Reduced Repertoire of Cortical Microstates and Neuronal Ensembles in Medically Induced Loss of Consciousness

Wenzel, Michael; Han, Shuting; Smith, Elliot H.; Hoel, Erik; Greger, Bradley; House, Paul; Yuste, Rafael

doi:10.1016/j.cels.2019.03.007

Cited by 57 publications

(54 citation statements)

References 65 publications

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“…Unlike sleep, all three GAs strongly reduced overall neuronal spiking compared to wakefulness. Moreover, opposite to what has been found in the neocortex [25][26][27], they decorrelated network activity, leading to a fragmented network state. However, the induced patterns of activity were highly distinct between the three different anesthetic conditions and recovered to the pre-anesthetic status with disparate rates.…”

Section: Introductioncontrasting

confidence: 79%

Anesthetics fragment hippocampal network activity, alter spine dynamics and affect memory consolidation

Wei

Chini

Pöpplau

et al. 2020

Preprint

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20General anesthesia is characterized by reversible loss of consciousness accompanied by 21 transient amnesia. Yet, long-term memory impairment is an undesirable side-effect. How 22 different types of general anesthetics (GAs) affect the hippocampus, a brain region central to 23 memory formation and consolidation, is poorly understood. Using extracellular recordings, 24 chronic 2-photon imaging and behavioral analysis, we monitor the effects of isoflurane (Iso), 25 medetomidine/midazolam/fentanyl (MMF), and ketamine/xylazine (Keta/Xyl) on network 26 activity and structural spine dynamics in the hippocampal CA1 area of adult mice. GAs robustly 27 reduced spiking activity, decorrelated cellular ensembles, albeit with distinct activity signatures, 28 and altered spine dynamics. Iso anesthesia most closely resembled wakefulness, and network 29 alterations recovered more readily than with Keta/Xyl and MMF. Correspondingly, memory 30 consolidation was impaired after exposure to Keta/Xyl and MMF, but not Iso. Thus, different 31 anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity, and memory 32 consolidation, with implications for GA strategy appraisal in animal research and clinical 33 settings. 34 35 KEYWORDS 36 General anesthesia, isoflurane, ketamine, fentanyl, hippocampus, population dynamics, 37 network activity, spine turnover, episodic memory 38 39 Here, using behavioral analysis, extracellular recordings and chronic 2-photon calcium 86 imaging, we systematically assessed how memory performance, CA1 network dynamics and 87 synaptic structure are affected by three commonly used combinations of GAs: isoflurane (Iso), 88 midazolam/medetomidine/fentanyl (MMF), and ketamine in combination with xylazine 89 (Keta/Xyl). All three GAs strongly reduced overall neuronal spiking and, opposite to what has 90 been found in the neocortex (Goltstein et al., 2015; Greenberg et al., 2008; Wenzel et al., 91 2019), decorrelated network activity, leading to a fragmented network state. However, the 92 induced patterns of activity were highly distinct between the three different conditions and 93 recovered to the pre-anesthetic status with disparate rates. Testing the effect of repeated 94 anesthesia on spine dynamics revealed that Keta/Xyl, the condition which most strongly 95 affected calcium activity, significantly reduced spine turnover, leading to an overall 96 (over)stabilization of hippocampal synapses. In contrast, Iso and MMF mildly increased spine 97 turnover. Finally, we show that the two anesthetic conditions which induce longer-lasting 98 network alterations, Keta/Xyl and MMF, negatively influenced hippocampus-dependent 99 memory consolidation. Thus, different anesthetics, despite reaching a similar physiological 100 state, strongly differ in their effects on synaptic stability, hippocampal network activity, and 101 memory consolidation. 102 103 RESULTS 104 Iso, Keta/Xyl and MMF induce distinct patterns of network activity 105Iso, Keta/Xyl and MMF have distinct molecular targets and modes of ac...

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Section: Introductioncontrasting

confidence: 79%

Anesthetics fragment hippocampal network activity, alter spine dynamics and affect memory consolidation

Wei

Chini

Pöpplau

et al. 2020

Preprint

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“…Our findings are consistent with tendency of ketamine to preserve consciousness in states of dreamlike "dissociative anaesthesia" in contrast to propofol. It is unsurprising that highly complex behavioural states should be underpinned by complex dynamics, and evidence from studies of anaesthesia [83][84][85][86][87][88], disorders of consciousness [89][90][91], sleep [92], and psychedelic states [25,26] bears this out. Our results are consistent with, and extend these previous findings using a more principled measure of "complexity" than randomness-based measures.…”

Section: Complexitymentioning

confidence: 99%

Differential effects of propofol and ketamine on critical brain dynamics

et al. 2020

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Whether the brain operates at a critical “tipping” point is a long standing scientific question, with evidence from both cellular and systems-scale studies suggesting that the brain does sit in, or near, a critical regime. Neuroimaging studies of humans in altered states of consciousness have prompted the suggestion that maintenance of critical dynamics is necessary for the emergence of consciousness and complex cognition, and that reduced or disorganized consciousness may be associated with deviations from criticality. Unfortunately, many of the cellular-level studies reporting signs of criticality were performed in non-conscious systems (in vitro neuronal cultures) or unconscious animals (e.g. anaesthetized rats). Here we attempted to address this knowledge gap by exploring critical brain dynamics in invasive ECoG recordings from multiple sessions with a single macaque as the animal transitioned from consciousness to unconsciousness under different anaesthetics (ketamine and propofol). We use a previously-validated test of criticality: avalanche dynamics to assess the differences in brain dynamics between normal consciousness and both drug-states. Propofol and ketamine were selected due to their differential effects on consciousness (ketamine, but not propofol, is known to induce an unusual state known as “dissociative anaesthesia”). Our analyses indicate that propofol dramatically restricted the size and duration of avalanches, while ketamine allowed for more awake-like dynamics to persist. In addition, propofol, but not ketamine, triggered a large reduction in the complexity of brain dynamics. All states, however, showed some signs of persistent criticality when testing for exponent relations and universal shape-collapse. Further, maintenance of critical brain dynamics may be important for regulation and control of conscious awareness.

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“…For the category other , only Microstates remained, out of four, with 8 studies out of 11. Microstates characterize temporal properties (here we summarized average duration) of four unique motifs in the EEG topography (Wenzel et al, 2019) . While this parameter was fairly consistent within frequency bands ( CI = 0.80 for broadband, delta, theta, and gamma; CI = 0.59 for alpha and beta), this was based on a relatively few number of results, 5 and 9, respectively.…”

Section: Multi-parameter / Othermentioning

confidence: 99%

Proposed EEG measures of consciousness: a systematic, comparative review.

Nilsen¹,

Juel²,

Thürer³

et al. 2020

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Knowledge of which brain properties are required for consciousness is essential for improving clinical diagnostics and therapy as well as for investigating consciousness per se. The search for such properties has yielded many methods and measures for distinguishing conscious and apparently unconscious brain states. Here, we present a systematic literature review of 255 electroencephalography (EEG)-based measures of consciousness in humans. We show that measures based on signal diversity and event related potentials appear to be the most consistent. Specifically, spectral entropy, Lempel Ziv complexity, and spectral edge frequency, seem most practical, consistent, and reproducible. However, since most studies did not collect current or retrospective subjective reports about experiences, the states of consciousness were usually assessed from behavior. Hence, the ground truth about presence or absence of phenomenological experience in such cases is often uncertain, thus limiting the conclusions that can be drawn. We provide detailed overviews of general categories and specific measures of consciousness, to serve as a basis for further studies and future development.

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Reduced Repertoire of Cortical Microstates and Neuronal Ensembles in Medically Induced Loss of Consciousness

Abstract: Highlights d Cellular resolution population recordings of mLOC in mice and humans d mLOC is associated with a decreased cortical repertoire of discriminable microstates d Neuronal ensemble fragmentation toward independent single neuron activity during mLOC

Cited by 57 publications

References 65 publications

Anesthetics fragment hippocampal network activity, alter spine dynamics and affect memory consolidation

Anesthetics fragment hippocampal network activity, alter spine dynamics and affect memory consolidation

Differential effects of propofol and ketamine on critical brain dynamics

Proposed EEG measures of consciousness: a systematic, comparative review.

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