Adrian M. Owen

Which systems/organisms are conscious? New tests for consciousness (‘C-tests') are urgently needed. There is persisting uncertainty about when consciousness arises in human development, when it is lost due to neurological disorders and brain injury, and how it is distributed in nonhuman species. This need is amplified by recent and rapid developments in artificial intelligence (AI), neural organoids, and xenobot technology. Although a number of C-tests have been proposed in recent years, most are of limited use, and currently we have no C-tests for many of the populations for which they are most critical. Here, we identify challenges facing any attempt to develop C-tests, propose a multidimensional classification of such tests, and identify strategies that might be used to validate them.

Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is a rare condition caused by severe ADAMTS13 deficiency, leading to platelet aggregation and thrombosis. Despite treatment, patients are prone to cognitive impairment and depression. We investigated brain changes in iTTP patients during remission using advanced magnetic resonance imaging (MRI) techniques, correlating these changes with mood and neurocognitive tests. Twenty iTTP patients in remission (30 days post‐haematological remission) were compared with six healthy controls. MRI scans, including standard and specialized sequences, were conducted to assess white matter health. Increased T1 relaxation times were found in the cingulate cortex (p < 0.05), and elevated T2 relaxation times were observed in the cingulate cortex, frontal, parietal and temporal lobes (p < 0.05). Pathological changes in these areas are correlated …

Degeneration in the substantia nigra (SN) pars compacta (SNc) underlies motor symptoms in Parkinson’s disease (PD). Currently, there are no neuroimaging biomarkers that are sufficiently sensitive, specific, reproducible, and accessible for routine diagnosis or staging of PD. Although iron is essential for cellular processes, it also mediates neurodegeneration. MRI can localize and quantify brain iron using magnetic susceptibility, which could potentially provide biomarkers of PD.We measured iron in the SNc, SN pars reticulata (SNr), total SN, and ventral tegmental area (VTA), using quantitative susceptibility mapping (QSM) and R2* relaxometry, in PD patients and age-matched healthy controls (HCs). PD patients, diagnosed within five years of participation and HCs were scanned at 3T (22 PD and 23 HCs) and 7T (17 PD and 21 HCs) MRI. Midbrain nuclei were segmented using a probabilistic subcortical atlas …

Behavioural diagnosis of patients with disorders of consciousness (DOC) is challenging and prone to inaccuracies. Consequently, there have been increased efforts to develop bedside assessment based on EEG and event-related potentials (ERPs) that are more sensitive to the neural factors supporting conscious awareness. However, individual detection of residual consciousness using these techniques is less established. Here, we hypothesize that the cross-state similarity (defined as the similarity between healthy and impaired conscious states) of passive brain responses to auditory stimuli can index the level of awareness in individual DOC patients. To this end, we introduce the global field time-frequency representation-based discriminative similarity analysis (GFTFR-DSA). This method quantifies the average cross-state similarity index between an individual patient and our constructed healthy templates …

Maintaining cognitive capacity through adulthood has been the target of many recent studies that have examined the influence of lifestyle choices such as exercise, diet, and sleeping habits. Many of these studies have focused on a single factor (e.g., diet) and its effect on cognitive abilities; however, humans make numerous lifestyle choices every single day, many of which interact and influence each other. Here, we investigated whether combinations of lifestyle choices can predict better or worse cognitive performance in the general population, and whether optimal combinations of choices existed depending on the cognitive domain. Specifically, we examined 20 self-reported lifestyle choices, such as playing video games, drinking alcohol, and amount of exercise taken, in a sample of almost 10,000 participants. All participants also completed 12 cognitive tests that have been shown to generate three composite cognitive domain scores pertaining to short-term memory, verbal abilities, and reasoning. Using recursive feature elimination and random forest regression, we were able to explain 9% of the variance in short-term memory scores, 8% of the variance in reasoning scores, and 7% of the variance in verbal ability scores. While the regression model provided predictive power in all three domains, these levels indicate that even when considering a large number of lifestyle choices, there remains a considerable degree of variability in predicting short-term memory, reasoning and verbal abilities. Thus, while some modifiable lifestyle factors may have an impact on cognitive capacity, there likely exists no single optimal design for life.

Correction to: Predicting neurologic recovery after severe acute brain injury using resting-state networks Correction to: Predicting neurologic recovery after severe acute brain injury using resting-state networks J Neurol. 2024 Jan;271(1):624-625. doi: 10.1007/s00415-023-12018-0. Authors Matthew Kolisnyk 1 , Karnig Kazazian 2 , Karina Rego 3 , Sergio L Novi 1 4 , Conor J Wild 1 , Teneille E Gofton 5 , Derek B Debicki 5 , Adrian M Owen 1 4 6 , Loretta Norton 1 7 Affiliations 1 Western Institute of Neuroscience, Western Interdisciplinary Research Building, Western University, 1151 Richmond Street, London, ON, N6A 3K7, Canada. 2 Western Institute of Neuroscience, Western Interdisciplinary Research Building, Western University, 1151 Richmond Street, London, ON, N6A 3K7, Canada. kkazazia@uwo.ca. 3 Temerty Faculty of Medicine, University of Toronto, Toronto, Canada. 4 Department of Physiology and …

There is an urgent need to understand the nature of awareness in people with severe Alzheimer’s disease (AD) to ensure effective person-centred care. Objective biomarkers of awareness validated in other clinical groups (e.g. anaesthesia, minimally conscious states) offer an opportunity to investigate awareness in people with severe AD. In this paper we demonstrate the feasibility of using Transcranial magnetic stimulation (TMS) combined with EEG, event related potentials (ERPs) and fMRI to assess awareness in severe AD. TMS-EEG was performed in 6 healthy older controls and 3 people with severe AD. The perturbational complexity index (PCIST) was calculated as a measure of capacity for conscious awareness. People with severe AD demonstrated a PCIST around or below the threshold for consciousness, suggesting reduced capacity for consciousness. ERPs were recorded during a visual perception paradigm. In response to viewing faces, two patients with severe AD provisionally demonstrated similar visual awareness negativity to healthy controls. Using a validated fMRI movie-viewing task, independent component analysis in two healthy controls and one patient with severe AD revealed activation in auditory, visual and fronto-parietal networks. Activation patterns in fronto-parietal networks did not significantly correlate between the patient and controls, suggesting potential differences in conscious awareness and engagement with the movie. Although methodological issues remain, these results demonstrate the feasibility of using objective measures of awareness in severe AD. We raise a number of challenges and research …

The neural correlates of narrative stimuli have been established in clinical contexts as an effective means for detecting covert consciousness in behaviourally unresponsive patients using both fMRI and EEG. In particular, synchronization in frontoparietal regions between behaviourally unresponsive patients and controls can indicate whether these patients are processing the movie in a similar fashion as controls. However, it is unclear whether functional near-infrared spectroscopy (fNIRS) is sufficiently sensitive and consistent to detect these neural correlates at the level required for effective clinical diagnoses. In this study, whole brain inter-subject synchronization was observed using fNIRS in healthy controls when they watched part of the movie Bang! You’re Dead and listened to an audio clip from the movie Taken. Importantly, synchronization was largely reduced or absent when participants viewed scrambled versions of those clips. Moreover, neural activity during intact clips could predict independently acquired ratings of suspense. To assess the prospect of using synchronization as a diagnostic tool in behaviourally unresponsive patients, single-participant reproducibility was estimated by measuring the consistency and sensitivity of the results. Consistency was quantified by estimating each participant’s dissimilarity in their synchronization using Euclidean distance, which determined that the synchronization was statistically similar in 14/15 participants in Bang! You are Dead and 15/15 participants in Taken. Moreover, machine learning algorithms were able to decode between both intact conditions and their scrambled counterparts using …

Integrated Information Theory was developed to explain and quantify consciousness, arguing that conscious systems consist of elements that are integrated through their causal properties. This study presents an implementation of Integrated Information Theory 3.0, the latest version of this framework, to functional MRI data. Data were acquired from 17 healthy subjects who underwent sedation with propofol, a short-acting anaesthetic. Using the PyPhi software package, we systematically analyze how Φmax, a measure of integrated information, is modulated by the sedative in different resting-state networks. We compare Φmax to other proposed measures of conscious level, including the previous version of integrated information, Granger causality, and correlation-based functional connectivity. Our results indicate that Φmax presents a variety of sedative-induced behaviours for different networks. Notably, changes to …

Predicting the outcome of critically ill patients after cardiac arrest is a substantial clinical challenge. As part of the 2023 George B. Moody PhysioNet Challenge, we used an ensemble of extreme gradient boosted (XGB) trees, trained on electroencephalogram (EEG) data across three distinct levels of analysis to predict neurological outcomes. To this end, we preprocessed raw EEG recordings via filtering and motion correction and extracted several features, including connectivity, power spectral density (PSD), and coherence. The first step of model training and optimization occurred at the Recording level, where we trained XGB trees on each feature set (e.g., PSD) derived from every EEG recording. These models predicted the neurologic outcome for each recording. At the Patient level, we computed the median of each feature set for each patient, which we used to make patient-specific predictions. Finally, the …

Given their recent success in counseling and psychiatry, the dialogue around psychedelics has mainly focused on their applications for mental health. Insights from psychedelic research, however, are not limited to treating mental health, but also have much to offer our current understanding of consciousness. The investigation of psychedelic states has offered new perspectives on how different aspects of conscious experience are mediated by brain activity; as such, much more has been learned about consciousness in terms of its phenomenology and potential mechanisms. One theory that describes how psychedelics influence brain activity is the “entropic brain theory” (EBT), which attempts to understand conscious states—normal and psychedelic—in terms of “brain entropy.” Given its wide explanatory reach, this theory has several implications for current debates in consciousness research, namely the issue …

Humor comprehension (i.e., getting a joke) and humor appreciation (i.e., enjoying a joke) are distinct, cognitively complex processes. Functional magnetic resonance imaging (fMRI) investigations have identified several key cortical regions but have overlooked subcortical structures that have theoretical importance in humor processing. The dorsal striatum (DS) contributes to working memory, ambiguity processing, and cognitive flexibility, cognitive functions that are required to accurately recognize humorous stimuli. The ventral striatum (VS) is critical in reward processing and enjoyment. We hypothesized that the DS and VS play important roles in humor comprehension and appreciation, respectively. We investigated the engagement of these regions in these distinct processes using fMRI. Twenty-six healthy young male and female human adults completed two humor-elicitation tasks during a 3 tesla fMRI scan …

Spindles are often temporally coupled to slow waves (SW). These SW-spindle complexes have been implicated in memory consolidation that involves transfer of information from the hippocampus to the neocortex. However, spindles and SW, which are characteristic of NREM sleep, can occur as part of this complex, or in isolation. It is not clear whether dissociable parts of the brain are recruited when coupled to SW vs. when spindles or SW occur in isolation. Here, we tested differences in cerebral activation time-locked to uncoupled spindles, uncoupled SW and coupled SW-spindle complexes using simultaneous EEG-fMRI. Consistent with the “active system model,” we hypothesized that brain activations time-locked to coupled SW-spindles would preferentially occur in brain areas known to be critical for sleep-dependent memory consolidation. Our results show that coupled spindles and uncoupled spindles recruit distinct parts of the brain. Specifically, we found that hippocampal activation during sleep is not uniquely related to spindles. Rather, this process is primarily driven by SWs and SW-spindle coupling. In addition, we show that SW-spindle coupling is critical in the activation of the putamen. Importantly, SW-spindle coupling specifically recruited frontal areas in comparison to uncoupled spindles, which may be critical for the hippocampal-neocortical dialogue that preferentially occurs during sleep.

Objective: We evaluate the feasibility of using functional near-infrared spectroscopy (fNIRS) to detect the neural correlates of conscious processing with one patient in the intensive care unit and 25 healthy controls. Background: Little is known about the extent of covert cognitive processing in unresponsive critically ill patients. Advanced neuroimaging techniques offer new ways of enhancing our understanding of brain function in this population by providing objective and quantifiable markers of neural activity. fNIRS is a promising modality for this application since the technology is portable, inexpensive, and susceptible to motion, making it ideal for the intensive care environment. Design/Methods: A series of validated neuroimaging paradigms were employed to assess somatosensory perception, auditory processing, and covert command following in a behaviourally unresponsive patient who sustained a brainstem stroke and with 25 healthy controls. An fNIRS system with 129 channels …

BackgroundSedation of critically ill patients with inhaled anaesthetics may reduce lung inflammation, time to extubation, and ICU length of stay compared with intravenous (i.v.) sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes in this population is unclear. In this systematic review, we aimed to summarise the effect of inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults.MethodsWe searched MEDLINE, EMBASE, and PsycINFO for case series, retrospective, and prospective studies in critically ill adults sedated with inhaled anaesthetics. Outcomes included delirium, psychomotor and neurological recovery, long-term cognitive dysfunction, ICU memories, anxiety, depression, post-traumatic stress disorder (PTSD), and instruments used for assessment.ResultsThirteen studies were included in distinct populations of post-cardiac arrest survivors (n=4 …

We investigated how repeated exposure to a stimulus affects intersubject synchrony in the brains of young and older adults. We used functional magnetic resonance imaging (fMRI) to measure brain responses to familiar and novel stimuli. Young adults participated in a familiarization paradigm designed to mimic ‘natural’ exposure while older adults were presented with stimuli they had known for more than 50 years. Intersubject synchrony was calculated to detect common stimulus-driven brain activity across young and older adults as they listened to the novel and familiar stimuli. Contrary to our hypotheses, synchrony was not related to the amount of stimulus exposure; both young and older adults showed more synchrony to novel than to familiar stimuli regardless of whether the stimuli had been heard once, known for a few weeks, or known for more than 50 years. In young adults these synchrony differences were …

Objective Little is known about residual cognitive function in the earliest stages of serious brain injury. Functional neuroimaging has yielded valuable diagnostic and prognostic information in chronic disorders of consciousness, such as the vegetative state (also termed unresponsive wakefulness syndrome). The objective of the current study was to determine if functional neuroimaging could be efficacious in the assessment of cognitive function in acute disorders of consciousness, such as coma, where decisions about the withdrawal of life‐sustaining therapies are often made. Methods A hierarchical functional magnetic resonance imaging (fMRI) approach assessed sound perception, speech perception, language comprehension, and covert command following in 17 critically ill patients admitted to the intensive care unit (ICU). Results Preserved auditory function was observed in 15 patients (88%), whereas 5 (29 …

It has been suggested that conscious experience is linked to the richness of brain state repertories, which change in response to environmental and internal stimuli. High-level sensory stimulation has been shown to alter local brain activity and induce neural synchrony across participants. However, the dynamic interplay of cognitive processes underlying moment-to-moment information processing remains poorly understood. Using naturalistic movies as an ecological laboratory model of the real world, here we investigate how the processing of complex naturalistic stimuli alters the dynamics of brain network interactions and how these in turn support information processing. Participants underwent fMRI recordings during movie watching, scrambled movie watching, and resting. By measuring the phase-synchrony between different brain networks, we analyzed whole-brain connectivity patterns. Our finding revealed …

(1) Background: Although cognitive impairments in coma survivors are common, methods of measuring long-term cognitive outcomes in this population are inconsistent, precluding the development of a strong evidence-base to support clinical decision making. In this literature review, we identify and characterize the measures used to track cognitive recovery in coma survivors to data. (2) Methods: We extracted the instrument used for cognitive assessment, the cognitive domains assessed, methods administration and scoring, and timing of assessment from 134 of 996 screened records. (3) Results: A total of 133 unique cognitive tests and cognitive testing batteries were identified, with 97 cognitive instruments used in less than three articles. The instruments assessed 20 different cognitive domains, with 73 articles also using tests that assess general “cognitive ability”. Cognitive instruments ranged from subjective assessments to comprehensive cognitive batteries. There were inconsistent points of reference for the timing of assessment across studies, with few studies repeating assessments at more than one time point, and arbitrary time intervals between tests. (4) Conclusions: Overall, this review illustrates the enormous disparity between studies that track cognitive outcome in coma survivors, and the need for a systematic, patient-accessible method of assessing cognitive functioning in future studies with this population.

Anaesthesia combined with functional neuroimaging provides a powerful approach for understanding the brain mechanisms of consciousness. Although propofol is used ubiquitously in clinical interventions that reversibly suppress consciousness, it shows large inter‐individual variability, and the brain bases of this variability remain poorly understood. We asked whether three networks key to conscious cognition—the dorsal attention (DAN), executive control (ECN), and default mode (DMN)—underlie responsiveness variability under anaesthesia. Healthy participants (N = 17) were moderately anaesthetized during narrative understanding and resting‐state conditions inside the Magnetic Resonance Imaging scanner. A target detection task measured behavioural responsiveness. An independent behavioural study (N = 25) qualified the attention demands of narrative understanding. Then, 30% of participants were …