Criticality supports cross-frequency cortical-thalamic information transfer during conscious states
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This manuscript investigates thalamocortical communication and cross-frequency coupling in humans and animal models under anesthesia and the effects of the serotonergic psychedelic compound 5-MeO-DMT. These findings are exciting because they put two different perturbations of brain functions - anesthesia and psychedelic stimulation - into a single modeling framework. The framework describes anesthesia and psychedelic stimulation as opposing perturbations from normal brain function that respectively reduce and enhance thalamocortical communication.
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Abstract
Consciousness is thought to be regulated by bidirectional information transfer between the cortex and thalamus, but the nature of this bidirectional communication - and its possible disruption in unconsciousness - remains poorly understood. Here, we present two main findings elucidating mechanisms of corticothalamic information transfer during conscious states. First, we identify a highly preserved spectral channel of cortical-thalamic communication that is present during conscious states, but which is diminished during the loss of consciousness and enhanced during psychedelic states. Specifically, we show that in humans, mice, and rats, information sent from either the cortex or thalamus via δ/θ/α waves (∼1–13 Hz) is consistently encoded by the other brain region by high γ waves (52–104 Hz); moreover, unconsciousness induced by propofol anesthesia or generalized spike-and-wave seizures diminishes this cross-frequency communication, whereas the psychedelic 5-methoxy- N , N -dimethyltryptamine (5-MeO-DMT) enhances this low-to-high frequency interregional communication. Second, we leverage numerical simulations and neural electrophysiology recordings from the thalamus and cortex of human patients, rats, and mice to show that these changes in cross-frequency cortical-thalamic information transfer may be mediated by excursions of low-frequency thalamocortical electrodynamics toward/away from edge-of-chaos criticality, or the phase transition from stability to chaos. Overall, our findings link thalamic-cortical communication to consciousness, and further offer a novel, mathematically well-defined framework to explain the disruption to thalamic-cortical information transfer during unconscious states.
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eLife assessment
This manuscript investigates thalamocortical communication and cross-frequency coupling in humans and animal models under anesthesia and the effects of the serotonergic psychedelic compound 5-MeO-DMT. These findings are exciting because they put two different perturbations of brain functions - anesthesia and psychedelic stimulation - into a single modeling framework. The framework describes anesthesia and psychedelic stimulation as opposing perturbations from normal brain function that respectively reduce and enhance thalamocortical communication.
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Reviewer #1 (Public Review):
This is an interesting paper that shows disruption of thalamocortical communication in anesthesia, and enhancement under 5-MeO-DMT in an animal model, combined with a model to establish that these changes can be understood as a displacement from a critical point of a neural mass model. Overall, these results are exciting as they constitute evidence that very different brain states can be understood as two different points of a continuum of states, with a critical transition point in the middle.
These are my main detailed comments about this manuscript:
1. Psychedelic drug dosage: 5 mg/kg is possibly a low dose of 5-MeO-DMT, which exhibits nonlinear pharmacokinetics presenting a transition in drug serum concentration between 2 mg/kg and 10 mg/kg. (Shen, H. W., Jiang, X. L., & Yu, A. M. (2011). Nonlinear …
Reviewer #1 (Public Review):
This is an interesting paper that shows disruption of thalamocortical communication in anesthesia, and enhancement under 5-MeO-DMT in an animal model, combined with a model to establish that these changes can be understood as a displacement from a critical point of a neural mass model. Overall, these results are exciting as they constitute evidence that very different brain states can be understood as two different points of a continuum of states, with a critical transition point in the middle.
These are my main detailed comments about this manuscript:
1. Psychedelic drug dosage: 5 mg/kg is possibly a low dose of 5-MeO-DMT, which exhibits nonlinear pharmacokinetics presenting a transition in drug serum concentration between 2 mg/kg and 10 mg/kg. (Shen, H. W., Jiang, X. L., & Yu, A. M. (2011). Nonlinear pharmacokinetics of 5-methoxy-N, N-dimethyltryptamine in mice. Drug Metabolism and Disposition, 39(7), 1227-1234.)
2. Novelty of the neural mass approach to establish critical dynamics. The neural mass model is interesting but it is also well established that the features of LFPs during anesthesia can be captured using these kinds of models, including phenomenology such as burst suppression, emergence of high amplitude synchronized oscillations, etc.; see for instance Kuhlmann, L., Freestone, D. R., Manton, J. H., Heyse, B., Vereecke, H. E., Lipping, T., ... & Liley, D. T. (2016). Neural mass model-based tracking of anesthetic brain states. NeuroImage, 133, 438-456.). The same applies to the modeling of wakefulness LPF using neural masses to show that alpha oscillations emerge in thalamocortical systems at the edge of a dynamic phase transition, which can be reproduced by the dynamics of a Hopf bifurcation.
3. Is it possible that some of the results in the essential tremor group were influenced by the disease and its effects on the LPF dynamics, as it is known that tremors and seizures are associated by themselves with departures from critical dynamics?
4. Table 1 and other parts of the manuscript: multiple independent tests were conducted, does this require a correction for multiple comparisons to avoid the reporting of false positive results or its control by FDR or related approaches?
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Reviewer #2 (Public Review):
Toker et al. use a frequency-resolved analysis of cortico-thalamic and thalamo-cortical information transfer to determine at which combinations of frequencies a frequency-specific transfer of information exists, and how this transfer is modulated by anesthesia, spike-and-wave seizures, and psychedelic states. They find that anesthesia and seizures lower the transfer of information at a specific combination of frequencies (sending: 1.5-13Hz, receiving 50-100Hz), whereas psychedelic states induced by 5-MeO-DMT increase. The reductions were observed for both directions whereas significant increases were only observed from cortex to thalamus.
Neural mean-field modeling shows that these empirical observations may be linked to a deviation of neural dynamics from the critical point between ordered and chaotic …
Reviewer #2 (Public Review):
Toker et al. use a frequency-resolved analysis of cortico-thalamic and thalamo-cortical information transfer to determine at which combinations of frequencies a frequency-specific transfer of information exists, and how this transfer is modulated by anesthesia, spike-and-wave seizures, and psychedelic states. They find that anesthesia and seizures lower the transfer of information at a specific combination of frequencies (sending: 1.5-13Hz, receiving 50-100Hz), whereas psychedelic states induced by 5-MeO-DMT increase. The reductions were observed for both directions whereas significant increases were only observed from cortex to thalamus.
Neural mean-field modeling shows that these empirical observations may be linked to a deviation of neural dynamics from the critical point between ordered and chaotic dynamics.
The manuscript tackles an important question using innovative methods. Yet, the analysis of spectrally resolved information transfer at present suffers from an unfortunate choice of analysis parameters (especially a history length of 1, and a low number of surrogate data), that need to be changed to fully install trust in the presented results. The statistical analysis seems to suffer from so-called 'double-dipping', but there are several possible ways to fix this issue.
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