Control of breathing was studied in a patient with a lesion in the ven
tral pens; no volitional behaviour, including voluntary breathing acts
, was possible (locked-in syndrome, LIS). Spontaneous breathing via a
tracheostomy maintained a normal PET(CO2) of 39-40 mmHg. Variability o
f ventilatory parameters awake was similar to that seen in five trache
ostomized control subjects during stage IV sleep but much smaller than
during resting wakefulness. Emotion associated with laughter caused d
isturbances of breathing. The ventilatory response to CO2 was normal a
nd was associated with 'hunger for air' when the PET(CO2) was 49-50 mm
Hg. Mechanical ventilation to reduce PET(CO2) by as little as 1 mmHg r
esulted in apnoea when the ventilator was disconnected; breathing resu
med when PET(CO2) crossed the threshold of 39-40 mmHg. These results d
emonstrate the functional dependence of the human medullary respirator
y oscillator on a threshold level of P-CO2 in the absence of cortico-b
ulbar input, even during wakefulness. The absence of such input may ex
plain the regularity of breathing.