Dynamic Functional Hyperconnectivity after Psilocybin Intake is Primarily Associated with Oceanic Boundlessness.

BACKGROUND: Psilocybin is a widely studied psychedelic substance, which leads to the psychedelic state, a specific altered state of consciousness. To date, the relationship between the psychedelic state's neurobiological and experiential patterns remains under-characterized as they are often analyzed separately. We investigated the relationship between neurobiological and experiential patterns after psilocybin by focusing on the link between dynamic cerebral connectivity and retrospective questionnaire assessment. METHODS: Healthy participants were randomized to receive either psilocybin (n=22) or placebo (n=27) and scanned for six minutes in eyes open resting state during the peak subjective drug effect (102 minutes post-treatment) in ultra-high field 7T MRI. The 5D-ASC Rating Scale was administered 360 minutes after drug intake. RESULTS: Under psilocybin, there were alterations across all dimensions of the 5D-ASC scale, and widespread increases in averaged brain functional connectivity. Further time-varying functional connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low BOLD signal amplitude, suggesting heightened cortical arousal. In terms of neuro-experiential links, canonical correlation analysis showed higher transition probabilities to the hyperconnected pattern with feelings of oceanic boundlessness, and secondly with visionary restructuralization. CONCLUSIONS: Psilocybin generates profound alterations both at the brain and at the experiential level. We suggest that the brain's tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental associations. These findings illuminate the intricate interplay between brain dynamics and subjective experience under psilocybin, providing insights into the neurophysiology and neuro-experiential qualities of the psychedelic state.

Whole-Brain Deactivations Precede Uninduced Mind-Blanking Reports.

Mind-blanking (MB) is termed as the inability to report our immediate-past mental content. In contrast to mental states with reportable content, such as mind-wandering or sensory perceptions, the neural correlates of MB started getting elucidated only recently. A notable particularity that pertains to MB studies is the way MB is instructed for reporting, like by deliberately asking participants to "empty their minds." Such instructions were shown to induce fMRI activations in frontal brain regions, typically associated with metacognition and self-evaluative processes, suggesting that MB may be a result of intentional mental content suppression. Here, we aim at examining this hypothesis by determining the neural correlates of MB without induction. Using fMRI combined with experience-sampling in 31 participants (22 female), univariate analysis of MB reports revealed deactivations in occipital, frontal, parietal, and thalamic areas, but no activations in prefrontal regions. These findings were confirmed using Bayesian region-of-interest analysis on areas previously shown to be implicated in induced MB, where we report evidence for frontal deactivations during MB reports compared with other mental states. Contrast analysis between reports of MB and content-oriented mental states also revealed deactivations in the left angular gyrus. We propose that these effects characterize a neuronal profile of MB, where key thalamocortical nodes are unable to communicate and formulate reportable content. Collectively, we show that study instructions for MB lead to differential neural activation. These results provide mechanistic insights linked to the phenomenology of MB and point to the possibility of MB being expressed in different forms.SIGNIFICANCE STATEMENT This study explores how brain activity changes when individuals report unidentifiable thoughts, a phenomenon known as mind-blanking (MB). It aims to detect changes in brain activations and deactivations when MB is reported spontaneously, as opposed to the neural responses that have been previously reported when MB is induced. By means of brain imaging and experience-sampling, the study points to reduced brain activity in a wide number of regions, including those mesio-frontally which were previously detected as activated during induced MB. These results enhance our understanding of the complexity of spontaneous thinking and contribute to broader discussions on consciousness and reportable experience.

In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape.

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain's rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganization of the brain's functional architecture.

Altered Brain Connectivity and Network Topological Organization in a Non-ordinary State of Consciousness Induced by Hypnosis.

Hypnosis has been shown to be of clinical utility; however, its underlying neural mechanisms remain unclear. This study aims to investigate altered brain dynamics during the non-ordinary state of consciousness induced by hypnosis. We studied high-density EEG in 9 healthy participants during eyes-closed wakefulness and during hypnosis, induced by a muscle relaxation and eyes fixation procedure. Using hypotheses based on internal and external awareness brain networks, we assessed region-wise brain connectivity between six ROIs (right and left frontal, right and left parietal, upper and lower midline regions) at the scalp level and compared across conditions. Data-driven, graph-theory analyses were also carried out to characterize brain network topology in terms of brain network segregation and integration. During hypnosis, we observed (1) increased delta connectivity between left and right frontal, as well as between right frontal and parietal regions; (2) decreased connectivity for alpha (between right frontal and parietal and between upper and lower midline regions) and beta-2 bands (between upper midline and right frontal, frontal and parietal, also between upper and lower midline regions); and (3) increased network segregation (short-range connections) in delta and alpha bands, and increased integration (long-range connections) in beta-2 band. This higher network integration and segregation was measured bilaterally in frontal and right parietal electrodes, which were identified as central hub regions during hypnosis. This modified connectivity and increased network integration-segregation properties suggest a modification of the internal and external awareness brain networks that may reflect efficient cognitive-processing and lower incidences of mind-wandering during hypnosis.

Low-dimensional organization of global brain states of reduced consciousness.

Brain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its properties remain unclear. We combine whole-brain modeling, data augmentation, and deep learning for dimensionality reduction to determine a mapping representing states of consciousness in a low-dimensional space, where distances parallel similarities between states. An orderly trajectory from wakefulness to patients with brain injury is revealed in a latent space whose coordinates represent metrics related to functional modularity and structure-function coupling, increasing alongside loss of consciousness. Finally, we investigate the effects of model perturbations, providing geometrical interpretation for the stability and reversibility of states. We conclude that conscious awareness depends on functional patterns encoded as a low-dimensional trajectory within the vast space of brain configurations.

Neuroplasticity in F16 fighter jet pilots.

Exposure to altered g-levels causes unusual sensorimotor demands that must be dealt with by the brain. This study aimed to investigate whether fighter pilots, who are exposed to frequent g-level transitions and high g-levels, show differential functional characteristics compared to matched controls, indicative of neuroplasticity. We acquired resting-state functional magnetic resonance imaging data to assess brain functional connectivity (FC) changes with increasing flight experience in pilots and to assess differences in FC between pilots and controls. We performed whole-brain exploratory and region-of-interest (ROI) analyses, with the right parietal operculum 2 (OP2) and the right angular gyrus (AG) as ROIs. Our results show positive correlations with flight experience in the left inferior and right middle frontal gyri, and in the right temporal pole. Negative correlations were observed in primary sensorimotor regions. We found decreased whole-brain functional connectivity of the left inferior frontal gyrus in fighter pilots compared to controls and this cluster showed decreased functional connectivity with the medial superior frontal gyrus. Functional connectivity increased between the right parietal operculum 2 and the left visual cortex, and between the right and left angular gyrus in pilots compared to controls. These findings suggest altered motor, vestibular, and multisensory processing in the brains of fighter pilots, possibly reflecting coping strategies to altered sensorimotor demands during flight. Altered functional connectivity in frontal areas may reflect adaptive cognitive strategies to cope with challenging conditions during flight. These findings provide novel insights into brain functional characteristics of fighter pilots, which may be of interest to humans traveling to space.

Prolonged microgravity induces reversible and persistent changes on human cerebral connectivity.

The prospect of continued manned space missions warrants an in-depth understanding of how prolonged microgravity affects the human brain. Functional magnetic resonance imaging (fMRI) can pinpoint changes reflecting adaptive neuroplasticity across time. We acquired resting-state fMRI data of cosmonauts before, shortly after, and eight months after spaceflight as a follow-up to assess global connectivity changes over time. Our results show persisting connectivity decreases in posterior cingulate cortex and thalamus and persisting increases in the right angular gyrus. Connectivity in the bilateral insular cortex decreased after spaceflight, which reversed at follow-up. No significant connectivity changes across eight months were found in a matched control group. Overall, we show that altered gravitational environments influence functional connectivity longitudinally in multimodal brain hubs, reflecting adaptations to unfamiliar and conflicting sensory input in microgravity. These results provide insights into brain functional modifications occurring during spaceflight, and their further development when back on Earth.

The Scientific Study of Consciousness Cannot and Should Not Be Morally Neutral.

A target question for the scientific study of consciousness is how dimensions of consciousness, such as the ability to feel pain and pleasure or reflect on one's own experience, vary in different states and animal species. Considering the tight link between consciousness and moral status, answers to these questions have implications for law and ethics. Here we point out that given this link, the scientific community studying consciousness may face implicit pressure to carry out certain research programs or interpret results in ways that justify current norms rather than challenge them. We show that because consciousness largely determines moral status, the use of nonhuman animals in the scientific study of consciousness introduces a direct conflict between scientific relevance and ethics-the more scientifically valuable an animal model is for studying consciousness, the more difficult it becomes to ethically justify compromises to its well-being for consciousness research. Finally, in light of these considerations, we call for a discussion of the immediate ethical corollaries of the body of knowledge that has accumulated and for a more explicit consideration of the role of ideology and ethics in the scientific study of consciousness.

Mind blanking is a distinct mental state linked to a recurrent brain profile of globally positive connectivity during ongoing mentation.

Mind blanking (MB) is a waking state during which we do not report any mental content. The phenomenology of MB challenges the view of a constantly thinking mind. Here, we comprehensively characterize the MB's neurobehavioral profile with the aim to delineate its role during ongoing mentation. Using functional MRI experience sampling, we show that the reportability of MB is less frequent, faster, and with lower transitional dynamics than other mental states, pointing to its role as a transient mental relay. Regarding its neural underpinnings, we observed higher global signal amplitude during MB reports, indicating a distinct physiological state. Using the time-varying functional connectome, we show that MB reports can be classified with high accuracy, suggesting that MB has a unique neural composition. Indeed, a pattern of global positive-phase coherence shows the highest similarity to the connectivity patterns associated with MB reports. We interpret this pattern's rigid signal architecture as hindering content reportability due to the brain's inability to differentiate signals in an informative way. Collectively, we show that MB has a unique neurobehavioral profile, indicating that nonreportable mental events can happen during wakefulness. Our results add to the characterization of spontaneous mentation and pave the way for more mechanistic investigations of MB's phenomenology.

Left parietal involvement in motion sickness susceptibility revealed by multimodal magnetic resonance imaging.

Susceptibility to motion sickness varies greatly across individuals. However, the neural mechanisms underlying this susceptibility remain largely unclear. To address this gap, the current study aimed to identify the neural correlates of motion sickness susceptibility using multimodal MRI. First, we compared resting-state functional connectivity between healthy individuals who were highly susceptible to motion sickness (N = 36) and age/sex-matched controls who showed low susceptibility (N = 36). Seed-based analysis revealed between-group differences in functional connectivity of core vestibular regions in the left posterior Sylvian fissure. A data-driven approach using intrinsic connectivity contrast found greater network centrality of the left intraparietal sulcus in high- rather than in low-susceptible individuals. Moreover, exploratory structural connectivity analysis uncovered an association between motion sickness susceptibility and white matter integrity in the left inferior fronto-occipital fasciculus. Taken together, our data indicate left parietal involvement in motion sickness susceptibility.

Vestibular Morphological Asymmetry Associated With Motion Sickness Susceptibility.

Sensory conflicts leading to motion sickness can occur not only between but also within sensory modalities. The vestibular organs are located in both left and right inner ears, and their misalignment can be a source of self-motion related sensory conflicts. In the current study, using inner ear magnetic resonance imaging, we examined whether morphological asymmetry of the bilateral vestibular organs was associated with motion sickness susceptibility. The results showed a larger position asymmetry of bilateral vestibular organs in individuals with high rather than low susceptibility. In addition, vestibular position asymmetry was associated with reciprocal interaction (negative resting state functional connectivity) between vestibular and visuocortical regions in lowly, but not highly, susceptible individuals. In conclusion, these findings suggest that vestibular morphological asymmetry can be a source of sensory conflicts in individuals with dysfunctional reciprocal visuo-vestibular interactions, a putative neural mechanism for resolving sensory conflicts.

Perturbations in dynamical models of whole-brain activity dissociate between the level and stability of consciousness.

Consciousness transiently fades away during deep sleep, more stably under anesthesia, and sometimes permanently due to brain injury. The development of an index to quantify the level of consciousness across these different states is regarded as a key problem both in basic and clinical neuroscience. We argue that this problem is ill-defined since such an index would not exhaust all the relevant information about a given state of consciousness. While the level of consciousness can be taken to describe the actual brain state, a complete characterization should also include its potential behavior against external perturbations. We developed and analyzed whole-brain computational models to show that the stability of conscious states provides information complementary to their similarity to conscious wakefulness. Our work leads to a novel methodological framework to sort out different brain states by their stability and reversibility, and illustrates its usefulness to dissociate between physiological (sleep), pathological (brain-injured patients), and pharmacologically-induced (anesthesia) loss of consciousness.

The Time Varying Networks of the Interoceptive Attention and Rest.

Focused attention to spontaneous sensations is a dynamic process that demands interoceptive abilities. Failure to control it has been linked to neuropsychiatric disorders like illness-anxiety disorder. Regulatory strategies, such as focused attention meditation (FAM), may enhance the ability to control focused attention particularly to body sensations, which can be reflected on functional neuroanatomy. The functional connectivity (FC) related to focused attention has been described, however, the dynamic brain organization associated to this process and the differences to the resting state remains to be studied. To quantify the cerebral dynamic counterpart of focused attention to interoception, we examined fifteen experienced meditators while performing a 20-min attentional task to spontaneous sensations. Subjects underwent three scanning sessions obtaining a resting-state scan before and after the task. Sliding window dynamic FC (DFC) and k-means clustering identified five recurrent FC patterns along the dorsal attention network (DAN), default mode network (DMN), and frontoparietal network (FPN). Subjects remained longer in a low connectivity brain pattern during the resting conditions. By contrast, subjects spent a higher proportion of time in complex patterns during the task than rest. Moreover, a carry-over effect in FC was observed following the interoceptive task performance, suggestive of an active role in the learning process linked to cognitive training. Our results suggest that focused attention to interoceptive processes, demands a dynamic brain organization with specific features that distinguishes it from the resting condition. This approach may provide new insights characterizing the neural basis of the focused attention, an essential component for human adaptability.

Complete hemispherotomy leads to lateralized functional organization and lower level of consciousness in the isolated hemisphere.

OBJECTIVE: To quantify whole-brain functional organization after complete hemispherotomy, characterizing unexplored plasticity pathways and the conscious level of the dissected hemispheres. METHODS: Evaluation with multimodal magnetic resonance imaging in two pediatric patients undergoing right hemispherotomy including complete callosotomy with a perithalamic section. Regional cerebral blood flow and fMRI network connectivity assessed the functional integrity of both hemispheres after surgery. The level of consciousness was tested by means of a support vector machine classifier which compared the intrinsic organization of the dissected hemispheres with those of patients suffering from disorders of consciousness. RESULTS: After hemispherotomy, both patients showed typical daily functionality. We found no interhemispheric transfer of functional connectivity in either patient as predicted by the operation. The healthy left hemispheres displayed focal blood hyperperfusion in motor and limbic areas, with preserved network-level organization. Unexpectedly, the disconnected right hemispheres showed sustained network organization despite low regional cerebral blood flow. Subcortically, functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. One patient further showed unusual ipsilateral right cerebello-cortical connectivity, which was explained by the mediation of the vascular system. The healthy left hemisphere had higher probability to be classified as in a minimally conscious state compared to the isolated right hemisphere. SIGNIFICANCE: Complete hemispherotomy leads to a lateralized whole-brain organization, with the remaining hemisphere claiming most of the brain's energetic reserves supported by subcortical structures. Our results further underline the contribution of nonneuronal vascular signals on contralateral connectivity, shedding light on the nature of network organization in the isolated tissue. The disconnected hemisphere is characterized by a level of consciousness which is necessary but insufficient for conscious processing, paving the way for more specific inquiries about its role in awareness in the absence of behavioral output.

Covert Cognition in Disorders of Consciousness: A Meta-Analysis.

Covert cognition in patients with disorders of consciousness represents a real diagnostic conundrum for clinicians. In this meta-analysis, our main objective was to identify clinical and demographic variables that are more likely to be associated with responding to an active paradigm. Among 2018 citations found on PubMed, 60 observational studies were found relevant. Based on the QUADAS-2, 49 studies were considered. Data from 25 publications were extracted and included in the meta-analysis. Most of these studies used electrophysiology as well as counting tasks or mental imagery. According to our statistical analysis, patients clinically diagnosed as being in a vegetative state and in a minimally conscious state minus (MCS-) show similar likelihood in responding to active paradigm and responders are most likely suffering from a traumatic brain injury. In the future, multi-centric studies should be performed in order to increase sample size, with similar methodologies and include structural and functional neuroimaging in order to identify cerebral markers related to such a challenging diagnosis.

Time-Delay Latency of Resting-State Blood Oxygen Level-Dependent Signal Related to the Level of Consciousness in Patients with Severe Consciousness Impairment.

Recent evidence on resting-state functional magnetic resonance imaging (rs-fMRI) suggests that healthy human brains have a temporal organization represented in a widely complex time-delay structure. This structure seems to underlie brain communication flow, integration/propagation of brain activity, as well as information processing. Therefore, it is probably linked to the emergence of highly coordinated complex brain phenomena, such as consciousness. Nevertheless, possible changes in this structure during an altered state of consciousness remain poorly investigated. In this work, we hypothesized that due to a disruption in high-order functions and alterations of the brain communication flow, patients with disorders of consciousness (DOC) might exhibit changes in their time-delay structure of spontaneous brain activity. We explored this hypothesis by comparing the time-delay projections from fMRI resting-state data acquired in resting state from 48 patients with DOC and 27 healthy controls (HC) subjects. Results suggest that time-delay structure modifies for patients with DOC conditions when compared with HC. Specifically, the average value and the directionality of latency inside the midcingulate cortex (mCC) shift with the level of consciousness. In particular, positive values of latency inside the mCC relate to preserved states of consciousness, whereas negative values change proportionally with the level of consciousness in patients with DOC. These results suggest that the mCC may play a critical role as an integrator of brain activity in HC subjects, but this role vanishes in an altered state of consciousness.

Ethics of life-sustaining treatment in locked-in syndrome: A Chinese survey.

BACKGROUND: Locked-in syndrome (LIS) characterizes individuals who have experienced pontine lesions, who have limited motor output but with preserved cognitive abilities. Despite their severe physical impairment, individuals with LIS self-profess a higher quality of life than generally expected. Such third-person expectations about LIS are shaped by personal and cultural factors in western countries. OBJECTIVE: We sought to investigate whether such opinions are further influenced by the cultural background in East Asia. We surveyed attitudes about the ethics of life-sustaining treatment in LIS in a cohort of medical and non-medical Chinese participants. RESULTS: The final study sample included 1545 respondents: medical professionals (n=597, 39%), neurologists (n=303, 20%), legal professionals (n=276, 18%) and other professionals (n=369, 24%), including 180 family members of individuals with LIS. Most of the participants (70%), especially neurologists, thought that life-sustaining treatment could not be stopped in individuals with LIS. It might be unnecessary to withdraw life-sustaining treatment, because the condition involved is not terminal and irreversible, and physical treatment can be beneficial for the patient. A significant proportion (59%) of respondents would like to be kept alive if they were in that condition; however, older people thought the opposite. Families experience the stress of caring for individuals with LIS. The mean (SD) quality of life score for relatives was 0.73 (2.889) (on a -5, +5 scale), which was significantly lower than that of non-relatives, 1.75 (1.969) (P<0.001). CONCLUSIONS: Differences in opinions about end of life in LIS are affected by personal characteristics. The current survey did not identify a dissociation between personal preferences and general opinions, potentially because of a social uniformity in China where individualism is less pronounced. Future open-ended surveys could identify specific needs of caregivers so that strategic interventions to reduce ethical debasement are designed.

Reconfiguration of large-scale functional connectivity in patients with disorders of consciousness.

INTRODUCTION: Functional connectivity alterations within individual resting state networks (RSNs) are linked to disorders of consciousness (DOC). If these alterations influence the interaction quality with other RNSs, then, brain alterations in patients with DOC would be characterized by connectivity changes in the large-scale model composed of RSNs. How are functional interactions between RSNs influenced by internal alterations of individual RSNs? Do the functional alterations induced by DOC change some key properties of the large-scale network, which have been suggested to be critical for the consciousness emergence? Here, we use network analysis to measure functional connectivity in patients with DOC and address these questions. We hypothesized that network properties provide descriptions of brain functional reconfiguration associated with consciousness alterations. METHODS: We apply nodal and global network measurements to study the reconfiguration linked with the disease severity. We study changes in integration, segregation, and centrality properties of the functional connectivity between the RSNs in subjects with different levels of consciousness. RESULTS: Our analysis indicates that nodal measurements are more sensitive to disease severity than global measurements, particularly, for functional connectivity of sensory and cognitively related RSNs. CONCLUSION: The network property alterations of functional connectivity in different consciousness levels suggest a whole-brain topological reorganization of the large-scale functional connectivity in patients with DOC.

General Anesthesia: A Probe to Explore Consciousness.

General anesthesia reversibly alters consciousness, without shutting down the brain globally. Depending on the anesthetic agent and dose, it may produce different consciousness states including a complete absence of subjective experience (unconsciousness), a conscious experience without perception of the environment (disconnected consciousness, like during dreaming), or episodes of oriented consciousness with awareness of the environment (connected consciousness). Each consciousness state may potentially be followed by explicit or implicit memories after the procedure. In this respect, anesthesia can be considered as a proxy to explore consciousness. During the recent years, progress in the exploration of brain function has allowed a better understanding of the neural correlates of consciousness, and of their alterations during anesthesia. Several changes in functional and effective between-region brain connectivity, consciousness network topology, and spatio-temporal dynamics of between-region interactions have been evidenced during anesthesia. Despite a set of effects that are common to many anesthetic agents, it is still uneasy to draw a comprehensive picture of the precise cascades during general anesthesia. Several questions remain unsolved, including the exact identification of the neural substrate of consciousness and its components, the detection of specific consciousness states in unresponsive patients and their associated memory processes, the processing of sensory information during anesthesia, the pharmacodynamic interactions between anesthetic agents, the direction-dependent hysteresis phenomenon during the transitions between consciousness states, the mechanisms of cognitive alterations that follow an anesthetic procedure, the identification of an eventual unitary mechanism of anesthesia-induced alteration of consciousness, the relationship between network effects and the biochemical or sleep-wake cycle targets of anesthetic agents, as well as the vast between-studies variations in dose and administration mode, leading to difficulties in between-studies comparisons. In this narrative review, we draw the picture of the current state of knowledge in anesthesia-induced unconsciousness, from insights gathered on propofol, halogenated vapors, ketamine, dexmedetomidine, benzodiazepines and xenon. We also describe how anesthesia can help understanding consciousness, we develop the above-mentioned unresolved questions, and propose tracks for future research.