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Biomedical subjects

P Ashby

Publications and source records attributed to P Ashby.

At least 55 records · Page 3Linked to original sources

Reflex effects from Golgi tendon organ (Ib) afferents are unchanged after spinal cord lesions in humans.

The reflex actions of medial gastrocnemius (MG) group I afferents on soleus motoneurons were examined in 20 normal subjects and 13 patients with well-defined chronic spinal cord lesions. In normal subjects, stimulation of the MG nerve with near-nerve electrodes at or below the threshold of the alpha motoneuron axons resulted in inhibition of the soleus H reflex at a condition-test interval of 6 msec. The central delay was estimated to be 2.5 msec. This inhibition was attributed to Ib afferents. We found that this inhibition was present in patients with spinal cord lesions. This contrasts with previous reports that stimulation of MG afferents facilitates the soleus H reflex in hemiplegic limbs, and it may represent a physiologic difference between cerebral and spinal spasticity.

Adolescent↗

Some spinal mechanisms of negative motor phenomena in humans.

A sudden pause in motoneuron firing can occur (1) because many motoneurons have just discharged, (2) because motoneurons have been directly inhibited, or (3) because there has been a pause in the tonic drive responsible for their activity (Fig. 9) If there is a preceding burst of EMG activity, the silent period may be simply a consequence of inhibitory mechanisms activated by the motoneuron discharge-as from the AHP, Renshaw cell activity, or inhibitory effects from afferents excited by the muscle contraction. If there is no preceding burst of EMG activity, the silent period may be due to direct inhibition of motoneurons. If so, the H-reflex will be inhibited at the time of the silent period with the subject at rest. This inhibition could result from one of the many spinal inhibitory systems. Inhibition from Ia reciprocal inhibitory interneurons may be distinguished from inhibition from interneurons in Ib, group II, or cutaneous afferent pathways by the distribution of their actions to various motoneuron pools. If there is no preceding burst of EMG activity and the H-reflex is not inhibited at the time of the silent period with the subject at rest, then the silent period results from a pause in the tonic drive to motoneurons.

Feedback↗

The processing of human ballistic movements explored by stimulation over the cortex.

1. When seated human subjects abducted one arm rapidly in response to a tone there was successively a burst of electromyographic (EMG) activity in the deltoid and latissimus dorsi muscles followed by another burst in the deltoid muscle. This triphasic pattern is typical of a ballistic 'focal movement'. There were also bursts of EMG activity in the contralateral latissimus dorsi, pectoralis major and abdominal muscles, which were assumed to be 'associated postural adjustments'. The same bilateral pattern of muscle activity occurred in a deafferented subject. 2. When subjects abducted the left arm rapidly, magnetic stimulation over the left motor cortex delayed the onset of the EMG burst in the right latissimus dorsi relative to the initial burst in the left deltoid. When subjects abducted the right arm rapidly, magnetic stimulation over the left motor cortex delayed the onset of the initial EMG burst in the right deltoid relative to the burst in the left latissimus. In each case, the delay of an EMG burst was greatest (about 80 ms) when the stimulus was given just before the burst was expected to occur. The inhibition of voluntary movements by transcranial stimulation was not associated with a reduction in the excitability of spinal motoneurons. 3. We conclude that focal ballistic movements and their associated postural adjustments are generated in exactly the same way. We postulate that these movements are preprogrammed, held in a memory until the 'go' signal and then released through both motor cortices to spinal motoneurons.

Adult↗

Neurodevelopment of children exposed in utero to phenytoin and carbamazepine monotherapy.

OBJECTIVE: To compare pregnancy outcome prospectively after phenytoin and carbamazepine monotherapy with outcome in matched mother-child pairs exposed to nonteratogens to evaluate the relative fetal safety of these drugs. DESIGN: A prospective, controlled, and blinded observational study. PATIENTS: Thirty-six mother-child pairs exposed to carbamazepine monotherapy and 34 pairs exposed to phenytoin monotherapy, all prospectively studied, were compared with mother-child pairs exposed to nonteratogens. The controls were matched for maternal age, time of consultation, obstetric history, and socioeconomic status. MAIN OUTCOME MEASURE: The primary end point of interest was the children's global IQ measured by either the Bayley or the McCarthy scale according to their ages. SETTING: A teratology consultation program and two neurology services in Toronto, Ontario. RESULTS: Children exposed to phenytoin in utero had a mean (+/- SD) global IQ 10 points lower (95% confidence interval, 4.9 to 15.8 points) than their matched controls (113.4 +/- 13.1 and 103.1 +/- 25.1; P = .038). The Reynell language development scores followed a similar trend, with children exposed to phenytoin scoring significantly lower than their controls. Phenytoin-exposed children had a global IQ of 84 or less significantly more often than the control group (P < .01). Children exposed in utero to carbamazepine did not differ from their controls on any of the neurobehavioral tests. CONCLUSIONS: Our study suggests a clinically important negative effect of phenytoin on neurobehavioral development, independent of maternal or environmental factors, causing a substantial number of children to achieve a lower score than expected on cognitive tests. No similar effects could be shown after gestational use of carbamazepine.

Carbamazepine↗

Segmental effects of epidural spinal cord stimulation in humans.

1. The segmental effects of spinal cord stimulation (SCS) were studied in twenty-four human subjects who had spinal cord stimulators implanted for the treatment of pain. The cathode was in the epidural space over the dorsum of the thoracic cord. 2. SCS generated action potentials in sensory, motor and mixed nerves which could be recorded with near-nerve electrodes. These action potentials could follow high frequencies of stimulation and appeared to be due to the antidromic activation of primary afferents in the dorsal columns. 3. Synaptic actions on single lumbosacral motoneurons were derived from peristimulus time histograms (PSTHs) of single motor units. SCS produced a brief short-latency period of increased firing probability (PIF) in motoneurons of all of the muscles examined, probably representing monosynaptic activation. It is argued that the facilitation arises from the antidromic activation of Ia afferents in the dorsal columns. This is the probable explanation for the muscle contractions that can be induced by SCS. 4. SCS inhibited short-latency group I homonymous facilitation and reciprocal inhibition. The mechanism appears to be presynaptic to the motoneurons and may represent collision in Ia afferents, presynaptic inhibition or homosynaptic depression. 5. It was difficult to demonstrate consistent effects of SCS on reflex pathways from cutaneous afferents to flexor motoneurons because the effects of stimulation of cutaneous nerves on these motoneurons were themselves variable. 6. It is concluded that SCS applied with epidural electrodes over the dorsal cord activates primary afferents in the dorsal columns. Antidromic activation of these afferents results in strong monosynaptic facilitation of motoneurons as well as reduction in transmission in some reflex pathways to motoneurons.

Action Potentials↗

Usefulness of single fiber EMG for distinguishing neuromuscular from other causes of ocular muscle weakness.

Consecutive patients (n = 114), who had single fiber electromyography of the frontalis muscles for symptoms suggestive of ocular myasthenia gravis, were followed up for a mean of 14 months (3-64 mos). At follow up, based on strict criteria, 23 patients were classified as having ocular myasthenia gravis, 8 patients were diagnosed as having mitochondrial myopathy or oculopharyngeal dystrophy, 18 patients were found to have other diseases and 65 patients remained without a definite diagnosis. The single fiber electromyography data of these patients were then reviewed. The patients with ocular myasthenia gravis had, on average, more than 7/20 single fiber pairs with jitter > 45 microseconds and mean jitter of 56 microseconds. The 8 patients with mitochondrial myopathy or oculopharyngeal dystrophy had an average of 5/20 single fiber pairs with jitter > 45 microseconds and a mean jitter of 52 microseconds and could not be separated from the group with ocular myasthenia gravis on the basis of the single fiber electromyography results. The 18 patients with definite other diagnosis had an average of less than 1/20 single fiber pair with jitter > 45 microseconds and a mean jitter of 25 microseconds. This group could be clearly separated from the group with ocular myasthenia gravis. We conclude that single fiber electromyelography is useful in the separation of ocular myasthenia gravis from other causes of oculomotor weakness except mitochondrial myopathy and oculopharyngeal dystrophy.

Adult↗

Excitability of human motor cortex during hyperventilation and hypercapnia.

We tested the hypothesis that the excitability of corticospinal neurons was altered by changes in PCO2. Magnetic stimulation was used to excite the neurons in the human motor cortex that give rise to the fast-conducting corticospinal pathway. The characteristics of the composite excitatory postsynaptic potentials (EPSPs) produced in individual spinal motoneurons by cortical stimulation were derived from changes in the firing probability of voluntarily activated motor units. The amplitudes of these composite EPSPs in response to a constant cortical stimulus were assumed to reflect the excitability of cortical neurons. In 10 healthy subjects, we found no statistically significant changes in the excitability of the cortical neurons during normocapnic conditions (mean end-tidal PCO2 5.1 kPa), during hyperventilation-induced hypocapnia (mean end-tidal PCO2 2.9 kPa), and during hyperoxic hypercapnia induced by a rebreathing technique (mean end-tidal PCO2 6.9 kPa). We conclude that the excitability of corticospinal neurons activated by magnetic stimulation is not significantly affected by changes in PCO2.

Adult↗

Effects of cortical stimulation on reciprocal inhibition in humans.

We attempted to demonstrate convergence onto human spinal Ia inhibitory interneurons from Ia afferents and from fast conducting corticospinal axons. Stimulation of the common peroneal nerve at or below the threshold of the alpha motoneuron axons resulted in inhibition of the soleus H-reflex, attributed to reciprocal inhibition. Magnetic stimulation over the contralateral motor cortex resulted in complex modulations of the soleus H-reflex, including a short latency-inhibition. To test for convergence, the two stimuli were given together so that the two inhibitions coincided. When each stimulus alone produced clear inhibition, the inhibition produced by both stimuli was less than expected, implying an interaction between the two volleys, for example, occlusion occurring in interneurons or motoneurons. When the H-reflex was relatively unaffected by one or other conditioning volley, the inhibition produced by the combined stimulation was greater than expected, as might be expected with convergence onto a common pool of interneurons.

Adult↗

Reflex responses in upper limb muscles to cutaneous stimuli.

Cutaneous reflexes in the upper limb were elicited by stimulating digital nerves and recorded by averaging rectified EMG from proximal and distal upper limb muscles during voluntary contraction. Distal muscles often showed a triphasic response: an inhibition with onset about 50 ms (I1) followed by a facilitation with onset about 60 ms (E2) followed by another inhibition with onset about 80 ms (I2). Proximal muscles generally showed biphasic responses beginning with facilitation or inhibition with onset at about 40 ms. Normal ranges for the amplitude of these components were established from recordings on 22 arms of 11 healthy subjects. An attempt was made to determine the afferent fibers responsible for the various components by varying the stimulus intensity, by causing ischemic block of larger fibers and by estimating the afferent conduction velocities. The central pathways mediating these reflexes were examined by estimating central delays and by studying patients with focal lesions.

Adult↗

Ipsilateral fast corticospinal pathways do not account for recovery in stroke.

We tested the hypothesis that in adult humans, recovery from stroke results from the emergence of ipsilateral, fast-conducting corticospinal pathways. In 10 patients recovering from stroke, the unaffected hemisphere was stimulated with an electromagnet and changes in the firing probability of single biceps motor units were used to derive postsynaptic potentials in single biceps motoneurons. Stimuli sufficient to excite the neurons of the fast-conducting corticospinal pathway (as shown by short-latency facilitation of contralateral biceps motoneurons) did not produce short-latency depolarization of ipsilateral biceps motoneurons. The hypothesis is therefore not supported.

Action Potentials↗

Single fiber EMG in the frontalis muscle in ocular myasthenia: specificity and sensitivity.

Patients (n = 41) with isolated weakness of the eyelids or extraocular muscles, who had been referred for single fiber electromyography (SFEMG), were followed up after 4 to 24 months, At follow-up the patients were classified as "definite ocular myasthenia gravis" (MG), "definite other diagnosis," or "no definite diagnosis" on the basis of the completed investigations and subsequent course. The original SFEMG findings in the frontalis muscle were then reviewed. The specificity and sensitivity of SFEMG for "definite ocular MG" could be maximized by using as criteria for abnormality greater than 8/20 pairs with jitter greater than 45 microseconds, or a mean jitter of 20 pairs of greater than 50 microseconds. Patients with abnormal SFEMG according to these criteria have MG, and are likely to require treatment in the immediate future. Patients who have normal SFEMG according to these criteria (and no other demonstrated disorder) may have MG, but it is so mild that they are unlikely to require treatment. Two patients whose final diagnosis was progressive external ophthalmoplegia had normal SFEMG according to these criteria.

Adult↗

Corticospinal projections to lower limb motoneurons in man.

The projections of cortical neurons activated by transcranial magnetic stimulation to single lower limb spinal motoneurons were examined in 34 normal subjects. Peristimulus time histograms of the discharge times of single, voluntarily activated motor units were used to derive information about postsynaptic potentials in single spinal motoneurons produced by magnetic stimuli applied over the contralateral scalp. All tibialis anterior motor units and the majority of motoneurons innervating the small muscles of the foot showed strong short latency facilitation. About half of the motoneurons of proximal lower limb muscles showed this facilitation. Short latency facilitation of the motoneurons of soleus and medial gastrocnemius was only rarely observed and when present was weak. The short latency facilitation is attributed to the projections of the fast corticospinal pathway with monosynaptic projections to motoneurons. The relative strength of the facilitation in different motoneuron pools is considered to reflect the density of corticospinal projections to that motoneuron pool. The observed pattern of projections in man shows some differences from the pattern of projections in subhuman primates that might reflect the different use of the limb.

Cerebral Cortex↗

The transcortical nature of the late reflex responses in human small hand muscle to digital nerve stimulation.

The hypothesis that long-latency reflex activity in human small hand muscles in response to stimulation of digital nerves involves a transcortical pathway was tested by combining digital nerve stimulation and magnetic stimulation over the motor cortex in 12 studies on nine normal subjects. Postsynaptic events in human single first dorsal interosseous (FDI) motoneurones were derived from changes in the firing probability of voluntarily activated single motor units. Electromagnetic stimulation over the contralateral motor cortex resulted in a short-latency, brief facilitation of FDI motor units considered to be due to the activation of "fast" corticospinal neurones making monosynaptic projections to motoneurones. Stimulation of the digital nerves of the index finger produced a period of reduced firing probability (I1), a period of increased firing probability (E2) and a further period of reduced firing probability (I2) in FDI motor units. When the two stimuli were given separately and then together, timed so that the magnetic stimulus occurred at the predicted transit time of the E2 through the cortex, the facilitation of FDI motoneurones by the combined stimulation was often less than the algebraic sum of the facilitations from each stimulus alone. Thus, in contrast to the results of similar studies on the late response to muscle stretch, there is no confirmation that the E2 from digital nerve stimulation is due to a transcortical reflex.

Adult↗

Stimulus-sensitive myoclonus in akinetic-rigid syndromes.

The cutaneous reflexes of upper limb muscles were studied in five patients with Parkinson's disease and 10 patients with stimulus-sensitive myoclonus associated with akinetic-rigid syndromes. The middle finger was stimulated with ring electrodes and rectified electromyographs were averaged from seven upper limb muscles and orbicularis oculi. Responses from subjects with Parkinson's disease without stimulus-sensitive myoclonus were similar to those of normal subjects. The responses from patients with stimulus-sensitive myoclonus associated with Parkinson's disease or multiple system atrophy had the normal pattern except that a long latency facilitation, which is present in normal subjects and known as E2, was greatly exaggerated. Patients with stimulus-sensitive myoclonus associated with cortical-basal ganglionic degeneration had a completely different pattern of responses. There was synchronous activation of all recorded upper limb muscles with latencies substantially shorter than those of the long latency facilitation (E2) in normal subjects. Cutaneous reflex testing may therefore be useful in the differentiation of akinetic-rigid syndromes.

Aged↗

Corticospinal projections to upper limb motoneurones in humans.

1. Magnetic stimulation was applied over the motor cortex in forty-five normal human subjects and peristimulus time histograms (PSTHs) of the discharges of single motor units were used to record changes in the firing probability of individual spinal motoneurones of contralateral upper limb muscles. Recordings were obtained from 153 motor units from fourteen upper limb muscles. 2. For the majority of motor units the initial effect was a short latency facilitation. The estimated central conduction velocities and the rise times of the underlying excitatory postsynaptic potentials (EPSPs) were compatible with monosynaptic facilitation by a fast corticospinal pathway. In some motor units the initial effect was a short latency inhibition. Other units showed no statistically significant changes in firing probability. The proportion of the tested motor units in each of these categories depended on the muscle. All of the sampled units of first dorsal interosseous (1DI) showed short latency facilitation, as did the majority of units in the forearm and the biceps brachii. More than half of the sampled motor units of triceps brachii and deltoid showed either no effect or were inhibited. 3. To compare the net short latency actions of the neurones activated by magnetic stimulation on various motoneurone pools, the magnitude of the short latency facilitation or inhibition in a given motor unit was normalized to the magnitude of the short latency facilitation in the 1DI motor unit of the same subject at the same stimulus intensity, and these data were pooled for a number of subjects. 4. 1DI motoneurones received strong net facilitation (estimated mean EPSP amplitude 2.9 +/- 0.2 mV), the motoneurones of forearm muscles and biceps brachii received weaker net facilitation and triceps brachii and deltoid received no net effect. 5. It is concluded that the short latency corticospinal projections to upper limb motoneurones in humans have a distinct pattern which is similar to that in other primates.

Adult↗

Evidence that a long latency stretch reflex in humans is transcortical.

1. The hypothesis that the long latency reflex response to muscle stretch in humans uses a transcortical pathway was tested by looking for convergence onto cortical neurones in eleven normal subjects. 2. Postsynaptic events in single flexor pollicis longus (FPL) motoneurones were derived from changes in the firing probability of individual FPL motor units. 3. Extension of the terminal phalynx of the thumb resulted in both short latency and long latency facilitations of individual FPL motoneurones. These were not reproduced by electrical stimulation of afferents in the terminal phalynx. Magnetic stimulation over the contralateral motor cortex produced strong, short latency facilitation of FPL motoneurones. 4. When the facilitation produced by stimulation over the cortex was superimposed on the long latency facilitation produced by extension of the thumb, the facilitation produced by both stimuli was greater than the sum of the individual facilitations produced by either stimulus given alone. This was not the case when the superimposition occurred on the short latency response to stretch. 5. We conclude that afferent systems excited by the stretch of FPL converge onto cortical neurones which are known to facilitate motoneurones. Thus the cortex is likely to contribute to the long latency stretch reflex in humans.

Adult↗

Changes in corticospinal facilitation of lower limb spinal motor neurons after spinal cord lesions.

The projections from the cortex to the motor neurons of lower limb muscles were examined in 33 normal subjects and 16 patients with incomplete spinal cord lesions. Corticospinal neurons were excited by transcranial magnetic stimulation and the effects on single spinal motor neurons determined from peristimulus time histograms (PSTHs) of single tibialis anterior (TA) and soleus (SOL) motor units. In normal subjects magnetic stimulation produced a short latency facilitation of TA motor units but had little or no effect on SOL motor units. In the patients with spinal cord lesions magnetic stimulation also produced facilitation of TA but not SOL motor units; however, the mean latency of the TA facilitation was significantly longer (by about 14 ms) in the patient group. The F wave latencies were normal in all patients tested, suggesting that central rather than peripheral conduction was slowed. The duration of the period of increased firing probability (in TA motor units) was also significantly longer in the patients with spinal cord lesions. These changes may reflect the slowing of conduction and dispersal of conduction velocities in the corticospinal pathways as a consequence of the spinal cord lesion. No significant correlations were found between the delay of the TA facilitation and the clinical deficits in this group of patients.

Adolescent↗