Long-term cognitive impairment is common among ICU survivors, but its natural history remains unclear. In this systematic review, we report the frequency of cognitive impairment in ICU survivors across various time points after ICU discharge that were extracted from 46 of the 3,350 screened records. Prior studies used a range of cognitive instruments, including subjective assessments (10 studies), single or screening cognitive test such as Mini-Mental State Examination or Trail Making Tests A and B (23 studies), and comprehensive cognitive batteries (26 studies). The mean prevalence of cognitive impairment was higher with objective rather than subjective assessments (54% [95% confidence interval (CI), 51-57%] vs. 35% [95% CI, 29-41%] at 3 months after ICU discharge) and when comprehensive cognitive batteries rather than Mini-Mental State Examination were used (ICU discharge: 61% [95% CI, 38-100%] vs. 36% [95% CI, 15-63%]; 12 months after ICU discharge: 43% [95% CI, 10-78%] vs. 18% [95% CI, 10-20%]). Patients with acute respiratory distress syndrome had higher prevalence of cognitive impairment than mixed ICU patients at ICU discharge (82% [95% CI, 78-86%] vs. 48% [95% CI, 44-52%]). Although some studies repeated tests at more than one time point, the time intervals between tests were arbitrary and dictated by operational limitations of individual studies or chosen cognitive instruments. In summary, the prevalence and temporal trajectory of ICU-related cognitive impairment varies depending on the type of cognitive instrument used and the etiology of critical illness. Future studies should use modern comprehensive batteries to better delineate the natural history of cognitive recovery across ICU patient subgroups and determine which acute illness and treatment factors are associated with better recovery trajectories.

A central goal of neuroscience is to understand how the brain synthesises information from multiple inputs to give rise to a unified conscious experience. This process is widely believed to require integration of information. Here, we combine information theory and network science to address two fundamental questions: how is the human information-processing architecture functionally organised? And how does this organisation support human consciousness? To address these questions, we leverage the mathematical framework of Integrated Information Decomposition to delineate a cognitive architecture wherein specialised modules interact with a “synergistic global workspace,” comprising functionally distinct gateways and broadcasters. Gateway regions gather information from the specialised modules for processing in the synergistic workspace, whose contents are then further integrated to later be made widely available by broadcasters. Through data-driven analysis of resting-state functional MRI, we reveal that gateway regions correspond to the brain’s well-known default mode network, whereas broadcasters of information coincide with the executive control network. Demonstrating that this synergistic workspace supports human consciousness, we further apply Integrated Information Decomposition to BOLD signals to compute integrated information across the brain. By comparing changes due to propofol anaesthesia and severe brain injury, we demonstrate that most changes in integrated information happen within the synergistic workspace. Furthermore, it was found that loss of consciousness corresponds to reduced integrated information between gateway, but not broadcaster, regions of the synergistic workspace. Thus, loss of consciousness may coincide with breakdown of information integration by this synergistic workspace of the human brain. Together, these findings demonstrate that refining our understanding of information-processing in the human brain through Integrated Information Decomposition can provide powerful insights into the human neurocognitive architecture, and its role in supporting consciousness.

The human brain entertains rich spatiotemporal dynamics, which are drastically reconfigured when consciousness is lost due to anaesthesia or disorders of consciousness (DOC). Here, we sought to identify the neurobiological mechanisms that explain how transient pharmacological intervention and chronic neuroanatomical injury can lead to common reconfigurations of neural activity. We developed and systematically perturbed a neurobiologically realistic model of whole-brain haemodynamic signals. By incorporating PET data about the cortical distribution of GABA receptors, our computational model reveals a key role of spatially-specific local inhibition for reproducing the functional MRI activity observed during anaesthesia with the GABA-ergic agent propofol. Additionally, incorporating diffusion MRI data obtained from DOC patients reveals that the dynamics that characterise loss of consciousness can also emerge from randomised neuroanatomical connectivity. Our results generalise between anaesthesia and DOC datasets, demonstrating how increased inhibition and connectome perturbation represent distinct neurobiological paths towards the characteristic activity of the unconscious brain.

Earlier this year, the Royal College of Physicians in the UK published national guidelines on the management of patients with prolonged disorders of consciousness, updating their 2013 guidance ‘particularly in relation to recent developments in assessment and management and … changes in the law governing … the withdrawal of clinically assisted nutrition and hydration’. The report’s primary focus is on patients who could live for many years with treatment and care. This update, by a neurologist, an imaging neuroscientist, and a lawyer-ethicist, questions the document’s rejection of any significant role for neuroimaging techniques including functional MRI and/or bedside EEG to detect covert consciousness in such patients. We find the reasons for this rejection unconvincing, given (i) the significant advances made in the use of this technology in recent years; and (ii) the wider scope for its use envisaged by the earlier (2018) guidelines issued by the American Academy of Neurology. We suggest that, since around one in five patients diagnosed with prolonged disorders of consciousness are in fact conscious enough to follow commands in a neuroimaging context (i.e. those who are ‘covertly conscious’ or those with ‘cognitive motor dissociation’), and given the clinical, ethical and legal importance of determining whether patients with prolonged disorders of consciousness are legally competent or at least able to express their views and feelings, the guidance from the Royal College of Physicians requires urgent review.

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