Corticospinal excitability and sleep: a motor threshold assessment by transcranial magnetic stimulation after awakenings from REM and NREM sleep

Abstract

SUMMAR Y Transcranial magnetic stimulation (TMS) is a recently established technique in theneurosciences that allows the non-invasive assessment, among other parameters, of the excitability of motor cortex. Up to now, its application to sleep research has been very scarce and because of technical problems it provided contrasting results. In fact delivering one single suprathreshold magnetic stimulus easily awakes subjects, or lightens their sleep. For this reason, in the present study we assessed motor thresholds (MTs) upon rapid eye movement (REM) and non-rapid eye movement (NREM) sleep awakenings, both in the first and in the last part of the night. Taking into account that a full re-establishment of wake regional brain activity patterns upon awakening from sleep needs up to 20-30 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. Ten female volunteers slept in the lab for four consecutive nights. During the first night the MTs were collected, following a standardized procedure: 5 min before lights off, upon stage 2 awakening (second NREM period), upon REM sleep awakening (second REM period), upon the final morning awakening (always from stage 2). Results showed that MTs increased linearly from presleep wakefulness to REM sleep awakenings, and from the latter to stage 2 awakenings. There was also a time-of-night effect on MTs upon awakening from stage 2, indicating that MTs decreased from the first to the second part of the night. The increase in corticospinal excitability across the night, which parallels the fulfillment of sleep need, is consistent with the linear decrease of auditory arousal thresholds during the night. The maximal reduction of corticospinal excitability during early NREM sleep can be related to the hyperpolarization of thalamocortical neurons, and is in line with the decreased metabolic activity of motor cortices during this sleep stage. On the contrary, the increase of MTs upon REM sleep awakenings should reflect peripheral factors. We conclude that our findings legitimate the introduction of the TMS technique as a new proper tool in sleep research.k e y w o r d s motor evoked potentials, motor thresholds, transcranial magnetic stimulation

Acute upper airway muscle and inspiratory flow responses to transcranial magnetic stimulation during sleep in apnoeic patients

“…This diminished excitability during NREM sleep is expected to result from the combined effects of the following factors: (i) thalamocortical system hyperpolarization, leading to decreased cortical excitability as well as modified reactivity to sensory inputs (Horner, 2008(Horner, , 2011; (ii) increased intracortical inhibitory networks, evidenced by pairedpulse TMS (Salih et al 2005;Avesani et al 2008); and (iii) prevailing tonic GABAergic and glycinergic inhibitory inputs to hypoglossal motoneurons (Horner, 2008). Our findings show that submental muscles respond like hand muscles during NREM sleep in healthy (Grosse et al 2002;Bertini et al 2004;Manganotti et al 2004) and apnoeic patients (Civardi et al 2004), i.e. with increased motor threshold and heightened MEP latency, and are susceptible to sleep-related motor inhibition as are other non-respiratory skeletal muscles.…”

“…To study submental muscle motor threshold (SUB MT ), single TMS-induced twitches (twitch stimulus of approximately 1 ms duration) were applied at endexpiration with a 45 mm figure-of-eight focal coil powered by a Magstim 200 stimulator (Magstim, Whiteland, Dyfed, UK) over the cortex in the antero-lateral area of the nondominant side (0-6 cm anterior and 6-10 cm lateral to the vertex), at the site where TMS elicited the largest Exp Physiol 98.4 (2013) pp 946-956 submental motor-evoked potential (SUB MEP ) at the lowest stimulator output intensity (Meyer et al 1997;Sériès et al 2008). The SUB MT was defined as the lowest stimulation intensity capable of producing at least three SUB MEP with 50-100 μV peak-to-peak amplitudes in six consecutive stimulations (Bertini et al 2004). The shape of the coil was drawn on the skull, and the same investigator (C.A.M.-S.) held the coil manually in place during the wakefulness and sleep studies (described below) to ascertain constant coil positioning throughout the experiments.…”

“…The upper airway dilator muscles are driven automatically by brainstem commands as well as by cortical outputs (responsible for their voluntary activation in non‐respiratory tasks), and both are conveyed to these muscles by peripheral motoneurons. Transcranial magnetic stimulation (TMS), a painless technique capable of activating skeletal muscles via dedicated corticomotor structures, is undertaken to assess cortical excitability regardless of the level of consciousness (Mills, 1999; Bertini et al 2004). Upper airway dilator muscle responsiveness to TMS has been systematically evaluated in conscious subjects via the stimulation of corticobulbar structures (Sériès et al 2008; Borel et al 2012 a ).…”

EEG-Guided Transcranial Magnetic Stimulation Reveals Rapid Shifts in Motor Cortical Excitability during the Human Sleep Slow Oscillation

“…This sleep-dependent suppression might be also reflected by the reduced MEP amplitude after sleep, an effect previously observed following a full night of sleep (Bergmann et al, 2008). Several mechanisms might contribute to this post-sleep reduction such as synaptic downscaling (Tononi and Cirelli, 2006), depression by limb immobilization , or possibly sleep inertia (Bertini et al, 2004), and the present study was not designed to distinguish them. The fact that we found no significant pre-sleep to postsleep changes in wake TEP amplitude (although the group signal averages in Fig.…”

Navigated transcranial magnetic stimulation and computed electric field strength reduce stimulator-dependent differences in the motor threshold

“…The MR-imaging has its own accuracy, which is directly transferred to the stimulation when the MR images are used to render a 3D model of the subject's head. Furthermore, the state of alertness of the subject may affect neuronal excitability (Bertini et al, 2004;Civardi et al, 2001) and thus interfere with the results. These factors are difficult to control, but can be standardized to a certain degree by continuous monitoring of background EMG activity and subject wakefulness.…”