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Biomedical subjects

J F Iles

Publications and source records attributed to J F Iles.

At least 19 recordsLinked to original sources

Simple models of stimulation of neurones in the brain by electric fields.

The excitation of pyramidal cells in the motor cortex, produced by electric fields generated by distant electrodes or by electromagnetic induction, has been modelled. Linear, steady-state models of myelinated axons capture most of the geometrical aspects of neurone activation in electric fields. Some non-linear features can be approximated. Models with a proximal sealed-end and distal infinite axon, or of finite length, are both serviceable. Surface anodal stimulation produces hyperpolarisation of the proximal axon (closest to the anode) and depolarisation in the distal axon. The point of maximum depolarisation can be influenced by the location of the cathode (greater separation of anode and cathode causes more distal depolarisation). Axon bends can produce very localised depolarisation. Cathodal stimulation may be less effective than anodal as a result of anodal block of conduction of action potentials in the distal axon. The latencies of responses to anodal stimulation, recorded in the distal axon, will decrease as the stimulus strength is increased and the point of action potential initiation moves distally node by node. Larger jumps in latency will be produced when the point of action potential initiation moves from one axon bend to another.

Action Potentials↗

Vestibular-evoked muscle responses in patients with spinal cord injury.

The vestibular system was activated by galvanic electrical stimulation in 22 patients with spinal cord injury. Three patients were studied standing and all were studied sitting. Electromyographic responses recorded in soleus (standing patients) and the erectores spinae (all patients) were compared with data from 18 control subjects. The vestibular stimulus polarity and head position were arranged so as to produce excitatory medium latency muscle responses in the controls. Responses in the patient group were present bilaterally, present unilaterally or absent below the level of injury. The amplitude of response recorded in erectores spinae at lumbar levels below the lesion in 21 patients (left and right side responses summed) and five control subjects was positively correlated with American Spinal Injuries Association (ASIA) grade: the smallest amplitudes were found in patients with the most severe impairment (Spearman rank correlation coefficient rs = 0.59; P = 0.002, two-tailed). The latency of response (averaged for both sides) was negatively correlated with ASIA grade in 21 patients: the longest latencies were found in patients with the most severe impairment (rs = -0.57; P < 0.01, two-tailed). Amplitude and latency were negatively correlated (rs = -0.72, P < 0.002, two-tailed). The latencies of responses recorded in the erectores spinae at different vertebral levels were linearly related to the vertical distance from the inion to the recording site in both patient and control groups. The conduction velocities of the spinal pathways activated by vestibular stimulation were 4.6 and 10.4 m/s in patient (recording below lesion) and control groups, respectively. Both clinical status (patients recording below lesion, patients recording above lesion and controls) and distance were significant predictors of latency (general linear model, P < 0.0005). It is concluded that measurement of vestibular-evoked responses could provide information on the level and density of spinal cord lesions.

Adult↗

Vestibular actions on back and lower limb muscles during postural tasks in man.

The vestibular system was activated by galvanic electrical stimulation in 19 normal subjects. With the head turned to one side so that the stimulating anode was on the posterior mastoid process, stimulation caused standing subjects to sway backwards in the sagittal plane. Electromyography showed bilateral activation of erector spinae, gluteus maximus, biceps femoris, soleus and intrinsic foot (toe flexor) muscles. When head direction or electrode polarity was reversed so that the anode was anterior, all those muscles became less active and the subjects swayed forwards. With the head facing forward, stimulation caused sideways sway in the coronal plane, towards the anode, with excitation of the erector spinae on the anode side and reduced activity on the cathode side. The limb muscles were activated on the side opposite the anode and showed complex responses on the anode side. Responses were detectable in the erectores spinae muscles in sitting subjects. No responses in limb muscles were detected in the sitting posture. Subject responses in erector spinae recorded at L3/L4 had latencies from 59 to 110 ms, using a 2 mA stimulus. Latencies in lower limb muscles were longer. The results suggest a role for the vestibular system and descending brain stem motor pathways to the erectores spinae muscles in the control of postural orientation of the back when sitting and standing. The conduction velocity in the motor pathway was estimated to be 13 +/- 10 m s(-1) (mean +/- S.D., n = 12 subjects).

Adult↗

Task-related changes of transmission in the pathway of heteronymous spinal recurrent inhibition from soleus to quadriceps motor neurones in man.

An H reflex conditioning technique was used to monitor the transmission of heteronymous recurrent inhibition from soleus to quadriceps motor neurones of the human lower limb. Inhibition declined during quadriceps muscle contraction under all conditions examined, falling to zero at around one-third of the maximum voluntary contraction. Inhibition declined during soleus muscle contraction in sitting, standing and bicycling tasks. The level of inhibition assessed at a given (weaker than 30%) level of quadriceps contraction was reduced during postural tasks involving quadriceps and soleus co-contraction (standing and late-stance phase of walking) when compared with sitting and performing matched voluntary muscle contractions. The level of inhibition during the mid-power stroke of a bicycling task, which also involved co-contraction of quadriceps and soleus, was greater than during matched voluntary muscle contractions while sitting. It is concluded that the pathway of heteronymous recurrent inhibition from soleus to quadriceps motor neurones is under at least two types of control: one related to the task, which sets the operating range, and a second which couples inhibition to the level of muscle contraction. Multiple control pathways are consistent with the diverse effects on recurrent inhibition reported in subjects with upper motor neurone lesions.

Action Potentials↗

Changes in transmission in the pathway of heteronymous spinal recurrent inhibition from soleus to quadriceps motor neurons during movement in man.

H reflexes were induced in the human quadriceps muscle by electrical stimulation of the femoral nerve. The reflexes were conditioned by prior stimulation of the inferior soleus nerve. The conditioning stimulus produced an inhibition of long duration (>20 ms). The threshold of this inhibition was at zero soleus motor discharge and the inhibition scaled with soleus motor discharge. It was concluded that the inhibition was a heteronymous recurrent inhibition of quadriceps motor neurons mediated by Renshaw cells which had been activated by soleus motor neuron discharge. This recurrent inhibition declined during voluntary tonic contraction of the quadriceps, falling to zero at around one-third of maximum voluntary contraction. Antagonist contraction and weak co-contraction of the quadriceps and its antagonists did not lead to any significant change in recurrent inhibition. It is concluded that motor commands descending from the brain reduce heteronymous recurrent inhibition during isolated quadriceps muscle contraction, but to a much lesser extent during co-contraction. No evidence was obtained for any descending facilitation of heteronymous recurrent inhibition.

Adult↗

Evidence for cutaneous and corticospinal modulation of presynaptic inhibition of Ia afferents from the human lower limb.

1. Presynaptic inhibition of soleus muscle Ia afferent fibres, produced by stimulation of group I afferents in the common peroneal nerve, was assessed from changes in the H reflex at long conditioning intervals, in six normal subjects. 2. Stimulation of the ipsilateral sural nerve at the malleolus, just before stimulation of the common peroneal nerve at the head of the fibula, decreased the presynaptic inhibition. This effect was strongest during voluntary plantar flexion and weaker during dorsiflexion or at rest. 3. Stimulation of other cutaneous nerve branches serving the dorsum of the ipsilateral foot, and also the contralateral sural nerve, decreased presynaptic inhibition. Adequate stimulation of low threshold cutaneous mechanoreceptors by light brushing of both distal dorsal and plantar surfaces of the ipsilateral foot decreased presynaptic inhibition. 4. Stimulation of the ipsilateral plantar nerves increased presynaptic inhibition, but this action is attributed to activation of group I afferents from the intrinsic muscles of the foot. 5. Transcranial magnetic stimulation of the lower limb area of the contralateral motor cortex decreased presynaptic inhibition. This effect was strongest during voluntary plantar flexion and weaker during dorsiflexion or at rest. 6. The actions of cutaneous and corticospinal pathways completely occluded each other. However, when both effects were adjusted to be liminal, a spatial facilitation between them was observed. 7. It is concluded that in man, as in the cat, cutaneous and corticospinal axons converge on interneurones that inhibit the machinery of presynaptic inhibition of group Ia afferents. These actions may be responsible for the modulation of presynaptic inhibition which has been observed to precede and accompany a wide range of human movements.

Adult↗

Fictive locomotion in the adult decerebrate rat.

In adult immobilised, decerebrate rats, administration of L-3,4-dihydroxyphenylalanine, stimulation of the mesencephalic locomotor centre, or a combination of the two elicited fictive locomotor patterns in hindlimb muscle nerves. The patterns correspond closely to those observed in decerebrate animals that were free to move.

5-Hydroxytryptophan↗

Vestibular-evoked postural reactions in man and modulation of transmission in spinal reflex pathways.

1. The effects of galvanic stimulation of the vestibular apparatus (with electrodes on the mastoid processes) have been studied in standing human subjects. With the head turned to one side, subjects swayed towards the anode. 2. Forwards sway was preceded by electromyographic (EMG) activity in quadriceps and tibialis anterior muscles. Backwards sway was preceded by EMG activity in soleus and hamstring muscles. 3. Using the method of H reflex conditioning, forward sway was found to be preceded by inhibition of soleus motoneurones. 4. Interaction between the vestibular-evoked inhibition of soleus motoneurones preceding forwards sway and peripheral reflex inhibition was examined by a spatial facilitation method. 5. Interaction was found between vestibular-evoked inhibition and Ia reciprocal, group I non-reciprocal and group Ia-Ia presynaptic inhibitory pathways. It is concluded that vestibular signals converge on spinal interneurones subserving these inhibitory actions. 6. A 'decoupling' of soleus motoneurons and soleus-coupled Renshaw cells was found in the period of soleus activation preceding backwards sway.

Adult↗

Cortical modulation of transmission in spinal reflex pathways of man.

1. The motor actions in the lower limb of transcranial electrical stimulation of the motor cortex have been studied in sitting human subjects. 2. Cortical stimulation induced a short latency inhibition of H reflexes evoked in soleus motoneurones both at rest and during small voluntary contractions of soleus. 3. Spatial interaction between cortical inhibition of soleus motoneurons and inhibition evoked through identified spinal reflex machinery was investigated. 4. Interactions were found between cortically evoked inhibition and spinal Ia reciprocal inhibition, group I non-reciprocal inhibition and higher threshold components of longer latency reciprocal inhibition (D1 and D2 inhibitions). 5. Interactions were facilitatory when cortical and spinal inhibitory actions were weak and reversed to occlusion when both actions were strong. 6. It is concluded that the corticospinal pathway converges on the interneurones which subserve Ia reciprocal, group I non-reciprocal, D1 and D2 inhibition of soleus motoneurones. 7. No significant interaction was found under the present experimental conditions between cortical stimulation and group Ia-Ia presynaptic inhibition of soleus afferents. 8. The statistical significance of spatial interactions observed with H reflex conditioning was investigated using a control experiment.

Adult↗

Reflex actions of knee joint afferents during contraction of the human quadriceps.

(1) The spinal reflex actions of afferents stimulated by knee joint distension have been investigated in man. (2) Cannulation of the knee and infusion of saline raised intra-articular pressure, especially during quadriceps contraction. High pressures did not induce any sensation of pain. Pressure was taken as an index of joint proprioceptor activation. (3) Increased pressure progressively depressed the quadriceps H-reflex, both at rest and during quadriceps contraction. There was no indication of a threshold pressure for this inhibitory action. (4) It is concluded that joint distension inhibits quadriceps motoneurons through spinal pathways that still operate during voluntary contraction. These pathways could thus contribute to pathological weakness after joint injury. (5) Joint distension produced spatial facilitation of non-reciprocal inhibition of quadriceps H-reflexes from afferents in the tibial nerve.

Adult↗

The mesencephalic centre controlling locomotion in the rat.

A mesencephalic locomotor region has been located in the rat brain. Electrical stimulation of the mid-brain in decerebrate animals was used to elicit locomotion on a freely mobile treadwheel. The lowest threshold stimulation sites were reconstructed from histology and accumulated from different experiments. An averaging procedure, taking into account the threshold stimulus current used in each experiment, was used to identify the brain region in which neurons would have been activated in most experiments. The mesencephalic locomotor region so defined corresponds closely to nucleus cuneiformis and the immediately surrounding pedunculopontine region.

Animals↗

The effects of lesions on autogenetic inhibition in the decerebrate cat.

1. The effects of spinal and brain lesions on autogenetic inhibition from contraction receptors were studied in the decerebrate cat. Inhibitory feedback gain was estimated by measuring the effect of tension perturbations on reflex contractions of the soleus muscle. Tendon vibration was used to clamp the firing rate of primary spindle afferents, to prevent spindle unloading from disfacilitating the reflex contraction. In addition, secondary spindle afferents could be selectively excited by stimulating fusimotor fibres during muscle vibration. 2. Following an acute contralateral or bilateral dorsal transection of the spinal cord at L3, the vibration reflex tension fell by between 50 and 74% in three decerebrate animals. This was accompanied by a variable increase in inhibitory feedback, ranging between 180 and 360%. 3. In two animals, selective stimulation of fusimotor fibres supplying soleus muscle was without effect in the presence of muscle vibration both before and after the spinal lesion. In the third animal, a small and variable reduction in tension could be obtained only after the lesion, implying that an inhibitory pathway from homonymous secondary spindle afferents to alpha-motoneurones was released. 4. In a separate series of experiments, contralateral cerebral lesions were made 2-12 months prior to the acute inhibitory feedback measurement. Inhibitory feedback gain was increased, on average twofold in decerebrate animals with chronic cerebral lesions, when compared to control decerebrate animals. 5. Selective stimulation of fusimotor fibres to excite spindle secondary afferents was uniformly without effect in decerebrate animals with chronic cerebral lesions. In one animal spinal transection had only a minor effect on extensor tone and on inhibitory feedback gain, in contrast to the control decerebrate cats. 6. The implications of these findings are discussed in relation to the use of animals with spinal and supraspinal lesions as models of spasticity.

Animals↗

Inhibition of monosynaptic reflexes in the human lower limb.

1. Presynaptic inhibition of muscle spindle Ia afferents by afferents from the same and other muscles has been studied in the human lower limb. The experiments have utilized conditioning of test monosynaptic reflexes by vibration of both the test and other muscles. 2. The pattern of inhibition invariably includes autogenetic actions. 3. There are powerful effects from flexor to extensor Ia afferents. Actions from flexor to flexor, and from extensor to extensor, are weaker. Actions from extensors to flexors are very weak. 4. The strength of presynaptic inhibition from one muscle type to another weakens as the muscles considered become more anatomically distant. 5. The inhibition studied both by vibration and by electrical conditioning stimulation of nerves becomes weaker during voluntary isometric contraction of the test muscle. It is strongest at rest and during antagonist contraction. 6. Evidence is provided suggesting that descending control is the primary cause of this modulation of inhibition during contraction. 7. Stimulation of afferents in cutaneous nerves reduces group I presynaptic inhibition of Ia afferents.

Adolescent↗

Effects of joint pathology on muscle.

The muscle wasting associated with joint damage may be highly selective; knee disorders produce quadriceps wasting but little change in the size of the hamstrings. This causes isolated quadriceps weakness, so predisposing to a position of knee flexion. Nociceptors and other receptors in and around the joint can have flexor excitatory and extensor inhibitory actions. At the knee, these receptors are likely to excite hamstrings and inhibit quadriceps. Although other actions could occur, quadriceps inhibition may be favored by a position of knee extension. Quadriceps inhibition will weaken voluntary contraction, reduce tone, and contribute to wasting of the muscle, further predisposing to a position of knee flexion. The potency of quadriceps inhibition may be considerable, even in the absence of perceived pain. A small, apparently trivial effusion (or even a clinically undetectable effusion) may cause important inhibition. In order to improve the orthopedist's ability to prevent flexion contracture of the injured or operated joint, he must look not only for ways of reducing joint pain, but also for ways of preventing activity in other joint afferents. For example, he must consider the possible effects of joint position, intraarticular pressure, suture-line tension, and afferent blockade.

Animals↗

Reciprocal inhibition during agonist and antagonist contraction.

Reciprocal inhibition of soleus motoneurones in man was studied during voluntary contraction of soleus or its antagonist. Inhibition was strongest during antagonist contraction or at rest and weak during contraction of soleus itself. Possible explanations for these changes are discussed.

Adult↗

Presynaptic inhibition of monosynaptic reflexes in the lower limbs of subjects with upper motoneuron disease.

Presynaptic inhibition of muscle spindle Ia afferents by group I afferents from the same and other muscles has been studied in the lower limbs of subjects with upper motoneuron lesions. The experiments utilised conditioning of soleus test monosynaptic reflexes during controlled voluntary contraction. The protocol was designed to isolate presynaptic inhibition from postsynaptic components. The relation between estimate of inhibition and test reflex amplitude was examined. The subjects showed less inhibition than controls at all levels of voluntary torque investigated (less than or equal 15 Nm). Two thirds had weak inhibition which did not show the decrease during muscle contraction characteristic of controls. The degree of difference from the normal situation correlated with severity of the clinical sign (weakness of voluntary ankle flexion).

Adult↗

Motor neuron columns in the lumbar spinal cord of the rat.

The location in the rat spinal cord of motor neurons innervating 23 muscles or muscle groups of the hind limb has been determined by using retrograde transport of horseradish peroxidase. The motor neurons supplying a single muscle form a discrete longitudinal column in the lateral ventral horn. The columns extend through up to three adjacent spinal segments and their longitudinal location varies by as much as one segment in different animals. The relative positions of the columns supplying different muscles and their transverse location in the spinal cord are very consistent between individuals and a stereotaxic map has been constructed. This is briefly compared with descriptions from other species. Counts of the numbers of motor axons in seven different muscles nerves have been made with the aid of acetylcholinesterase histochemistry to identify the motor component. The numbers of motor neuron somata labelled with horseradish peroxidase are on average 70% of the axon counts.

Animals↗