Unconscious/implicit processes are increasingly conceptualized as biologically instantiated, multisystem regulatory functions rather than purely psychological constructs. This review examines whether an integrative framework linking psychoneuroimmuneendocrine (PINE) regulation, epigenetic mechanisms, and principles of morphogenetic organization can help organize evidence relevant to "unconscious ontogenesis." To systematically review empirical evidence on PINE-related regulation and epigenetic modifications associated with unconscious/implicit processing, and to evaluate developmental morphogenetic principles as an organizing conceptual template (distinct from direct evidence of adult unconscious processing). We searched PubMed/MEDLINE, Web of Science, and Scopus (1990-2024), plus gray literature sources, for experimental and observational studies, systematic reviews/meta-analyses, and a limited set of theoretical/historical works used only for conceptual context. Unconscious/implicit processing was operationalized as outcomes measured with implicit or non-conscious paradigms (behavioral tasks) and/or biological proxies of automatic regulation (e.g., autonomic, endocrine, immune, epigenetic, or neuroimaging markers) when the study design or authors' framework explicitly linked these measures to implicit/unconscious processing. Risk of bias was assessed with RoB 2, ROBINS-I, Newcastle-Ottawa Scale, and GRADE as appropriate; theoretical works were excluded from quantitative synthesis and bias assessment. No language restrictions were applied at the search stage; non-English studies were screened via available abstracts and full texts were used when accessible. From 1,245 records identified, 58 studies met inclusion criteria; 30 contributed to the quantitative synthesis. Evidence most consistently supported associations between PINE-system dysregulation and stress-adaptive behavioral/physiological outcomes, as well as between environmental exposures and epigenetic modifications relevant to neurodevelopment and stress regulation. In contrast, morphogenetic fields and morphogen-gradient principles were supported as established developmental biology mechanisms but did not provide direct quantitative evidence for adult unconscious processes, and were therefore treated exclusively as a conceptual organizational layer. Available evidence supports PINE regulation and epigenetic mechanisms as empirically grounded contributors to multisystem integration relevant to unconscious/implicit regulation. Morphogenetic principles are best interpreted as a developmental organizing template rather than as empirically supported mechanisms of unconscious processing, generating testable hypotheses for future prospective and mechanistic studies. https://www.crd.york.ac.uk/prospero/, identifier [CRD42024594352].
Philosophical discussions of the "hard problem" often invoke "problem intuitions", as consciousness intuitions and consciousness are believed to be "closely connected" (Chalmers, 2018). Here, I challenge this assumption. In two experiments, I demonstrate that consciousness intuitions are illusory-they shift across different "problem intuitions", akin to perceptual illusions. When presented with a duplication scenario, people do not view consciousness as physical (i.e., they believe that copying one's physical body will not copy one's conscious states). But when probed about a second scenario (that of Mary in the Black-and-White Room), consciousness now seems squarely physical, as people expect Mary's novel experience of color to "show up" in a brain scan. I trace this shift to two psychological biases-intuitive Dualism and Essentialism. The shift in consciousness intuitions demonstrates that consciousness judgments are illusory, and as such, they cannot be trusted to reflect what consciousness is.
(In)equity in admissions is a global conversation. Approaches to addressing these inequities include affirmative action, holistic admissions and race-conscious admissions. Different countries vary in their usage of these approaches: while some have nationwide policies to implement affirmative action through quota systems, others utilise more holistic approaches, which are determined by individual institutions. This study explored the perspectives of Asian American physicians regarding race-conscious admissions in medical education, using Poon and colleagues' multidimensional model of race class frames to understand how individuals navigate tensions between private and public interests. Using an interpretive qualitative approach, we employed an inductive-deductive qualitative research methodology using purposeful, snowball sampling to identify participants. One-hour interviews were conducted with 25 Asian American physicians across the Northeastern, Southern, Midwestern and Western regions of the United States. Interview transcriptions were analysed using inductive and deductive thematic analysis. The majority of participants supported race-conscious admissions, but both groups (supporters and non-supporters) had fundamentally different interpretations of educational equity. We constructed five themes. (1) Understandings of Race-conscious Admissions examines whether participants held accurate understandings of race-conscious admissions policies; (2) Intersectional Realities versus Individual Merit explores how supportive participants viewed race and socioeconomic status as inextricably intertwined whereas unsupportive participants treated them as separate variables; (3) Public versus Private Interests demonstrates how supportive participants wanted to expand educational opportunities whereas unsupportive participants emphasised individual interests; (4) Evolution of Consciousness documents transformative experiences that facilitated movement from individualistic merit-based frameworks toward systemic understanding; and (5) Coalition versus Competition illustrates divergent visions for Asian American physicians. Critically, widespread misunderstanding of race-conscious admissions practices was identified, particularly among unsupportive participants. This study challenges monolithic representations of Asian American perspectives on race-conscious admissions, demonstrating significant heterogeneity that aligns with Poon's multidimensional framework. These results have significant implications for medical education policy, suggesting that efforts to build support for equitable admissions practices must address both factual misunderstandings and deeper philosophical differences about individual versus structural explanations for educational disparities. Future research should explore intervention effectiveness and examine how physicians' admissions policy attitudes relate to their clinical practice patterns with diverse patient populations.
Accurate diagnosis of disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), remains a long-standing and unresolved challenge in clinical practice. Current diagnostic frameworks rely predominantly on behavioral responsiveness, with the Coma Recovery Scale-Revised (CRS-R) serving as the clinical gold standard. However, behavior-based evaluation is intrinsically vulnerable to examiner subjectivity and cognitive-motor dissociation, contributing to misdiagnosis rates of up to 40%. From a theoretical perspective, consciousness comprises both external awareness and self-awareness, yet existing DoC assessments focus almost exclusively on external sensory processing, leaving self-awareness substantially underassessed. This imbalance highlights a critical gap that motivates for complementary assessment approaches targeting underexplored dimensions of consciousness. This study protocol aims to develop an EEG-based paradigm and evaluate its feasibility for assessing gut-related interoceptive processing in patients with DoC, using controlled, non-invasive rectal balloon distension. Standardized stimulation procedures, synchronized EEG acquisition, and predefined analytical pipelines will be implemented to characterize the temporal and spatial features interoceptive event-related potentials. Electrophysiological and statistical analyses will be conducted to assess the feasibility, signal characteristics, and response profiles of gut-related interoceptive EEG activity across diagnostic categories. Exploratory analyses will further examine associations between interoceptive EEG markers and clinical behavioral measures. By systematically investigating an under assessed dimension of consciousness, this study protocol aims to establish the feasibility and signal-level characteristics of gut-related interoceptive EEG responses in patients with disorders of consciousness. By providing methodological and exploratory evidence at the group level, the findings are intended to inform the design of future hypothesis-driven and validation studies, and to support the longer-term development of complementary assessment approaches that extend beyond behavior-based evaluation, with potential relevance for clinical research and public health-oriented diagnostic strategies. [ClinicalTrials.gov], identifier [NCT07208942].
While foundational, classic legal consciousness scholarship is insufficient to capture the complexity of contemporary citizen-law relations. This article distinguishes legal consciousness from rights consciousness, treating the latter as the claim-oriented subset of legality-making concerned with entitlement, remedy, and institutional redress, and proposes a dynamic, multi-layered framework for analyzing their interaction. Synthesizing classic and recent socio-legal work, the framework is organized into three interconnected layers: (1) a foundational layer, which recasts legality as relational, plural, and cognitively mediated; (2) a mobilization and resistance layer, which theorizes rights mobilization, strategic withdrawal, and legal insufficiency in relation to adjacent concepts such as legal alienation, legal estrangement, and legal cynicism; and (3) a contemporary contextual layer, which defines digital legal consciousness through online dispute navigation, algorithmic curation and affect, platform governance, and digitally networked rights-claiming, thereby showing how digital legal consciousness reshapes and partially decouples legal sense-making from national legal cultures, while specifying the scope conditions under which geopolitical comparison and cultural intimacy matter most-especially in semi-peripheral and post-transitional settings. To facilitate empirical use, the article also maps the framework's three cross-layer mechanisms-mediation, feedback, and re-framing-to concise scope conditions, observable indicators, and exemplary literatures. The result is an analytically sharper tool for explaining when legality is experienced as claimable, insufficient, estranging, or strategically withdrawable in an increasingly interconnected and mediated world.
This paper addresses the problem of integrating phenomenal consciousness with physical laws by seeking to identify and define its function. The central claim is that the hard problem is caused by the same epistemic paradox that makes quantum and classical physics mutually incompatible: the measure-theoretic limit. It is logically impossible to explain the mechanism by which state transitions occur within continuous time except by using approximations, because the mathematics requires point-equivalent instants of zero duration, which cannot exist ontologically when time is continuous. Classical and quantum physics use mutually incompatible frameworks to model causality and overcome this dt→0 limit. It is argued here that consciousness functions as an ontological workaround for this and all problems related to temporally extended information in continuous time, including sensory qualia. The temporal uncertainty principle (TUP) defines consciousness as a superposition of two contradictory temporal perspectives, synchronous and diachronic, within a single "now". These perspectives interact recursively to reduce uncertainty to a point where further reduction is logically and physically impossible. This mechanism prevents computational paralysis when the system confronts unresolvable causal boundaries, and enables the generation of novel concepts and adaptive behaviours. The bi-directional electromagnetic model (BIDEM) postulates how the brain can achieve this mechanism within a general resonance theory (GRT) framework. By demonstrating how phase-amplitude coupling integrates two dimensionally orthogonal substrates, BIDEM enables diachronic information to act within simultaneously experienced instants. The model yields testable predictions for cross-frequency EM interactions and introduces a "simultaneity barrier" as the basis for an objective Turing test of artificial consciousness.
To analyze the change in the level of consciousness using the Coma Recovery Scale-Revised (CRS-R) in correlation with the reduction of the post-intensive care syndrome (PIC-syndrome) in patients with chronic disorders of consciousness (CDC). The study included 76 patients, 47 males and 29 females. In the Department of Early Medical Rehabilitation, the mean treatment duration was 13.3 bed-days. During this time, patients received an average rehabilitation load of 84 hours. On admission, the most common domain was Neuromuscular Disorders, detected in 73 of 76 patients. Critical illness polymyoneuropathy and ICU-acquired dysphagia were the most persistent until discharge. The most significant improvement was observed in the Autonomous-Metabolic domain, with complete elimination of disorders in 8 patients. Overall, the mean PIC-syndrome score decreased from severe (6.2) to moderate (4.2) after medical rehabilitation. Also, a linear regression analysis showed that each decrease in PIT syndrome by 1 point was associated with a mean of +0.78 points on the CRS-R scale. With partial regression of PIC-syndrome during rehabilitation treatment, a true level of consciousness in CDC patients was manifested by an increase in the CRS-R score. Проанализировать динамику уровня сознания по данным клинической шкалы восстановления после комы (CRS-R) в корреляции с купированием проявлений синдрома последствий интенсивной терапии (ПИТ-синдрома) у пациентов с хроническим нарушением сознания (ХНС). В исследование включено 76 пациентов: 47 мужчин и 29 женщин. В отделении ранней медицинской реабилитации средняя длительность лечения составила 13,3 койко-дня. За это время пациенты получали реабилитационную нагрузку в среднем объеме 84 ч. Наибольшей распространенностью при поступлении характеризовался домен «Нейромышечные нарушения», который был выявлен у 73 из 76 пациентов, причем такие проявления, как полимионейропатия критических состояний и дисфагия бездействия, сохранялись наиболее устойчиво вплоть до выписки. Наиболее благоприятная динамика отмечена в «Вегетативно-метаболическом» домене, где полное устранение нарушений произошло у 8 пациентов. В целом после курса реабилитации средний показатель ПИТ-синдрома снизился с тяжелой (6,2) до средней (4,2) степени. Также в результате линейного регрессионного анализа установлено: каждое снижение ПИТ-синдрома на 1 балл дает в среднем +0,78 балла к шкале CRS-R. При частичном регрессе ПИТ-синдрома во время реабилитационного лечения проявляется истинная клиническая картина уровня сознания пациентов с ХНС, что выражается в повышении оценки по шкале CRS-R.
As health professions educators heed the call for more robust disability-conscious education, we must look beyond the entrenched methods and epistemologies of the biomedical sciences. Health professions education (HPE) rooted solely in a "medical model" of disability presents an incomplete portrait of living with disability, reinforcing ableist stigma and misconceptions of disability as an individual limitation rather than a simultaneously social, structural, and embodied phenomenon. This perpetuates stark health disparities that result from health care provider (HCP)'s insufficient medical knowledge, poor communication skills, implicit bias, and general discomfort caring for people with disability (PWD). Moreover, it draws a false divide between patients and providers with disabilities, contributing to discrimination against HCPs with disabilities. Both to address curricular gaps and to improve access and inclusion for HCPs with disabilities, curricular efforts to prepare health professions students to care for PWD must be grounded in disability theory and the health humanities. Applying Moniz and colleagues' 2021 "Prism Model for Integrating the Arts and Humanities into Medical Education" to the development of a disability curriculum, this article models the centrality of the health humanities not only for developing future HCPs' disability competencies, but also for encouraging students' disability consciousness. From mastering skills to promoting perspective taking, personal insight, and social advocacy, the epistemic functions of the health humanities provide the foundation for humility, accessibility, and disability consciousness.
Burst suppression (BS) is a clinically important EEG pattern in disorders of consciousness (DoC), but routine identification still relies on visual review, and automated methods developed in anesthesia or otherwise controlled settings may generalize poorly to heterogeneous DoC EEG. To develop an adaptive framework for automated BS detection and algorithm-aligned BS-burden quantification, and to characterize BS-associated neurophysiological features in DoC. We developed an unsupervised two-stage pipeline that screens EEG segments for BS using differential-signal enhancement and adaptive thresholding, then quantifies BS-positive segments using a burst-to-suppression ratio (Rbs). Segment-level performance was evaluated on one baseline validation dataset and two stress-test datasets, each including 63 BS and 192 non-BS segments, and benchmarked against two re-implemented detectors. In the DoC-BS cohort, spectral, complexity, and phase-synchrony features were extracted. Patient-level Rbs was correlated with same-day and day-7 total Glasgow Coma Scale (GCS) scores; exploratory feature-level correlations with day-7 GCS and Rbs were also examined. The detector achieved strong performance across datasets (F1, 93.9%-98.4%; MCC, 0.920-0.979) and fewer false positives than the comparator methods. BS was characterized by frontal δ predominance, elevated DAR, reduced SampEn, denser δ and θ phase synchrony, and weaker α-band coupling. Rbs showed positive nominal associations with same-day GCS and day-7 GCS, whereas exploratory feature-level correlations did not survive BH-FDR correction. This study provides an adaptive BS screening-and-quantification framework for heterogeneous DoC EEG. Rbs is an objective descriptor of BS burden, and associated EEG features represent candidate neurophysiological signatures requiring multicenter validation.
Patients undergoing transfemoral aortic valve replacement are particularly vulnerable and require a more sophisticated anesthetic therapeutic approach. According to the literature, no study has directly compared general anaesthesia with conscious analgosedation using postoperative infections as the primary endpoint. Patients undergoing transcatheter aortic valve implantation (TAVI) were analyzed retrospectively. A total of 3313 patients from a large heart center in Western Europe were included in this study. One group received general anaesthesia, and the other group received analgosedation for TAVI. The primary outcome was postinterventional pneumonia; secondary outcomes included myocardial infarction, renal failure, stroke, and 30-day mortality. Propensity score matching using 16 matching criteria yielded over 1000 pairs. No difference was observed in the incidence of postinterventional pneumonia (p = 0.148). The occurrence of myocardial infarction (p = 0.2) and stroke (p = 0.4) also did not differ significantly between the two groups. In contrast, the need for transient renal replacement therapy (p = 0.02) and 30-day mortality (p = 0.02) were lower in the analgosedation group. Regarding postinterventional pneumonia, general anaesthesia can be used as safely as analgosedation during TAVI. However, since renal failure requiring temporary replacement therapy and mortality are both increased with general anaesthesia, analgosedation should be the standard of care for TAVI in high-volume centers. The anesthetic regimen must be determined on an individual basis and discussed during the heart team briefing. The conversion to, or primary use of, general anaesthesia when clinically indicated is safe. Overall, ensuring the continuous presence of a senior consultant anesthetist, specifically trained in cardiac anaesthesia, throughout the procedure is essential.
Thalamic low-intensity transcranial focused ultrasound (tFUS) has shown promise for increasing behavioral responsiveness in disorders of consciousness (DOC), but no study has examined whether it can causally modulate the well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC impairment. Sixteen adult patients (44% Female; Age, M=37.81, SD=15.97) with a chronic DOC (Time Since Injury, M=3.39, SD=1.94 years) secondary to severe brain injury (TBI 44%, non-TBI 56%) underwent a 10-day inpatient, longitudinal, single-arm, open-label protocol. tFUS was delivered in a single session targeting the left central thalamus. Well-known behavioral (CRS-R), electrophysiological (EEG δ/β ratio), metabolic (18F-FDG PET), and polysomnographic outcomes were assessed at baseline and after sonication. The maximum CRS-R total score increased significantly following tFUS compared to baseline (M=13.27 vs. M=10.33; t(14)=7.407, p<0.001, d=1.913), as did the global EEG δ/β ratio (N=14; W=17, p=0.025, r=0.68), with the degree of frontal slowing positively predicting behavioral gains (τ b =0.51, p=0.016). Glucose metabolism decreased bilaterally in thalamus and frontal, temporal, and parietal cortices at both post-tFUS timepoints compared to baseline. Finally, N2 sleep increased by 33% following tFUS (N=11; t(10)=2.386, p=0.038, d=0.72), though this did not survive correction. No severe adverse events were observed. Thalamic tFUS can causally modulate well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC. The convergent inhibitory signature across these measures suggests a thalamocortical reset mechanism, complementing existing excitatory neuromodulation approaches and providing the mechanistic foundation for a large, randomized sham-controlled trial.
The renewal of psychedelic medicine has garnered significant scientific interest, with large efforts dedicated to the understanding of the complex subjective experiences induced by these substances. The Altered States of Consciousness (ASC) questionnaire represents the most comprehensive instrument for measuring such experiences yet lacks a validated French translation despite its centrality to research. A psychometric validation of the French 5D-ASC and 11 OAV subscales was conducted using data from 777 participants recruited through online platforms. Participants completed the 94-item questionnaire based on a past naturalistic psychedelic experience induced by a classical or non-classical psychedelic substance. Confirmatory factor analysis (CFA) of established factorial structures, multiple-indicator multiple-cause (MIMIC) modeling assessing measurement invariance across substance categories, and comprehensive reliability analyses were used. The 11-subscale solution demonstrated better fit compared to higher-order structures (CFI = 0.882, RMSEA = 0.051, SRMR = 0.061), though comparative fit indices remained marginally below conventional thresholds. Internal consistency was excellent for global scores (α = 0.95) and satisfactory across individual subscales (α = 0.63-0.84). Construct validity was supported by theoretically consistent inter-scale correlations and convergent validity with single-item validators. MIMIC modeling revealed modest differential item functioning but confirmed measurement invariance, with latent factor differences aligning with known pharmacological profiles. This study provides preliminary evidence for the psychometric validity of the French 5D-ASC. These findings enable future research examining the relationship between subjective experience and therapeutic outcomes in francophone contexts, contributing to the international standardization of psychedelic research instruments.
This article argues that the question of whether we are alone in the universe is a symptom of Western apparatuses that produce an ontological rift between human beings and other species. This rift comprises instrumental, ruling epistemologies that depersonalize other species, thus legitimating our indifference to their manifold intelligences and communications. The Western apparatuses that produce the rift can be understood in terms of a normative and historical unconscious, as well as the defenses of weak dissociation and projection. These defenses operate to secure a conscious and preconscious sense of existential significance while rendering unconscious the terrifying reality of existential insignificance. This analysis also provides a partial explanation for the sources of the climate polycrisis and the strong resistance to effective climate action. That is, dissonant subjects have an antagonistic relation to "nature," deeming all that falls under this abstraction mute and dumb (unintelligent).
Equids slaughtered for human consumption in many countries are stunned with penetrating captive bolt (PCB) to produce an irreversible state of unconsciousness to prevent pain and distress before exsanguination. This topic is much-studied for the most commonly slaughtered species, while literature remains limited on Equidae, particularly donkeys (Equus asinus). This study, in a Mexican commercial abattoir, examined the effectiveness of pneumatic PCB stunning with electroencephalographic (EEG) and behavioural signs in 13 donkeys. Forty-six percent (6/13) of donkeys had periods of 'normal-like' EEG after PCB stunning, between 1 to 9 s in duration. However, in all animals, this changed to either 'transitional' EEG or 'isoelectric' waveforms. The normal-like EEG phases were characterised by increased theta, alpha and beta activity in the EEG power spectrum. Just one donkey showed behavioural signs of incomplete concussion after stunning, showing both rhythmic breathing and spontaneous blinking, alongside normal-like EEG. In addition, four animals did not reach isoelectric EEG during the 30 s of recording. Shot position frequently deviated caudally from the suggested position and this was significantly associated with the presence of normal-like EEG and behavioural signs. These results highlight welfare concerns related to delayed or incomplete loss of consciousness in these animals, indicating the need for species-specific stunning guidelines. In conclusion, EEG is a useful research tool to substantially assist in understanding the risks of a potential return of consciousness after stunning. This could help to refine ideal airline pressure, shot position and validate behavioural signs that better evaluate consciousness in donkeys.
Emergence from general anesthesia, defined by a recovery of consciousness to the wakeful state, is a clinically consequential state transition that remains a passive process dependent on drug clearance. Despite the critical use of anesthesia, the neural circuitry underlying behavioral recovery remains poorly defined. Here, we map whole-brain neural activity during emergence from isoflurane anesthesia in mice using Fos immunolabeling, tissue clearing, and light-sheet microscopy. This approach enables unbiased quantification of neural activity at cellular resolution across the intact whole brain and supports subsequent network analysis. Rather than resembling wakefulness, emergence exhibits widespread cortical suppression alongside selective activation of discrete subcortical nuclei. This pattern of activity includes both previously implicated arousal-related regions and lesser-studied structures linked to respiratory, autonomic, interoceptive, and cerebellar function. By comparing emergence to two behaviorally distinct wakeful control states, we find that control state selection substantially shapes interpretation of whole-brain activity maps. This establishes dual-state comparisons as a broadly useful strategy for state-dependent circuit mapping. Functional network analysis further elucidates candidate central regions that strongly covary together during emergence, with the most integrated region being the ventral orbital cortex. This approach allows for targeted causal investigation, linking brain-wide circuit discovery with future hypothesis-driven mechanistic interrogation. Together, we find that emergence from isoflurane anesthesia reflects selective subcortical recruitment rather than broad global reactivation toward wakefulness. Millions of people undergo general anesthesia each year. While anesthetic unconsciousness is induced rapidly, emergence from altered consciousness is unpredictable. Neural mechanisms that underlie behavioral emergence remain poorly defined. Using whole-brain Fos mapping at cellular resolution, we found that emergence from isoflurane anesthesia is characterized by widespread cortical suppression alongside selective activation of discrete subcortical, autonomic, hindbrain, and cerebellar nuclei. This selective systems-level activity pattern identifies behavioral emergence as more than a simple global return toward wakefulness and highlights underappreciated neural circuitry involved in post-anesthetic recovery. Network analysis of the Fos maps further identifies candidate regions for targeted causal investigation of emergence-related regions.
The autoimmune nodopathy affecting the node of Ranvier was formerly classified within the spectrum of chronic inflammatory demyelinating polyradiculoneuropathy. However, as a result of comprehensive pathological and immunological investigations conducted in recent years, it has increasingly been recognized as a distinct clinical entity. To date, there have been no reported cases linking autoimmune nodopathy at the node of Ranvier with anti-CNTN2 antibodies. This paper presents a case study demonstrating such an association, detailing the clinical and electrophysiological features, and thereby contributing to the global understanding and recognition of this condition. The patient, a 48-year-old female of Han nationality, was admitted to the intensive care unit (ICU) after experiencing a period of unconsciousness, accompanied by a high-grade fever lasting over 4 h. Diagnostic evaluations, including blood tests and imaging studies, indicated the presence of heat stroke and coagulation dysfunction. The therapeutic interventions administered included endotracheal intubation and mechanical ventilation, continuous cooling with electric ice blankets and ice caps, treatments to correct coagulopathy, and aggressive fluid resuscitation. Following these interventions, the patient regained consciousness, and her body temperature returned to normal. However, upon cessation of mechanical ventilation, she exhibited limb weakness and produced indistinct vocalizations, although she was capable of sound production. Routine electromyography identified peripheral nerve injury of the axonal type, while cerebrospinal fluid analysis revealed protein-cell dissociation. Laboratory assays of both blood and cerebrospinal fluid samples tested positive for the anti-CNTN2 antibody IgG. Given the limited availability of effective therapeutic research for this condition at the time, intravenous immunoglobulin therapy was administered with the patient's informed consent, although it did not result in significant improvement of her symptoms. Clinically, impairments in limb motor abilities, dysarthria, respiratory insufficiency, protein-cell dissociation within the cerebrospinal fluid, and early axonal degeneration as evidenced by electromyography are critical diagnostic criteria for autoimmune nodopathy of the Ranvier nodes in patients who test seropositive for anti-CNTN2 antibodies. For individuals presenting with these phenotypes and suspected of having Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy, it is essential to conduct comprehensive assessments for node, paranode, and juxtaparanode antibodies, along with their specific subtypes, to refine therapeutic strategies.
The human brain exhibits inherent multistability, with Energy Landscape Analysis (ELA) providing effective frameworks for investigating this property through BOLD signals. However, traditional amplitude-based approaches fundamentally neglect critical phase synchronization dynamics that mediate large-scale neural coordination, while existing phase-based methods like Leading Eigenvector Dynamic Analysis (LEiDA) lack thermodynamic formalism for state stability quantification. Here, we introduce Energy-based Phase-Locking State Analysis (EPLSA), a transformative computational framework that synergistically integrates instantaneous phase-coupling dynamics with rigorous energy landscape principles, addressing fundamental limitations of conventional methodologies. Comprehensive validation across two independent neuroimaging datasets (HCP and Natural Sleep) demonstrated EPLSA's marked superiority over LEiDA and conventional ELA in terms of test-retest reliability, task-specific brain state differentiation, and individual-level classification performance. To demonstrate the physiological and clinical utility of the proposed method, sleep-wake analysis was performed to reveal EPLSA's enhanced sensitivity to consciousness state transitions, identifying decreased primary state occupancy and increased minor state prevalence during sleep, with significantly reduced direct transition probabilities. Furthermore, application to patients with Alzheimer's disease using the OASIS-3 dataset identified shortened dwell time and occurrence frequency for the frontoparietal control network-default mode network (FPCN-DMN) co-activation state, and prolonged dwell time and occurrence frequency for the visual network-limbic network (VIS-LMN) co-activation state, with these metrics significantly correlating with cognitive impairment. By unifying phase-coupling and thermodynamic principles, EPLSA provides novel insights into neurodynamic mechanisms across cognitive tasks, consciousness states, and neurodegenerative conditions, offering a transformative analytical tool for investigating brain function in health and disease with particular promise for early detection and monitoring of neurological disorders.
The evolution of transcatheter aortic valve implantation (TAVI) technology has enabled a shift towards less invasive, patient-centred perioperative and anaesthetic care. Current evidence from randomised trials indicates that conscious sedation and minimalist approaches are safe in appropriately selected patients, but conversion rates and patient experience highlight the need for careful case selection. The Italian expert consensus in a recent issue of the British Journal of Anaesthesia provides timely and clinically relevant guidance, supporting a default minimally invasive strategy (local anaesthesia or conscious sedation) delivered by anaesthetists, with escalation of monitoring and anaesthetic intensity only in higher-risk clinical scenarios. In the absence of robust comparative evidence for many aspects of care, Ajello and colleagues introduce a pragmatic clinical approach, individualised towards patients' needs, which helps to standardise practice, optimise patient comfort and outcomes, and reduce unnecessary invasiveness of monitoring. Future pragmatic clinical research is needed to better integrate patient-centred outcomes into anaesthetic practice.
We report a female patient who underwent computed tomography (CT)-guided percutaneous lung biopsy due to a right lung mass. After the procedure, she developed impaired consciousness. Non-contrast cranial CT revealed small intracranial air bubbles. Diffusion-weighted magnetic resonance imaging showed multiple acute cerebral infarctions. Whole-brain angiography did not reveal any major vessel occlusion. She was diagnosed as iatrogenic cerebral air embolism. After admission, she received intensive treatment including 100% oxygen inhalation and hyperbaric oxygen therapy. Eventually, she regained consciousness and was discharged successfully. Cerebral air embolism is a rare but severe complication of percutaneous lung biopsy with a generally poor prognosis. Clinicians should maintain a high index of suspicion for this condition in patients presenting with acute neurological deficits after lung biopsy. Hyperbaric oxygen therapy demonstrates significant neuroprotective effects and improves clinical outcomes.