Electrical Stimulation Of Peripheral Nerves Research Articles

Dissociated effects of diazepam and lorazepam on short‐latency afferent inhibition

Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short-latency afferent inhibition, SAI). This can be tested by coupling electrical stimulation of peripheral nerve with transcranial magnetic stimulation (TMS) of the motor cortex. SAI is reduced by the anticholinergic drug scopolamine, and in patients with Alzheimer's disease. Therefore, it is possible that SAI is a marker of central cholinergic activity important for memory function. The benzodiazepine lorazepam also reduces SAI. Since benzodiazepines impair memory formation, but do not do so uniformly, with a maximum amnesic effect after lorazepam but less or no effect after diazepam, we were interested in testing in this non-behavioural study to what extent the effects of lorazepam and diazepam on circuits involved in SAI could be dissociated. In addition, and for control, we tested the effects of lorazepam and diazepam on short-interval intracortical inhibition (SICI), a motor cortical inhibition mediated through the GABA(A) receptor. Lorazepam markedly reduced SAI, whereas diazepam slightly increased it. In contrast, both benzodiazepines uniformly increased SICI. Our findings demonstrate opposite effects of lorazepam and diazepam on SAI, an inhibition modulated by central cholinergic activity, but the same effects on SICI, a marker of neurotransmission through the GABA(A) receptor. This dissociation suggests, for the first time, that TMS measures of cortical inhibition provide the opportunity to segregate differences of benzodiazepine action in human central nervous system circuits.

Corticospinal Excitability Is Lower During Rhythmic Arm Movement Than During Tonic Contraction

Humans perform rhythmic, locomotor movements with the arms and legs every day. Studies using reflexes to probe the functional role of the CNS suggest that spinal circuits are an important part of the neural control system for rhythmic arm cycling and walking. Here, by studying motor-evoked potentials (MEPs) in response to transcranial magnetic stimulation (TMS) of the motor cortex, and H-reflexes induced by electrical stimulation of peripheral nerves, we show a reduction in corticospinal excitability during rhythmic arm movement compared with tonic, voluntary contraction. Responses were compared between arm cycling and tonic contraction at four positions, while participants generated similar levels of muscle activity. Both H-reflexes and MEPs were significantly smaller during arm cycling than during tonic contraction at the midpoint of arm flexion (F = 13.51, P = 0.006; F = 11.83, P = 0.009). Subthreshold TMS significantly facilitated the FCR H-reflex during tonic contractions, but did not significantly modulate H-reflex amplitude during arm cycling. The data indicate a reduction in the responsiveness of cells constituting the fast, monosynaptic, corticospinal pathway during arm cycling and suggest that the motor cortex may contribute less to motor drive during rhythmic arm movement than during tonic, voluntary contraction. Our results are consistent with the idea that subcortical regions contribute to the control of rhythmic arm movements despite highly developed corticospinal projections to the human upper limb.

Respiratory evoked potentials and occlusion elicited sympathetic skin response

Introduction. – Neurophysiological study of respiratory structures usually relies upon diaphragm electromyography and phrenic nerve conduction study, which do not assess the afferent sensory pathways. Objective. – To assess the feasibility of respiratory evoked potentials (REPs) and sympathetic skin responses (SSRs) elicited by inspiratory occlusion. Methods. – REPs and SSRs were studied in 12 healthy adults. REPs were elicited by inspiratory occlusions triggered by the physician within 1 s after the onset of a respiratory effort. They were recorded from C3, C4 and Cz needle electrodes (referenced to Fz). Each individual trial consisted of two superimposed 30-sweep averaged responses to inspiratory occlusions. SSRs were recorded from surface electrodes placed on the subject’s hand and elicited by similar inspiratory occlusions. Results. – Reproducible REPs and SSRs were obtained in all subjects. Mean latencies of initial P1 and N1 cortical responses were 41 and 72 ms, respectively. SSRs were similar to those usually elicited by peripheral nerve electrical stimulation. Conclusion. – Brief occlusion of inspiration induces cortical and sympathetic activation, both are easily recordable. Since REPs are considered to be the neurophysiological substrate of certain types of respiratory sensations and are altered in different chronic respiratory diseases, they, in addition to SSR, represent attractive new techniques that may provide better understanding of respiratory dysfunction.

New Perspectives on Improving Upper Extremity Function after Spinal Cord Injury

Injury to the cervical spinal cord adversely affects arm and hand function to varying degrees depending on the level and severity of injury. These impairments typically result in reduced independence in the performance of activities of daily living and limit participation in recreational activities. There is evidence to suggest individuals with incomplete spinal cord injury may benefit from intensive rehabilitation interventions aimed at improving hand and arm function. Massed practice (repetitive activity-based training) and somatosensory stimulation (prolonged peripheral nerve electrical stimulation at submotor threshold intensity) are 2 interventions that have been shown to improve strength and function in individuals with stroke, presumably by changing cortical excitability. These techniques, however, had not previously been investigated in individuals with spinal cord injury (SCI). In this article the stroke and SCI literature supporting the use of massed practice and somatosensory stimulation as a potential rehabilitative tool to promote recovery of function in individuals with incomplete cervical spinal cord injury (SCI) is reviewed. Recently published research using these novel techniques in which a combination of massed practice and somatosensory stimulation resulted in increased pinch grip strength and upper extremity function in individuals with incomplete cervical SCI when compared to subjects participating in massed practice alone is presented.

Motor cortex excitability after thalamic infarction

Objective We examined 8 patients with hemihypesthesia due to an ischemic thalamic lesion to explore the effects of a central sensory dysfunction on motor cortex excitability. Methods Motor excitability was assessed using transcranial magnetic stimulation techniques and electrical peripheral nerve stimulation. Motor function was evaluated by the Nine-Hole-Peg Test and measurement of hand grip strength. The affected side was compared with the non-lesioned side and with an age-matched control group. Results Patients had a loss of inhibition and an increase of facilitation in the motor cortex of the affected side. The silent period was prolonged and motor function was impaired on the affected side. Conclusions A thalamic lesion can modulate motor cortical excitability. Significance This study suggests that, under normal conditions, somatosensory afferents influence inhibitory and excitatory properties in the motor cortex.

Peripheral Electrical Stimulation in Alzheimer’s Disease

In a number of studies, peripheral electrical nerve stimulation has been applied to Alzheimer’s disease (AD) patients who lived in a nursing home. Improvements were observed in memory, verbal fluency, affective behavior, activities of daily living and on the rest-activity rhythm and pupillary light reflex. The aim of the present, randomized, placebo-controlled, parallel-group clinical trial was to examine the effects of electrical stimulation on cognition and behavior in AD patients who still live at home. Repeated measures analyses of variance revealed no effects of the intervention in the verum group (n = 32) compared with the placebo group (n = 30) on any of the cognitive and behavioral outcome measures. However, the majority of the patients and the caregivers evaluated the treatment procedure positively, and applying the daily treatment at home caused minimal burden. The lack of treatment effects calls for reconsideration of electrical stimulation as a symptomatic treatment in AD.

Dextrose 5% in water: fluid medium for maintaining electrical stimulation of peripheral nerves during stimulating catheter placement

It is well documented that a higher electrical current is required to elicit a motor response following a normal saline (NS) injection during the placement of stimulating catheters for peripheral nerve block. We present three cases of continuous brachial plexus catheter placement in which Dextrose 5% in water (D5W) was used to dilate the perineural space instead of NS. Three brachial plexus blocks (two interscalene and one axillary) were performed in three different patients for pain relief. In each case, an insulated needle was advanced towards the brachial plexus. A corresponding motor response was elicited with a current less than 0.5 mA after needle repositioning. A stimulating catheter was advanced with ease after 3-5 ml of D5W was injected to dilate the perineural space. A corresponding motor response was maintained when the current applied to the stimulating catheter was less than 0.5 mA. Local anesthetic was then injected and the motor response immediately ceased. All blocks were successful and provided excellent pain relief with the continuous infusion of local anesthetics.

Modulation of heart activity during withdrawal reflexes in the snail Helix aspersa

The beating activity of the molluscan heart is myogenic, but it is influenced by nervous signals of central origin. Previous studies have demonstrated changes in cardiac output during feeding and other behaviors. Here, we describe a short latency, transient cardiac response that accompanies withdrawal reflexes. When evoked by electrical stimulation of peripheral nerves, the response was detected within one or two heartbeats. Beat amplitudes increased on average 11.6%, and inter-beat intervals decreased on average 2.1%. The mean duration of the response was 28.1 s. A transient inhibitory phase often preceded the excitatory response. Results from testing various nerves and tissues show that the cardiac responses invariably occur whenever contractions of the tentacle retractor muscle are elicited. Even stimulation of the ovotestis and the kidney elicit responses despite their protected locations within the mantle cavity. Three excitatory cardioactive neurons are identified in the central nervous system of Helix aspersa, and their involvement in the reflex response is documented. The results suggest that the heart output is initially inhibited to relax the hydroskeleton and thereby aid withdrawal movements. A delayed increase in cardiac output then facilitates the re-inflation, hence eversion, of the withdrawn body parts.

Role of afferent input in motor organization in health and disease

In the healthy brain, there is a highly organized relationship between sensory input from one part of the body and the motor cortical output to muscles acting on that same part. This work investigates whether a change in purely sensory input have an impact on the organization of the motor cortex. In a previous study transcranial magnetic stimulation (TMS) techniques were used to probe the excitability of the motor cortex hand area. A measurement of the amplitude of the motor evoked potential (MEP) to standard single-pulse stimuli given through a focal coil was done. The excitability of two types of intracortical inhibition, SICI and LICI, was also measured using a paired-pulse TMS design. SICI is thought to be sensitive to activity in GABA/sub A/-ergic systems, whereas LICI may involve activation of GABA/sub B/-ergic systems. The work of other researchers has shown that these measures could be influenced by sensory input. Yet, all of them used electrical stimulation of peripheral nerve rather than a natural input. In order to investigate a more natural input, we delivered very low-amplitude vibration to the muscle belly of individual hand muscles through a small probe. This work explores the pattern of effects on MEPs and SICI in three different intrinsic hand muscles after vibration of each muscle in turn. In addition, the study also tested LICI with a paired-pulse TMS paradigm. In conclusion, it was seen that a period of sensory input, with or without the subject's attention, produces a specific pattern of sensory-motor reorganization in human cortex which develops quickly (after only 15 minutes) and lasts for at least 30 min. Since this produces changes in the motor cortex without requiring any active motor output, it may be a promising tool for neurorehabilitation even in patients who are unable to perform the active movements conventionally employed in therapy.

Extracellular voltage profile for reversing the recruitment order of peripheral nerve stimulation: a simulation study

Electrical stimulation of peripheral nerve activates large-diameter fibers before small ones. A physiological recruitment order, from small to large-diameter axons, is desirable in many applications. Previous studies using computer simulations showed that selective activation of small fibers could be achieved by reshaping the extracellular voltage profile along the nerve using an array of nine electrodes. In this study, several electrode-array configurations were tested in order to minimize the number of contacts. Electrode arrays of 5, 7, 9, and 11 contacts with 0.75 mm contact separation were performed in computer simulations of dog sacral root (S2). Electrode arrays of 5 and 7 contacts recruited 40% of small axons (<10 µm) when recruiting only 10% of larger axons. Effectiveness of 9- and 11-contact arrays decreased with the presence of epineurium and perineurium. The effectiveness of electrode arrays was independent of stimulation pulsewidth. The biphasic-pulse stimulation with the amplitude of the second phase set as low as possible should be used to prevent the excitation of large axons during the second phase and to minimize the electrode corrosion. Arrays of 5 and 7 contacts also decreased the recruitment curve slope to 26% and 51% of the tripolar electrode, respectively. This modeling study predicts that reversing the recruitment order of peripheral nerve stimulation could be achieved by reshaping the extracellular voltage using electrode arrays of 5 or 7 contacts.

Estimated magnitude and interactions of cortico-motoneuronal and Ia afferent input to spinal motoneurones of the human hand

Magnitude and interactions of cortico-motoneuronal (CM) and Ia afferent input to spinal alpha-motoneurones (MNs) of the human hand are largely unknown. This is, however, an important question, which bears on the cortical versus peripheral-segmental ‘interest’ in controlling alpha-MN excitation. Alpha-MN excitation can be quantified by estimating the amplitude of alpha-MN compound excitatory post-synaptic potentials (cEPSPs) from single motor unit (SMU) recordings, if certain assumptions about the membrane trajectory are made [Exp. Brain Res. 47 (1982) 33]. Here we recorded 29 SMUs from three different hand muscles (FDI, first dorsal interosseous; ADM, abductor digiti minimi; APB, abductor pollicis brevis) of healthy subjects. Each SMU was tested for CM input by transcranial magnetic stimulation of the contralateral motor cortex, for Ia afferent input by electrical peripheral nerve stimulation, and for the interaction between inputs by paired stimulation timed to arrive coincidently at the alpha-MN. Mean cEPSP amplitude elicited by CM input was larger in the alpha-MNs of the FDI than in those of the ADM or APB, whereas mean cEPSP amplitude elicited by Ia input was larger in the alpha-MNs of the APB than in those of the FDI. Generally, cEPSP amplitude evoked by paired input closely matched the arithmetic sum of the cEPSP amplitudes evoked by the single inputs. In conclusion, alpha-MNs of the human hand can be viewed as linear integrators of CM and Ia excitatory inputs. The weights of these inputs may relate to the specific functions of the different intrinsic hand muscles in skilled finger movements.

Nerve blocks: Percutaneous neuromodulation therapy: A minimally invasive technique for the treatment of acute and chronic pain

Interest in nonpharmacologic alternatives to conventional analgesic drugs for the management of acute and chronic pain has led to a continued interest in the use of electroanalgesic therapies. Recent reports of a novel form of peripheral nerve stimulation known as Percutaneous Neuromodulation Therapy (PNT) have shown it to be an effective form of treatment in a growing number of disorders including low back pain and sciatica, neck pain, headaches, bone pain secondary to metastatic cancer, and painful diabetic neuropathy. In addition, several studies have demonstrated that Percutaneous Neuromodulation Therapy may be helpful in other medical conditions believed to arise from autonomic nervous system dysfunction such as sympathetically maintained pain, urinary incontinence and irritable bowel syndrome. Although the exact mechanism of action of PNT remains unknown, the improvement brought about by this form of neuronal stimulation may be due to a “resetting” of one or several of the parallel neuronal feedback systems involved in the regulation and maintenance of pain. Recent neurophysiological evidence suggests that patterned electrical stimulation of peripheral nerves may modulate sodium channel expression in sensory neurons and dorsal root ganglia thereby affecting neuronal discharge contributing to ongoing pain. In addition, electrical stimulation of peripheral nerves may also spread in an antidromic fashion to modify local reflex arcs regulating pain. This report describes the historical evolution and conceptual basis of this new technique, current clinical applications, details of its implementation and proposed mechanisms of action. The technique is minimally invasive, requires only 30 minutes per week to perform and is not associated with any significant adverse effects or safety issues. It is hoped that this information will encourage other clinicians and researchers to utilize this procedure and report their findings to help determine the overall applicability of this treatment modality in other acute and chronic pain syndromes.

Surface EMG recording of heteronymous reflex excitation of semitendinosus motoneurones by group II afferents

Objective A potent stretch reflex originates in muscle spindle secondary endings and is mediated by group II muscle afferents. Electrical stimulation of peripheral nerve could also induce group II facilitation, as found in single motor unit recordings for various nerve–muscle combinations in man. The aim of the present investigation was to use surface electromyogram (EMG) to record and to quantify heteronymous excitation of semitendinosus (ST) motoneurones by group II afferents of the tibial nerve. Methods This study included 20 healthy subjects. The conditioning stimulation of the tibial nerve was delivered at the popliteal fossa at two intensity levels and for two levels of ST contraction. EMG activity was recorded by surface electrodes placed over the ST muscle, and the averaged and rectified ST EMG signal was analyzed. Results We observed 4 periods of interest: a first period of prestimulus background EMG activity; a second period of early reinforcement of ST EMG activity starting 30 ms poststimulus and lasting for 35–45 ms; a third period of relative inhibition of ST contraction; a fourth period of late reinforcement of poststimulus ST EMG activity. Conclusions We hypothesized that the early period of facilitation was mainly related to heteronymous excitation of ST motoneurones by group II afferents on the basis of the following observations: (i) the amount of facilitation increased for a high stimulus intensity level, which was suitable for group II recruitment; (ii) the onset latency of this facilitation was consistent with the theoretically calculated latency of a group II-mediated reflex. Significance Surface EMG recording offers various advantages compared to single motor unit recording to study group II facilitation in the ST muscle. This technique could be applied in the future to confirm that heteronymous reflex excitation by group II afferents is enhanced in spastics and plays an important role in the development of lower limb spasticity.

A review of contralateral responses to a unilateral inflammatory lesion.

Symmetry is a remarkably constant clinical feature of chronic inflammatory disease. Rheumatoid arthritis is almost by definition symmetrical [1]. Osteoarthritis, psoriasis and some of its associated arthritides are also symmetrical [2–4]. Pulmonary fibrosis, glomerulonephritis and sympathetic ophthalmia are also symmetrical inflammatory conditions. Whilst the pathophysiology behind this symmetry is unexplained, we and others have speculated that it is likely to be mediated via neurological mechanisms crossing through the spinal cord [5, 6]. The two sides of the spinal column have largely been thought to function independently of each other. There are three lines of evidence to suggest that this is not true. Careful anatomical studies of the spinal cord show transmedian fibres decussating posteriorly at all levels of the spinal cord to synapse in the laminae on the contralateral dorsal horn. These neuronal connections have been seen in many different species, including several primates (Fig. 1). Szentagothai [7], using Golgi analysis on young cats and dogs, showed that neurons with their cell bodies in the substantia gelatinosa send contralateral axons that appear to synapse in the contralateral substantia gelatinosa. Perl and Light [8] corroborated these findings after they had applied horseradish peroxidase to rat, cat and monkey dorsal rootlets. They found projections into the contralateral substantia gelatinosa as well as the ventral portion of the nucleus propius. Culberson et al. [9], using cresyl violet acetate (Fink-Heimer method), identified crossed afferent projections throughout the spinal cord, originating and terminating in laminae III–IV, in four mammalian species. These anatomical studies provide evidence that the opportunity exists for crosstalk between the left and the right sides of the spinal column. Functional studies of decerebrate rats demonstrate that such cross-communication can produce contralateral responses. Electrical stimulation of contralateral peripheral nerves is known to inhibit flexor reflex pathways in the spinal cord [10] as well as the long latency of C-fibre-evoked activity in dorsal horn cells [11, 12]. Contralateral dorsal horn cells are inhibited in response to noxious stimuli applied to the limb or tails of rats [13, 14]. Further electrophysiological studies confirm the presence of neurons in the dorsal horn that have bilateral receptive fields. Of relevance to this article is that the number of these neurons with bilateral receptive fields increases in the presence of unilateral inflammation [15, 16]. Grubb et al. [17] also showed that some of the fields on the contralateral side can become excitatory rather than inhibitory. At what level are these contralateral responses mediated? Woolf [16] documented the persistent reduction in flexor reflex thresholds contralaterally after noxious thermal stimuli had been applied to decerebrate rats with an intact brainstem. Fitzgerald [18], using a decerebrate, spinalized rat model, showed that a contralateral effect on dorsal horn fibres need not involve such higher pathways. Although direct contralateral spinal pathways exist in experimental conditions, there are likely to be significant supraspinal influences in vivo. This is suggested by several studies detailing an attenuation of central sensitization and secondary hyperalgesia following spinalization or inactivation of the rostral ventral medulla in a review of rat models of acute pain [19].

Electrophysiological analysis of synaptic transmission in central neurons of Drosophila larvae.

We report functional neuronal and synaptic transmission properties in Drosophila CNS neurons. Whole cell current- and voltage-clamp recordings were made from dorsally positioned neurons in the larval ventral nerve cord. Comparison of neuronal Green Fluorescent Protein markers and intracellular dye labeling revealed that recorded cells consisted primarily of identified motor neurons. Neurons had resting potentials of -50 to -60 mV and fired repetitive action potentials (APs) in response to depolarizing current injection. Acetylcholine application elicited large excitatory responses and AP bursts that were reversibly blocked by the nicotinic receptor antagonist D-tubocurarine (dtC). GABA and glutamate application elicited similar inhibitory responses that reversed near normal resting potential and were reversibly blocked by the chloride channel blocker picrotoxin. Multiple types of endogenous synaptically driven activity were present in most neurons, including fast spontaneous synaptic events resembling unitary excitatory postsynaptic currents (EPSCs) and sustained excitatory currents and potentials. Sustained forms of endogenous activity ranged in amplitude from smaller subthreshold "intermediate" sustained events to large "rhythmic" events that supported bursts of APs. Electrical stimulation of peripheral nerves or focal stimulation of the neuropil evoked sustained responses and fast EPSCs similar to endogenous events. Endogenous activity and evoked responses required external Ca(2+) and were reversibly blocked by dtC application, indicating that cholinergic synaptic transmission directly underlies observed activity. Synaptic current amplitude and frequency were reduced in shibire conditional dynamin mutants and increased in dunce cAMP phosphodiesterase mutants. These results complement and advance those of recent functional studies in Drosophila embryonic neurons and demonstrate the feasibility of in-depth synaptic transmission and plasticity studies in the Drosophila CNS.

Electrical stimulation for the treatment of bladder dysfunction: Current status and future possibilities

Electrical stimulation of peripheral nerves can be used to cause muscle contraction, to activate reflexes, and to modulate some functions of the central nervous system (neuromodulation). If applied to the spinal cord or nerves controlling the lower urinary tract, electrical stimulation can produce bladder or sphincter contraction, produce micturition, and can be applied as a medical treatment in cases of incontinence and urinary retention. This article first reviews the history of electrical stimulation applied for treatment of bladder dysfunction and then focuses on the implantable Finetech-Brindley stimulator to produce bladder emptying, and on external and implantable neuromodulation systems for treatment of incontinence. We conclude by summarizing some recent research efforts including: (a) combined sacral posterior and anterior sacral root stimulator implant (SPARSI), (b) selective stimulation of nerve fibers for selective detrusor activation by sacral ventral root stimulation, (c) microstimulation of the spinal cord, and (d) a newly proposed closed-loop bladder neuroprosthesis to treat incontinence caused by bladder overactivity. [Neurol Res 2002; 24: 413-430]

Clinical elements for the neuromuscular stimulation and functional electrical stimulation protocols in the practice of neurorehabilitation.

The physicians and their multidisciplinary teams involved in the clinical practice of neurological rehabilitation have more and more opportunities to apply neuromuscular stimulation (NMS) and functional electrical stimulation (FES) of peripheral nerves as a part of their daily practice. In this article, we outline clinical protocols of NMS and FES in the following clinical conditions of upper motor neuron dysfunction: to prevent consequences of disuse of the neuromuscular system of the upper motor neuron, to facilitate recovery processes of impaired upper motor neuron functions due to acute and/or subacute neurological conditions, to maintain or enhance the trophic state of the muscle, to modify altered control of muscle tone, to modify altered patterns of automatic and volitional functional movements, to enhance functional movement of the single joint muscle group within intact functional multijoint movement, and to modify altered neurocontrol of posture, locomotion, and skillful movements. We emphasize the importance of understanding the motor control alteration while developing clinical protocols and defining the goals. It is very important to be aware that similar clinical findings and due to the same cause can have different features of residual motor control, and therefore potentials for recovery or modification can be very different.

Organisation of the sympathetic skin response in spinal cord injury

Objectives: The sympathetic skin response (SSR) is a technique to assess the sympathetic cholinergic pathways, and it can be used to study the central sympathetic pathways in spinal cord injury...

Motor cortex activation by transcranial magnetic stimulation in ataxia patients depends on the genetic defect.

In patients with degenerative ataxia, various abnormalities in motor cortex activation by transcranial magnetic stimulation (TMS) have been observed, including a reduction of intracortical facilitation and a lengthening of the silent period. However, the groups of patients examined in previous studies were heterogeneous, involving patients with autosomal-dominant and idiopathic cerebellar ataxia, and showing different clinical features. The aim of our present study was to investigate whether differences in motor cortex activation by TMS could be observed in genetically defined subtypes of degenerative ataxia. We examined six patients with Friedreich's ataxia, three patients with spinocerebellar ataxia (SCA) type 1, seven patients with SCA2, 12 patients with SCA3, nine patients with SCA6 and 14 healthy controls. In all subjects, motor threshold, central motor conduction time, cortical silent period after TMS, and intracortical inhibition and facilitation (as assessed by TMS using a paired pulses paradigm) were determined. Additionally, F wave amplitudes evoked by electrical peripheral nerve stimulation were measured. We found a significant reduction of intracortical facilitation in SCA2 and SCA3 patients. Furthermore, motor threshold was elevated in SCA1, central motor conduction time was lengthened in patients with Friedreich's ataxia and SCA1, and F wave amplitudes were enlarged in all the genetic subgroups except for SCA6. Silent period and intracortical inhibition did not differ between patients and controls. We conclude that changes of intracortical facilitation induced by TMS and other excitability parameters of the motor system are not a common phenomenon in degenerative ataxia, but are restricted to specific subtypes. This points to differences in the underlying pathophysiological processes in genetic subtypes of ataxia.

Mechanisms of motor‐evoked potential facilitation following prolonged dual peripheral and central stimulation in humans

1. Repetitive electrical peripheral nerve or muscle stimulation can induce a lasting increase in the excitability of the corticomotor projection. By pairing peripheral stimulation with transcranial magnetic brain stimulation it is possible to shorten the duration of stimulation needed to induce this effect. This ability to induce excitability changes in the motor cortex may be of significance for the rehabilitation of brain-injured patients. The mechanisms responsible for the increases in excitability have not been investigated thoroughly. 2. Using two paired transcranial magnetic stimuli protocols we investigated the excitability of intracortical inhibitory and excitatory systems before and following a period of repetitive dual muscle and brain stimulation. The dual stimulation consisted of motor point stimulation of first dorsal interosseous (FDI; 10 Hz trains of 1 ms square waves for 500 ms) delivered at one train every 10 s, paired with single transcranial magnetic stimulation given 25 ms after the onset of the train. 3. Following 30 min of dual stimulation, motor-evoked potentials (MEPs) were significantly increased in amplitude. During this period of MEP facilitation there was no significant difference in the level of intracortical inhibition. There was, however, a significant increase in the intracortical facilitation demonstrated with paired magnetic stimuli. The increase in facilitation was seen only at short interstimulus intervals (0.8-2.0 ms). These intervals comprised a peak in the time course of facilitation, which is thought to reflect I wave interaction within the motor cortex. 4. The relevance of this finding to the MEP facilitation seen following dual peripheral and central stimulation is discussed.