Local orchestration of distributed functional patterns supporting loss and restoration of consciousness in the primate brain.

A central challenge of neuroscience is to elucidate how brain function supports consciousness. Here, we combine the specificity of focal deep brain stimulation with fMRI coverage of the entire cortex, in awake and anaesthetised non-human primates. During propofol, sevoflurane, or ketamine anaesthesia, and subsequent restoration of responsiveness by electrical stimulation of the central thalamus, we investigate how loss of consciousness impacts distributed patterns of structure-function organisation across scales. We report that distributed brain activity under anaesthesia is increasingly constrained by brain structure across scales, coinciding with anaesthetic-induced collapse of multiple dimensions of hierarchical cortical organisation. These distributed signatures are observed across different anaesthetics, and they are reversed by electrical stimulation of the central thalamus, coinciding with recovery of behavioural markers of arousal. No such effects were observed upon stimulating the ventral lateral thalamus, demonstrating specificity. Overall, we identify consistent distributed signatures of consciousness that are orchestrated by specific thalamic nuclei.

Implications of conscious AI in primary healthcare.

The conversation about consciousness of artificial intelligence (AI) is an ongoing topic since 1950s. Despite the numerous applications of AI identified in healthcare and primary healthcare, little is known about how a conscious AI would reshape its use in this domain. While there is a wide range of ideas as to whether AI can or cannot possess consciousness, a prevailing theme in all arguments is uncertainty. Given this uncertainty and the high stakes associated with the use of AI in primary healthcare, it is imperative to be prepared for all scenarios including conscious AI systems being used for medical diagnosis, shared decision-making and resource management in the future. This commentary serves as an overview of some of the pertinent evidence supporting the use of AI in primary healthcare and proposes ideas as to how consciousnesses of AI can support or further complicate these applications. Given the scarcity of evidence on the association between consciousness of AI and its current state of use in primary healthcare, our commentary identifies some directions for future research in this area including assessing patients', healthcare workers' and policy-makers' attitudes towards consciousness of AI systems in primary healthcare settings.

Stimulus-elicited involuntary autobiographical memories.

The reflexive imagery task (RIT) has been used to investigate stimulus-elicited involuntary mental processes. The task has been successful in eliciting involuntary perceptual experiences, urges, and even higher-order cognitions, but it has never been used to elicit autobiographical memories, even though in everyday life these memories are often activated involuntarily by external stimuli. These memories are different in interesting ways from the kinds of mental representations that have been activated involuntarily in the RIT. The memories have properties which might make them insusceptible to such a form of external influence. Perhaps substantive effects will not arise because the mental representations associated with autobiographical memories are complex, poly-sensory, and rich in terms of content. To investigate this matter, we developed a variant of the RIT in which participants were presented with external stimuli (line drawings of everyday objects) and instructed not to recall any autobiographical memories. We investigated whether the nature of the involuntary memories was influenced by the nature of the stimulus. In two experiments, the involuntary memories were associated to the stimulus on a majority of the trials (∼80%). We discuss theoretical implications of this finding and of identifying the conditions in which such involuntary effects will not arise. The boundary conditions of the RIT effect illuminate the limits of unconscious processing and also the role of conscious processing in nervous function.

Criticality supports cross-frequency cortical-thalamic information transfer during conscious states.

Consciousness is thought to be regulated by bidirectional information transfer between the cortex and thalamus, but the nature of this bidirectional communication - and its possible disruption in unconsciousness - remains poorly understood. Here, we present two main findings elucidating mechanisms of corticothalamic information transfer during conscious states. First, we identify a highly preserved spectral channel of cortical-thalamic communication that is present during conscious states, but which is diminished during the loss of consciousness and enhanced during psychedelic states. Specifically, we show that in humans, mice, and rats, information sent from either the cortex or thalamus via δ/θ/α waves (∼1-13 Hz) is consistently encoded by the other brain region by high γ waves (52-104 Hz); moreover, unconsciousness induced by propofol anesthesia or generalized spike-and-wave seizures diminishes this cross-frequency communication, whereas the psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) enhances this low-to-high frequency interregional communication. Second, we leverage numerical simulations and neural electrophysiology recordings from the thalamus and cortex of human patients, rats, and mice to show that these changes in cross-frequency cortical-thalamic information transfer may be mediated by excursions of low-frequency thalamocortical electrodynamics toward/away from edge-of-chaos criticality, or the phase transition from stability to chaos. Overall, our findings link thalamic-cortical communication to consciousness, and further offer a novel, mathematically well-defined framework to explain the disruption to thalamic-cortical information transfer during unconscious states.

Cerebellar Purkinje cell firing promotes conscious recovery from anesthesia state through coordinating neuronal communications with motor cortex.

Background: The neurobiological basis of gaining consciousness from unconscious state induced by anesthetics remains unknown. This study was designed to investigate the involvement of the cerebello-thalamus-motor cortical loop mediating consciousness transitions from the loss of consciousness (LOC) induced by an inhalational anesthetic sevoflurane in mice. Methods: The neural tracing and fMRI together with opto-chemogenetic manipulation were used to investigate the potential link among cerebello-thalamus-motor cortical brain regions. The fiber photometry of calcium and neurotransmitters, including glutamate (Glu), γ-aminobutyric acid (GABA) and norepinephrine (NE), were monitored from the motor cortex (M1) and the 5th lobule of the cerebellar vermis (5Cb) during unconsciousness induced by sevoflurane and gaining consciousness after sevoflurane exposure. Cerebellar Purkinje cells were optogenetically manipulated to investigate their influence on consciousness transitions during and after sevoflurane exposure. Results: Activation of 5Cb Purkinje cells increased the Ca2+ flux in the M1 CaMKIIα+ neurons, but this increment was significantly reduced by inactivation of posterior and parafascicular thalamic nucleus. The 5Cb and M1 exhibited concerted calcium flux, and glutamate and GABA release during transitions from wakefulness, loss of consciousness, burst suppression to conscious recovery. Ca2+ flux and Glu release in the M1, but not in the 5Cb, showed a strong synchronization with the EEG burst suppression, particularly, in the gamma-band range. In contrast, the Glu, GABA and NE release and Ca2+ oscillations were coherent with the EEG gamma band activity only in the 5Cb during the pre-recovery of consciousness period. The optogenetic activation of Purkinje cells during burst suppression significantly facilitated emergence from anesthesia while the optogenetic inhibition prolonged the time to gaining consciousness. Conclusions: Our data indicate that cerebellar neuronal communication integrated with motor cortex through thalamus promotes consciousness recovery from anesthesia which may likely serve as arousal regulation.

Music, occupational, physical, and speech therapy interventions for patients in disorders of consciousness: An umbrella review.

BACKGROUND: Current clinical guidelines recommend that a multidisciplinary team inclusive of allied healthcare practitioners deliver assessment and intervention for disorders of consciousness. Allied health professionals include music, occupational, physical, and speech therapists. These allied health clinicians are challenged to select interventions due to a lack of evidence-based recommendations regarding rehabilitation interventions that support recovery of consciousness. This umbrella review synthesizes available systematic reviews (SRs) that describe occupational, speech and language, physical and/or musical therapeutic interventions for people with disorders of consciousness. OBJECTIVES: Identify and summarize evidence from systematic reviews (SRs) that examine allied healthcare interventions for patients with disorders of consciousness. Additionally, this umbrella review aims to evaluate the impact of allied health interventions on recovery of consciousness, methodological quality and risk of bias for the included systematic reviews. METHODS: An umbrella review was completed. The review was reported according to the Preferred Reporting Items for Overview of Reviews (PRIOR) guidance. Five academic databases (PubMed, CINAHL, PsycInfo, Web of Science, and the Cochrane Library) were searched for SRs and/or meta-analyses of allied health (i.e., music, occupational, physical, and speech therapy) interventions for disorders of consciousness. For included studies, data were extracted and quality of the SRs appraised using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2 checklist. Data extracted from each SR identified the authors and years of primary studies, interventions, comparators, and outcomes related to recovery of consciousness (i.e., neurobehavioral/cognitive), functional status, physiological response pain, and adverse events. Rehabilitation interventions were categorized and described. RESULTS: Fifteen SRs were included and three of these reviews conducted meta-analyses. Identified rehabilitation interventions included: 1) sensory stimulation, 2) median nerve stimulation, 3) communication/environmental control through assistive technology, 4) mobilization, and 5) music-based therapy. SRs were published between 2002 and 2022 and included 2286 participants. Using the AMSTAR 2, the quality of reviews was critically low (k = 6), low (k = 3), moderate (k = 4), and high (k = 2). SRs within this umbrella review demonstrated significant heterogeneity in research methods and use of outcome measures to evaluate the recovery of consciousness within the primary studies. These factors influenced the ability to conduct meta-analyses. CONCLUSIONS: Sensory stimulation, median nerve stimulation, music therapy and mobilization are all interventions that demonstrate some level of benefit, but current SRs fail to prove benefit through high-level quality evidence. There is an indisputable need for continued rehabilitation research to expand options for treatment modalities and to ensure that the interventions being applied to DoC rehabilitation are evidence-based to improve consciousness and recovery.

Aspiring to Disability Consciousness in Health Professions Training.

Lack of disability-competent health care contributes to inequitable health outcomes for the largest minoritized population in the world: persons with disabilities. Health care professionals hold implicit and explicit bias against disabled people and report receiving inadequate disability training. While disability competence establishes a baseline standard of care, health professional educators must prepare a disability conscious workforce by challenging ableist assumptions and promoting holistic understanding of persons with disabilities. Future clinicians must recognize disability as an aspect of diversity, express respect for disabled patients, and demonstrate flexibility about how to care for disabled patients' needs. These skills are currently undervalued in medical training, specifically. This article describes how integrating disability consciousness into health professions training can improve health equity for patients with disabilities.

Disturbance of consciousness caused by dyclonine hydrochloride mucilage: a case report.

BACKGROUND: Dyclonine hydrochloride mucilage is a topical anaesthetic formulated for mucosal surfaces. It is employed frequently for topical anaesthesia of the pharynx prior to endoscopic examinations such as electronic gastroscopy, and few adverse reactions have been reported. This article describes a patient who experienced a transient but severe disturbance of consciousness following oral dyclonine hydrochloride mucilage administration. CASE PRESENTATION: A 75-year-old female presenting with gastrointestinal bleeding was examined by electronic gastroscopy. Six minutes after oral dyclonine hydrochloride mucilage administration, the patient entered a comatose-like state accompanied by loss of limb muscle tone and profuse perspiration. This response was not accompanied by changes in cardiac rhythm, blood pressure, or respiration rate, suggesting an effect on higher brain centres. After ten minutes, the patient's symptoms were alleviated. CONCLUSION: We suggest that sites of dyclonine hydrochloride mucilage use be equipped with appropriate rescue devices for these rare events.

Family Constellation therapy: A nascent approach for working with non-local consciousness in a therapeutic container.

Family Constellations are an emerging therapeutic approach for working with local and non-local consciousness. First developed by German psychoanalyst Bert Hellinger, and now practiced by thousands of licensed and un-licensed facilitators globally, Family Constellations are a transpersonal and systemically oriented therapeutic process. Their aim is to address a focus client's emotional, behavioral, relational, or somatic issues by uncovering and resolving transgenerational entanglements within their family system. The author expands on the proposal of symbiogenesis as a mediator of local and non-local consciousness to query whether applying the Observer Effect to inherited trauma may influence epigenetic marks. An expanded perspective on consciousness, life, death, and quantum fields may provide a more comprehensive framework to address therapeutic interventions for common emotional and behavioral disorders. Innovative features of Family Constellations are its phenomenological orientation, reference to family system entanglements, and potential for symptom relief through cellular mediation of ancestral memory. Family Constellations utilize techniques called representative perception and tuning-in to identify and release ancestral traumas. These are akin to remote viewing and mediumship. While the scientific basis for Family Constellations is speculative, the text references research on the quantum theory of consciousness, mediumship and remote viewing as potential supporting evidence. Four case studies are presented.

Intensive whole-brain 7T MRI case study of volitional control of brain activity in deep absorptive meditation states.

Jhanas are profound states of mind achieved through advanced meditation, offering valuable insights into the nature of consciousness and tools to enhance well-being. Yet, its neurophenomenology remains limited due to methodological difficulties and the rarity of advanced meditation practitioners. We conducted a highly exploratory study to investigate the neurophenomenology of jhanas in an intensively sampled adept meditator case study (4 hr 7T fMRI collected in 27 sessions) who performed jhana meditation and rated specific aspects of experience immediately thereafter. Linear mixed models and correlations were used to examine relations among brain activity and jhana phenomenology. We identified distinctive patterns of brain activity in specific cortical, subcortical, brainstem, and cerebellar regions associated with jhana. Furthermore, we observed correlations between brain activity and phenomenological qualities of attention, jhanic qualities, and narrative processing, highlighting the distinct nature of jhanas compared to non-meditative states. Our study presents the most rigorous evidence yet that jhana practice deconstructs consciousness, offering unique insights into consciousness and significant implications for mental health and well-being.

Culture influences conscious appraisal of, but not automatic aversion to, acoustically rough musical intervals.

There is debate whether the foundations of consonance and dissonance are rooted in culture or in psychoacoustics. In order to disentangle the contribution of culture and psychoacoustics, we considered automatic responses to the perfect fifth and the major second (flattened by 25 cents) intervals alongside conscious evaluations of the same intervals across two cultures and two levels of musical expertise. Four groups of participants completed the tasks: expert performers of Lithuanian Sutartines, English speaking musicians in Western diatonic genres, Lithuanian non-musicians and English-speaking non-musicians. Sutartines singers were chosen as this style of singing is an example of 'beat diaphony' where intervals of parts form predominantly rough sonorities and audible beats. There was no difference in automatic responses to intervals, suggesting that an aversion to acoustically rough intervals is not governed by cultural familiarity but may have a physical basis in how the human auditory system works. However, conscious evaluations resulted in group differences with Sutartines singers rating both the flattened major as more positive than did other groups. The results are discussed in the context of recent developments in consonance and dissonance research.

Pupil dilation response elicited by violations of auditory regularities is a promising but challenging approach to probe consciousness at the bedside.

Pupil dilation response (PDR) has been proposed as a physiological marker of conscious access to a stimulus or its attributes, such as novelty. In a previous study on healthy volunteers, we adapted the auditory "local global" paradigm and showed that violations of global regularity elicited a PDR. Notably without instructions, this global effect was present only in participants who could consciously report violations of global regularities. In the present study, we used a similar approach in 24 non-communicating patients affected with a Disorder of Consciousness (DoC) and compared PDR to ERPs regarding diagnostic and prognostic performance. At the group level, global effect could not be detected in DoC patients. At the individual level, the only patient with a PDR global effect was in a MCS and recovered consciousness at 6 months. Contrasting the most regular trials to the most irregular ones improved PDR's diagnostic and prognostic power in DoC patients. Pupillometry is a promising tool but requires several methodological improvements to enhance the signal-to-noise ratio and make it more robust for probing consciousness and cognition in DoC patients.

Electrophysiological characteristics of CM-pf in diagnosis and outcome of patients with disorders of consciousness.

BACKGROUND: Deep brain stimulation (DBS) in the centromedian-parafascicular complex (CM-pf) has been reported as a potential therapeutic option for disorders of consciousness (DoC). However, the lack of understanding of its electrophysiological characteristics limits the improvement of therapeutic effect. OBJECTIVE: To investigate the CM-pf electrophysiological characteristics underlying disorders of consciousness (DoC) and its recovery. METHODS: We collected the CM-pf electrophysiological signals from 23 DoC patients who underwent central thalamus DBS (CT-DBS) surgery. Five typical electrophysiological features were extracted, including neuronal firing properties, multiunit activity (MUA) properties, signal stability, spike-MUA synchronization strength (syncMUA), and the background noise level. Their correlations with the consciousness level, the outcome, and the primary clinical factors of DoC were analyzed. RESULTS: 11 out of 23 patients (0/2 chronic coma, 5/13 unresponsive wakefulness syndrome/vegetative state (UWS/VS), 6/8 minimally conscious state minus (MCS-)) exhibited an improvement in the level of consciousness after CT-DBS. In CM-pf, significantly stronger gamma band syncMUA strength and alpha band normalized MUA power were found in MCS- patients. In addition, higher firing rates, stronger high-gamma band MUA power and alpha band normalized power, and more stable theta oscillation were correlated with better outcomes. Besides, we also identified electrophysiological properties that are correlated with clinical factors, including etiologies, age, and duration of DoC. CONCLUSION: We provide comprehensive analyses of the electrophysiological characteristics of CM-pf in DoC patients. Our results support the 'mesocircuit' hypothesis, one proposed mechanism of DoC recovery, and reveal CM-pf electrophysiological features that are crucial for understanding the pathogenesis of DoC, predicting its recovery, and explaining the effect of clinical factors on DoC.

[Application characteristics and modern research progress of "bone-approaching" acupuncture].

The paper explores the evolution of "bone-approaching" acupuncture, its effect target and mechanism. The concrete operation procedure of "bone-approaching" method is recorded originally in Huangdi Neijing (Inner Canon of Yellow Emperor) as short needling and Shu needling (referring to the category of the five needling technique). The periosteum is the most effective stimulation target of "bone-approaching" acupuncture for analgesia, regaining consciousness and regulating spirit. The "bone-approaching" acupuncture is not only prominently effective on bone bi syndrome, but also has the unique effect on painful, encephalogenic and emotional diseases. The paper summarizes and improves "bone-approaching" acupuncture, i.e. "touching bone surface" with needle tip by slow insertion, "touching bone surface" without pain by swift insertion and "touching bone" with needle body by oblique insertion. It contributes to the inheritance, development and supplementation to the bone needling techniques in Huangdi Neijing and is significant for broadening the clinical application range of acupuncture.

Conscious entry into sleep: Yoga Nidra and accessing subtler states of consciousness.

Human sleep is a dynamic and complex process comprising sleep stages with REM and NREM sleep characteristics that come in cycles. During sleep, there is a loss of responsiveness or a perceptual loss of conscious awareness with increasing thresholds for wakefulness as sleep progresses. There are brief bursts of wakefulness or Wake After Sleep Onset (WASO) throughout a nocturnal sleep. Conscious experience during nocturnal sleep is known to occur during lucid dreaming when one is aware during dreams when the dream is occurring. Most cultures have known lucid dreaming since antiquity. However, conscious experience during dreamless sleep is relatively lesser known. Nevertheless, selected Indo-Tibetan meditation literature has documented it since antiquity. Minimal Phenomenal Experience (MPE) research describes lucid dreamless sleep as its target phenomenology. "Conscious entry into sleep" posits tonic alertness is maintained post sleep onset through the sleep stages for sustained durations of time until an eventual loss of conscious awareness. Entering sleep consciously and being aware during dreamless sleep, including Slow Wave Activity, is plausibly to be in the state of "Yoga Nidra" or Yogic sleep. An attentive sleepful state provides access to subtler states of consciousness and significantly deepens the levels of silence. It is phenomenologically distinct from hypnagogic hallucinations and lucid dreaming. Unfortunately, sleep studies validating this phenomenology are yet to be done. Therefore, an experimental methodology akin to those used in lucid dreaming experiments is described.

Cessations of consciousness in meditation: Advancing a scientific understanding of nirodha samapatti.

Absence of consciousness can occur due to a concussion, anesthetization, intoxication, epileptic seizure, or other fainting/syncope episode caused by lack of blood flow to the brain. However, some meditation practitioners also report that it is possible to undergo a total absence of consciousness during meditation, lasting up to 7 days, and that these "cessations" can be consistently induced. One form of extended cessation (i.e., nirodha samapatti) is thought to be different from sleep because practitioners are said to be completely impervious to external stimulation. That is, they cannot be 'woken up' from the cessation state as one might be from a dream. Cessations are also associated with the absence of any time experience or tiredness, and are said to involve a stiff rather than a relaxed body. Emergence from meditation-induced cessations is said to have profound effects on subsequent cognition and experience (e.g., resulting in a sudden sense of clarity, openness, and possibly insights). In this paper, we briefly outline the historical context for cessation events, present preliminary data from two labs, set a research agenda for their study, and provide an initial framework for understanding what meditation induced cessation may reveal about the mind and brain. We conclude by integrating these so-called nirodha and nirodha samapatti experiences-as they are known in classical Buddhism-into current cognitive-neurocomputational and active inference frameworks of meditation.

The Arousal-Related "Central Thalamus" Stimulation Site Simultaneously Innervates Multiple High-Level Frontal and Parietal Areas.

In human and nonhuman primates, deep brain stimulation applied at or near the internal medullary lamina of the thalamus [a region referred to as "central thalamus," (CT)], but not at nearby thalamic sites, elicits major changes in the level of consciousness, even in some minimally conscious brain-damaged patients. The mechanisms behind these effects remain mysterious, as the connections of CT had not been specifically mapped in primates. In marmoset monkeys (Callithrix jacchus) of both sexes, we labeled the axons originating from each of the various CT neuronal populations and analyzed their arborization patterns in the cerebral cortex and striatum. We report that, together, these CT populations innervate an array of high-level frontal, posterior parietal, and cingulate cortical areas. Some populations simultaneously target the frontal, parietal, and cingulate cortices, while others predominantly target the dorsal striatum. Our data indicate that CT stimulation can simultaneously engage a heterogeneous set of projection systems that, together, target the key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.SIGNIFICANCE STATEMENT In human and nonhuman primates, deep brain stimulation at a specific site near the internal medullary lamina of the thalamus ["central thalamus," (CT)] had been shown to restore arousal and awareness in anesthetized animals, as well as in some brain-damaged patients. The mechanisms behind these effects remain mysterious, as CT connections remain poorly defined in primates. In marmoset monkeys, we mapped with sensitive axon-labeling methods the pathways originated from CT. Our data indicate that stimulation applied in CT can simultaneously engage a heterogeneous set of projection systems that, together, target several key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.

Autonomic nervous system modulation during self-induced non-ordinary states of consciousness.

Self-induced cognitive trance (SICT) is a voluntary non-ordinary state of consciousness characterized by a lucid yet narrowed awareness of the external surroundings. It involves a hyper-focused immersive experience of flow, expanded inner imagery, modified somatosensory processing, and an altered perception of self and time. SICT is gaining attention due to its potential clinical applications. Similar states of non-ordinary state of consciousness, such as meditation, hypnosis, and psychedelic experiences, have been reported to induce changes in the autonomic nervous system. However, the functioning of the autonomic nervous system during SICT remains poorly understood. In this study, we aimed to investigate the impact of SICT on the cardiac and respiratory signals of 25 participants proficient in SICT. To accomplish this, we measured various metrics of heart rate variability (HRV) and respiration rate variability (RRV) in three conditions: resting state, SICT, and a mental imagery task. Subsequently, we employed a machine learning framework utilizing a linear discriminant analysis classifier and a cross-validation scheme to identify the features that exhibited the best discrimination between these three conditions. The results revealed that during SICT, participants experienced an increased heart rate and a decreased level of high-frequency (HF) HRV compared to the control conditions. Additionally, specific increases in respiratory amplitude, phase ratio, and RRV were observed during SICT in comparison to the other conditions. These findings suggest that SICT is associated with a reduction in parasympathetic activity, indicative of a hyperarousal state of the autonomic nervous system during SICT.

The non-specific matrix thalamus facilitates the cortical information processing modes relevant for conscious awareness.

The neurobiological mechanisms of arousal and anesthesia remain poorly understood. Recent evidence highlights the key role of interactions between the cerebral cortex and the diffusely projecting matrix thalamic nuclei. Here, we interrogate these processes in a whole-brain corticothalamic neural mass model endowed with targeted and diffusely projecting thalamocortical nuclei inferred from empirical data. This model captures key features seen in propofol anesthesia, including diminished network integration, lowered state diversity, impaired susceptibility to perturbation, and decreased corticocortical coherence. Collectively, these signatures reflect a suppression of information transfer across the cerebral cortex. We recover these signatures of conscious arousal by selectively stimulating the matrix thalamus, recapitulating empirical results in macaque, as well as wake-like information processing states that reflect the thalamic modulation of large-scale cortical attractor dynamics. Our results highlight the role of matrix thalamocortical projections in shaping many features of complex cortical dynamics to facilitate the unique communication states supporting conscious awareness.