The role of afferent inflow and efferent outflow (or command) signals in judgements of limb position has been debated for over a century. One way to assess this is to check for changes during complete paralysis, with the current view being that perceived movements or position changes do not usually accompany attempts to contract paralysed muscles. To re-examine this, we asked six naïve subjects to carry out a simple position-matching task at the wrist. In the absence of vision, subjects accurately perceived the position to which their right wrist had been moved by the experimenter by matching it with their left hand. There was no significant change in perception when position was matched during sustained flexion or extension efforts. Then we paralysed and anaesthetized the right arm with ischaemia in order to produce a 'phantom' hand. The perceived position of the wrist changed by more than 20 deg when subjects attempted to flex or extend their hand when it was paralysed and anaesthetized. Further studies showed that this illusion was not dependent on the way in which the paralysis was produced and that the size of the position illusion increased when the level of effort during paralysis increased. These results establish for the first time a definitive role for 'outflow' signals in position sense.

SUMMARY1. To determine whether discomfort associated with breathing (dyspnoea) is related to the chemical drive to breath, three subjects were totally paralysed while fully conscious. Subjective responses to a rising C02 stimulus were obtained during rebreathing, rebreathing with C02 added, and breath holding. Dyspnoea was measured with a 10-point Borg scale.2. Following nasotracheal intubation and ventilation (oxygen saturation, 02,Sat' 98-100°% and end-tidal C02, PET,CO,, 30-40 mmHg), total neuromuscular blockade was induced by a rapid injection of atracurium (>2'5 mg kg1) and complete paralysis was maintained with an infusion (5 mg (kg h)-'). Paralysis was confirmed by abolition of the compound muscle action potentials of both the diaphragm and abductor hallucis evoked by supramaximal electrical stimulation of the relevant nerves. Communication via finger movement was preserved for the first 20-30 min following paralysis by inflation of a sphygmomanometer cuff on one arm.3. Before and during complete paralysis, dyspnoea increased progressively during hypercapnia produced by rebreathing (with or without C02 added to the circuit at 250 ml min-'). The mean PET,CO, eliciting 'severe' dyspnoea was 46 mmHg during rebreathing, 42 mmHg during 'breath holding', and 52 mmHg during rebreathing with added C02. There were no significant differences between the values obtained during paralysis and in the control study immediately before paralysis. S. C. GANDEVIA AND OTHERS evokes, can lead to discomfort in the absence of any contraction of respiratory muscles. 5. During paralysis, attempted contraction of arm, leg and trunk muscles increased heart rate and blood pressure. For attempted handgrip contractions, the increases in heart rate (range, 7-15 beats min-') and mean arterial pressure (range, 20-32 mmHg) were similar to those recorded with actual contractions in trials immediately before paralysis. In one subject, graded increases in heart rate and blood pressure occurred for attempted contractions of 45 s duration over a range of intensities (0-100% maximal effort).6. During complete paralysis, transcranial electromagnetic stimulation of the motor cortex produced illusory twitch-like movements of the wrist and digits. This also occurred in separate studies during complete ischaemic paralysis and anaesthesia of the forearm and hand. These illusory movements thus reflect activation of intracerebral structures by the induced currents. No sensation of effort accompanied the transcranial stimuli delivered during whole-body paralysis.7. Attempted voluntary movement of a limb paralysed with intravenous atracurium was accompanied by a marked sense of effort, but it also produced definite illusions of movement. The limb appeared to move slowly in the opposite direction to that desired. However, in separate studies, these illusions were absent when all large diameter axons in the arm were blocked by ischaemia. This suggests that the illusory limb movements were due to incomplete neuromuscular block of the intrafusal endplates.

SUMMARY1. The effects of graded transcranial magnetic and anodal electrical stimulation of the human motor cortex were compared in human subjects undergoing orthopaedic operations on the spine, before and after withdrawal of volatile anaesthesia.Corticospinal volleys were recorded from the spinal cord in the low-cervical and lowthoracic regions (six subjects) or the mid-thoracic region (two subjects) using bipolar electrodes inserted into the epidural space.2. Electrical stimuli were delivered using anode at the vertex and cathode 7 cm laterally. The corticospinal volley at threshold consisted of a single deflection with a mean latency to peak of 4*17 ms at the rostral recording site. With further increases in stimulus strength the latency of this D wave shortened in two steps, first by 0-89 ms (seven subjects) and then by a further 0-8 ms (two subjects), indicating that the site of activation of some corticospinal neurones had shifted to deep subcortical sites.3. When volatile anaesthetics were given, a corticospinal volley could not be defined in three subjects with magnetic stimuli of 70, 80 and 100% maximal stimulator output with the coil at the vertex (Novametrix Magstim 200, round coil, external diameter 14 cm). In the remaining five subjects, the component of lowest threshold was a D wave recorded at the rostral site at 4 0 ms when stimulus intensity was, on average, 70 %. With stimuli of 90-100 % a total of five small I waves could be defined in the five subjects (i.e. on average one I wave per subject).4. After cessation of volatile anaesthetics in seven subjects, the thresholds for D and I waves were lower and their amplitudes were greater. The D wave remained the component of lowest threshold in all subjects, appearing at the low-cervical level with magnetic stimuli of 50 %. However, in three subjects I waves also appeared at D wave threshold, and the D wave was smaller than with electrical stimulation at I wave threshold. There was no consistent change in latency of the magnetic D wave as stimulus intensity was increased to 100 %.5. These findings suggest that the previously reported difference in latency of the