment of the P2 or P3 peak relative to that of the P0 peak. In the other subject, the P3 peak was recruited before the P0 peak. 5. Anticlockwise magnetic [corrected] stimulation, at threshold, often produced several peaks. These always included a P1 peak, and usually a P3 peak. A P0 peak in the PSTH was never produced by an anticlockwise stimulation [corrected] at intensities which we could explore with the technique. 6. Clockwise magnetic [corrected] stimulation never recruited a P1 peak; in most subjects a P3 peak was recruited first and at higher intensities was accompanied by P0 or P2 peaks. 7. On most occasions when more than one peak was observed in a PSTH, the unit fired in only one of the preferred intervals after each shock. However, double firing was seen in five units when high intensities of stimulation were used.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of digital nerve stimuli on responses to electrical or magnetic stimulation of the human brain.

1. Reflexes were elicited in the first dorsal interosseous muscle of seven normal subjects by electrical stimulation of the digital nerves of the index finger at 3 times perceptual threshold while subjects maintained a constant voluntary contraction of the muscle. The average response in the surface‐rectified electromyogram (EMG) consisted of an early inhibitory (I1) component followed by a later excitation (E2). 2. Low intensity anodal electrical or magnetic scalp stimuli were given over the motor cortex in order to elicit muscle responses within the period of the I1 and E2 reflex components. 3. Compared with control responses elicited in the absence of digital nerve stimulation, responses to electrical cortex stimulation were suppressed in the I1 period and facilitated during the E2 period of the reflex. In contrast, responses evoked by magnetic stimulation were suppressed during I1 and also for the first 10 ms or so of the E2 response. Magnetically evoked responses were facilitated during the later part of the E2 reflex. 4. Similar effects were seen when the probability of firing of single motor units was studied. 5. In three subjects, small taps were given to the abducted index finger in order to stretch the first dorsal interosseous muscle and evoke reflexes which were of comparable size to the E2 reflex evoked by digital nerve stimulation. In contrast to the experiments in which digital nerve stimuli were given, responses evoked by magnetic stimulation over motor cortex were facilitated at all times during the course of the reflex evoked when the muscle was stretched. 6. We conclude that single electrical stimuli applied to the digital nerves can reduce for a short period the excitability of motor cortex to magnetic stimulation. This occurs at a time when the same stimulus is evoking an excitatory (E2) reflex in the average surface‐rectified EMG.

Further observations on the facilitation of muscle responses to cortical stimulation by voluntary contraction

The effect of voluntary contraction on the discharge of single motor units following electrical and magnetic stimulation of the motor cortex was examined using the post-stimulus time histogram (PSTH) technique. The latencies of responses in single motor units of the first dorsal interosseous muscle to cortical stimulation were 2-4 msec shorter when the muscle was contracting than when at rest in 9 of 10 units studied. These latency differences are comparable with those recorded by surface electromyography for compound muscle action potentials following cortical stimulation in relaxed and active muscles. The new findings are that the intensity of cortical stimulation required to discharge a resting motor unit to produce a single PSTH peak produced multiple PSTH peaks when the same unit was contracting. The timing of the PSTH peak of relaxed motor unit discharge corresponded to one of the later PSTH peaks (usually the second) when the motor unit was voluntarily activated. These findings are in keeping with our previous suggestions that the longer latency of responses in relaxed muscles is due to the time taken for temporal summation of multiple descending corticospinal volleys at the cortico-motoneurone synapse. Facilitation produced by voluntary contraction occurs at least in part at the level of the spinal cord by lowering motoneurone threshold to enable discharge on the initial descending volley. The higher threshold of relaxed muscles is related to the higher intensities of stimulation needed to recruit multiple descending volleys and discharge resting motoneurones.

Percutaneous electrical stimulation of lumbosacral roots in man.

High voltage percutaneous electrical stimulation over the lumbosacral spinal column was used to assess conduction in the cauda equina of 13 normal subjects. Electromyographic activity elicited by such stimulation was recorded from various muscles of the lower limbs. The stimulating cathode was placed over the spinous process of each vertebral body and the anode kept on the iliac crest contralateral to the studied limb. Shifting the cathode in a rostro-caudal direction shortened the response latency in quadriceps, tibialis anterior and extensor digitorum brevis muscles. At moderate intensities (60% maximum), this occurred abruptly when the cathode was placed at levels corresponding to the exit sites from the spinal canal of the roots innervating these muscles. At these intensities, the size of the response in each muscle was largest when the cathode was placed over the conus medullaris or at or below the exit of the motor roots from the spine. Latencies were always equal to or shorter than those obtained with F-wave measurements, suggesting that peripheral motor axons, rather than intraspinal structures were activated by the stimulus. Collision experiments demonstrated that activation occurred at two sites: near the spinal cord and at the root exit site in the vertebral foramina. Recordings made from soleus indicated that larger diameter proprioceptive afferent fibres also could be activated. This technique might have useful clinical applications in the study of both proximal and distal lesions of the cauda equina and provide a non-invasive method of localising such lesions electrophysiologically.

Contingent Negative Variation and Efficacy of Beta-Blocking Agents in Migraine:

Thirty-three patients with common migraine underwent contingent negative variation (CNV) recordings before receiving prophylactic beta-blocker treatment with either metoprolol (27 patients) or propranolol (6 patients) at mean daily dosages of 110 mg and 122 mg, respectively. After 3 months the therapeutic efficacy of the beta-blocker was assessed in each patient by means of a global severity score and compared with the initial CNV recordings. The mean clinical improvement was 62%. A significant positive correlation was found between CNV amplitude before prophylaxis and the clinical response to beta-blockers: patients with higher CNV tended to respond better to therapy. Eight of 10 patients with a CNV amplitude higher than -25 V had a more than 50% reduction of the severity score—that is, a good or excellent response to the beta-blocking agent—whereas only 2 of 9 patients with an amplitude lower than -20 V had a good response.

Induction of long‐lasting changes of visual cortex excitability by five daily sessions of repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers and migraine patients

We have shown that in healthy volunteers (HV) one session of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the visual cortex induces dishabituation of visual evoked potentials (VEPs) on average for 30 min, while in migraineurs one session of 10 Hz rTMS replaces the abnormal VEP potentiation by a normal habituation for 9 min. In the present study, we investigated whether repeated rTMS sessions (1 Hz in eight HV; 10 Hz in eight migraineurs) on 5 consecutive days can modify VEPs for longer periods. In all eight HV, the 1 Hz rTMS-induced dishabituation increased in duration over consecutive sessions and persisted between several hours (n = 4) and several weeks (n = 4) after the fifth session. In six out eight migraineurs, the normalization of VEP habituation by 10 Hz rTMS lasted longer after each daily stimulation but did not exceed several hours after the last session, except in two patients, where it persisted for 2 days and 1 week. Daily rTMS can thus induce long-lasting changes in cortical excitability and VEP habituation pattern. Whether this effect may be useful in preventative migraine therapy remains to be determined.

Percutaneous magnetic stimulation of the motor cortex in migraine.

We have used transcranial magnetic stimulation of the motor cortex interictally in 12 patients with unilateral classic migraine with sensorimotor auras and 10 patients with common migraine and unilateral headache. In classic migraine, the threshold of activation of the FDI muscle by the cortical stimulus was significantly increased on the side of the auras, when compared to the unaffected side (P less than 0.01) and to normal subjects (P less than 0.01). The amplitude of EMG responses was also reduced in FDI on the affected side when compared to normals (P less than 0.02). Responses obtained in common migraine patients were normal on both sides. We suggest that some permanent subclinical dysfunction of the motor cortex might play a role in the pathogenesis of attacks of classic migraine with sensorimotor auras.

Motor and somatosensory evoked potentials in cervical spondylotic myelopathy

We recorded upper and lower limb MEPs and SEPs in 55 patients with clinically suggestive and myelography-documented cervical cord compression due to spondylotic changes. MEPs were abnormal in biceps brachii of 21 patients (38%), in first dorsal interosseous muscle of the hand of 49 patients (89%) and in tibialis anterior of 47 patients (85%). Overall, MEP abnormalities were present in at least one muscle of 51/55 patients (93%). Median SEPs were abnormal in 20 cases (36%), ulnar SEPs in 24 (44%) and posterior tibial SEPs in 40 (73%). Overall incidence of SEP alterations was 73% (40/55) and SEPs detected clinically silent sensory dysfunction in 10 patients (18%). Among the 43 patients who underwent surgical decompression, first dorsal interosseous (FDI) MEPs and tibial SEPs remained abnormal in most cases 1 year after surgery, independently of clinical outcome. On the other hand, serial EP studies seemed useful to confirm and monitor the clinical evolution of unoperated patients.

Reduced excitability of the motor cortex in untreated patients with de novo idiopathic “grand mal” seizures

OBJECTIVES Transcranial magnetic stimulation (TMS) was used to investigate motor cortex excitability, intracortical excitatory, and inhibitory pathways in 18 patients having experienced a first “grand mal” seizure within 48 hours of the electrophysiological test. All had normal brain MRI, and were free of any treatment, drug, or alcohol misuse. Results were compared with those of 35 age matched normal volunteers. METHODS The following parameters of responses to TMS were measured: motor thresholds at rest and with voluntary contraction, amplitudes of responses, cortical silent periods, and responses to paired pulse stimulation with interstimulus intervals of 1 to 20 ms. RESULTS In patients, there were significantly increased motor thresholds with normal amplitudes of motor evoked potentials (MEPs), suggesting decreased cortical excitability. Cortical silent periods were not significantly different from those of normal subjects. Paired TMS with short interstimulus intervals (1–5 ms) induced normal inhibition of test MEPs, suggesting preserved function of GABAergic intracortical inhibitory interneurons. On the contrary, the subsequent period of MEP facilitation found in normal subjects (ISIs of 6–20 ms) was markedly reduced in patients. This suggests the existence of abnormally prolonged intracortical inhibition or deficient intracortical excitation. In nine patients retested 2 to 4 weeks after the initial seizure, these abnormalities persisted, although to a lesser extent. CONCLUSION The present findings together with abnormally high motor thresholds could represent protective mechanisms against the spread or recurrence of seizures.