State-dependent effects of neural stimulation on brain function and cognition

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

“…Such discordance between results obtained in slices and in living brains has already been described in studies on activity‐dependent plasticity, in which opposite changes in synaptic efficacy could be induced in vivo and in vitro at the same synapses by the same stimulation paradigm (Mahon et al., 2004). These differences between in vitro and our in vivo findings further support the dependence of rTMS effects on ongoing activity in the targeted neural networks during stimulation (Bradley et al., 2022; Gersner et al., 2011; Silvanto & Pascual‐Leone, 2008).…”

“…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). Interestingly, TMS‐evoked potentials closely resembling those associated with wakefulness have been observed during paradoxical sleep, a sleep state associated with cortical rhythms reminiscent of the brain activity recorded in our experimental condition (Bradley et al., 2022; Massimini et al., 2010). Furthermore, the physiological relevance of LI‐rTMS‐induced hyperpolarization and reduced excitability in S1 neurons is supported by the absence of time‐dependent effects in sham and rCPS neuronal groups, which undergo the same sedation procedure.…”

“…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.…”

“…The influence of brain state on rTMS outcome is well established in both animal (Gersner et al, 2011;Poh et al, 2018Poh et al, , 2022 and human studies (see Bradley et al, 2022;Silvanto & Pascual-Leone, 2008 for reviews). Brain state varies with the level of vigilance, voluntary attention, concurrent behaviour and anaesthesia.…”

Modeling Brain Dysconnectivity in Rodents

“…However, how changes in single neuron firing pattern characteristics driven by NMS propagate into large-scale phenomena, such as large-scale fMRI network activity, is far less known. Recent studies have produced initial evidence that sustained neuromodulatory release exerts a powerful modulatory effect on coordinated neural activity and fMRI connectivity (104)(105)(106)(107). In humans, Shine and colleagues have shown that brain-wide fMRI responses across a range of cognitive tasks aligns with regional differences in the density of neuromodulatory receptors (105).…”