Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China.

INTRODUCTION: Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC). METHODS AND ANALYSIS: The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 µs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073950.

Developmental changes of bodily self-consciousness in adolescent girls.

The body and the self change markedly during adolescence, but how does bodily self-consciousness, the pre-reflexive experience of being a bodily subject, change? We addressed this issue by studying embodiment towards virtual avatars in 70 girls aged 10-17 years. We manipulated the synchrony between participants' and avatars' touch or movement, as well as the avatar visual shape or size relative to each participant's body. A weaker avatar's embodiment in case of mismatch between the body seen in virtual reality and the real body is indicative of a more robust bodily self-consciousness. In both the visuo-tactile and the visuo-motor experiments, asynchrony decreased ownership feeling to the same extent for all participants, while the effect of asynchrony on agency feeling increased with age. In the visuo-tactile experiment, incongruence in visual appearance did not affect agency feeling but impacted ownership, especially in older teenage girls. These findings highlight the higher malleability of bodily self-consciousness at the beginning of adolescence and suggest some independence between body ownership and agency.

A global neuronal workspace model of functional neurological disorders.

We introduce here a general model of Functional Neurological Disorders based on the following hypothesis: a Functional Neurological Disorder could correspond to a consciously initiated voluntary top-down process causing involuntary lasting consequences that are consciously experienced and subjectively interpreted by the patient as involuntary. We develop this central hypothesis according to Global Neuronal Workspace theory of consciousness, that is particularly suited to describe interactions between conscious and non-conscious cognitive processes. We then present a list of predictions defining a research program aimed at empirically testing their validity. Finally, this general model leads us to reinterpret the long-debated links between hypnotic suggestion and functional neurological disorders. Driven by both scientific and therapeutic goals, this theoretical paper aims at bringing closer the psychiatric and neurological worlds of functional neurological disorders with the latest developments of cognitive neuroscience of consciousness.

Christof Koch.

In this talk with Neuron, Christof Koch, a physicist and neuroscientist, advocates for a pragmatic program to track the footprints of consciousness in the brain and for team science, explains the recent pseudo-controversy regarding integrated information theory of consciousness, and speaks about the joy of exploring the mysteries around us.

Stanislas Dehaene.

Stanislas Dehaene is a cognitive neuroscientist elucidating the biological mechanisms that give rise to human perception and cognition. In a conversation with Neuron, he talks about his ongoing interest in consciousness research, the role of theory in neuroscience, and his current work on education and the science of learning.

Toward an interventional science of recovery after coma.

Recovery of consciousness after coma remains one of the most challenging areas for accurate diagnosis and effective therapeutic engagement in the clinical neurosciences. Recovery depends on preservation of neuronal integrity and evolving changes in network function that re-establish environmental responsiveness. It typically occurs in defined steps: it begins with eye opening and unresponsiveness in a vegetative state, then limited recovery of responsiveness characterizes the minimally conscious state, and this is followed by recovery of reliable communication. This review considers several points for novel interventions, for example, in persons with cognitive motor dissociation in whom a hidden cognitive reserve is revealed. Circuit mechanisms underlying restoration of behavioral responsiveness and communication are discussed. An emerging theme is the possibility to rescue latent capacities in partially damaged human networks across time. These opportunities should be exploited for therapeutic engagement to achieve individualized solutions for restoration of communication and environmental interaction across varying levels of recovery.

Can we detect consciousness in newborn infants?

Conscious experiences in infants remain poorly understood. In this NeuroView, Passos-Ferreira discusses recent evidence for and against consciousness in newborn babies. She argues that the weight of evidence from neuroimaging and behavioral studies supports the thesis that newborn infants are conscious.

Thalamic contributions to the state and contents of consciousness.

Consciousness can be conceptualized as varying along at least two dimensions: the global state of consciousness and the content of conscious experience. Here, we highlight the cellular and systems-level contributions of the thalamus to conscious state and then argue for thalamic contributions to conscious content, including the integrated, segregated, and continuous nature of our experience. We underscore vital, yet distinct roles for core- and matrix-type thalamic neurons. Through reciprocal interactions with deep-layer cortical neurons, matrix neurons support wakefulness and determine perceptual thresholds, whereas the cortical interactions of core neurons maintain content and enable perceptual constancy. We further propose that conscious integration, segregation, and continuity depend on the convergent nature of corticothalamic projections enabling dimensionality reduction, a thalamic reticular nucleus-mediated divisive normalization-like process, and sustained coherent activity in thalamocortical loops, respectively. Overall, we conclude that the thalamus plays a central topological role in brain structures controlling conscious experience.

An integrative view of the role of prefrontal cortex in consciousness.

The involvement of the prefrontal cortex (PFC) in consciousness is an ongoing focus of intense investigation. An important question is whether representations of conscious contents and experiences in the PFC are confounded by post-perceptual processes related to cognitive functions. Here, I review recent findings suggesting that neuronal representations of consciously perceived contents-in the absence of post-perceptual processes-can indeed be observed in the PFC. Slower ongoing fluctuations in the electrophysiological state of the PFC seem to control the stability and updates of these prefrontal representations of conscious awareness. In addition to conscious perception, the PFC has been shown to play a critical role in controlling the levels of consciousness as observed during anesthesia, while prefrontal lesions can result in severe loss of perceptual awareness. Together, the convergence of these processes in the PFC suggests its integrative role in consciousness and highlights the complex nature of consciousness itself.

Autonomous Sensory Meridian Response (ASMR) and the Functions of Consciousness.

"Autonomous Sensory Meridian Response" (ASMR) refers to a sensory-emotional experience that was first explicitly identified and named within the past two decades in online discussion boards. Since then, there has been mounting psychological and neural evidence of a clustering of properties common to the phenomenon of ASMR, including convergence on the set of stimuli that trigger the experience, the properties of the experience itself, and its downstream effects. Moreover, psychological instruments have begun to be developed and employed in an attempt to measure it. Based on this empirical work, we make the case that despite its nonscientific origins, ASMR is a good candidate for being a real kind in the cognitive sciences. The phenomenon appears to have a robust causal profile and may also have an adaptive evolutionary history. We also argue that a more thorough understanding of the distinctive type of phenomenal experience involved in an ASMR episode can shed light on the functions of consciousness, and ultimately undermine certain "cognitive" theories of consciousness. We conclude that ASMR should be the subject of more extensive scientific investigation, particularly since it may also have the potential for therapeutic applications.

The enlightenment.

The period begins with the work of Richard Wiseman who was associated with royalists in the English Civil War. A little later Dionis was the first to note a relationship between a disturbance of consciousness and extravasation of blood. This notion was continued and expanded by Le Dran, Pott, and Benjamin Bell, with Pott providing a pathophysiological explanation of the phenomenon. Daniel Turner commented on how confusing Galenic teaching was on the topic of consciousness. Heister further emphasized the relationship between clinical disturbance and the extravasation of blood. Le Dran stated that symptoms following cranial trauma related to cerebral injury, an opinion supported by Pott and never subsequently challenged. Latta noted the importance of meningeal arteries in the development of hematomas. Benjamin Bell considered trepanation only appropriate for a clinical deterioration consistent with hemorrhagic extravasation. The two Irish surgeons made it clear that the presence of periosteal separation was not in fact a reliable indicator of an extravasation. The most striking change of instruments was disappearance of simple straight trepans with non-perforating tips for making small holes safely. The use of scrapers gradually declined as did that of lenticulars. There was a great debate about the value of a conical rather than a cylindrical crown. The former was said to be safer. But this opinion faded and the cylindrical crown became preferred. Another improvement in technique involved the use of constant probing to check the depth of the drilled groove.

Shared EEG correlates between non-REM parasomnia experiences and dreams.

Sleepwalking and related parasomnias result from incomplete awakenings out of non-rapid eye movement sleep. Behavioral episodes can occur without consciousness or recollection, or in relation to dream-like experiences. To understand what accounts for these differences in consciousness and recall, here we recorded parasomnia episodes with high-density electroencephalography (EEG) and interviewed participants immediately afterward about their experiences. Compared to reports of no experience (19%), reports of conscious experience (56%) were preceded by high-amplitude EEG slow waves in anterior cortical regions and activation of posterior cortical regions, similar to previously described EEG correlates of dreaming. Recall of the content of the experience (56%), compared to no recall (25%), was associated with higher EEG activation in the right medial temporal region before movement onset. Our work suggests that the EEG correlates of parasomnia experiences are similar to those reported for dreams and may thus reflect core physiological processes involved in sleep consciousness.

Re-awakening the brain: Forcing transitions in disorders of consciousness by external in silico perturbation.

A fundamental challenge in neuroscience is accurately defining brain states and predicting how and where to perturb the brain to force a transition. Here, we investigated resting-state fMRI data of patients suffering from disorders of consciousness (DoC) after coma (minimally conscious and unresponsive wakefulness states) and healthy controls. We applied model-free and model-based approaches to help elucidate the underlying brain mechanisms of patients with DoC. The model-free approach allowed us to characterize brain states in DoC and healthy controls as a probabilistic metastable substate (PMS) space. The PMS of each group was defined by a repertoire of unique patterns (i.e., metastable substates) with different probabilities of occurrence. In the model-based approach, we adjusted the PMS of each DoC group to a causal whole-brain model. This allowed us to explore optimal strategies for promoting transitions by applying off-line in silico probing. Furthermore, this approach enabled us to evaluate the impact of local perturbations in terms of their global effects and sensitivity to stimulation, which is a model-based biomarker providing a deeper understanding of the mechanisms underlying DoC. Our results show that transitions were obtained in a synchronous protocol, in which the somatomotor network, thalamus, precuneus and insula were the most sensitive areas to perturbation. This motivates further work to continue understanding brain function and treatments of disorders of consciousness.

Consciousness and sleep.

Sleep is a universal, essential biological process. It is also an invaluable window on consciousness. It tells us that consciousness can be lost but also that it can be regained, in all its richness, when we are disconnected from the environment and unable to reflect. By considering the neurophysiological differences between dreaming and dreamless sleep, we can learn about the substrate of consciousness and understand why it vanishes. We also learn that the ongoing state of the substrate of consciousness determines the way each experience feels regardless of how it is triggered-endogenously or exogenously. Dreaming consciousness is also a window on sleep and its functions. Dreams tell us that the sleeping brain is remarkably lively, recombining intrinsic activation patterns from a vast repertoire, freed from the requirements of ongoing behavior and cognitive control.

Electrophysiological correlates of sustained conscious perception.

Previous research on the neural correlates of consciousness (NCC) in visual perception revealed an early event-related potential (ERP), the visual awareness negativity (VAN), to be associated with stimulus awareness. However, due to the use of brief stimulus presentations in previous studies, it remains unclear whether awareness-related negativities represent a transient onset-related response or correspond to the duration of a conscious percept. Studies are required that allow prolonged stimulus presentation under aware and unaware conditions. The present ERP study aimed to tackle this challenge by using a novel stimulation design. Male and female human participants (n = 62) performed a visual task while task-irrelevant line stimuli were presented in the background for either 500 or 1000 ms. The line stimuli sometimes contained a face, which needed so-called visual one-shot learning to be seen. Half of the participants were informed about the presence of the face, resulting in faces being perceived by the informed but not by the uninformed participants. Comparing ERPs between the informed and uninformed group revealed an enhanced negativity over occipitotemporal electrodes that persisted for the entire duration of stimulus presentation. Our results suggest that sustained visual awareness negativities (SVAN) are associated with the duration of stimulus presentation.

Reduced processing of afforded actions while observing mental content as ongoing mental phenomena.

While consciousness is typically considered equivalent to mental contents, certain meditation practices-including open monitoring (OM)-are said to enable a unique conscious state where meditators can experience mental content from a de-reified perspective as "ongoing phenomena." Phenomenologically, such a state is considered as reduction of intentionality, the mental act upon mental content. We hypothesised that this de-reified state would be characterised by reduced mental actional processing of affording objects. We recruited two groups of participants, meditators with long-term experience in cultivating a de-reified state, and demographically-matched novice meditators. Participants performed a task with images in two configurations-where objects did (high-affordance) and did not imply actions (low-affordance)-following both a baseline and OM-induced de-reified state, along with EEG recordings. While long-term meditators exhibited preferential processing of high-affordance images compared to low-affordance images during baseline, such an effect was abolished during the OM state, as hypothesised. For novices, however, the high-affordance configuration was preferred over the low-affordance one both during baseline and OM. Perceptual durations of objects across conditions positively correlated with the degree of µ-rhythm desynchronization, indicating that neural processing of affordance impacted perceptual awareness. Our results indicate that OM styles of meditation may help in mentally decoupling otherwise automatic cognitive processing of mental actions by affording objects.

Correlation between Thalamocortical Tract and Default Mode Network with Consciousness Levels in Hypoxic-Ischemic Brain Injury Patients: A Comparative Study Using the Coma Recovery Scale-Revised.

BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network (DMN) comprises bilateral, symmetrical, isolated cortical regions of the lateral and medial parietal and temporal brain cortex. The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment of disorders of consciousness (DOC). In the present study, 31 patients with hypoxic-ischemic brain injury (HI-BI) were compared for changes in the TCT and DMN with consciousness levels assessed using the CRS-R. MATERIAL AND METHODS In this retrospective study, 31 consecutive patients with HI-BI (17 DOC,14 non-DOC) and 17 age- and sex-matched normal control subjects were recruited. Magnetic resonance imaging was used to diagnose HI-BI, and the CRS-R was used to evaluate consciousness levels at the time of diffusion tensor imaging (DTI). The fractional anisotropy (FA) values and tract volumes (TV) of the TCT and DMN were compared. RESULTS In patients with DOC, the FA values and TV of both the TCT and DMN were significantly lower compared to those of patients without DOC and the control subjects (p<0.05). When comparing the non-DOC and control groups, the TV of the TCT and DMN were significantly lower in the non-DOC group (p<0.05). Moreover, the CRS-R score had strong positive correlations with the TV of the TCT (r=0.501, p<0.05), FA of the DMN (r=0.532, p<0.05), and TV of the DMN (r=0.501, p<0.05) in the DOC group. CONCLUSIONS This study suggests that both the TCT and DMN exhibit strong correlations with consciousness levels in DOC patients with HI-BI.

Non-invasive electrical brain stimulation modulates human conscious perception of mental representation.

Mental representation is a key concept in cognitive science; nevertheless, its neural foundations remain elusive. We employed non-invasive electrical brain stimulation and functional magnetic resonance imaging to address this. During this process, participants perceived flickering red and green visual stimuli, discerning them either as distinct, non-fused colours or as a mentally generated, fused colour (orange). The application of transcranial alternating current stimulation to the medial prefrontal region (a key node of the default-mode network) suppressed haemodynamic activation in higher-order subthalamic and central executive networks associated with the perception of fused colours. This implies that higher-order thalamocortical and default-mode networks are crucial in humans' conscious perception of mental representation.