Anesthesia inhibited corticospinal excitability and attenuated the modulation of repetitive transcranial magnetic stimulation

Abstract

Background Lots of studies have measured motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in anesthetized animals. However, in awake animals, the measurement of TMS-induced MEP is scarce as lack of sufficient restraint. So far, the explicit study of anesthesia effects on corticospinal excitability and repetitive TMS (rTMS) induced modulation is still lacking. This study aimed to: (1) measure TMS-induced MEP in both awake restrained and anesthetized rats, (2) investigate the effect of anesthesia on corticospinal excitability, and (3) on rTMS-induced modulation. Methods MEP of eighteen rats were measured under both wakefulness and anesthesia using flexible binding and surface electrodes. Peak-to-peak MEP amplitudes, resting motor threshold (RMT) and the slope of stimulus response (SR) were extracted to investigate anesthesia effects on corticospinal excitability. Thereafter, 5 or 10 Hz rTMS was applied with 600 pulses, and the increase in MEP amplitude and the decrease in RMT were used to quantify rTMS-induced modulation. Results The RMT in the awake condition was 44.6 ± 1.2% maximum output (MO), the peak-to-peak MEP amplitude was 404.6 ± 48.8 μV at 60% MO. Under anesthesia, higher RMT (55.6 ± 2.9% MO), lower peak-to-peak MEP amplitudes (258.6 ± 32.7 μV) and lower slope of SR indicated that the corticospinal excitability was suppressed. Moreover, under anesthesia, high-frequency rTMS still showed significant modulation of corticospinal excitability, but the modulation of MEP peak-to-peak amplitudes was weaker than that under wakefulness. Conclusions This study measured TMS-induced MEP in both awake and anesthetized rats, and provided explicit evidence for the inhibitory effects of anesthesia on corticospinal excitability and on high-frequency rTMS-induced modulation of MEP.

In vivo low‐intensity magnetic pulses durably alter neocortical neuron excitability and spontaneous activity

“…Previous studies also demonstrated that neuronal excitability and sensory responses in the somatosensory cortex did not present obvious differences between sedation with sufentanil and wakefulness (Bruno & Sakmann, 2006; Simons et al., 1992), probably due to the relatively sparse levels of μ‐opioid receptors in this cortical region (Sahin et al., 1992). Sufentanil sedation thus avoids significant anaesthesia‐related modulation of cortical responses to magnetic stimulation, as observed in both animal and human studies (Bradley et al., 2022; Gersner et al., 2011; Silvanto & Pascual‐Leone, 2008; Wang et al., 2022). Heart rate and ECoG activity were continuously monitored to assess the depth of sedation, and we ensured the stability of physiological parameters, i.e.…”

“…Brain state varies with the level of vigilance, voluntary attention, concurrent behaviour and anaesthesia. Unlike in human rTMS studies, in which changes to neuron excitability are only measured indirectly, assessment of single neuron intrinsic excitability over time in animals requires long‐lasting stable intracellular recordings and the use of anaesthesia, which depresses responses to rTMS (Chong et al., 2014; Sykes et al., 2016; Wang et al., 2022). To obtain physiologically relevant data, our LI‐rTMS protocol was conducted in animals sedated with the synthetic opioid sufentanil, which not only retains fast and small‐amplitude cortical waves that resemble those encountered in wakefulness (Altwegg‐Boussac et al., 2014, 2017), but also does not significantly modify somatosensory cortical neuron excitability and sensory responses in comparison to those measured in awake animals (Bruno & Sakmann, 2006; Simons et al., 1992).…”