Amplitude, latencies and 100 ms pre-stimulus RMS EMG of diaphragm motor-evoked potentials (DiMEPs) before/after SMA inhibitory (cTBS) and facilitatory (5 Hz) conditioning protocols.

<p>DiMEP values had a normal distribution and are therefore presented as mean±SD. * = p<0.05 vs. baseline values following <i>post hoc</i> tests. † = p<0.05 between cTBS and 5 Hz conditions. The baseline values were statistically different (F = 5.39, p<0.05). This difference was entirely accounted for by the one subject who dropped out of the study before participating in the 5 Hz part of the experiment. When this subject was removed from the analysis, the difference between baselines disappeared, but the cTBS-related inhibition did persist (F = 4.508, p<0.012).</p

Schematic representation of the method used to identify pre-inspiratory potentials from the raw EEG signal and the ventilatory flow signal.

<p>(Adapted from Raux et al., <i>Anesthesiology</i>—<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084534#pone.0084534-Raux3" target="_blank">[19]</a>—with permission from the authors and the publisher.) Artwork Robin Jacqueline. The EEG signal is segmented in epochs defined according to the ventilatory flow signal (1). These epochs are ensemble averaged (2). The resulting signal is inspected visually for a putative pre-inspiratory potential (3) of which the presence is ascertained through the calculation of a linear regression over the region of interest and comparison of the slope of this regression with 0. See “<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084534#s2" target="_blank">Methods</a>” for details. Pre-inspiratory potentials and the related motor potentials are normally absent during quiet breathing.</p

Average pre-inspiratory EEG tracings in one of the congenital central hypoventilation syndrome patient.

<p>In each of the panels, the top trace depicts the Cz-EEG signal, and the bottom trace depicts ventilatory flow. The vertical line indicates the onset of inspiration. In the “inspiratory threshold loading” panel, inspiration is preceded by a shift upward of the EEG trace (horizontal double arrowed red line) that is characteristic of a pre-inspiratory potential. This observation is similar to that made in normal individuals <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084534#pone.0084534-Raux1" target="_blank">[12]</a>. In contrast to normal individuals however, a pre-inspiratory potential can also be seen, abnormally, in the three “control condition” panels (control 1: resting ventilation with minimal constraint, namely a respiratory inductance plethysmography vest only; control 2: resting ventilation while breathing through a pneumoatchograph; control 3: as control 2, but during the washout period following inspiratory loading) and in the “CO₂ stimulated breathing” panel.</p

Average pre-inspiratory EEG tracings in one of the control subjects.

<p>In each of the panels, the top trace depicts the Cz-EEG signal, and the bottom trace depicts ventilatory flow. The vertical line indicates the onset of inspiration. In the three “control condition” panels (control 1: resting ventilation with minimal constraint, namely a respiratory inductance plethysmography vest only; control 2: resting ventilation while breathing through a pneumoatchograph; control 3: as control 2, but during the washout period following inspiratory loading), inspiration is not preceded by any change in the EEG signal (absence of pre-inspiratory potentials). In the “CO₂ stimulated breathing” panel, inspiration is also not preceded by any change in the EEG signal (absence of pre-inspiratory potentials). In contrast, in the “inspiratory threshold loading” panel, inspiration is preceded by a shift upward of the EEG trace (horizontal double arrowed red line) that is characteristic of a pre-inspiratory potential. This pattern exactly corresponds to what is expected in normal individuals <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084534#pone.0084534-Raux1" target="_blank">[12]</a>.</p

Resting (RMT) and active (AMT) motor thresholds for the diaphragm, first dorsal interosseous (FDI) and abductor hallucis (AH).

<p>Values shown are% of maximum stimulator output and expressed as median [range]. Definition of abbreviations: FDI = first dorsal interosseous, AH = abductor hallucis.</p

Amplitude, latencies and 100 ms pre-stimulus RMS EMG of first dorsal interosseous motor-evoked potentials (FDIMEPs) before/after SMA inhibitory (cTBS) and facilitatory (5 Hz) conditioning protocols.

<p>FDIMEP values had a non-normal distribution and are therefore presented as median and [Q1–Q3]. * = p<0.05 vs. baseline values following <i>post hoc</i> tests.</p

Average amplitude of diaphragm motor-evoked potentials (DiMEPs) for all subjects evoked at baseline and at 3 time-points following inhibitory (cTBS, white circles) and excitatory (5 Hz, black circles) conditioning of the SMA.

<p>Values are expressed as% of baseline and as mean±SD. * = p<0.05 vs. baseline following <i>post hoc</i> tests.</p

Schematic representations of descending projections to the phrenic motoneurones and corticocortical projections between the SMA and diaphragm primary motor representation (M1Dia).

<p>We showed that inhibitory conditioning of the SMA by repetitive transcranial magnetic stimulation (rTMS, “1”) results in a depressed response of the diaphragm to stimulation of M1dia (“2”). We hypothesise that this is due to inhibition of the corticocortical connections between the SMA and MIdia (“3”) and this suggests that there is a resting facilitatory tonic projection between these areas (shown in red). There are other descending pathways to the phrenic motoneurones that are not shown for clarity (i.e. from the limbic cortex).</p

Experimental design.

<p>Twenty motor-evoked potentials were recorded for both the diaphragm (DiMEPs) and the first dorsal interosseous (FDIMEPs) at baseline and at three time points (Post 1, Post 2 and Post 3) after the rTMS protocols (cTBS or 5 Hz) over the supplementary motor area (SMA). The time indicates time after the end of rTMS.</p

Average waveform of diaphragm motor-evoked potentials (DiMEPs) for a single subject evoked by single-pulse TMS over the motor cortex at baseline and at 3 time-points following the inhibitory protocol (cTBS) over the SMA.

<p>Arrows indicate the time of stimulation.</p