Paired TMS studies the effect of a conditioning stimulus (CS) of 80% motor threshold on the response to a suprathreshold test stimulus (TS) of 125% threshold, with an interval between them of either 3 or 11 ms to assess inhibitory and facilitatory

intracortical circuits, respectively (Demoule et al., 2003b, Hopkinson et al., 2004 and Kujirai et al., 1993). Ten paired stimuli were delivered at each interstimulus interval and ten C59 wnt price single stimuli at TS intensity in a random order. Values of MEP3 ms and MEP11 ms were expressed as a percentage of MEPTS. The amplitude of the resting MEPTS was normalized in each patient by dividing by the amplitude of the phrenic CMAP obtained during the same study period. This was delivered via the patient’s own ventilator using a pressure support mode with pressures and back-up rate adjusted to minimize the patient’s Pdi curve as far as possible. Subjects were instructed to ‘relax and let the ventilator breathe for you’. PetCO2 was kept stable by entraining CO2 as required. Once patients had been optimally ventilated for 20 min, diaphragm phrenic nerve CMAP and TMS motor threshold were measured as well as the response to paired stimulation at 3 ms and 11 ms intervals. Patients sat quietly for 30 min after the end of the ventilation period and a further set

of measurements were made. Data was analyzed using StatView 5.0 software (Abucus Concepts, Berkeley, CA). Variables were compared between groups and between study conditions using Wilcoxon signed rank tests, INCB024360 Mann–Whitney or Chi2 tests as appropriate. Univariate linear regression using Pearson correlation coefficient was used to test which disease severity factors were associated with the degree of intracortical facilitation or inhibition. Those with a correlation coefficient of more than 0.3 were included in a forward

stepwise regression analysis. Data is given as mean (SD). The diaphragm motor cortex response Rho to transcranial magnetic stimulation during resting breathing did not differ between patients who were (n = 8) or were not (n = 6) on home NIV in terms of motor threshold, latency or the response to paired stimulation (available in 5 non-ventilated and 6 ventilated patients respectively) with either inhibitory or facilitatory intrastimulus intervals ( Table 2). There was also no significant difference in the amplitude of the rectus abdominis response to TMS between the two groups. Correlates of the responses to paired stimulation, assessed in 11 subjects (all six NIV users and five non-users) are given in Table 3. Intracortical inhibition, reflected by the value of normalized MEP3 ms, was more pronounced with higher PaCO2, lower PaO2, lower SNiP, and worse SGRQ. By stepwise analysis only PaCO2 was retained as an independent correlate (r2 0.51, p = 0.01) ( Fig. 1).