Cortico-thalamo-cortical interactions modulate electrically evoked EEG responses in mice

Abstract

Perturbational complexity analysis predicts the presence of consciousness in volunteers and patients by stimulating the brain with brief pulses, recording electroencephalographic (EEG) responses, and computing their spatiotemporal complexity. We examined the underlying neural circuits in mice by directly stimulating cortex while recording with EEG and Neuropixels probes during wakefulness and isoflurane anesthesia. When mice are awake, stimulation of deep cortical layers reliably evokes locally a brief pulse of excitation, followed by a bi-phasic sequence of 120 ms profound off period and a rebound excitation. A similar pattern, partially attributed to burst spiking, is seen in thalamic nuclei, and is associated with a pronounced late component in the evoked EEG. We infer that cortico-thalamo-cortical interactions drive the long-lasting evoked EEG signals elicited by deep cortical stimulation during the awake state. The cortical and thalamic off period and rebound excitation, and the late component in the EEG, are reduced during running and absent during anesthesia.

Laminar evoked responses in mouse somatosensory cortex suggest a special role for deep layers in cortical complexity

“…Conversely, the long‐lasting, phase‐locked responses that we observed in layers 6, 5 and 1 match more closely the input from thalamic matrix and intralaminar nuclei (Harris et al, 2019) and may even directly reflect synaptic input from these nuclei, which contribute to cortical arousal in humans (Schiff et al, 2007), monkeys (Bastos et al, 2021; Redinbaugh et al, 2020) and rats (Xu et al, 2020). Indeed, a recent study suggested that long‐lasting EEG responses following cortical stimulation are sustained through cortico–thalamo–cortical interactions in wake but not anesthetized mice (Claar et al, 2023).…”

“…In contrast, when consciousness is lost or strongly reduced, for example, in slow‐wave sleep or anaesthesia, the cortical responses are short‐lasting and stereotypic, resulting in low PCI values (Casali et al, 2013; Massimini et al, 2005). Similarly, recent experiments in rats and mice have shown that general anaesthesia and deep sleep reduce PCI and global functional connectivity following electrical stimulation in vivo (Arena et al, 2021, 2022; Cavelli et al, 2023; Claar et al, 2023). In vitro studies in cortical slices showed that the application of noradrenaline and a cholinergic agonist increased the PCI (D'Andola et al, 2018), whereas GABA antagonists reduced PCI (Barbero‐Castillo et al, 2021).…”

Corticothalamic modelling of sleep neurophysiology with applications to mobile EEG

“…The principal brain structure that drives brain state changes during sleep, including our measurement of them with EEG, is the corticothalamic system [28][29][30]. Different stages of sleep have been linked to changes in corticothalamic activity [29,[31][32][33][34] and to changes in the periodic and aperiodic components of the EEG signals over those changes [35,36,34,37]. For instance, the transition from wakefulness to N1 sleep is also characterized by an increase in the slope of the 1/f component and the low-frequency band powers [35,36], which is itself observed to be associated with corticothalamic communication [30].…”

Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans

“…The neuronal excitation spreads along the stimulated axons and causes secondary activations of connected neuronal populations generating later components of the EPs. These late responses have been ascribed to recurrent interactions across cortical areas 17 , cortico-thalamo-cortical loops 18,19 and in the case of non-invasive stimulation to somatosensory and auditory confounds due to the activation of somatosensory and auditory receptors 20 . Brain areas generating scalp EPs can be coarsely identified using parameter-dependent source reconstruction methods 21–25 ; however, the relationship between EP components and the spiking activity of the underlying neuronal populations is far from clear.…”

“…A multiscale approach that combines EEG, local currents, and single neurons’ recordings is therefore important to identify the origin of the late EP component. The neuronal mechanisms generating local field potentials ( LFPs ) have been explored in classical studies 26–28 , but only few studies have combined and linked LFP, EEG and units’ activity 18,29,29 . We previously inferred that cortico-thalamo-cortical interactions drive the long-lasting EPs 18 , however we did not causally link the contribution of the thalamus to a specific EP component.…”