Neuronal-spiking-based closed-loop stimulation during cortical ON and OFF states in freely moving mice

Kahn, Martin; Krone, Lukas B.; Blanco‐Duque, Cristina; Guillaumin, Mathilde C. C.; Mann, Edward O.; Vyazovskiy, Vladyslav V.

doi:10.1101/2022.02.28.482319

Cited by 3 publications

(3 citation statements)

References 67 publications

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“…To address this possibility, we carefully inspected the local field potentials (LFP) and corresponding multi-unit activity (MUA), which were recorded in a subset of animals in the primary visual cortex (V1). As well known, slow waves during physiological sleep are accompanied by the occurrence of OFF periods – generalised periods of synchronised neuronal silence, when the recorded populations of neurons do not emit action potentials, typically lasting 100-200 ms. 58,59 As expected, after vehicle condition, LFPs and MUA showed well known signatures of wakefulness and SWS, where the latter was characterised by frequent OFF periods during LFP slow waves (Figure 5A-B, Supplementary Video 2). In contrast, OFF periods were rare during PS (Figure 5C, Supplementary Video 2).…”

Section: Resultssupporting

confidence: 73%

“Paradoxical wakefulness” induced by psychedelic 5-methoxy-N,N-dimethyltryptamine in mice

Bréant

Prius-Mengual

Bannerman

et al. 2022

Preprint

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Vigilance states - waking, slow-wave sleep (SWS) and paradoxical sleep, are thought to be controlled by several cortical and subcortical neuromodulatory circuits, among which the serotonergic (5-HT) system plays an important role. Recently, serotonergic psychedelics have attracted attention as potent antidepressants. While they are known to induce profound changes in subjective experience, the immediate and delayed effects of psychedelics on classical signatures of sleep-wake states remain under-investigated. To address this, we performed chronic electrophysiological recordings in the cortex of freely moving adult male mice following an injection of a short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). The most noticeable effect of 5-MeO-DMT administration was the suppression of paradoxical sleep and an acute induction of a mixed state of vigilance, characterised instead by prominent SWS-like slow waves on the EEG and LFP in awake, moving animals. We posit that the occurrence of this state in mice, which we refer to as 'paradoxical wakefulness', may be a rodent equivalent of the altered state of consciousness induced by psychedelics in humans.

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Section: Resultssupporting

confidence: 73%

“Paradoxical wakefulness” induced by psychedelic 5-methoxy-N,N-dimethyltryptamine in mice

Bréant

Prius-Mengual

Bannerman

et al. 2022

Preprint

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“…We are therefore hoping to lay a roadmap towards responsive, closed-loop (CL) DBS protocols modulating sleep and wakefulness. Such protocols could be tailored according to either macro or micro-scale of circuit excitability -although direct, spike-based approaches 60 may not be currently feasible with human implants. In the vein of our two-population hypothesis, we would expect a protocol, delivering stimulation that enhances endogenous PPNR beta during the DOWN-state and gamma during the transition to the cortical UP-state, to be the most efficient at promoting wakefulness through maximal cortical activation.…”

Section: Discussionmentioning

confidence: 99%

Tailoring Human Sleep: selective alteration through Brainstem Arousal Circuit Stimulation

Deli

Duchet

et al. 2023

Preprint

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Brainstem nuclei, such as the pedunculopontine nucleus, send activating projections to cortex, modulating states of sleep, wakefulness and arousal levels. Surgical modulation of subcortical activity using deep brain stimulation (DBS) is utilised in the management of pain and movement disorders. DBS of brainstem arousal circuits in a state-dependent manner could offer an attractive alternative in severe pharmacoresistant cases of hypersomnia and in disorders of consciousness, where behavioural activation is desired. We wanted to investigate if we can selectively induce wakefulness and/or alter sleep state through DBS of the PPN region (PPNR). To this end, we used the opportunity of implanted PPNR electrodes in stimulation-naive patients with multiple systems atrophy. PPNR activity was recorded during both slow wave sleep (SWS) and quiet wakefulness with simultaneous cortical EEG, in order to identify differences in brainstem oscillatory patterns during different states of excitability. PPNR DBS in two gamma frequency protocols (40Hz and 100Hz) was delivered during SWS of the same sleep stage and with comparable pre-trial levels of slow wave activity. Additionally, SHAM trials were used as a control where no stimulation was applied. We examined changes in cortical oscillatory power, changes in functional connectivity (coherence and causality) from pre- to post- stimulation and phase-locking of cortical oscillations with DBS frequencies and their sub-harmonics during stimulation. We also evaluated connectivity changes induced by DBS and corresponding differences in circuit dynamics between SWS and wakefulness. Beta and gamma PPNR oscillatory power increased when wake was compared to sleep. We saw clear PPNR power modulation by the phase of EEG slow wave, with significant increase in gamma compared to beta power during the excitable part of the slow-wave cycle. Gamma PPNR DBS induced transitions to wakefulness and REM, while it truncated sleep time compared to baseline. The 40Hz stimulation protocol was more efficient in reducing slow wave activity and increasing cortical beta power, compared to PPNR DBS at 100Hz. Furthermore, intrinsic cortical rhythms phase-locked with 40 Hz PPNR DBS to a significantly higher degree compared to the 100Hz protocol, with regional differences in phase-locking, suggesting a complex biological phenomenon. Finally, functional connectivity changes induced by PPNR DBS were consistent with differences in circuit dynamics between SWS and wakefulness. Overall, these results highlight the possibility of using DBS of brainstem arousal circuits to promote arousal and wakefulness, which opens new perspectives for using closed-loop approaches to modulate vigilance states in humans for therapeutic benefit.

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“…A 16-channel laminar probe (NeuroNexus Technologies Inc., Ann Arbor, MI, USA; model: A1×16-3mm-100-703-Z16) was implanted in primary motor cortex (AP +1.1 mm; ML −1.75 mm; rotated 15° in the AP axis towards the side of the implant) to perform intracortical recordings (LFP and MUA as described in Krone et al 2021). Each animal was also implanted with a bipolar concentric electrode (PlasticsOne Inc., Roanoke, VA, USA) in the right primary motor cortex, anterior to the frontal EEG screw in relation to a separate study (as described in Kahn et al 2022). All electrodes were attached to an 8-pin surface mount connector (8415-SM, Pinnacle Technology Inc, KS) affixed to the skull with dental cement (Associated Dental Products Ltd, Swindon, UK).…”

Section: Methodsmentioning

confidence: 99%

Detection of neuronal OFF periods as low amplitude neural activity segments

Harding

Guillaumin

Krone

et al. 2022

Preprint

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During non-rapid eye movement sleep (NREM), synchronised neuronal activity is reflected in a specific neural oscillation observed in neocortical electrophysiological signals: a low frequency component characterised by depth-positive/surface-negative potentials known as slow waves, corresponding to alternating periods of high (ON period) and low (OFF period) spiking activity. Often overlooked in favour of slow waves, there is an interest in understanding how neuronal silencing during OFF periods leads to the generation of slow waves and whether this relationship changes between cortical layers. The foremost issue in detecting population OFF periods is the absence of a formal, widely adopted definition. Here, we grouped segments of high frequency neural activity containing spikes, recorded from the neocortex, on the basis of amplitude and asked whether the population of low amplitude (LA) segments displayed the expected characteristics of OFF periods. We corroborate previous studies showing that low amplitude segments in neural activity signals are a uniquely identifiable structure with distinct characteristics from the surrounding signal spiking that identify them as OFF periods including NREM sleep predominance and association with a local field potential (LFP) slow wave. In addition, we attribute new characteristics to these segments not previously associated with OFF periods: vigilance-state-dependent duration and duration-dependent homeostatic response. This could suggest that ON/OFF periods are currently underdefined, and their appearance is less binary than previously considered, instead representing a continuum.

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Neuronal-spiking-based closed-loop stimulation during cortical ON and OFF states in freely moving mice

Cited by 3 publications

References 67 publications

“Paradoxical wakefulness” induced by psychedelic 5-methoxy-N,N-dimethyltryptamine in mice

“Paradoxical wakefulness” induced by psychedelic 5-methoxy-N,N-dimethyltryptamine in mice

Tailoring Human Sleep: selective alteration through Brainstem Arousal Circuit Stimulation

Detection of neuronal OFF periods as low amplitude neural activity segments

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