Effects of External Stimulation on Psychedelic State Neurodynamics.

Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes, such as personality changes. These findings are particularly intriguing, given that a decrease of brain entropy is a robust indicator of loss of consciousness (e.g., from wakefulness to sleep). However, little is known about how context impacts the entropy-enhancing effect of psychedelics, which carries important implications for how it can be exploited in, for example, psychedelic psychotherapy. This article investigates how brain entropy is modulated by stimulus manipulation during a psychedelic experience by studying participants under the effects of lysergic acid diethylamide (LSD) or placebo, either with gross state changes (eyes closed vs open) or different stimuli (no stimulus vs music vs video). Results show that while brain entropy increases with LSD under all of the experimental conditions, it exhibits the largest changes when subjects have their eyes closed. Furthermore, brain entropy changes are consistently associated with subjective ratings of the psychedelic experience, but this relationship is disrupted when participants are viewing a video─potentially due to a "competition" between external stimuli and endogenous LSD-induced imagery. Taken together, our findings provide strong quantitative evidence of the role of context in modulating neural dynamics during a psychedelic experience, underlining the importance of performing psychedelic psychotherapy in a suitable environment.

Reduced emergent character of neural dynamics in patients with a disrupted connectome.

High-level brain functions are widely believed to emerge from the orchestrated activity of multiple neural systems. However, lacking a formal definition and practical quantification of emergence for experimental data, neuroscientists have been unable to empirically test this long-standing conjecture. Here we investigate this fundamental question by leveraging a recently proposed framework known as "Integrated Information Decomposition," which establishes a principled information-theoretic approach to operationalise and quantify emergence in dynamical systems - including the human brain. By analysing functional MRI data, our results show that the emergent and hierarchical character of neural dynamics is significantly diminished in chronically unresponsive patients suffering from severe brain injury. At a functional level, we demonstrate that emergence capacity is positively correlated with the extent of hierarchical organisation in brain activity. Furthermore, by combining computational approaches from network control theory and whole-brain biophysical modelling, we show that the reduced capacity for emergent and hierarchical dynamics in severely brain-injured patients can be mechanistically explained by disruptions in the patients' structural connectome. Overall, our results suggest that chronic unresponsiveness resulting from severe brain injury may be related to structural impairment of the fundamental neural infrastructures required for brain dynamics to support emergence.

Psychedelics and schizophrenia: Distinct alterations to Bayesian inference.

Schizophrenia and states induced by certain psychotomimetic drugs may share some physiological and phenomenological properties, but they differ in fundamental ways: one is a crippling chronic mental disease, while the others are temporary, pharmacologically-induced states presently being explored as treatments for mental illnesses. Building towards a deeper understanding of these different alterations of normal consciousness, here we compare the changes in neural dynamics induced by LSD and ketamine (in healthy volunteers) against those associated with schizophrenia, as observed in resting-state M/EEG recordings. While both conditions exhibit increased neural signal diversity, our findings reveal that this is accompanied by an increased transfer entropy from the front to the back of the brain in schizophrenia, versus an overall reduction under the two drugs. Furthermore, we show that these effects can be reproduced via different alterations of standard Bayesian inference applied on a computational model based on the predictive processing framework. In particular, the effects observed under the drugs are modelled as a reduction of the precision of the priors, while the effects of schizophrenia correspond to an increased precision of sensory information. These findings shed new light on the similarities and differences between schizophrenia and two psychotomimetic drug states, and have potential implications for the study of consciousness and future mental health treatments.

The strength of weak integrated information theory.

The integrated information theory of consciousness (IIT) is divisive: while some believe it provides an unprecedentedly powerful approach to address the 'hard problem', others dismiss it on grounds that it is untestable. We argue that the appeal and applicability of IIT can be greatly widened if we distinguish two flavours of the theory: strong IIT, which identifies consciousness with specific properties associated with maxima of integrated information; and weak IIT, which tests pragmatic hypotheses relating aspects of consciousness to broader measures of information dynamics. We review challenges for strong IIT, explain how existing empirical findings are well explained by weak IIT without needing to commit to the entirety of strong IIT, and discuss the outlook for both flavours of IIT.

A synergistic core for human brain evolution and cognition.

How does the organization of neural information processing enable humans' sophisticated cognition? Here we decompose functional interactions between brain regions into synergistic and redundant components, revealing their distinct information-processing roles. Combining functional and structural neuroimaging with meta-analytic results, we demonstrate that redundant interactions are predominantly associated with structurally coupled, modular sensorimotor processing. Synergistic interactions instead support integrative processes and complex cognition across higher-order brain networks. The human brain leverages synergistic information to a greater extent than nonhuman primates, with high-synergy association cortices exhibiting the highest degree of evolutionary cortical expansion. Synaptic density mapping from positron emission tomography and convergent molecular and metabolic evidence demonstrate that synergistic interactions are supported by receptor diversity and human-accelerated genes underpinning synaptic function. This information-resolved approach provides analytic tools to disentangle information integration from coupling, enabling richer, more accurate interpretations of functional connectivity, and illuminating how the human neurocognitive architecture navigates the trade-off between robustness and integration.

Greater than the parts: a review of the information decomposition approach to causal emergence.

Emergence is a profound subject that straddles many scientific disciplines, including the formation of galaxies and how consciousness arises from the collective activity of neurons. Despite the broad interest that exists on this concept, the study of emergence has suffered from a lack of formalisms that could be used to guide discussions and advance theories. Here, we summarize, elaborate on, and extend a recent formal theory of causal emergence based on information decomposition, which is quantifiable and amenable to empirical testing. This theory relates emergence with information about a system's temporal evolution that cannot be obtained from the parts of the system separately. This article provides an accessible but rigorous introduction to the framework, discussing the merits of the approach in various scenarios of interest. We also discuss several interpretation issues and potential misunderstandings, while highlighting the distinctive benefits of this formalism. This article is part of the theme issue 'Emergent phenomena in complex physical and socio-technical systems: from cells to societies'.

Whole-brain modelling identifies distinct but convergent paths to unconsciousness in anaesthesia and disorders of 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.

Ketamine and sleep modulate neural complexity dynamics in cats.

There is increasing evidence that the level of consciousness can be captured by neural informational complexity: for instance, complexity, as measured by the Lempel Ziv (LZ) compression algorithm, decreases during anaesthesia and non-rapid eye movement (NREM) sleep in humans and rats, when compared with LZ in awake and REM sleep. In contrast, LZ is higher in humans under the effect of psychedelics, including subanaesthetic doses of ketamine. However, it is both unclear how this result would be modulated by varying ketamine doses, and whether it would extend to other species. Here, we studied LZ with and without auditory stimulation during wakefulness and different sleep stages in five cats implanted with intracranial electrodes, as well as under subanaesthetic doses of ketamine (5, 10, and 15 mg/kg i.m.). In line with previous results, LZ was lowest in NREM sleep, but similar in REM and wakefulness. Furthermore, we found an inverted U-shaped curve following different levels of ketamine doses in a subset of electrodes, primarily in prefrontal cortex. However, it is worth noting that the variability in the ketamine dose-response curve across cats and cortices was larger than that in the sleep-stage data, highlighting the differential local dynamics created by two different ways of modulating conscious state. These results replicate previous findings, both in humans and other species, demonstrating that neural complexity is highly sensitive to capture state changes between wake and sleep stages while adding a local cortical description. Finally, this study describes the differential effects of ketamine doses, replicating a rise in complexity for low doses, and further fall as doses approach anaesthetic levels in a differential manner depending on the cortex.

Integrated information as a common signature of dynamical and information-processing complexity.

The apparent dichotomy between information-processing and dynamical approaches to complexity science forces researchers to choose between two diverging sets of tools and explanations, creating conflict and often hindering scientific progress. Nonetheless, given the shared theoretical goals between both approaches, it is reasonable to conjecture the existence of underlying common signatures that capture interesting behavior in both dynamical and information-processing systems. Here, we argue that a pragmatic use of integrated information theory (IIT), originally conceived in theoretical neuroscience, can provide a potential unifying framework to study complexity in general multivariate systems. By leveraging metrics put forward by the integrated information decomposition framework, our results reveal that integrated information can effectively capture surprisingly heterogeneous signatures of complexity-including metastability and criticality in networks of coupled oscillators as well as distributed computation and emergent stable particles in cellular automata-without relying on idiosyncratic, ad hoc criteria. These results show how an agnostic use of IIT can provide important steps toward bridging the gap between informational and dynamical approaches to complex systems.

Assessing awareness in severe Alzheimer's disease.

There is an urgent need to understand the nature of awareness in people with severe Alzheimer's disease (AD) to ensure effective person-centered care. Objective biomarkers of awareness validated in other clinical groups (e.g., anesthesia, minimally conscious states) offer an opportunity to investigate awareness in people with severe AD. In this article 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 six healthy older controls and three 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 questions that should be addressed using these biomarkers of awareness in future studies to improve understanding and care for people with severe AD.

Understanding Alzheimer's disease as a disorder of consciousness.

People with Alzheimer's disease (AD) demonstrate a range of alterations in consciousness. Changes in awareness of cognitive deficit, self-awareness, and introspection are seen early in AD, and dysfunction of awareness and arousal progresses with increasing disease severity. However, heterogeneity of deficits between individuals and a lack of empirical studies in people with severe dementia highlight the importance of identifying and applying biomarkers of awareness in AD. Impairments of awareness in AD are associated with neuropathology in regions that overlap with proposed neural correlates of consciousness. Recent developments in consciousness science provide theoretical frameworks and experimental approaches to help further understand the conscious experience of people with AD. Recognition of AD as a disorder of consciousness is overdue, and important to both understand the lived experience of people with AD and to improve care.

What it is like to be a bit: an integrated information decomposition account of emergent mental phenomena.

A central question in neuroscience concerns the relationship between consciousness and its physical substrate. Here, we argue that a richer characterization of consciousness can be obtained by viewing it as constituted of distinct information-theoretic elements. In other words, we propose a shift from quantification of consciousness-viewed as integrated information-to its decomposition. Through this approach, termed Integrated Information Decomposition (ΦID), we lay out a formal argument that whether the consciousness of a given system is an emergent phenomenon depends on its information-theoretic composition-providing a principled answer to the long-standing dispute on the relationship between consciousness and emergence. Furthermore, we show that two organisms may attain the same amount of integrated information, yet differ in their information-theoretic composition. Building on ΦID's revised understanding of integrated information, termed ΦR, we also introduce the notion of ΦR-ing ratio to quantify how efficiently an entity uses information for conscious processing. A combination of ΦR and ΦR-ing ratio may provide an important way to compare the neural basis of different aspects of consciousness. Decomposition of consciousness enables us to identify qualitatively different 'modes of consciousness', establishing a common space for mapping the phenomenology of different conscious states. We outline both theoretical and empirical avenues to carry out such mapping between phenomenology and information-theoretic modes, starting from a central feature of everyday consciousness: selfhood. Overall, ΦID yields rich new ways to explore the relationship between information, consciousness, and its emergence from neural dynamics.

Decomposing Spectral and Phasic Differences in Nonlinear Features between Datasets.

When employing nonlinear methods to characterize complex systems, it is important to determine to what extent they are capturing genuine nonlinear phenomena that could not be assessed by simpler spectral methods. Specifically, we are concerned with the problem of quantifying spectral and phasic effects on an observed difference in a nonlinear feature between two systems (or two states of the same system). Here we derive, from a sequence of null models, a decomposition of the difference in an observable into spectral, phasic, and spectrum-phase interaction components. Our approach makes no assumptions about the structure of the data and adds nuance to a wide range of time series analyses.

Increasing Patient Access to MRI Examinations in an Integrated Multispecialty Practice.

A multidisciplinary team evaluated and improved the MRI processes within the authors' integrated health care system, with the aim to increase patient access to MRI. The authors created a SMART (specific, measurable, achievable, relevant, and time-based) goal of decreasing the average number of days to wait for MRI examination by 50%, from 15 to 7.5 days, while also creating capacity to meet demand for same-day and next-day MRI appointment requests. The current performance metrics and processes were compared with available benchmarking and best practice data. Several work groups were created to empower and support frontline teams to identify and capture improvement opportunities. Across all MRI processes, teams focused on creating standard work, advancing practice to top of scope, removing waste, improving communication, reducing rework, and improving patient experience. Patient access to MRI was monitored, measured as the average number of days to wait from the time of scheduling to the MRI examination and time to the third-available appointment. The authors also monitored secondary outcomes (patient satisfaction, throughput metrics) and a balancing measure (technical repeat examination rates). The access improved after intervention: the average number of days to wait for MRI access decreased from 14.2 days to 5.8 days after the intervention (-8.4 days, -59.2%, P < .0001) and third-available appointment decreased from 18 days to 0 days. Ten to 20 same-day and next-day appointments became routinely available. The throughput metrics improved, and balancing measures were not changed. This project resulted in significant improvements in patient access to MRI examinations. The findings demonstrate the value of a multidisciplinary team applying comprehensive improvement strategies to increase patient access to complex services, such as MRI. ©RSNA, 2021.

Reconciling emergences: An information-theoretic approach to identify causal emergence in multivariate data.

The broad concept of emergence is instrumental in various of the most challenging open scientific questions-yet, few quantitative theories of what constitutes emergent phenomena have been proposed. This article introduces a formal theory of causal emergence in multivariate systems, which studies the relationship between the dynamics of parts of a system and macroscopic features of interest. Our theory provides a quantitative definition of downward causation, and introduces a complementary modality of emergent behaviour-which we refer to as causal decoupling. Moreover, the theory allows practical criteria that can be efficiently calculated in large systems, making our framework applicable in a range of scenarios of practical interest. We illustrate our findings in a number of case studies, including Conway's Game of Life, Reynolds' flocking model, and neural activity as measured by electrocorticography.

Neurophenomenology of induced and natural synaesthesia.

People with synaesthesia have additional perceptual experiences, which are automatically and consistently triggered by specific inducing stimuli. Synaesthesia therefore offers a unique window into the neurocognitive mechanisms underlying conscious perception. A long-standing question in synaesthesia research is whether it is possible to artificially induce non-synaesthetic individuals to have synaesthesia-like experiences. Although synaesthesia is widely considered a congenital condition, increasing evidence points to the potential of a variety of approaches to induce synaesthesia-like experiences, even in adulthood. Here, we summarize a range of methods for artificially inducing synaesthesia-like experiences, comparing the resulting experiences to the key hallmarks of natural synaesthesia which include consistency, automaticity and a lack of 'perceptual presence'. We conclude that a number of aspects of synaesthesia can be artificially induced in non-synaesthetes. These data suggest the involvement of developmental and/or learning components in the acquisition of synaesthesia, and they extend previous reports of perceptual plasticity leading to dramatic changes in perceptual phenomenology in adults. This article is part of a discussion meeting issue 'Bridging senses: novel insights from synaesthesia'.

Sustained Increases in the Quality of Imaging Histories Provided by Ordering Providers Resulting From Multidisciplinary Collaboration and Systems Design.

OBJECTIVE. The purpose of this quality improvement project was to create sustained improvement in the frequency of more complete imaging histories provided with imaging examinations submitted directly by ordering providers. A secondary purpose was increasing the number of characters submitted by ordering providers with imaging examinations. MATERIALS AND METHODS. A multidisciplinary team defined the components of a complete imaging history, a process that underwent several improvement cycles. Audits were regularly performed using consensus, and the project team regularly evaluated the completeness of the imaging histories. The final components of the definition of a complete imaging history included responses regarding what happened, when it happened, where the patient was experiencing pain, and the ordering provider's concern. Prompts were inserted into the electronic physician order entry process, and performance was monitored for an additional 18 months. RESULTS. A total of 10,236 orders were placed by providers in the study clinic from March 13, 2017, to December 16, 2018. Of the orders audited in the baseline period, 16.0% (64/397) of orders audited in the baseline period contained all four history components, which increased to 52.0% (2200/4234; absolute increase of 36.0%, relative increase of 225.0%; p < 0.0001) in the subsequent time periods, and improvement was sustained. The mean number of characters providers entered in the imaging histories they submitted increased from 45.4 characters per order during the baseline period to 75.4 (66.1% increase, p < 0.0001) after the intervention. CONCLUSION. By collaborating with a multidisciplinary team, we created a standardized definition of an imaging history, engineered our systems to include supportive prompts in the order entry interface, and sustainably improved the quality of imaging histories provided.

Response to Ruby et al: On a 'failed' attempt to manipulate conscious perception with transcranial magnetic stimulation to prefrontal cortex.

Does disruption of prefrontal cortical activity using transcranial magnetic stimulation (TMS) impair visual metacognition? An initial study supporting this idea (Rounis, Maniscalco, Rothwell, Passingham, & Lau, 2010) motivated an attempted replication and extension (Bor, Schwartzman, Barrett, & Seth, 2017). Bor et al. failed to replicate the initial study, concluding that there was not good evidence that TMS to dorsolateral prefrontal cortex impairs visual metacognition. This failed replication has recently been critiqued by some of the authors of the initial study (Ruby, Maniscalco, & Peters, 2018). Here we argue that these criticisms are misplaced. In our response, we encounter some more general issues concerning good practice in replication of cognitive neuroscience studies, and in setting criteria for excluding data when employing statistical analyses like signal detection theory. We look forward to further studies investigating the role of prefrontal cortex in metacognition, with increasingly refined methodologies, motivated by the discussions in this series of papers.

Coordinated neural, behavioral, and phenomenological changes in perceptual plasticity through overtraining of synesthetic associations.

Synesthesia is associated with additional perceptual experiences, which are automatically and consistently triggered by specific inducing stimuli. Synesthesia is also accompanied by more general sensory and cortical changes, including enhanced modality-specific cortical excitability. Extensive cognitive training has been shown to generate synesthesia-like phenomenology but whether these experiences are accompanied by neurophysiological changes characteristic of synesthesia remains unknown. Addressing this question provides a unique opportunity to elucidate the neural basis of perceptual plasticity relevant to conscious experiences. Here we investigate whether extensive training of letter-color associations leads not only to synesthetic experiences, but also to changes in cortical excitability. We confirm that overtraining synesthetic associations results in synesthetic phenomenology. Stroop tasks further reveal synesthesia-like performance following training. Electroencephalography and transcranial magnetic stimulation show, respectively, enhanced visual evoked potentials (in response to untrained patterns) and lower phosphene thresholds, demonstrating specific cortical changes. An active (using letter-symbol training) and a passive control confirmed these results were due to letter-color training and not simply to repeated testing. Summarizing, we demonstrate specific cortical changes, following training-induced acquisition of synesthetic phenomenology that are characteristic of genuine synesthesia. Collectively, our data reveal dramatic plasticity in human visual perception, expressed through a coordinated set of behavioral, neurophysiological, and phenomenological changes.