How hot is the hot zone? Computational modelling clarifies the role of parietal and frontoparietal connectivity during anaesthetic-induced loss of consciousness

Abstract

In recent years, specific cortical networks have been proposed to be crucial for sustaining consciousness, including the posterior hot zone and frontoparietal resting state networks (RSN). Here, we computationally evaluate the relative contributions of three RSNs – the default mode network (DMN), the salience network (SAL), and the central executive network (CEN) – to consciousness and its loss during propofol anaesthesia. Specifically, we use dynamic causal modelling (DCM) of 10 minutes of high-density EEG recordings (N = 10, 4 males) obtained during behavioural responsiveness, unconsciousness and post-anaesthetic recovery to characterise differences in effective connectivity within frontal areas, the posterior “hot zone”, frontoparietal connections, and between-RSN connections. We estimate – for the first time – a large DCM model (LAR) of resting EEG, combining the three RSNs into a rich club of interconnectivity. Consistent with the hot zone theory, our findings demonstrate reductions in inter-RSN connectivity in the parietal cortex. Within the DMN itself, the strongest reductions are in feed-forward frontoparietal and parietal connections at the precuneus node. Within the SAL and CEN, loss of consciousness generates small increases in bidirectional connectivity. Using novel DCM leave-one-out cross-validation, we show that the most consistent out-of-sample predictions of the state of consciousness come from a key set of frontoparietal connections. This finding also generalises to unseen data collected during post-anaesthetic recovery. Our findings provide new, computational evidence for the importance of the posterior hot zone in explaining the loss of consciousness, highlighting also the distinct role of frontoparietal connectivity in underpinning conscious responsiveness, and consequently, suggest a dissociation between the mechanisms most prominently associated with explaining the contrast between conscious awareness and unconsciousness, and those maintaining consciousness.HighlightsModelling shows that connectivity within hot zone tracks change of conscious stateSeparately, frontoparietal connections support maintenance of conscious stateStrength of frontoparietal connections predicts conscious state in unseen dataBoth parietal hot zone and frontoparietal connectivity important for consciousnessFundingThis work was supported by the UK Engineering and Physical Sciences Research Council (EP/P033199/1), Belgian National Funds for Scientific Research (FRS-FNRS), the University and University Hospital of Liege, the Fund Generet, the King Baudouin Foundation, the AstraZeneca Foundation, the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3), DOCMA project (EU-H2020-MSCA–RISE–778234), the BIAL Foundation, the European Space Agency (ESA) and the Belgian Federal Science Policy Office (BELSPO) in the framework of the PRODEX Programme, the Center-TBI project (FP7-HEALTH-602150), the Public Utility Foundation ‘Université Européenne du Travail’, “Fondazione Europea di Ricerca Biomedica”, the Mind Science Foundation, the European Commission, and the Special Research Fund of Ghent University. O.G. is research associate and S.L. is research director at the F.R.S-FNRS.Declaration of interestNone.Significance StatementVarious connectivity studies have suggested multiple network-level mechanisms driving changes in the state of consciousness, such as the posterior hot zone, frontal-, and large-scale frontoparietal networks. Here, we computationally evaluate evidence for these mechanisms using dynamic causal modeling for resting EEG recorded before and during propofol-anaesthesia, and demonstrate that, particularly, connectivity in the posterior hot zone is impaired during propofol-induced unconsciousness. With a robust cross-validation paradigm, we show that connectivity in the large-scale frontoparietal networks can consistently predict the state of consciousness and further generalise these findings to an unseen state of recovery. These results suggest a dissociation between the mechanisms most prominently associated with explaining the contrast between conscious awareness and unconsciousness, and those maintaining consciousness.

Highly Connected and Highly Variable: A Core Brain Network during Resting State Supports Propofol-induced Unconsciousness

“…Together, our study provides an analytic framework based on graph-theoretical tools to locate the NCC architecture, which complements our understanding about the anatomical footprints underlying consciousness by demonstrating their superior ability not only in functional integration, but also in dynamic functional diversification with modular processors. Furthermore, our results showed that the NCC candidates are not limited within the posterior cortical regions, but are distributed in wide-spread frontal-parietal cortices, which contribute to the ongoing discussion of whether the NCC are residing in the anterior or posterior regions 37,38 .…”

“…Notably, the medial prefrontal region exhibited reduction in both FCS and temporal MV associated with propofol anesthesia, indicating a crucial role of this anterior cluster in contributing to conscious experience. Taking together, these observations provide evidence for the pivotal contribution of the identified putative NCC, which covered most key structures predicted by both GNW and IIT, in supporting human consciousness, and more importantly, highlight the potential differential roles between prefrontal GNW regions and posterior IIT regions during propofolinduced loss of consciousness 37 .…”