A transcranial magnetic stimulation approach to assess intracortical inhibition and facilitation upon awakening from SWS and REM sleep

Transcranial magnetic stimulation (TMS) is now an established technique in cognitive neurosciences allowing, besides many other applications, the non-invasive assessment of motor cortical excitability. However its application to sleep research has been limited by the fact that delivering one single suprathreshold magnetic stimulus easily awakens subjects, or lightens their sleep. To avoid this methodological problem, in the present study intracortical facilitation and inhibition, as assessed by the cortico–cortical paired pulse TMS technique with a subthreshold conditioning pulse followed by a suprathreshold test pulse, was studied in a group of 10 subjects upon awakening from REM and slow-wave sleep (SWS) and compared to an equivalent wake assessment. Taking into account that a full re-establishment of wake regional brain activity patterns upon awakening from sleep needs up to 30 min, it is possible to make inferences about the neurophysiological characteristics of the different sleep stages by analyzing the variables of interest immediately after provoked awakenings. The motor thresholds during muscle rest and the MEP amplitudes to the suprathreshold stimuli were also assessed, as further measures of the corticospinal system’s excitability. Independently of sleep stage at awakening, intracortical inhibition was found at 1–3 ms interstimulus intervals and facilitation at 7–15 ms interstimulus intervals. Motor thresholds were higher in the SWS condition, with no differences between REM and wakefulness, while motor evoked potential amplitude to unconditioned stimuli decreased upon REM awakening as compared to the other conditions. REM condition showed a significant increase of intracortical facilitation at 10 and 15 ms, while intracortical inhibition was not affected by sleep stage at awakening. While the dissociation between motor thresholds and motor evoked potential amplitudes could be explained by the different excitability of the corticospinal system during SWS and REM sleep respectively, the heightened cortical facilitation in the REM sleep condition points to a cortical motor activation during this stage. Our findings legitimate the introduction of the TMS technique as a new proper tool in sleep research.