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Biomedical subjects

J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 181 records · Page 10Linked to original sources

Comparison of regional cerebral blood flow with transcranial magnetic stimulation at different forces.

This study's objective was to investigate regional cerebral blood flow (rCBF) within the primary motor cortex (M1) and to compare it with thresholds of transcranial magnetic stimulation (TMS) and electromyographic recordings during exertion of different force levels with the right index finger. Quantitative electromyographic recordings, TMS, and positron emission tomography scans were performed while five and six volunteers, respectively, pressed a Morse key repetitively or with constant force with the right hand at five different force levels: 5, 10, 20, 40, and 60% of the individual's maximum voluntary contraction (MVC). Although at 5% MVC muscle activity was restricted to the first dorsal interosseus muscle, superficial finger flexors, and extensors, there was progressive involvement of proximal muscles during finger flexion with increasing force. rCBF increased logarithmically in the contralateral M1 with increasing force. In ipsilateral M1, rCBF decreased at 5% MVC and then increased logarithmically at higher force levels. TMS thresholds in the contralateral hemisphere declined logarithmically to reach a plateau at high force levels. The threshold in the ipsilateral hemisphere decreased slightly at high force levels. The logarithmic increase of rCBF and decrease of TMS thresholds in the contralateral hemisphere suggest related underlying physiological phenomena; increased cortical synaptic activity and increased excitability. It suggested that the pronounced ipsilateral rCBF alterations reflect transcallosal inhibition and are more prominent during repetitive movements (as used in the positron emission tomography study) than during the generation of a constant force (as exerted during TMS).

Adult↗

Preliminary clinical observations on a new trigeminal reflex: the trigemino-cervical reflex.

Short latency trigemino-cervical reflexes can be recorded from sternocleidomastoid muscle after stimulation of the infraorbital branch of the trigeminal nerve. We studied the trigemino-cervical reflexes and the conventional blink reflex in three patients with an isolated lesion in the medulla oblongata, eight patients with multiple sclerosis, and two patients with supratentorial ischemic lesion. The trigemino-cervical response was abnormal in the patients with an isolated lesion in the medulla oblongata and in all multiple sclerosis patients, whereas both components of the blink reflex were preserved in the patients with a lesion in the medulla oblongata and in half of the patients with multiple sclerosis. The trigemino-cervical reflex was preserved in patients with supratentorial lesions, whereas the late component of the blink reflex was abnormal. These findings suggest that central pathways generating the trigemino-cervical reflex are confined to the medulla oblongata and that they are independent from those generating the long latency (R2) component of the blink reflex. The trigemino-cervical reflex may help in disclosing and localizing brainstem lesions.

Adult↗

Distribution of Ia effects onto human hand muscle motoneurones as revealed using an H reflex technique.

1. The possibility of eliciting H reflexes in relaxed hand muscles using a collision between the orthodromic impulses generated by magnetic cortical stimulation and the antidromic motor volley due to a supramaximal (SM) peripheral nerve stimulus was investigated in seven subjects. 2. Magnetic stimuli, applied through a circular coil (outer diameter, 13 cm) centred at the vertex, evoking EMG responses of 3-5 mV amplitude in the relaxed abductor digit minimi (ADM) muscle, and SM test stimuli to the ulnar nerve at the wrist producing a direct maximal motor response (Mmax) in the ADM muscle, were given either alone or combined. 3. In all subjects, combined cortical and SM ulnar stimulation produced a response after the Mmax with the latency of an H reflex evoked by the ulnar stimulus. This response occurred only within interstimulus intervals (1-20 ms) compatible with collision in the motor axons. The response behaved like an H reflex being time-locked to the SM ulnar stimulus, facilitated by voluntary activation of ADM muscle, depressed by vibration (4 s, 100 Hz) of ADM tendon and by a submotor-threshold ulnar nerve stimulus applied 50 and 80 ms before the combined stimulation, respectively. 4. In some subjects, it was also possible to distinguish an earlier response preceding the H reflex by 3 ms. Evidence is given that this response is probably of cortical origin. 5. Varying the intensity of magnetic stimulation resulted in a non-linear relationship between the H reflex size and the size of the cortical response. When the latter was between 5-25% of Mmax, H reflexes were small (2.5-7.5% of Mmax); with cortical responses between 25-50% of Mmax, there was a steep increase in H reflex amplitude (10-30% of Mmax). We suggest that this behaviour is due to an uneven distribution of Ia effects within the motoneurone pool.

Adult↗

Ipsilateral cortical stimulation inhibited the long-latency response to stretch in the long finger flexors in humans.

1. Transcranial magnetic stimulation over the motor cortex of one hemisphere is known to decrease the excitability of the motor cortex of the other hemisphere. We investigated the effect of this interhemispheric or transcallosal inhibition of the motor cortex on the reflex response to stretch in the long flexors of the fingers in human subjects. 2. Stretch of the long finger flexors, through extension of the proximal interphalangeal joints with a torque pulse, resulted in a reflex EMG response with short- and long-latency components. Magnetic stimulation was applied over the motor cortex ipsilateral to the muscles being stretched. When a magnetic shock but not stretch was given, a decrease in background EMG in the ipsilateral finger flexors occurred at a latency of 33 +/- 6.2 ms after the stimulus and with a duration of 25 +/- 8.5 ms. 3. If the magnetic shock and the stretch were given at appropriate interstimulus intervals, the long-latency stretch reflex (LLSR) showed inhibition in all subjects. LLSR was reduced to 49.2 +/- 19% (S.D.; n = 9) of the area of the control response. 4. The LLSR did not act as a single event in response to the magnetic shock. That is, part of the LLSR could be reduced in amplitude while the remainder was unaffected. The reduction in LLSR had an onset latency of 27 +/- 3.8 ms after the magnetic stimulus and a duration of 29-55 ms. Inhibition was only obvious when this interval after the magnetic stimulus coincided with the LLSR. 5. In most subjects the short-latency stretch reflex (SLSR) also showed some inhibition (83.4 +/- 11.2% of the control). However, this was less than the effect on the LLSR in all subjects. 6. The site of stimulation, over the ipsilateral motor cortex, was specific for inhibition of the LLSR. When the coil was moved anteriorly or to the midline, inhibition was significantly decreased. 7. We suggest that the inhibition of the LLSR of the long flexors of the fingers resulted from a reduction in excitability of the motor cortex produced by an inhibitory transcallosal pathway and conclude that the LLSR in this muscle has a transcortical component.

Electromyography↗

The effect of voluntary contraction on cortico-cortical inhibition in human motor cortex.

1. It has been previously shown that in a relaxed target muscle, at short interstimulus intervals (ISIs) (up to 6 ms) a conditioning subthreshold transcranial magnetic stimulus can cause suppression of the EMG response evoked by a magnetic test stimulus. At longer ISIs (7-15 ms) facilitation of the test response is seen. This type of inhibition has been termed ipsilateral cortico-cortical inhibition. 2. The effect of a minimal tonic contraction on ipsilateral cortico-cortical inhibition has been investigated in the first dorsal interrosseous (FDI). 3. At short ISIs there was significantly less inhibition of the test response during the maintenance of minimal voluntary tonic contraction of the target muscle (FDI). 4. At longer ISIs (7-15 ms) there was significantly less facilitation of the test response during a tonic contraction than during relaxation. 5. Minimal activation of an ipsilateral proximal muscle (biceps) had no significant effect on the degree of inhibition seen in the relaxed target muscle (FDI). 6. We suggest that voluntary drive reduces the excitability of inhibitory circuits in cortical areas that project to the active muscle.

Adult↗

Changes in excitability of motor cortical circuitry in patients with Parkinson's disease.

Using the technique of transcranial magnetic stimulation over the motor areas of cortex and recording electromyographic (EMG) responses from the first dorsal interosseous muscle, we measured the excitability of corticocortical inhibitory circuits at rest using a double pulse paradigm, in 11 patients with Parkinson's disease (PD) studied both on (ON) and off (OFF) (after overnight withdrawal) their normal medication and in 10 age-matched control subjects. There was a significant decrease in the amount of corticocortical inhibition at short (1-5 msec) interstimulus intervals in patients relative to their controls, which improved after L-dopa intake. For comparison with previous reports using transcranial magnetic stimulation we also measured the duration of the EMG silent period when stimuli were given to voluntarily active muscle, and the threshold for evoking an EMG response in both the active and relaxed states. There was no change in the threshold for evoking EMG responses whether muscles were active or relaxed. However, the silent period was significantly prolonged when ON compared with OFF, although in neither state was the duration significantly different from that seen in normals. We suggest that there may be abnormalities of motor cortical inhibitory mechanisms in patients with Parkinson's disease that are not readily detected using threshold or silent period measurements alone.

Aged↗

Movement-related cortical potentials preceding repetitive and random-choice hand movements in Parkinson's disease.

The movement-related cortical electroencephalographic potential was recorded from scalp electrodes in 8 patients with idiopathic Parkinson's disease studied at least 12 hours after withdrawal of their normal drug therapy, and compared with the results from a group of 8 age-matched control subjects. Two types of self-paced voluntary arm movements were examined: repetitive forward movement of a joystick, and random-choice movements of the same joystick in which subjects had to choose freely the direction in which they were to move the stick (forward, backward, left, or right). In normal subjects, the movement-related cortical potential was larger prior to random-choice movements, whereas in the patients, the amplitude was the same in both tasks. The implication is that processes involved in self-selection of movement are abnormal in Parkinson's disease. This may contribute to the difficulty that patients have in initiating voluntary movement in the absence of any external cues.

Adult↗

Tonic vibration reflex and muscle afferent block in writer's cramp.

Patients with focal dystonia take advantage of certain cutaneous or proprioceptive sensory inputs to alleviate their symptoms ("sensory trick"). We examined the effects of increasing muscle spindle activity by the tonic vibration reflex maneuver and decreasing it by intramuscular injection of lidocaine. The vibration was applied to the palm or the tendon of forearm muscles in 15 patients with writer's cramp and 15 age-matched normal subjects. In 11 patients, the vibration induced dystonic postures or movements typical of those seen during writing. Normal subjects showed either no response to the vibration or a gradually developing tonic vibration reflex only in the wrist and finger flexors, which produced visible movements with a significantly longer latency (12.5 +/- 6.7 seconds [mean +/- standard deviation]) than what was observed in the patients (2.7 +/- 2.5 seconds, p < 0.0001). Local injection of lidocaine (0.5%, 5-40 ml/muscle) attenuated the tendon reflex with relatively little effect on the M response. Injection into muscles with increased activity produced marked reduction of dystonic movements and significant clinical improvement in 13 patients, whereas injection into the other muscles had no effect. The clinical benefit lasted for 1 to 24 hours after injection. In 13 patients who had additional injections of 10% ethanol, which blocks sodium channels for a longer period than does lidocaine, the duration of action was prolonged to 5 to 21 days. These findings suggest that muscles causing dystonic movements have abnormal sensitivities to vibration at rest and that muscle afferents may play a pivotal role in producing dystonic movements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The bereitschaftspotential preceding stepping in patients with isolated gait ignition failure.

The cerebral activity preceding voluntary, self-paced ankle dorsiflexion movements while seated was compared with that before a stepping movement of the same foot while standing in four patients with isolated gait ignition failure. Results within the patients group were variable, but all exhibited some increase in the Bereitschaftspotential (BP) amplitude when stepping as compared with sitting, similar to that seen in normal subjects. This differs from previous results in patients with Parkinson's disease in which stepping was not accompanied by a normal increase in BP amplitude. This difference suggests that the mechanisms responsible for the start hesitation that is common to both Parkinson's disease and gait ignition failure may differ in the two conditions.

Aged↗

Click-evoked vestibulocollic reflexes in torticollis.

A total of 26 patients with torticollis were studied using a recently developed technique for recording vestibulocollic reflexes from the sternocleidomastoid muscles in addition to conventional caloric tests of vestibular function. Previous reports of abnormalities of vestibulo-ocular reflexes in these patients were confirmed with just fewer than half having significant canal pareses or directional preponderances (nine of 20 tested). In addition, there was a high incidence of abnormal click-evoked vestibulocollic reflexes (17 of 26 tested), which were not simply the result of prior treatment with botulinum toxin, nor due to unequal levels of muscle activation. In patients never previously treated with botulinum toxin (14 patients), the effect almost always consisted of suppressed responses in the sternocleidomastoid muscle ipsilateral to the direction of head turning. Because responses were not abnormal in all patients tested, and more commonly so in those with a history of torticollis of > or = 5 years (eight of nine patients) than in de novo patients, we suggest that the changes are more likely to be compensatory than causal.

Acoustic Stimulation↗

The movement-related cortical potential is abnormal in patients with idiopathic torsion dystonia.

Voluntary movements, such as the self-paced finger extension task used in the present experiments, are preceded by a slowly rising negative electroencephalographic potential [the movement-related cortical potential (MRCP)]. The early NS1 component of the potential was no different in patients with primary dystonia affecting the arm (n = 6) compared with matched controls. In contrast, the peak amplitude of the MRCP was smaller in the patients, despite the fact that the movements made by the two groups were very similar; it was of equal size over both left and right hemispheres, rather than being larger on the side contralateral to the movement. These results are similar to those observed by others in patients with symptomatic dystonia secondary to lesions of the basal ganglia or their output pathways and may reflect abnormal basal ganglia input to motor areas of cortex before the onset of a self-paced movement.

Adult↗

Short-latency trigemino-cervical reflexes in man.

We describe a reflex evoked in neck muscles by stimulation of afferent fibres in the trigeminal nerve. The clearest responses were seen in averaged, unrectified, monopolar surface electromyographic (EMG) recordings from active sternocleidomastoid muscles after stimulation of the infraorbital nerve. They consisted of a bilateral positive/negative (p19, n31) wave with a mean onset latency of 12.9 ms which corresponded to a period of inhibition in the underlying motor unit activity. Responses also could be seen in splenius and trapezius, but not in arm muscles. Stimuli to other branches of the trigeminal nerve (supraorbital or mental) did not produce such clear effects. The threshold for the reflex was relatively low (2-4 times perceptual threshold) and its size scaled with the level of background EMG in an approximately linear fashion. Responses to infraorbital stimulation did not interact with other short-latency inhibitory responses in the sternocleidomastoid muscle evoked by loud acoustic clicks or stimulation of the median nerve at the wrist. We suggest that the infraorbital response is part of a head withdrawal reflex involving an oligosynaptic trigemino-cervical system similar to that described in the cat.

Acoustic Stimulation↗

Modulation of esophageal responses to magnetic stimulation of the human brain by swallowing and by vagal stimulation.

BACKGROUND & AIMS: Although magnetic stimulation of the human cerebral cortex activates corticoesophageal pathways, it is not known whether these pathways are mediated via brain stem neurons activated during swallowing and by vagal afferents. The aim of this study was to determine the effect of swallowing and vagal stimulation on esophageal electromyographic responses evoked by magnetic stimulation of the human cortex. METHODS: Magnetic stimulation of the cortex was performed in 7 subjects at variable intervals after swallows and at intervals ranging from 10 to 200 milliseconds after vagal stimulation in 5 subjects. RESULTS: Between swallows, cortical stimulation induced both early (10.1 +/- 0.5 milliseconds) and late (52.3 +/- 2.3 milliseconds) esophageal electromyographic responses with amplitudes of 66.9 +/- 23.4 microV and 32.9 +/- 7.4 microV, respectively. During swallowing, both responses were facilitated because their latencies decreased (8.9 +/- 0.5 milliseconds and 47.3 +/- 4.8 milliseconds, respectively), whereas their amplitudes increased (203.1 +/- 54 microV and 79.8 +/- 22.5 microV, respectively). Vagal stimulation facilitated the early cortically evoked response. Its latency decreased from 10.2 +/- 0.2 milliseconds to 8 +/- 0.2 milliseconds, whereas its amplitude increased from 145.1 +/- 44 microV to 230.5 +/- 41.6 microV. CONCLUSIONS: Corticoesophageal pathways activated by magnetic stimulation of the human cortex share the same population of brain stem motor neurons to the upper esophagus that are activated during swallowing and vagal stimulation.

Adult↗

Inhibition of hand muscle motoneurones by peripheral nerve stimulation in the relaxed human subject. Antidromic versus orthodromic input.

In active muscle, a supramaximal conditioning stimulus to peripheral nerve produces a classic silent period in the EMG. The present experiments examined the effect of this type of conditioning stimulus on motoneurone excitability in relaxed muscle. EMG responses evoked by transcranial magnetic stimulation of the brain were recorded from the first dorsal interosseus muscle (FDI) in 10 healthy subjects and 5 patients with sensory neuropathy. These responses (motor evoked potentials) were conditioned by supramaximal peripheral nerve stimuli given 0-150 msec beforehand. In the normal subjects, the classic silent period in the FDI lasted about 100 msec. The same conditioning stimulus only abolished motor evoked potentials when the conditioning-test interval was so short that the antidromic peripheral nerve volley collided with the orthodromic volley set up by magnetic brain stimulation. At longer conditioning-test intervals, although remarkably inhibited (65% mean suppression between 10 and 40 msec), the test motor potential was never completely abolished and gradually recovered by 100 msec. Inhibition of cortically evoked motor potentials did not depend upon activity set up by the conditioning stimulus in peripheral nerve sensory fibres. The patients with complete peripheral sensory neuropathy had the same extent and time-course of inhibition as the normal subjects. We conclude that in relaxed subjects the inhibitory effect of peripheral conditioning results almost exclusively from the motoneuronal inhibitory mechanisms consequent to antidromic invasion.

Adult↗

Physiological study of cervical dystonia. Task-specific abnormality in contingent negative variation.

To investigate the pathophysiology of dystonia, we recorded contingent negative variation (CNV) in 12 patients with cervical dystonia and in 12 age-matched normal subjects. In a simple reaction time paradigm, the subjects were given a pair of a warning stimulus and a subsequent stimulus that triggered head rotation to either side or extension of the fingers. In normal subjects, CNVs for head rotation were not affected by neck muscle pre-activation simulating torticollis, and were always symmetrical with equally high amplitudes over the frontal and central leads. By contrast, CNVs for finger movement had the maximum over the central lead and showed a characteristic distribution; those for the right finger movement had the left hemisphere dominance, whereas those for the left finger movement had similar amplitudes over both hemispheres. In patients with rotatory torticollis (rotatocollis), the components of CNVs for head rotation were markedly attenuated in all the leads, except for the initial negative deflection (orienting response). As a whole, cervical dystonia patients had significantly lower amplitudes of late CNVs for head rotation than normal subjects (P < 0.001), whereas late CNV amplitudes in finger extension did not differ in the two groups. Their reaction times for head rotation were similar, but durations of EMG activities were prolonged in the patients because of co-contractions of the antagonists. The task-specific CNV amplitude loss is therefore not explained by reaction times or by the abnormal neck muscle activities prior to the movement, but it reflects a failure of neural activities preparing for a phasic neck movement, resulting in co-contraction of the agonists and the antagonist. Dystonia may be associated with defective retrieval or retaining of specific motor programmes or subroutines in response to sensory stimuli.

Adult↗

Primary writing tremor.

Primary writing tremor (PWT) is considered to be a type of task-specific tremor in which tremor predominantly occurs and interferes with handwriting. We describe the clinical and neurophysiological features of 21 patients (20 male and one female) with PWT. Mean age at tremor onset was 50.1 years. A family history of PWT was obtained from seven patients. Ten patients obtained benefit from drug treatment (mainly propranalol or primidone) and seven responded to alcohol. The writing speeds of the patients (mean +/- SEM: 73.1 +/- 6.6 letters per minute) when using their preferred hand were significantly reduced (Student's t test: P < 0.001) compared with those of healthy control subjects (mean +/- SEM: 127.7 +/- 6.4). Surface polymyography performed during writing showed 4.1-7.3 Hz rhythmic activity predominantly in the intrinsic hand and forearm muscles. Alternating, extensor activation alone, skipping from alternating to extensor activation, and co-contracting EMG patterns were recorded from the flexor and extensor muscles of the forearm. There was no evidence for excessive 'overflow' of this rhythmic EMG activity, as similar activity was detected in comparable muscle groups of healthy control subjects. Accelerometry confirmed that the frequency of PWT ranged from 4.1-7.3 Hz (median 5.5 Hz) and that normal subjects wrote with a 4.0-7.7 Hz oscillation (median 4.6 Hz). Forearm reciprocal inhibition was normal in PWT (n = 13), and thus patients with PWT can be distinguished from those with writer's cramp in whom decreased presynaptic inhibition has been found. Patients were sub-classified as having either type A (n = 11) or B (n = 10) PWT depending on whether tremor appeared during writing (type A: task induced tremor) or whilst writing and adopting the hand position used in writing (type B: positionally sensitive tremor). However, the only differences between these two groups were that a co-contracting EMG pattern and tremor induced by tendon taps to the volar aspect of the wrist were present in type B but not type A cases.

Adult↗