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Biomedical subjects

J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 253 records · Page 14Linked to original sources
PubMed1991

Modulation of motor cortical excitability by electrical stimulation over the cerebellum in man.

1. We have stimulated over the cerebellum of intact human subjects by applying single electrical stimuli through electrodes placed on the back of the head, approximately at the level of the inion. The intensity of stimulation used was below that required to produce direct EMG responses in pre-activated muscles of the hand. 2. In ten subjects the effect of the stimulus over the cerebellum was to reduce the size of the EMG response in first dorsal interosseous muscle evoked by a magnetic stimulus to the cerebral cortex. In all subjects the onset of the period of suppression occurred when the test magnetic cortical shock followed the conditioning cerebellar shock by 5 ms. The duration of the suppression lasted from 3 to 7 ms. 3. The amount of suppression was related to the intensity of stimulation over the cerebellum. At 15% below the threshold for direct motor activation there was no effect; increasing suppression was evident at 10, 5 and 0% below motor threshold. 4. With a conditioning-test interval of 5-6 ms the suppression was the same whether the target muscle was relaxed or active. With longer conditioning-test intervals (12 and 15 ms) the amount of suppression was greater in active than relaxed muscles. 5. The short-latency suppression was greatest when the stimulating anode was ipsilateral to the target muscle and contralateral to the stimulated sensorimotor cortex. The later period of suppression was insensitive to the polarity of stimulation. When the stimulating electrodes were moved 2 cm caudally or cranially the short latency suppression disappeared whereas the longer latency suppression was still observed with the electrodes in the lower position. 6. Different results were obtained when the test EMG response was produced by an electrical (rather than magnetic) stimulus over the sensorimotor cortex. The short latency effect was no longer visible whereas the longer latency effect was the same as when testing with a magnetic cortical stimulus. 7. We suggest that a single electrical stimulus across the base of the skull (particularly with the anode over one cerebellar hemisphere) produces a short latency (5-6 ms) disfacilitation of the contralateral motor cortex through activation of cerebellar structures. A later (12 and 15 ms), less specific suppression which is present when testing in active muscles is thought to be mediated by a different mechanism and probably produces its effect at the level of the spinal cord.

Action Potentials↗
PubMed1991

The effect of posture on the normal and pathological auditory startle reflex.

The effect of posture on the EMG pattern of the normal auditory startle reflex was investigated. The startle response to an unexpected auditory tone was studied in eleven normal subjects when standing, and in six normal subjects when sitting relaxed or tonically plantar flexing both feet. Reflex EMG activity was recorded in the tibialis anterior and soleus about twice as frequently when standing, than when sitting relaxed. In addition, the median latencies to onset of reflex EMG activity in the tibialis anterior and soleus were about 40 and 60 ms shorter during standing, than when sitting relaxed. No short latency EMG activity was recorded in the calf muscles during tonic plantar flexion of the feet, while sitting. The effect of posture on the EMG pattern of the pathological auditory startle reflex was studied in five patients with hyperekplexia. In three patients the latency to onset of reflex EMG activity in the tibialis anterior was shorter when standing, than when sitting relaxed. The EMG pattern of the reflex response to sound was studied in detail in two of these patients and consisted of up to three successive components. The expression of each EMG component depended on the postural set of the limbs. In particular, a distinct short latency component was found in posturally important muscles following auditory stimulation. This short latency component was not recorded when sitting relaxed. It is concluded that the EMG pattern of the physiological and pathological auditory startle response is not fixed, but may change with the postural stance of the body. This finding supports the theory that the normal startle reflex and the abnormal startle reflex in hyperekplexia have a common brainstem origin.

Adolescent↗
PubMed1991

Intra-operative recording of motor tract potentials at the cervico-medullary junction following scalp electrical and magnetic stimulation of the motor cortex.

Activity in descending motor pathways after scalp electrical and magnetic brain stimulation of the motor cortex was recorded from the exposed cervico-medullary junction in six patients having trans-oral surgery of the upper cervical spine. Recordings during deep anaesthesia without muscle paralysis revealed an initial negative potential (D wave) at about 2 ms with electrical stimulation in five of the six patients. This was followed by a muscle potential which obscured any later waveforms. Magnetic stimulation produced clear potentials in only one patient. The earliest wave to magnetic stimulation during deep anaesthesia was 1-2 ms later than the earliest potential to electrical stimulation. Following lightening of the anaesthetic and the administration of muscle relaxants a series of later negative potentials (I waves) were more clearly seen to both electrical and magnetic stimulation. More I waves were recorded to magnetic stimulation during light anaesthesia than during deep anaesthesia. Increasing the intensity of electrical stimulation also produced an extra late I wave. At the highest intensity of magnetic stimulation the latency of the earliest potential was comparable to the D wave to electrical stimulation. The intervals between these various D and I waves corresponded to those previously described for the timing of single motor unit discharge after cortical stimulation.

Adult↗
PubMed1991

Physiological studies of electric and magnetic stimulation of the human brain.

It is suggested that transcranial electric stimulation can activate pyramidal tract projections both directly and indirectly in a manner similar to that described after direct stimulation of the exposed cortex in the monkey. This produces both D- and I-waves in the pyramidal tract. At high intensities of stimulation, the stimulus can spread into the brain and activate pyramidal tract axons several centimeters below the cortical surface. Magnetic stimulation at moderate intensities produces electromyographic (EMG) responses with latencies 1-2 msec longer than those after electric stimulation. Two possible explanations have been put forward to account for this effect: (1) because of the difference in the direction of electric current flow induced in the brain by the 2 forms of stimulation, magnetic stimulation preferentially excites pyramidal tract cells indirectly, and hence evokes only I-waves in the pyramidal tract. (2) Electric stimulation (even at threshold) activates pyramidal axons deep in the white matter, whereas magnetic stimulation activates the pyramidal cells in the gray matter, probably at their initial segment. There is one interesting consequence common to both explanations. Whether magnetic stimulation activates the pyramidal neurons transsynaptically or at their initial segment, the size of the descending volley evoked will depend on the level of excitability of the motor cortex. In contrast, the response to electric stimulation will be less affected, since a proportion of the descending volley is initiated directly at the axon of the pyramidal cell. This differential effect of cortical excitability on the responses to electrical and magnetic stimulation can be useful in describing excitatory or inhibitory influences on motor cortex from other structures.

Action Potentials↗
PubMed1991

Axial myoclonus of propriospinal origin.

Three patients are described with nonrhythmic repetitive axial myoclonic jerks causing symmetric flexion of the neck, trunk, hips and knees. No electrophysiological evidence of a cortical or brainstem reticular origin for the myoclonus was found. In the first patient the axial jerks only occurred spontaneously. The latencies of recruitment of spinal segments during a jerk indicated that the discharge arose in the mid thoracic cord and then slowly spread at about 5 ms-1 up and down the cord to involve rostral and caudal segments. No structural lesion was identified in this patient. In the second patient spontaneous and reflex axial jerks developed following the excision of a cervical haemangioblastoma. In the stimulus-induced jerks the relative latencies of muscles innervated by rostral and caudal spinal segments suggested that the myoclonus originated between the upper cervical and midthoracic cord. In the final patient, EMG activity during spontaneous and stimulus-induced jerks commenced in the rectus abdominis, and was followed by later activity in muscles innervated by rostral spinal segments, suggesting that the myoclonus originated in the midthoracic cord. No structural lesion was identified in this patient. Electrophysiological evidence is used to argue a spinal origin for these axial jerks in all 3 cases. There are striking features common both to this form of human myoclonus and to long propriospinal pathways identified in animals. The new concept of propriospinal myoclonus is suggested.

Adult↗
PubMed1990

Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease.

Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-[18F]fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the "on-off" phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.

Brain↗
PubMed1990

The blink reflex in patients with idiopathic torsion dystonia.

The blink reflex and its recovery cycle were examined in 57 patients with idiopathic dystonia affecting different parts of the body. The group comprised 9 patients with generalized and 15 with segmental forms, 19 with torticollis, and 14 with focal arm dystonia. None had blepharospasm. The duration and amplitude of the R2 component of the blink reflex showed only minor changes. However, its recovery cycle to paired supraorbital nerve stimuli was abnormal in all groups of patients, except those with focal arm dystonia. These findings may be interpreted as showing abnormal control of the interneuronal networks mediating the blink reflex in patients with dystonia affecting sites other than the facial muscles. The fact that the principal changes were seen in patients with torticollis, and generalized or segmental dystonia, suggests that the extent of dystonia (rather than the severity) and, therefore, the close proximity to the cranial muscles was important in determining the extent of the abnormal interneuron function.

Arm↗
PubMed1990

Diaphragmatic flutter, the moving umbilicus syndrome, and "belly dancer's" dyskinesia.

Five patients presenting with focal abnormal involuntary movements of the abdominal wall are described. One was shown to have diaphragmatic flutter, which may represent a variant of the palatal myoclonus syndrome. The other four had writhing movements and contractions of the abdominal wall at frequencies of approximately 30 per minute. In two of the latter cases, these abdominal movements were profoundly influenced by respiratory manoeuvres. They were quite unlike the movements of spinal myoclonus or axial torsion dystonia. None of the patients were taking drugs that might have provoked their abnormal movements, or had any other evidence of neurological deficit. No cause was established in any of the cases.

Abdominal Muscles↗
PubMed1990

Cortical outflow to proximal arm muscles in man.

Corticospinal influences on two antagonistic muscles of the shoulder were studied in 6 normal volunteers. Recordings were made of the discharges of single motor units from the deltoid and pectoralis major muscles and poststimulus time histograms constructed following either anodal electrical or magnetic cortical stimulation via the scalp. Contralateral anodal stimulation caused narrow short-latency peaks of excitation in motor units from both muscles, probably indicative of the arrival of the D or direct corticospinal volley. The size of the peaks led to estimates of the underlying excitatory postsynaptic potentials (EPSP) amplitude of 5.5 mV for the deltoid and 2.2 mV for the pectoralis motor units. Magnetic stimulation over the vertex caused multiple early peaks of excitation in motor units from both muscles but these peaks began at a greater latency than those produced by anodal stimulation. Additionally, magnetic cortical stimulation (and, occasionally, contralateral anodal stimulation) caused a previously undescribed period of medium latency excitation in both muscles. These medium latency periods of excitation differed from the earlier events in that they occurred independently of the direction of current flow in the magnetic coil. This raises the possibility that they are the consequence of stimulation of bilaterally distributed cortical motor outflow pathways. The short-latency excitation strongly suggests that, in man, corticomotoneuronal projections exist to proximal as well as distal muscles of the contralateral arm. The strength of the projection to deltoid assessed by this method is similar to that to an intrinsic muscle of the hand and significantly larger than that to its antagonist, pectoralis. The possible bilateral organization of the additional medium-latency projection to these proximal arm muscles may contribute to two characteristic clinical features after a unilateral cerebral lesion, such as stroke: the relative sparing of proximal arm strength compared with distal and, secondly, ipsilateral weakness.

Adult↗
PubMed1990

Cutaneous effects on presynaptic inhibition of flexor Ia afferents in the human forearm.

1. In six subjects, H reflexes obtained in the flexor muscles in the forearm were inhibited by single motor threshold shocks to the radial nerve in the spiral groove. The first two phases of the inhibitory time course were studied: with intervals between the radial and median nerve shocks of -1 to +1 ms, and +5 to +30 ms. These two phases are thought to be due respectively to disynaptic inhibition between radial Ia afferents and flexor alpha-motoneurones, and to presynaptic inhibition of flexor Ia afferents. 2. Single or short trains (10 ms, 400 Hz) of cutaneous stimuli to the dorsal or palmar aspect of the proximal phalanx of the index finger or to the superficial radial nerve at the wrist, reduced the amount of presynaptic inhibition by 10-20%, but had no effect on the earlier disynaptic inhibition. Single stimuli to either side of the index finger or trains of stimuli to the ventral side, had no effect on the size of control H reflexes elicited alone. 3. Effects of cutaneous nerve shocks on presynaptic inhibition could be seen with stimuli as small as 1.5 x perceptual threshold. 4. Anaesthesia of the hand in one subject reversibly increased the amount of presynaptic inhibition and decreased the amount of disynaptic inhibition. 5. We conclude that, as in the cat, cutaneous input can modulate transmission in presynaptic inhibitory pathways in man.

Adult↗
PubMed1990

Activation of fusimotor neurones by motor cortical stimulation in human subjects.

1. Neural recordings were made from motor fascicles of the ulnar or radial nerves while the motor cortex was stimulated percutaneously using high-voltage electrical stimuli or transient magnetic pulses to determine whether human muscle spindle endings could be activated by such stimuli and, if so, whether this occurred before the recruitment of alpha-motoneurones. 2. In relaxed subjects, no evidence of muscle spindle activation could be detected in nine recordings of multiunit neural activity and four recordings from single spindle afferents using stimulus levels up to 600 V and 1.5 T. These levels produced a prominent twitch contraction of the intrinsic muscles of the hand and of forearm muscles. Passive stretch of the contracting muscle did not reveal a fusimotor action too weak to be detected under isometric circumstances. 3. With twenty-six single spindle afferents, the stimuli were delivered during a voluntary contraction of the receptor-bearing muscle. This served to 'focus' the effects of the stimulus on the relevant motoneurone pools and increased the probability that fusimotor neurones innervating the endings were active. 4. None of the twenty-six spindle afferents could be activated by stimuli subthreshold for alpha-motoneurones, even when the stimuli were delivered during passive stretch of the contracting muscle. With eighteen afferents, stimuli above threshold for alpha-motoneurones were delivered: twelve remained unaffected but the discharge of six altered. 5. Three afferents were activated at latencies of 35, 39 and 40 ms, respectively 16, 20 and 20 ms after the onset of the EMG potentials in the receptor-bearing muscles. This latency difference is too short to be attributable to activation of gamma-motoneurones: arguments are presented that the increase in spindle discharge could result from activation of beta-motoneurones. 6. The discharge of three afferents increased at latencies of 70, 75 and 85 ms, too early to be due to stretch on the falling phase of the twitch contraction of the receptor-bearing muscle. Responses at these latencies could involve activation of gamma- or beta-motoneurones. 7. These findings in human subjects suggest that transient stimulation of the motor cortex may effectively access fusimotor neurones.

Action Potentials↗
PubMed1989

Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up.

By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.

Contingent Negative Variation↗
PubMed1989

Interruption of motor programmes by electrical or magnetic brain stimulation in man.

These experiments describe the effect on voluntary movement of an electrical or magnetic stimulus delivered to the brain through the scalp. Subjects were trained to flex or extend their wrists as rapidly as possible in response to an auditory tone. A single brain stimulus delivered after the tone, and before the usual time of onset of the voluntary reaction, could delay the movement for up to 150 ms, without affecting the pattern of agonist and antagonist EMG bursts. Movement was not delayed when similar experiments were performed with supramaximal stimulation of the median nerve instead of the brain stimulus. The delay following a cortical shock was not due to spinal motoneurones being inaccessible to input during the delay, since H-reflexes given in the middle of the delay period were capable of activating the muscle. Neither could the delay be explained by the brain stimulus altering the time of the subject's intention to respond, since a stimulus delivered to one hemisphere prior to an attempted simultaneous bilateral wrist movement produced a far greater delay on the contralateral than the ipsilateral side. We suggest that the brain stimulus delayed movement by inhibiting a group of strategically placed neurones in the brain (probably in the motor cortex) which made them unresponsive for a brief period to the command signals which initiate agonist and antagonist muscle activity.

Cerebral Cortex↗
PubMed1989

The Bereitschaftspotential is abnormal in Parkinson's disease.

The average Bereitschaftspotential (BP) preceding a rapid, self-paced voluntary extension movement of the index finger was recorded from 6 scalp locations in 14 patients with Parkinson's disease who had been withdrawn from their normal drug therapy for at least 12 h before testing. The amplitude of the potential was measured at the peak negativity (N1) and 650 ms prior to this (NS1), and compared with that recorded in a group of 12 age-matched control subjects. The N1 amplitude was the same as in the normals, but the NS1 component was smaller in the patients, especially in midline leads. As a result, the rise in the BP between the peak NS1 and N1 component (termed NS2) was larger in the patient group. The NS1 component of the BP is thought to reflect preparatory activity in the supplementary motor area (SMA) of cortex. Since the basal ganglia provide a major source of afferent input to SMA, the reduction in NS1 in the patients probably results from inadequate basal ganglia activation of SMA. The larger NS2 component may reflect extra activity in other brain areas to compensate for the reduced SMA activity.

Aged↗
PubMed1989

Delay in the execution of voluntary movement by electrical or magnetic brain stimulation in intact man. Evidence for the storage of motor programs in the brain.

Experiments were undertaken to study the effect on voluntary movement of an electrical or magnetic stimulus delivered to the brain through the scalp. Subjects were trained to flex or extend their wrist rapidly in response to an auditory tone. A single brain stimulus (electrical or magnetic) delivered after the tone and before the usual time of onset of the voluntary reaction could delay the execution of the movement for up to 150 ms, without affecting the pattern of the agonist and antagonist EMG bursts. The delay increased with increasing stimulus intensity and with stimuli which were applied nearer to the usual time of onset of the voluntary reaction. A stimulus given after the onset of the first voluntary agonist EMG burst only delayed the onset of the first antagonist and later EMG bursts. Movement was not delayed when similar experiments were performed with supramaximal stimulation of the median nerve instead of the brain stimulus. The delay following a cortical shock was not due to spinal motoneurons being inaccessible to descending input during the delay period since a second brain stimulus, given in the middle of the delay period, was capable of producing a direct muscle response. Neither could the delay be explained by the brain stimulus altering the time of the subject's intention to respond since a stimulus delivered to one hemisphere before an attempted simultaneous bilateral wrist movement produced a far greater delay of the contralateral than the ipsilateral movement. We suggest that the brain stimulus delayed movement by inhibiting a group of strategically placed neurons in the brain (probably in the motor cortex) which made them unresponsive for a brief period to the command signals they receive which initiate the motor program of agonist and antagonist muscle activity. The results have implications for the issues of the storage of motor programs, internal monitoring of central movement commands and the site of organization of the antagonist EMG burst.

Adult↗