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Biomedical subjects

K R Mills

Publications and source records attributed to K R Mills.

At least 73 records · Page 4Linked to original sources
PubMed1991

Responses of single spinal motoneurons to magnetic brain stimulation in healthy subjects and patients with multiple sclerosis.

Magnetic stimuli delivered over the scalp can cause single motor units to discharge in intrinsic hand muscles. The discharge characteristics of 26 tonically active, low threshold single motor units in the first dorsal interosseous muscle of 13 healthy subjects and of 21 motor units in 9 patients with multiple sclerosis (MS) were studied. Up to 500 transcranial magnetic stimuli were delivered at the vertex and were given randomly with respect to, or at a fixed delay after, the previous voluntary discharge. Peristimulus time histograms (PSTHs) of motor unit discharges were constructed. In healthy subjects, two periods of increased firing probability were seen at onset latencies of 20-31 ms and 56-90 ms after the stimulus. These periods have been termed the primary peak and the secondary peak. The primary peak had a mean duration of 4.6 ms and was found to be multimodal in 17 motor units. Subpeaks had intermodal intervals of between 0.6 and 2.4 ms. Subpeaks probably result from a sequence of excitatory postsynaptic potentials (EPSPs) induced at the motoneuron by corticospinal impulses. In patients with MS, the primary peak could be absent, delayed in onset, of increased duration without discernible subpeaks, or showing increased intermodal intervals between subpeaks. In 3 motor units from patients with MS, PSTHs with normal features were found. It is postulated from this study of the corticospinal inputs to single motoneurons that motor impairment in MS can be due to a number of mechanisms including slowed conduction in corticospinal fibres, dispersion of arrival times of corticospinal impulses at spinal motoneurons and conduction block in corticospinal fibres, which may be frequency dependent.

Adult↗
PubMed1991

Origin of the secondary increase in firing probability of human motor neurons following transcranial magnetic stimulation. Studies in healthy subjects, type I hereditary motor and sensory neuropathy and multiple sclerosis.

In tonically active human motor neurons serving upper limb muscles there is a late rise in firing probability following transcranial magnetic stimulation termed the secondary peak (SP). The aim was to study the mechanism of SP and the pathway that mediates it. For this purpose, the response to transcranial magnetic stimulation of 62 repetitively firing low threshold single motor units from upper limb muscles was studied with peri-stimulus time histograms in 8 healthy subjects and in 13 patients with either Type I hereditary motor and sensory neuropathy (HMSN) or multiple sclerosis (MS). Separate peri-stimulus time histograms, constructed for trials in which the motor unit fired in the primary peak (PP) and those in which it fired in SP, showed that SP was not caused by a resumption of firing after the preceding PP. In the first dorsal interosseous muscle, the observed increase in the interval between PP and SP in patients with either HMSN or MS, when compared with healthy subjects, suggested that the pathway mediating SP had both peripheral and central components. Evidence for a peripheral component was substantiated by the observed slope of the line relating the latency of SP in different upper limb muscles to peripheral conduction distance, which was more than 3 times greater than that for PP, and by comparisons in the same motor unit made between the latency of responses to finger taps and to transcranial magnetic stimulation. Evidence for the origin of SP was consistent with a long loop reflex, or with collateral activation of gamma motor neurons and subsequent motor neuron firing from muscle afferent inputs. SP discharges were found to occur earlier than expected on the basis of the spontaneous motor unit firing rate, suggesting that SP was caused by the rising phase of an excitatory post-synaptic potential, rather than by the decay of an inhibitory postsynaptic potential.

Action Potentials↗
PubMed1991

The firing probability of single motor units following transcranial magnetic stimulation in healthy subjects and patients with neurological disease.

Magnetic stimuli applied to the scalp can cause single motor units (MUs) to discharge in intrinsic hand or more proximal arm muscles. MUs are much more likely to be fired by stimuli if they are being activated voluntarily at the same time. The changes in firing probability induced by magnetic stimuli in such tonically active MUs have been studied in healthy subjects and patients using peri-stimulus time histograms (PeSTHs). The mean firing level in the 250 msec before the stimulus, was used to define 2 peaks of increased firing after the stimulus. The first, termed the primary peak (PP), was always present, had an onset latency in first dorsal interosseous (FDI) muscle of 20-31 msec and was short in duration (mean 4.9 msec). A second increase in firing probability, the secondary peak (SP), was present in about half the FDI MUs studied, had a mean peak latency of 81.5 msec and had a duration up to about 40 msec. PP often consisted of a number of sub-peaks with intermodal intervals of around 1.5 msec. It is believed that PP is the result of activation of corticospinal (CS) fibres making monosynaptic connections and that sub-peaks within PP are due to the arrival at the motoneuron of successive CS impulses produced by the stimulus. SP is probably due to operation of other excitatory inputs to the motoneuron. In patients, a number of different abnormalities have been identified. PP has been found to be normal, absent, delayed and dispersed or having abnormally separated sub-peaks. Clearly the technique is a powerful tool for dissecting abnormalities in CS projections at the synaptic level.

Action Potentials↗
PubMed1991

[Changes in the responses of motor units to transcranial magnetic stimulation in patients with multiple sclerosis and stroke].

In multiple sclerosis and stroke the muscle responses to transcranial magnetic stimulation are frequently delayed, reduced in amplitude or absent. To investigate the underlying pathophysiological mechanisms, responses of single motor units to transcranial magnetic stimulation were analysed using peri-stimulus time histograms. The following response patterns were detected: 1. prolongation of latency and duration of the primary peak which occurs in healthy controls 17 to 30 ms after the stimulus and has a duration of 2 to 8 ms, 2. lack of an excitatory response, 3. prolongation of the interval between sub-peaks within the primary peak and 4. multimodal responses. Possible mechanisms for these changes are: reduction and dispersion of conduction velocities in corticospinal axons associated with impaired summation of excitatory post-synaptic potentials at the spinal motoneurone, frequency-dependent or complete conduction block in corticospinal neurones and compensatory activation of other descending motor pathways.

Adult↗
PubMed1991

Effect of an anticholinesterase compound on the ultrastructure and function of the rat blood-brain barrier: a review and experiment.

Soman, an organophosphorous irreversible inhibitor of acetylcholinesterase, was studied for its effect on the rat blood-brain barrier (BBB) during the first 24 h of intoxication. Young adult male Sprague-Dawley rats, injected with Evans blue-dye and surviving a subsequent single convulsive dose of soman (114 micrograms/kg, 0.9LD50), presented focal and diffuse penetration of dye in areas of brain normally considered protected by the BBB. Invasion was widest during the first hour when signs of excitation, respiratory distress and convulsions peaked and was absent at 24 h. During this time period, cholinesterase inhibition, as measured by enzyme assay, persisted in brain and blood at 10% and 6% of control values respectively. Brains of nonconvulsing animals and animals pretreated with nembutal (45 mg/kg, I.P.) or with diazepam (10 mg/kg, I.P.) were free of extravasated dye. A ranking of dye-breached brain areas suggested that cerebellar and cerebral cortex were most frequently involved while brain stem was rarely stained. Ultrastructural analysis of breached areas with horseradish peroxidase as a tracer molecule, revealed that the probable subcellular mechanism of the induced breach was enhanced vesicular transport, a mechanism similarly described for seizure. Consequences of the breach were emphasized with the detection of significantly elevated levels of an exogenously administered quaternary compound, 3H-hexamethonium. These findings present additional evidence that an anticholinesterase-induced breach of the rat blood-brain barrier is convulsive dependent, demonstrates BBB mechanisms similar to that of seizure, and can allow CNS penetration of blood-borne drugs and circulatory proteins that normally would be slowed or excluded by an intact BBB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Familial multiple symmetric lipomatosis with peripheral neuropathy.

We describe coexisting peripheral neuropathy and multiple symmetric lipomatosis in 4 of 7 siblings. The absence of either condition in 3 other generations of this family suggests autosomal recessive inheritance. None of the affected siblings were alcoholic, a factor some have proposed to explain the frequent occurrence of peripheral neuropathy in sporadic multiple symmetric lipomatosis. Serum lipid studies, including apoprotein A levels, were normal. Sural nerve biopsy from 1 patient showed nerve fiber loss, predominantly affecting large myelinated fibers. The relationship between myelin sheath thickness and axon diameter was normal, arguing that this neuropathy is not due to primary axonal atrophy.

Adult↗
PubMed1989

Changes in muscle fiber conduction velocity, mean power frequency, and mean EMG voltage during prolonged submaximal contractions.

Average muscle fiber conduction velocity, mean power frequency, and mean EMG voltage have been measured in human vastus lateralis during prolonged isometric knee extensions at 10, 20, 30, and 40% of the maximum knee extension force. During contractions at 10 and 20% of maximum force, conduction velocity and mean power frequency rose as the contraction progressed, whereas the conduction velocity and mean power frequency fell at 30 and 40% of the maximum force. The mean EMG voltage rose during the contractions, with steeper increases for higher forces. It is argued that two principal factors influence the EMG during prolonged submaximal contractions: firstly, the fatigue of current active motor units, and, secondly, recruitment of fresh motor units. These factors act in opposition to muscle fiber conduction velocity. Recruitment gives an increase in average conduction velocity, whereas fatigue provokes a slowing in conduction velocity.

Adult↗
PubMed1989

Changes in human alpha-motoneurone excitability following mechanical muscle stimuli.

Short mechanical stretches given to partially activated human abductor digiti minimi muscle (ADM) evoke early (M1) and late (M2) reflex responses. Transcranial magnetic brain stimuli were used to evoke compound muscle action potentials in ADM and hence to estimate motoneuronal excitability at various times after mechanical stimuli. There was no evidence that Ia volleys produce additional facilitation in motoneurones of muscles which are already voluntarily activated. However, the inhibitory phase between M1 and M2 was associated with a reduction in size of muscle responses from brain stimuli. This may reflect reduced Ia input, polysynaptic Ia inhibition or Renshaw inhibition.

Adult↗
PubMed1988

Excitatory and inhibitory effects on human spinal motoneurones from magnetic brain stimulation.

Stimulation of baboon motor cortex causes in the motoneurones (MNs) of intrinsic hand muscles monosynaptic excitatory postsynaptic potentials (EPSPs) and a disynaptic inhibitory postsynaptic potential (IPSP). These phenomena have been investigated in human MNs by applying pulsed magnetic stimuli over the scalp at random times during the tonic discharge of single hand muscle motor units (MUs). Post-stimulus time histograms (PSTHs) demonstrated an increased firing probability at between 25 and 35 ms. This major firing peak showed a multimodal form with interpeak intervals of 1.4-1.8 ms. When MUs were not fired by the stimulus, they were nevertheless inhibited from firing spontaneously. There are thus short latency excitatory and inhibitory cortical inputs to human MNs.

Brain↗
PubMed1988

Facilitation of muscle responses to magnetic brain stimulation by mechanical stimuli in man.

Transcranial magnetic brain stimuli were applied to 9 normal subjects and compound muscle action potentials were recorded from the right abductor digiti minimi with surface electrodes. Vibration of 120 Hz, 0.6 mm peak to peak amplitude, applied to the muscle tendon enhanced its responses to magnetic brain stimuli. This facilitation corresponds to the tonic vibration reflex. Inhibition of muscle responses was not seen with vibration. Thus it is likely that the known inhibition of stretch reflexes by vibration is purely presynaptic. Small rectangular mechanical stimuli (rise time 200 mm/s, amplitude 1 mm) applied to ADM elicited short and long loop reflex responses. When brain stimuli were give 7-16 ms after the muscle tap, muscle responses were enhanced. It is argued that this is a result of the summation of the effects of Ia afferent impulses and descending pyramidal volleys at the alpha motoneurones. A separate late facilitation corresponding with the arrival of muscle afferent inputs to the sensori-motor cortex was not seen.

Action Potentials↗
PubMed1988

Muscle fibre conduction velocity, mean power frequency, mean EMG voltage and force during submaximal fatiguing contractions of human quadriceps.

In 5 healthy male subjects the changes in muscle fibre conduction velocity, mean power frequency, mean EMG voltage, and force in the quadriceps were measured during submaximal fatiguing contractions, ranging from 60 to 100% of maximum force. Surface EMG was recorded from vastus lateralis. The analysis was divided into 2 parts - before and after force had begun to decline (endurance point). The conduction velocity and mean power frequency declined less before the endurance point than after this point. For all forces, the mean EMG voltage increased up to the endurance point. After the endurance point, the effect of fatigue had a decreasing influence on mean EMG voltage.

Adult↗
PubMed1988

The influence of vibration on the excitability of alpha motoneurones.

Transcranial magnetic brain stimuli were delivered to 6 healthy subjects at different time intervals after the beginning of muscle vibration. Vibration of 6 sec duration in 4 subjects and of 100 msec duration in 6 subjects was applied to the right abductor digiti minimi muscle using an electromagnetic mechanical stimulator. The responses to brain stimuli were enhanced in this muscle when vibration began 9 msec before the transcranial stimulus, i.e., when the descending volley and the monosynaptic afferent Ia volley arrived simultaneously at the anterior horn cell. With long lasting vibration an enhancement of responses to brain stimuli was seen, which began after 120 msec and continued for up to 5 sec after the onset of vibration. This is consistent with a tonic, probably polysynaptic, excitatory Ia influence on homonymous alpha motoneurones, as well as the well known monosynaptic effect.

Action Potentials↗
PubMed1988

Evaluation of proximal facial nerve conduction by transcranial magnetic stimulation.

A magnetic stimulator was used for direct transcutaneous stimulation of the intracranial portion of the facial nerve in 15 normal subjects and in patients with Bell's palsy, demyelinating neuropathy, traumatic facial palsy and pontine glioma. Compound muscle action potentials (CMAPs) thus elicited in the orbicularis oris muscle of controls were of similar amplitude but longer latency (1.3 SD 0.15 ms) compared with CMAPs produced by conventional electrical stimulation at the stylomastoid foramen. No response to magnetic stimulation could be recorded from the affected side in 15 of 16 patients with Bell's palsy. Serial studies in two patients demonstrated that the facial nerve remained inexcitable by magnetic stimulation despite marked improvement in clinical function. In the patient with a pontine glioma, the CMAP elicited by transcranial magnetic stimulation was of low amplitude but normal latency. In six of seven patients with demyelinating neuropathy, the response to intracranial magnetic stimulation was significantly delayed. Magnetic stimulation produced no response in either patient with traumatic facial palsy. Although the precise site of facial nerve stimulation is uncertain, evidence points to the labyrinthine segment of the facial canal as the most likely location.

Adult↗
PubMed1988

Central motor conduction in degenerative ataxic disorders: a magnetic stimulation study.

Central motor conduction to small hand muscles was measured using magnetic stimulation of the motor cortex and electrical stimulation of proximal motor roots in 11 patients with Friedreich's ataxia, 10 patients with early onset cerebellar ataxia with retained tendon reflexes (EOCA) and 13 patients with late onset degenerative cerebellar disease (LOCD). Central motor conduction was abnormal in 91% with Friedreich's ataxia, 70% with EOCA and 38% with LOCD. Central motor conduction abnormalities were not specific to individual disorders but were more severe and were related to disease duration in Friedreich's ataxia and EOCA.

Adult↗
PubMed1988

[Interaction of transcranial magnetic stimulation and mechanical stimuli].

The influence of different mechanical stimuli on the excitability of spinal motoneurones was investigated in 5 different experiments using transcranial magnetic brain stimulation. A servo controlled moving coil was used to deliver rectangular mechanical stimuli or vibration to the right abductor digiti minimi muscle (ADM) thus exciting spindle primaries. With the ADM relaxed, vibration produced an early enhancement of compound responses (CMAPs) after transcranial magnetic brain stimuli. This is thought to be due to simultaneous arrival of the descending corticospinal volley and of the afferent la volley at the anterior horn cell. With long lasting vibration an enhancement of responses to brain stimuli continued up to 5 seconds after the onset of vibration. Voluntary muscle contraction increased the CMAP. CMAPs measured with voluntary muscle contraction plus mechanical muscle stimulation did not differ from those with muscle contraction alone. Therefore an excitatory influence of mechanical stimuli cannot be seen with ADM contracted.

Afferent Pathways↗
PubMed1988

[Characteristics of electrical discharges by transcranial cortex stimulation activated motor units of the hand muscles of the human].

Using concentric needle electrode recording from hand muscles (abductor digiti minimi, first dorsal interosseus, or abductor pollicis brevis muscle) the latencies of single motor unit potentials in response to threshold magnetic brain stimuli were studied under different conditions. It has been shown that the motor units activated by threshold brain stimuli had the lowest threshold for voluntary activation (A = vol. activated, B = brain stim.). Onset latencies of 23 motor unit potentials from different sites in the relaxed muscles of four healthy subjects ranged from 22.4 to 32.4 ms (average: 26.4 ms; SD: 2.80 ms) but proved to be relatively stable when stimulating and recording conditions were kept constant (variation less than 0.5 ms, see poststimulus time histogram in Fig. 2). With concurrent contraction of an ipsilateral neighbouring or of the contralateral homologous muscle the motor unit potentials from the relaxed target muscle jumped to an earlier latency by 1.2 to 1.7 ms (C in Fig. 3 and B-2 in Fig. 4). On one occasion another motor unit of higher threshold was alternatively activated by this procedure (B-3 in Fig. 4). Since the same procedures are known to enhance the compound muscle action potentials as recorded from the relaxed muscle with surface electrodes, the shorter latencies of single motor units are considered to be caused by a facilitatory influence on the motoneurones. A possible explanation for these latency shifts would be that the motor units discharge later in response to the brain stimulus induced repetitive cortico-spinal impulses when there is no facilitation, whereas during facilitation the firing level is reached earlier.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Excitability of the human motor cortex is enhanced during REM sleep.

A conspicuous feature of rapid eye movement (REM) sleep is atonia of postural muscles due to a powerful brainstem inhibitory effect on spinal motoneurones. However, small myoclonic jerks occur during REM sleep and increased activity of cortical neurones is suggested by the EEG. Transcranial cortical stimulation with magnetic pulses has been used to investigate motor excitability during sleep in man. Motor responses were evoked during sleep using stimuli identical to those used in wakefulness. Response amplitudes were depressed during slow wave sleep (SWS) and enhanced or the same during REM sleep. These findings suggest that the susceptibility of the human motor cortex to stimulation is enhanced during REM sleep.

Electric Stimulation↗