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Biomedical subjects

J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 217 records · Page 12Linked to original sources

Click-evoked vestibular activation in the Tullio phenomenon.

Click-evoked vestibulocollic reflexes were studied in a patient with a unilateral Tullio phenomenon (sound induced vestibular symptoms) and the findings were compared with those of a group of normal subjects. Compared with normal subjects, the reflexes elicited from her symptomatic side were large and had an abnormally low threshold, but retained a normal waveform. The click-evoked responses in this patient show changes consistent with her symptomatology and are indicative of a pathological increase in the normal vestibular sensitivity to sound.

Adult↗

Esophageal myoelectric responses to magnetic stimulation of the human cortex and the extracranial vagus nerve.

We describe the use of magnetic stimulation of the human motor cortex and the extracranial vagus nerve in the neck to study human esophageal electromyographic (EMG) responses. Diffuse cortical stimulation produced both an early and a late EMG response in the proximal esophagus with latencies of 10.9 +/- 0.5 and 43.4 +/- 4.3 ms, respectively. Increasing the stimulation intensity increased the amplitude and duration, but reduced the latency, of the early response (P < 0.01), whereas the late response remained unchanged. The early response, but not the late response, was facilitated when cortical stimulation was performed during valsalva maneuver. Maximal early response amplitudes were obtained by focal stimulation of either hemisphere 4-8 cm lateral to the vertex. Stimulation of the neck over the extracranial vagus nerve at the angle of the jaw also produced an early and a late EMG response in the proximal esophagus with latencies of 4.3 +/- 0.4 and 56.8 +/- 14.5 ms, respectively. Early responses were also recorded in the midesophagus and distal esophagus from either cortical or vagal stimulation, but amplitudes were smaller and rise times were longer, suggesting passive "volume conduction" from the proximal esophagus. Comparison of laryngeal, pharyngeal, and esophageal early EMG responses showed similar amplitudes and rise times, suggesting that the action potentials were generated locally at each site and that true esophageal responses were being detected.

Adult↗

Reorganization of cortical blood flow and transcranial magnetic stimulation maps in human subjects after upper limb amputation.

1. Two complimentary techniques were used to study cortical function in six human upper limb amputees: positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) were made in subjects during limb movements to study activation of the primary motor (M1), primary somatosensory (S1), and association cortices; and electromyographic responses to transcranial magnetic stimulation (TMS) were measured in proximal upper limb muscles to assess the excitability of corticospinal neurons in subjects at rest. 2. To explore possible cortical mechanisms governing the phantom limb phenomenon, PET and TMS findings were compared between subjects with acquired, traumatic upper limb amputations (n = 3), in whom phantom limb symptoms were prominent, and congenital upper limb amputees (n = 3) without phantom limbs. 3. Paced shoulder movements were associated with significant blood flow increases in the contralateral M1/S1 cortex of both groups of amputees. In traumatic amputees, these increases were present over a wider area and were of significantly greater magnitude in the partially deafferented cortex contralateral to the amputation. In congenital amputees blood flow increases were also present over a wider area in the partially deafferented M1/S1 cortex, but their magnitude was not significantly different from that in the normally afferented M1/S1 cortex. 4. Abnormal blood flow increases also were present in the partially deafferented M1/S1 cortex of traumatic amputees during movement of the ipsilateral, intact arm. Abnormal ipsilateral M1/S1 responses were not present during movement of the intact arm in the congenital group. 5. TMS studies showed that the abnormal blood flow increases in the partially deafferented M1 cortex of traumatic amputees were associated with increased corticospinal excitability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cortical function in progressive lower motor neuron disorders and amyotrophic lateral sclerosis: a comparative PET study.

OBJECTIVE: To compare cortical function at rest and during limb movement in patients with progressive lower motor neuron degeneration (LMND) and amyotrophic lateral sclerosis (ALS). METHODS: PET was used to measure regional cerebral blood flow (rCBF) in five patients with progressive LMND, six patients with classic ALS with a similar degree of motor impairment, and six age-matched control subjects; measurements were taken in the resting state and while subjects moved a joystick with their right hand. RESULTS: rCBF at rest in the primary sensorimotor cortex (SMC) was significantly (p < 0.001) lower in ALS patients than in control subjects or LMND patients. rCBF at rest did not differ significantly between LMND patients and controls. During joystick movement, ALS patients showed significantly (p < 0.001) greater rCBF increases than controls or LMND patients in the hand/arm area of the SMC bilaterally, the face area of the contralateral SMC, the second somatic sensory (SII) cortex bilaterally, and the contralateral premotor and supplementary motor cortices. LMND patients showed significantly (p < 0.001) greater rCBF increases than controls and ALS patients only in the anterior insular cortex bilaterally. CONCLUSIONS: The finding of reduced rCBF at rest, together with abnormal bilateral activation and altered somatotopy during movement, in the sensorimotor cortex of ALS but not LMND patients suggests that these abnormalities reflect loss of pyramidal neurons. Abnormal activation of perisylvian areas (insular and SII cortices) during limb movement in both LMND and ALS patients suggests that these may be accessory sensorimotor areas that are recruited nonspecifically in response to limb weakness.

Adult↗

Modulation of postural wrist tremors by magnetic stimulation of the motor cortex in patients with Parkinson's disease or essential tremor and in normal subjects mimicking tremor.

The effect of magnetic brain stimulation on postural wrist tremor was studied in 10 patients with Parkinson's disease, 12 with hereditary essential tremor, and 10 normal subjects who mimicked tremor by making rapid alternating wrist movements. In all patients and normal subjects, magnetic brain stimulation over the contralateral motor cortex at an intensity approximately 10% above threshold produced the following sequence of events: (1) a small direct electromyographic (EMG) response, followed by (2) suppression of the rhythmic EMG activity responsible for the tremor, before (3) reappearance of the tremor time-locked to the stimulus. It is concluded that magnetic brain stimulation over the motor cortex can modulate the oscillatory mechanisms responsible for the generation of postural tremors. Group analysis revealed that the time to reappearance of rhythmic EMG activity varied significantly with the period of parkinsonian postural tremors, but not with the period of essential or mimicked tremors. Magnetic stimulation also significantly shortened the period of parkinsonian postural tremors, but did not influence the period of essential or mimicked tremors. These behavioral differences indicate differences in the pathophysiological mechanisms underlying parkinsonian postural tremor and essential tremor.

Adult↗

Effectiveness of piracetam in cortical myoclonus.

Twenty-one patients with disabling spontaneous, reflex, or action myoclonus due to various causes, who had shown apparent clinical improvement on introduction of piracetam, entered a placebo-controlled double-blind crossover trial of piracetam (2.4-16.8 g daily). All but one patient had electrophysiological evidence of cortical myoclonus. Patients were randomly allocated to a 14-day course of piracetam followed by identical placebo, or placebo followed by piracetam. Nineteen patients received piracetam/placebo in addition to their routine antimyoclonic treatment (carbamazepine, clonazepam, phenytoin, primidone, sodium valproate, or tryptophan plus isocarboxazid, alone or in combination) and two received piracetam/placebo as monotherapy. All patients were rated at the end of each treatment phase using stimulus sensitivity, motor, writing, functional disability, global assessment, and visual analogue scales. Ten of the 21 patients had to be rescued from the placebo phase of the trial because of a severe and intolerable exacerbation of their myoclonus. No patients required rescue from the piracetam phase of the double-blind trial. When the 21 patients were considered together, there was a significant improvement in motor, writing, functional disability, global assessment, and visual analogue scores during treatment with piracetam compared with placebo. The total rating score also improved significantly with piracetam, by a median of 22%. Piracetam, usually in combination with other antimyoclonic drugs, is a useful treatment for myoclonus of cortical origin.

Adult↗

Postural electromyographic responses in the arm and leg following galvanic vestibular stimulation in man.

Application of a small (around 1 mA), constant electric current between the mastoid processes (galvanic stimulation) of a standing subject produces enhanced body sway in the approximate direction of the ear behind which the anode is placed. We examined the electromyographic (EMG) responses evoked by such stimulation in the soleus and in the triceps brachii muscles. For soleus, subjects stood erect, with their eyes closed, leaning slightly forward. The head was turned approximately 90 degrees to the right or left relative to the feet. In averaged records (n = 40), current pulses of 25 ms or longer modulated the EMG in a biphasic manner: a small early component (latency 62 +/- 2.4 ms, mean +/- SEM) was followed by a larger late component (latency 115 +/- 5.2 ms) of opposite sign, which was appropriate to produce the observed body sway. The early component produced no measurable body movement. Lengthening the duration of the stimulus pulse from 25 to 400 ms prolonged the late component of the response but had little effect on the early component. Short- and long-latency EMG responses were also evoked in the triceps brachii muscle if subjects stood on a transversely pivoted platform and had to use the muscle to maintain their balance in the anteroposterior plane by holding a fixed handle placed by the side of their hip. The latency of the early component was 41 +/- 2.6 ms; the latency of the late component was 138 +/- 4.3 ms and was again of appropriate sign for producing the observed body sway. Galvanic stimulation evoked no comparable responses in either triceps brachii or soleus muscles if these muscles were not being used posturally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Transcranial electric and magnetic stimulation of the leg area of the human motor cortex: single motor unit and surface EMG responses in the tibialis anterior muscle.

We compared single motor unit and surface EMG responses in the active right tibialis anterior following anodal electrical or magnetic stimulation of the motor cortex over the vertex. Magnetic stimulation used a monophasic current pulse through a circular coil centred 3 cm anterior to the vertex. Lowest threshold magnetic stimulation occurred when the current in the coil flowed from the left to the right side at the posterior rim of the coil. Such stimulation produced single unit and surface EMG responses which had the same latency as those produced by anodal electric stimulation. If the direction of the magnetic stimulating current was reversed, response latencies became more variable from unit to unit, and on average they occurred 1.0 +/- 0.5 msec later. In single motor units anodal and magnetic post-stimulus time histogram (PSTH) peaks had the same duration. This was similar to the duration of the PSTH peaks produced by a single low intensity stimulus given to the common peroneal nerve. We conclude that magnetic stimulation can produce direct activation of corticospinal neurones to the tibialis anterior if the direction of induced current flow is optimal. This projection is likely to be either monosynaptic or oligosynaptic.

Adult↗

The effect of transcranial magnetic stimulation on median nerve somatosensory evoked potentials.

Somatosensory evoked potentials (SEPs) evoked by electrical stimulation of the median nerve at the wrist were conditioned by a preceding magnetic stimulus given over the contralateral central scalp using interstimulus intervals of 0-50 msec. The conditioning stimulus had no effect on the size of sub-cortical or N20 components of the response, but caused a large increase in the P25 parietal wave. Later components (P40/N65) of the SEP were reduced in size. The optimum position for producing the effect was with the magnetic stimulator held over the best point on the scalp for evoking muscle responses in the contralateral hand. The threshold for affecting the SEP was approximately the same as the threshold for evoking EMG responses in active hand muscles. We conclude that the magnetic conditioning shock changed the excitability of somatosensory cortex neurones involved in producing the P25. The subsequent decrease in the later components of the SEP may be related to the increase in somatosensory detection thresholds produced by a conditioning magnetic shock.

Adult↗

Some saccadic eye movements can be delayed by transcranial magnetic stimulation of the cerebral cortex in man.

In 15 normal subjects we investigated the effect on visually guided saccadic eye movements of giving a single transcranial magnetic stimulus through a circular coil centered at the vertex. In the normal paradigm, subjects fixated a target which moved randomly to the left or right by 11 degrees. The mean saccadic reaction time of 189 ms was increased by 40-50 ms if a magnetic stimulus was given in random trials some 60 ms prior to the expected onset time of control saccades. The duration and amplitude of the saccades was unchanged. The delay was smaller if the stimulus was given earlier in the reaction period, or if the coil was moved anterior or posterior to the vertex. Larger stimulus intensities produced longer delays. Three subjects were trained to produce express saccades (mean saccadic reaction times of 107-141 ms) in a 'gap' paradigm. The latency of these saccades, which are thought to be mediated by collicular mechanisms without involvement of the cortex, was not affected by magnetic stimulation. This suggests that magnetic stimulation delays normal visually guided saccades by an action on the cerebral cortex, rather than on the oculomotor centres of the brainstem. Five subjects made non-targeted saccades in darkness in response to an auditory stimulus. These saccades, like visually guided saccades, could be delayed by magnetic brain stimulation. We conclude that saccadic delay is produced by interference with cortical areas involved in the execution of saccades rather than by interfering with the perception of the visual or auditory 'go' stimulus. These probably include supplementary and frontal eye field and posterior parietal cortex. The fact that visually guided saccades emerged intact after the delay indicates that the instructions for amplitude and direction were stored separately from those involved in timing when the movement was to occur.

Acoustic Stimulation↗

Evoked potentials, magnetic stimulation studies, and event-related potentials.

With the technique of transcranial magnetic stimulation it is possible to study the function of motor pathways in normal subjects and in patients with neurologic disease. In conjunction with both evoked and event-related potentials, transcranial magnetic stimulation can be used to probe the processes involved in analyzing sensory input and in preparing for motor output.

Afferent Pathways↗

Corticocortical inhibition in human motor cortex.

1. In ten normal volunteers, a transcranial magnetic or electric stimulus that was subthreshold for evoking an EMG response in relaxed muscles was used to condition responses evoked by a later, suprathreshold magnetic or electric test shock. In most experiments the test stimulus was given to the lateral part of the motor strip in order to evoke EMG responses in the first dorsal interosseous muscle (FDI). 2. A magnetic conditioning stimulus over the hand area of cortex could suppress responses produced in the relaxed FDI by a suprathreshold magnetic test stimulus at interstimulus intervals of 1-6 ms. At interstimulus intervals of 10 and 15 ms, the test response was facilitated. 3. Using a focal magnetic stimulus we explored the effects of moving the conditioning stimulus to different scalp locations while maintaining the magnetic test coil at one site. If the conditioning coil was moved anterior or posterior to the motor strip there was less suppression of test responses in the FDI. In contrast, stimulation at the vertex could suppress FDI responses by an amount comparable to that seen with stimulation over the hand area. With the positions of the two coils reversed, conditioning stimuli over the hand area suppressed responses evoked in leg muscles by vertex test shocks. 4. The intensity of both conditioning and test shocks influenced the amount of suppression. Small test responses were more readily suppressed than large responses. The best suppression was seen with small conditioning stimuli (0.7-0.9 times motor threshold in relaxed muscle); increasing the intensity to motor threshold or above resulted in less suppression or even facilitation. 5. Two experiments suggested that the suppression was produced by an action on cortical, rather than spinal excitability. First, a magnetic conditioning stimulus over the hand area failed to produce any suppression of responses evoked in active hand muscles by a small (approximately 200 V, 50 microsecond time constant) anodal electric test shock. Second, a vertex conditioning shock had no effect on forearm flexor H reflexes even though responses in the same muscles produced by magnetic cortical test shocks were readily suppressed at appropriate interstimulus intervals. 6. Small anodal electric conditioning stimuli were much less effective in suppressing magnetic test responses than either magnetic or cathodal electric conditioning shocks.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Modulation of postural tremors at the wrist by supramaximal electrical median nerve shocks in essential tremor, Parkinson's disease and normal subjects mimicking tremor.

The response of postural wrist tremors to supramaximal median nerve stimulation was examined in patients with hereditary essential tremor (n = 10) and Parkinson's disease (n = 9), and in normal subjects mimicking wrist tremor (n = 8). The average frequency of on-going tremor was the same in all three groups. Supramaximal peripheral nerve shocks inhibited and then synchronised the rhythmic electromyographic (EMG) activity of all types of tremor. The duration of inhibition ranged from 90 to 210ms, varying inversely with the frequency of on-going tremor. There was no significant difference in mean duration of inhibition or in the timing of the first peak after stimulation on the average rectified EMG records between the three groups. The degree to which supramaximal peripheral nerve shocks could modulate the timing of rhythmic EMG bursts in the forearm flexor muscles was also quantified by deriving a resetting index. No significant difference in mean resetting index of the three groups was found. These results suggest that such studies cannot be used to differentiate between the common causes of postural wrist tremors.

Adult↗

Assessing tremor severity.

A clinical rating scale which measured the severity of tremor in 20 patients (12 with essential tremor and 8 with "dystonic" tremor) was assessed at specific anatomical sites for both inter and intra-rater reliability using four raters. The scores obtained with the scale were compared with the results of upper limb accelerometry, an activity of daily living self-questionnaire and estimates of the tremor induced impairment in writing and drawing specimens. The results show that, for the purposes of routine assessment and therapeutic trials, a clinical rating scale can produce reliable results which are a more valid index of tremor induced disability than standard postural accelerometry.

Activities of Daily Living↗

The Bereitschaftspotential preceding simple foot movement and initiation of gait in Parkinson's disease.

We compared the Bereitschaftspotential preceding a simple foot movement while sitting and a stepping movement while standing in a group of normal subjects and seven patients with mild to moderate Parkinson's disease (PD) while off medication. None had major difficulties stepping to initiate gait. Electromyographic signals from tibialis anterior triggered the averaging of electroencephalographic signals from the scalp. Bereitschaftspotential preceding a standing stepping movement were larger than those before a foot movement while sitting in normal subjects, but no difference was observed in patients with PD. The absence of an increase in the Bereitschaftspotential when stepping in PD may reflect an impairment of the preparation and assembly of the complex sequences of movement necessary to initiate walking, even in the early stages of the illness.

Adult↗

Transplantation of fetal dopamine neurons in Parkinson's disease: one-year clinical and neurophysiological observations in two patients with putaminal implants.

Ventral mesencephalic tissue from aborted human fetuses (age, 6-7 weeks' postconception) was implanted unilaterally into the putamen using stereotaxic surgery in 2 immunosuppressed patients (Patients 3 and 4 in our series) with advanced idiopathic Parkinson's disease. Tissue from 4 fetuses was grafted to each patient. Compared with our previous 2 patients, the following changes in the grafting procedure were introduced: the implantation instrument was thinner, more tissue was placed in the operated structure, and the time between abortion and grafting was shorter. There were no postoperative complications. Both patients showed a gradual and significant amelioration of parkinsonian symptoms (most marked in Patient 3) starting at 6 and 12 weeks after grafting, respectively, reaching maximum stability at approximately 4 to 5 months; patients remained relatively stable thereafter during the 1-year follow-up period. Clinical improvement was observed as a reduction of the time spent in the "off" phase and the number of daily "off" periods; a lessening of bradykinesia and rigidity during the "off" phase, mainly but not solely on the side contralateral to the graft; and a prolongation and change in the pattern of the effect of a single dose of L-dopa. Neurophysiological measurements revealed a more rapid performance of simple and complex arm and hand movements bilaterally, but primarily contralateral to the graft. The results indicate that patients with Parkinson's disease can show significant and sustained improvement of motor function after intrastriatal implantation of fetal dopamine-rich mesencephalic tissue. The accompanying paper by Sawle and colleagues describes the results of repeated positron emission tomography scans in these patients.

Combined Modality Therapy↗

"Resetting" of postural tremors at the wrist with mechanical stretches in Parkinson's disease, essential tremor, and normal subjects mimicking tremor.

The response of postural wrist tremors to brief mechanical displacements was compared in two groups of patients, one with classical hereditary essential tremor (n = 18) and another with typical Parkinson's disease (n = 13). These groups were compared with an additional group of normal subjects mimicking wrist tremor (n = 9). The degree to which brief mechanical displacements of the wrist produced by torque pulses of three different sizes could modulate the timing of rhythmic electromyographic bursts in the forearm flexor muscles was quantified by deriving a resetting index, which could range between 0 (no phase resetting) and 1 (complete phase resetting). In all three groups of subjects studied, the resetting index varied significantly with the size of the mechanical perturbation and, in an inverse fashion, with the ongoing tremor amplitude. When due allowance for these factors was made, the difference in mean resetting indexes between the three groups of patients and subjects was reduced to the extent that no definitive statement could be made as to whether brief mechanical perturbations had more effect on essential tremor than parkinsonian tremor. The method is therefore unlikely to be useful in differentiating the common causes of postural wrist tremors.

Adult↗

Voluntary stimulus-sensitive jerks and jumps mimicking myoclonus or pathological startle syndromes.

Five patients who presented with stimulus-induced jerking as part of an apparent myoclonic or pathological startle syndrome are reported. Neurophysiological observations in these patients suggested the jerks were voluntary in origin. These included (a) variable latencies to the onset of stimulus induced jerks, (b) latencies were greater than that seen in reflex myoclonus of cortical or brainstem origin, and were (c) longer than the fastest voluntary reaction times of normal subjects, (d) variable patterns of muscle recruitment within each jerk and, (e) significant habituation with repeated stimulation. It is argued that these features are consistent with a voluntary origin for the jerks and enable them to be distinguished from the stereotyped electrophysiological characteristics of myoclonus of cortical and brainstem origin. Electrophysiological recordings may help identify patients with this form of psychogenic movement disorder.

Adult↗