Intensity-dependent effects of 1 Hz rTMS on human corticospinal excitability.

OBJECTIVES: This study explored whether the effects of repetitive transcranial magnetic stimulation (rTMS) on corticospinal excitability are dependent on the stimulation intensity and examined the effect of rTMS on inhibitory function.METHODS: Nine normal volunteers received 15min of 1Hz rTMS at 85 and 115% of the resting motor threshold (RMT). Cortical excitability was measured before and after rTMS.RESULTS: rTMS at both intensities produced an increase in the RMT but only 115% stimulation reduced the size of motor evoked potentials (MEPs). rTMS had no effects on the cortical silent period or cortical inhibition measured with paired pulse TMS.CONCLUSIONS: The effects of 1Hz rTMS on motor cortex excitability are partially dependent on stimulus intensity and the effects of rTMS on motor thresholds and MEP size may differ.     

Decreased sensory cortical excitability after 1 Hz rTMS over the ipsilateral primary motor cortex.

OBJECTIVES: To study changes in the excitability of the sensory cortex by repetitive transcranial magnetic stimulation (rTMS) in humans. METHODS: Somatosensory evoked potentials (SEPs) and antidromic sensory nerve action potentials (SNAPs) were elicited by right median nerve stimulation at the wrist before and after low frequency (1 Hz) rTMS over the left motor cortex, lateral premotor cortex, sensory cortex, and also after sham stimulation. The intensity of rTMS was fixed at 1.1 times the active motor threshold at the hand area of motor cortex. RESULTS: N20 peak (N20p)-P25 and P25-N33 amplitudes were suppressed after rTMS over the motor cortex, whereas the N20 onset (N20o)-N20p and SNAP amplitudes were not affected. They recovered to the baseline about 100 min after the rTMS. rTMS over the premotor cortex or sensory cortex or sham stimulation had no suppressive effect on SEPs. CONCLUSIONS: The reduction of N20p-P25 and P25-N33 components without any changes of N20o-N20p amplitude suggests that the suppression occurs in the sensory cortex. rTMS (1 Hz) of the motor cortex induces a long-lasting suppression of the ipsilateral sensory cortex even at an intensity as low as 1.1 times the active motor threshold, probably via cortico-cortical pathways between motor and sensory cortex.     

Effects of hyperkalaemia on the excitability of peripheral nerve

An experimental animal model has been developed for the study of excitability change in peripheral nerve during limb ischaemia. This model has been used to investigate the effects of hyperkalaemia on the sequence of excitability change that occurs during cuff-induced limb ischaemia and in the post-ischaemic recovery period. The results lend support to the hypothesis that the dynamics of K ion concentration in the periaxonal space play a critical role in determining these excitability changes and that the polyanionic mucopolysaccharide gap substance of the node of Ranvier is likely to constitute the diffusion barrier that defines the periaxonal space.     

Influence of peripheral afferents on cortical and spinal motoneuron excitability.

The objective of this study was to establish to what extent muscle, cutaneous, and joint afferents alter the excitability of spinal and cortical motor neurons. This question was examined by studying the impact of electrical stimulation of the second and third digits, the median nerve at the wrist, and the recurrent thenar motor branch on the F/H and magneto-electrical cortical motor responses (MEPs) of the thenar muscles. The firing frequencies of single F/H motor unit action potentials were unaltered by the foregoing conditioning peripheral stimuli. MEPs conditioned by motor threshold stimulation of the median nerve at the wrist or the recurrent motor branch were significantly increased in size at conditioning to test intervals of 50 to 80 milliseconds. No significant change in MEP size resulted from conditioning stimulation of the digital nerves. We conclude that muscle afferents were primarily responsible for the increase in MEP size. Conditioning stimuli may allow examiners to assess central motor conduction where it would otherwise be impossible.     

Reduction of cortical excitability and increase of thalamic activity in a low-frequency rTMS treatment for chronic tinnitus

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has received increasing attention for the treatment of tinnitus, but its therapeutic mechanisms are unclear. We performed low-frequency rTMS treatment for a patient with chronic tinnitus and examined changes of cortical excitability and cerebral blood flow using paired-pulse TMS and single-photon emission computed tomography. After the rTMS treatment, tinnitus loudness was decreased, cortical excitability was reduced, and blood flow in the thalamus was increased. Our results suggest that low-frequency rTMS treatment reduces tinnitus loudness by an inhibitory effect on the cortical excitability and a remote activation effect on the thalamus through the corticothalamic networks.     

Anticipation and execution of a simple reading task enhance corticospinal excitability.

OBJECTIVE: Electromyographic responses (EMG) evoked in the right hand by transcranial magnetic stimulation (TMS) of the left motor cortex are enhanced during continuous reading. This enhancement is the result of increased excitability of the motor cortex. We proposed that anticipation and reading of single words would also enhance corticospinal excitability. We studied the temporal course of corticospinal excitability changes following left and right hemisphere TMS. METHODS: Ten normal volunteers were studied. A warning stimulus (S1) was followed by an imperative stimulus (S2) whereupon a word was presented. Subjects responded by reading the word aloud or reading it silently. In other conditions, no word was displayed and the subjects responded to S2 by saying the word 'Cat', pursing their lips, or doing nothing. EMG was recorded over the contralateral hand following a TMS pulse over the motor cortex during and after the S1-S2 period. RESULTS: Enhancement of EMG amplitudes was significantly greater following left hemisphere TMS. The enhancement in the S1-S2 period and that following S2 had a time course similar to several event-related brain potentials. CONCLUSIONS: There may be a common mechanism underlying both corticospinal excitability and the contingent negative variation, readiness potential and N400.     

Homeostatic effects of plasma valproate levels on corticospinal excitability changes induced by 1Hz rTMS in patients with juvenile myoclonic epilepsy.

OBJECTIVE: The preliminary results of noninvasive brain stimulation for epilepsy treatment have been encouraging, but mixed. Two important factors may contribute to this heterogeneity: the altered brain physiology of patients with epilepsy and the variable presence of antiepileptic drugs. Therefore, we aimed to study the effects of 1 Hz rTMS on corticospinal excitability in patients with juvenile myoclonic epilepsy (JME) in two different conditions: low- or high-plasma valproate levels. METHODS: Fifteen patients with JME and 12 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS was assessed in JME patients with low- and high-plasma valproate levels; and these results were compared with those in healthy subjects. RESULTS: In patients with chronic use of valproate and low-plasma concentrations, 1 Hz rTMS had a similar significant inhibitory effect on corticospinal excitability as in healthy subjects. However, in the same patients when the serum valproate concentration was high, 1 Hz rTMS increased the corticospinal excitability significantly. In addition, there was a significant positive correlation between plasma valproate levels and the motor threshold changes after 1 Hz rTMS. CONCLUSIONS: Our findings can be accounted for by mechanisms of homeostatic plasticity and illustrate the dependency of the modulatory effects of rTMS on the physiologic state of the targeted brain cortex. SIGNIFICANCE: The therapeutic use of rTMS in epilepsy should take into consideration the interaction between rTMS and drugs that change cortical excitability.     

Suppression of motor cortical excitability by electrical stimulation over the cerebellum in ataxia

We studied the effect of electrical stimulation over the cerebellum on electromyographic responses evoked by magnetic stimulation over the cerebral motor cortex in 14 normal volunteers and 32 patients with ataxia due to various disorders. In all the normal subjects, stimulation over the cerebellum significantly reduced the size of electromyographic response in the first dorsal interosseous muscle evoked by magnetic cortical stimulation, when the cerebellar stimulus preceded the cortical stimulus by 5, 6, and 7 msec. This suppression was absent or reduced in ataxic patients who had atrophy of the cerebellar hemispheres as demonstrated by magnetic resonance imaging and in patients with dysfunction of the cerebellothalamocortical pathway who had lesions in the superior cerebellar peduncle or in the motor thalamus. In contrast, suppression was normal in ataxic patients who had pontine lesions that affected the pontocerebellar afferent pathway to the cerebellum. Results were also normal in patients without cerebellar ataxia, such as those with Parkinson's disease, sensory ataxia, and cerebrovascular disease without ataxia. We conclude that electrical stimulation activates cerebellar structures that suppress motor cortical excitability through a cerebellothalamocortical pathway and that the afferent systems to the cerebellum make no or little contribution to the effect. The technique described here would be useful for distinguishing ataxia due to lesions of cerebellar afferent pathway from other types of cerebellar ataxia.     

Long-lasting increase in corticospinal excitability after 1800 pulses of subthreshold 5 Hz repetitive TMS to the primary motor cortex.

OBJECTIVE: To study the after effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) on corticospinal excitability. METHODS: Eight healthy volunteers received either 150 or 1800 stimuli of 5 Hz rTMS on two separate days in a counterbalanced order. rTMS was given over the 'motor hot spot' of the right first dorsal interosseus (FDI) muscle using an intensity of 90% of resting motor threshold (referred to as subthreshold rTMS). We evaluated the amplitude of the motor-evoked potential (MEP), short-latency intracortical inhibition (SICI), short-latency intracortical facilitation (SICF), and cortical silent period (CSP) before and for about 30 min after rTMS. MEPs were recorded from the right FDI muscle and abductor digiti minimi (ADM) muscle. RESULTS: 1800 stimuli induced an increase in MEP amplitude in the relaxed FDI muscle, but not in the relaxed ADM muscle. This facilitatory after effect was stable for at least 30 min. Prolonged 5 Hz rTMS had no effect on the relative magnitude of SICI and SICF. 150 stimuli caused no lasting modulation of MEP amplitudes in either muscle. In a subgroup of 5 subjects, 900 conditioning stimuli caused only a short-lived MEP facilitation. 5 Hz rTMS did not modify the duration of the CSP during tonic contraction. CONCLUSIONS: A single session of subthreshold 5 Hz rTMS to the M1 can induce a long-lasting and muscle-specific increase in resting corticospinal excitability. However, a sufficient number of conditioning stimuli is necessary to produce persistent corticospinal facilitation.     

Formation of functional endplates by spinal axons regenerating through a peripheral nerve graft. A study in the adult rat

Peripheral nerve (PN) autografts were used in the adult rat to join the midcervical spinal cord to a nearby denervated skeletal muscle. Retrograde tracing, morphological and electrophysiological studies indicated the following: 1) a great number of neurons, located bilaterally, between C3 and C7 in most laminae of the grey matter, extended axons into the PN grafts, 2) a lesser number of neurons regenerated up to the reconnected muscle, but most of them were typical motoneurons, 3) neuromuscular junctions were formed in ectopic locations, around the tip of the grafted nerve, and at the sites of original endplates, 4) these junctions were functional and formed by axons that had regenerated into the PN bridges, as muscle contraction was obtained by electrical stimulation of the grafted nerves, 5) they were proved to be cholinergic since endplate potentials, evoked by stimulating the PN graft, were suppressed by curare. These results strongly suggest that spinal neurons, and especially motoneurons, are involved in the formation, through PN bridges, of new functional cholinergic connections with denervated skeletal muscles.     

Regeneration of peripheral nerve through a polyglactin tube

Polyglactin 910, a resorbable synthetic material, was used as a mesh-tube to bridge defects (7 to 9 mm in length) in sectioned rabbit tibial nerve. After absorption of the mesh a new nerve sheath was formed which enclosed numerous minute fascicles of regenerating axons. The polyglactin tube influenced the direction taken by the regenerating axons and guided them into the distal segment. The tube also reduced the formation of neuromas and the growth of scar tissue from surrounding structures.     

The role of diffusion barriers in determining the excitability of peripheral nerve

The excitability changes occurring in normal isolated peripheral nerves of rats have been studied during exposure to hypoxic and anoxic conditions before and after the administration of insulin. The changes observed have been explained in terms of the dynamics of K' equilibrium in the periaxonal spaces, and attention is drawn to the importance of the relative impermeability of the periaxonal diffusion barrier in determining this equilibrium. Isolated peripheral nerves from alloxan-diabetic rats, studied under similar conditions, show significant differences in the sequence of their excitability changes. It has been shown that the rate of change of excitability in these nerves is slower than those of control nerves. These results have now been interpreted in terms of the K' changes in the periaxonal space. It is concluded that these slower excitability changes are due to an increase in the permeability of the diffusion barrier of the diabetic nerve to potassium.