Disturbances of consciousness and cognition that happen during the perioperative period remain a critical challenge in anesthesiology, manifested as intraoperative awareness, delayed emergence, and postoperative delirium. These disorders arise from complex interactions among neural connectivity, neurotransmitter dynamics, and the pharmacological modulation of cortical and subcortical circuits. The thalamocortical network, brainstem arousal centers, and frontoparietal integration systems are crucial in facilitating transitions between drug-induced unconsciousness and recovery; however, their functional disruptions are only partially comprehended. This paper synthesizes recent research that connecting consciousness neurobiology with anesthetic mechanisms, examining how dysregulated GABAergic, NMDA, and adrenergic signaling underlies perioperative neural states. It examines the dual spectrum of intraoperative awareness and postoperative cognitive disturbances through a comprehensive neurophysiological framework. Furthermore, novel diagnostic technologies, including EEG-based depth indices, functional near-infrared spectroscopy, and AI-assisted models, are analyzed for their potential in the real-time detection and prediction of states of consciousness. This study seeks to establish a comprehensive framework for understanding perioperative disturbances of consciousness and cognition by integrating mechanistic, clinical, and technological perspectives. It stresses the importance of personalized anesthetic approaches, multimodal monitoring, and neuroinformatics-informed interventions to avert cognitive sequelae and enhance neural recovery. This perspective positions anesthesiology at the intersection of neuroscience, data science, and consciousness research.
Accurate assessment of residual awareness in patients with Prolonged Disorders of Consciousness (PDoC) remains a major clinical challenge, as conventional behavioural tools can underestimate covert cognition. This study evaluates whether a structured, multi-phase motor imagery Brain-Computer Interface (MI-BCI) protocol provides objective electroencephalography (EEG)-based indicators of awareness that complement behavioural assessments. Forty-four participants (N = 44) completed repeated imagined-movement tasks using wearable EEG (PDoC: Unresponsive Wakefulness Syndrome (UWS, n = 14), Minimally Conscious State (MCS, n = 17), Locked-In Syndrome (LIS, n = 11); two able-bodied participants as benchmarks; ClinicalTrials.gov: NCT03827187; 30-01-2019). The protocol assessed sensorimotor rhythm modulation, training with and without neurofeedback, and binary question answering across phases. Standard behavioural assessments (CRS-R and WHIM) were administered at each session. Significant MI-BCI decoding accuracy (DA) is achieved by 73.8% of patients, of whom 90% progress to Q&A testing and frequently exceed the 70% usability threshold, revealing marked inter-individual heterogeneity. For significant MI-BCI runs, LIS outperform MCS (p = 0.007) and UWS (p = 0.048), while UWS exceed MCS during Q&A (p = 0.049), driven by familiar-voice stimuli. Using leave-one-subject-out cross-validation, combining predictions from DA and behavioural assessments improves balanced diagnostic accuracy to 62% (from 55%), increasing sensitivity to MCS (39% to 69%), with a modest reduction in LIS sensitivity (78% to 67%). Task-related activity over sensorimotor and parietal cortices differentiate diagnostic groups. The structured MI-BCI protocol demonstrates potential as a movement-independent, EEG-based tool for distinguishing UWS, MCS and LIS. Integrating DA and spatial patterns yields diagnostic information that may augment behavioural assessment and advance objective tools for evaluating awareness in PDoC. Some people with severe brain injuries seem unresponsive, yet their brains may still show signs of awareness. This study tested a brain-computer system that detects these signs by recording tiny electrical signals from the scalp when a person imagines moving. We worked with people in different states of consciousness and those with locked-in syndrome, a rare condition marked by complete paralysis, but intact consciousness – across hospitals, care homes, and private homes. The results showed that many could change their brain signals, suggesting intentional thinking, especially those with locked-in syndrome. These findings show that this kind of brain-computer system could help doctors detect hidden awareness in people who cannot move or speak, and may eventually assist with diagnosis and basic communication.
Converging operations allow one to home in on a construct, be this an altered state of consciousness (ASC), or trait and/or state impulsivity. Unfortunately (or, perhaps fortunately), measures that should provide converging operations for such a construct sometimes present with diverging results. Three cases are considered here: trait impulsivity, which should be positively correlated with state or cognitive impulsivity, but which can also be not correlated; the subjective experience of state absorption, which should be positively correlated with trait absorption, but sometimes is not; and trait mindfulness, which should be negatively correlated with trait impulsivity, but this may be undermined by the semantic ambiguity of a questionnaire item. It is suggested that the defining characteristic of the construct of impulsivity should be the self-report regarding trait impulsivity. Likewise, the defining characteristic of the construct of an ASC should be the report regarding subjective experience. In both cases, predominant weight is placed on the evidence supplied by one's subjective experience and appraisal. Three areas for future research and theoretical consideration are suggested: (1) Given that converging measures are not of equal standing, one should consider which measure is a defining one of the construct under investigation, and which measures are critical for delimiting its extent; (2) when a mismatch appears between measures, it is important to clarify what this means for the construct; and (3) one should consider whether the demand characteristics of a study have clouded the interpretation of the construct under investigation.
Herpes simplex virus (HSV) encephalitis is characterised by inflammation and swelling of the brain, resulting in death or severe neurocognitive sequelae. HSV encephalitis is treated with the antiviral aciclovir but still has substantial mortality and morbidity. Adjunct corticosteroids are sometimes used, but whether they improve the outcome is unclear. We aimed to establish the safety and efficacy of adjunct corticosteroids in HSV encephalitis. In this multicentre, observer-blind, randomised, phase 3 trial, adults with HSV encephalitis admitted to 53 hospitals in the UK were randomly assigned to receive intravenous dexamethasone (10 mg/kg, four times daily for 4 days) plus intravenous aciclovir (10 mg/kg three times daily for at least 14 days; dexamethasone group), or intravenous aciclovir alone (control group). Eligible patients aged 16 years or older had suspected encephalitis (a febrile illness with new onset seizure, new focal neurological signs or alteration in consciousness, cognition, personality, or behaviour), with positive HSV type 1 or type 2 PCR test in CSF. Participants were randomly assigned by the trial team at the recruiting site, using a secure web-based randomisation programme. The primary outcome was verbal memory score at 26 weeks, measured by the Wechsler Memory Scale (WMS)-IV auditory memory index. Analyses of primary and secondary outcomes were performed according to the modified intention-to-treat principle, and safety analyses were based on whether participants received at least one dose of the study drug. Trial neuropsychologists assessing the primary outcome, and statisticians involved in the study's primary outcome, were masked to treatment group allocation. The trial is registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN11774734, and EudraCT, EudraCT2016-004835-19, and is completed. Between Sept 22, 2016, and Feb 2, 2022, 94 patients with HSV encephalitis were recruited, 47 (20 [43%] female and 27 [57%] male) to the dexamethasone group, and 47 (24 [51%] female and 23 [49%] male) to the control group. Dexamethasone was initiated a median 7 (IQR 4-8) days after hospital admission. Seven patients withdrew consent, and six were lost to follow-up. Thus, 81 were included in the modified intention-to-treat analysis (39 in the treatment group and 42 in the control group). The primary outcome, verbal memory score at 26 weeks, did not differ significantly between the groups (71 [SD 26] in the dexamethasone group, and 69 [SD 25] in the control group; adjusted difference 1·77 [95% CI -9·57 to 13·12; p=0·76). There were 27 adverse events involving 18 (38%) participants in the control group, and 25 adverse events involving 18 (40%) participants in the dexamethasone group. The most common serious adverse events were seizures requiring readmission to hospital (affecting one [2%] patient in the dexamethasone group and one [2%] patient in the control group) and thrombotic events, including deep vein thrombosis (affecting one [2%] patient in the dexamethasone group) and pulmonary embolism (affecting one [2%]patient in the dexamethasone group). There were no treatment-related deaths. In adults with HSV encephalitis, dexamethasone plus aciclovir had a satisfactory safety profile but did not improve verbal memory score compared with aciclovir alone. Given the established role of corticosteroids in other inflammatory encephalitides, our findings suggest that their early use in suspected encephalitis is unlikely to be harmful. Future studies should assess more targeted immunomodulatory approaches in HSV encephalitis. National Institute for Health and Care Research.
Metaphors have long played multiple roles in conceptualizing the mind and brain, guiding the development and refinement of theoretical models and empirical questions. Early analogies (comparing the brain to hydraulic systems, telephone exchanges, factories, or libraries) offered shortcuts to understanding aspects of cognition, memory, and brain dynamics. From theoretical frameworks, metaphors like the mind as a computer evolved into central scientific metaphors, shaping core theoretical frameworks, inspiring predictions, and informing research methodologies. As such, metaphors play a key role in guiding scientific inquiries. Building on that premise, we propose music as a scientific metaphor for understanding multiple brain dynamics and cognitive functions. Unlike metaphors focusing on static components or linear flows, music emphasizes continuous adaptation, context-dependence, and cultural embedding, and presents a model for simultaneous engagement with multiple layers of meaning. Integrating analytical techniques from music theory and experiential insights from performance and listening, we can deepen our understanding of mind and brain dynamics and provide fresh epistemological pathways for interdisciplinary research. Music has a hierarchical structure, temporal complexity, and capacity to integrate multiple processes that parallel key features of the brain's architecture and cognitive functions. Drawing from research on neural oscillations, plasticity, predictive coding, and emotional processing, we illustrate how the musical paradigm can capture the rich entanglement of mind and brain, from large-scale brain dynamics and developmental trajectories to the emergence of consciousness and the interplay of affective states.
Mind-wandering refers to the shift of attention towards task-unrelated thoughts. The current study aims to explore the impact of mind-wandering on learning and decision-making under uncertain circumstances. This study investigated the interplay of trait (spontaneous and deliberate) and state mind-wandering on learning and decision making using the Iowa Gambling Task. Intermittent thought probes were used to measure state mind wandering, and a standardised 8-item mind-wandering questionnaire was used to measure trait mind wandering. Results revealed that participants demonstrated enhanced learning across task trials when engaged in task-unrelated thoughts (mind-wandering). Furthermore, an interaction effect emerged between trait spontaneous mind-wandering and state mind-wandering, significantly predicting learning under uncertainty. Specifically, the beneficial impact of state mind-wandering on learning was most pronounced in individuals with moderate to high levels of spontaneous mind-wandering traits. However, there was no significant effect of mind-wandering on the percentage of risky choices. These findings suggest that spontaneous mind-wandering facilitates cognitive adaptability under uncertain environments, highlighting its adaptive role in learning processes.
The brainstem connects the forebrain to the spinal cord. It consists of three layers, the ventral basis, the intermediate tegmentum, and the dorsal tectum. Caudo-rostrally, the brainstem is divided into the medulla oblongata or myelencephalon, the metencephalon, and the mesencephalon. The tegmentum is the most conserved part of the brainstem and contains the motor and sensory nuclei of cranial nerves (CN) III-XII. They are arranged in a mediolateral direction, and, unlike the spinal cord, their afferent and efferent fibers are not macroscopically separated. The tegmental reticular formation, the brainstem core, has a lattice structure with manifold longitudinal and transverse fibers and stacked neurons. Its architecture provides maximum convergence and divergence of intrinsic and ascending/descending information from the spinal cord and forebrain. It coordinates brainstem-based vital functions, and its integrity is essential for arousal, consciousness, and goal-directed behavior. Its small aminergic and cholinergic telencephalic projection nuclei have a profound impact on mood, motivation, and cognition. Human telencephalic evolution manifests in volume increases of the cerebral crura, pons, cerebellar hemispheres, olives, pyramidal tract, and medial lemniscus. However, the spatial constraints of the posterior fossa limited the proportional expansion of the brainstem during human telencephalic evolution, rendering this evolutionarily conserved structure increasingly vulnerable to malfunction and disease.
Unusual bodily experiences (UBEs) are illusory bodily perceptions that are not coherent with typical wakeful experiences, including flying or floating sensations, body distortions, and out-of-body experiences. This study examines UBEs in a controlled sleep laboratory using meditation and light stimulation to facilitate their occurrence. A total of N = 35 healthy participants underwent high-density EEG, with additional EMG, EOG, and ECG recordings. Participants signalled UBEs by performing left-right-left-right eye movements, providing an objective marker for analysis. Interviews adapted from the micro-phenomenological technique were conducted to capture detailed subjective reports and to guide subsequent sleep and EEG analyses. Of the 35 participants, N = 20 reported a total of n = 36 UBEs, occurring primarily during meditation (wakefulness) but also during sleep arousals, rapid eye-movement (REM) sleep and non-REM sleep. Spectral EEG analyses and generalized linear mixed models were used to investigate the neural correlates of these experiences, suggesting that UBEs emerge during intermediate states of consciousness combining EEG features of both wakefulness and sleep. Specifically, exploratory EEG analyses showed that UBEs across sleep and wakefulness were associated with EEG reactivation, marked by increased high-frequency activity (beta and gamma) and decreased low-frequency activity (delta and theta), with a particularly pronounced effect around temporal regions. Collectively, these results provide novel insights into the EEG correlates associated with UBEs and contribute to a deeper understanding of self-consciousness and body perception across sleep and wakefulness.
The intensity of the psychedelic experience has been shown to be associated with its clinical efficacy. This study aims to investigate the factors that may influence the level of altered consciousness during naturalistic psychedelic use, which serves as a proxy for the intensity of the psychedelic experience. A retrospective online survey was conducted on individuals who reported a psychedelic experience. Demographic data, intensity of the psychedelic experience as assessed by the Altered States of Consciousness questionnaire (5D-ASC and its 11 subscales) and characteristics of the psychedelic experience were documented. A total of 804 participants were included in this study. Significant predictors of 5D-ASC scores following a psychedelic experience included the intended purpose of the experience (with spiritual/religious, therapeutic, and self-exploratory intentions exerting a greater influence than recreational intentions); the type of substance (with dissociative and serotonergic psychedelics associated with stronger effects than entactogens); the estimated dose (with moderate, high, and very high doses yielding greater effects relative to very low doses); as well as participants' age at the time of the experience and their gender. Our findings indicate that the intensity of psychedelic experiences is influenced by a multifaceted interplay of pharmacological, individual, and contextual factors. The close correspondence between determinants of mystical experiences and altered states of consciousness suggests that experiential intensity may reflect a shared underlying neurobiological sensitivity, rather than being specific to a given phenomenological category.
Mind-wandering is widely assumed to impair ongoing task performance, yet findings from creative cognition research suggest that it can be beneficial under some conditions - an inconsistency rooted in coarse mental state classifications and low-ecological-validity tasks. We tested whether mind-wandering during active creative production facilitates or impairs real-time creative output in the ecologically valid setting of live jazz improvisation. 52 musicians performed a musical improvisation task while random thought-probes sampled ongoing mental states: focused attention, mind-wandering, mind-blanking, and task-related interference. Expert judges rated each performance for creativity and overall improvisational quality. Mental states were phenomenologically distinct across dimensions of intentionality and meta-awareness, and critically, this phenomenological heterogeneity translated into functional heterogeneity in their associations with creative output. Mind-wandering predicted higher creativity than focused attention, task-related interference suppressed creativity, and mind-blanking was neutral to modestly positive. Overall quality was mainly driven by expertise. State × expertise interactions revealed that the creative benefits of mind-wandering were strongest for less- and mid-experienced improvisers. These findings show that during improvisatory creative action, mind-wandering need not derail performance. Instead, it may mark adaptive loosening of cognitive control that supports generative spontaneity and flexibility crucial to creative expression.
During sleep, the human brain transitions to a "sentinel processing mode," enabling the continued processing of environmental stimuli despite the absence of consciousness. We employed advanced information-theoretic analyses, including mutual information (MI) and co-information (co-I), alongside event-related potential (ERP) and temporal generalization analyses (TGA), to characterize auditory prediction error processing across wakefulness and sleep. We hypothesized that a shared neural code would be present across sleep stages, with deeper sleep being associated with reduced information content and increased information redundancy. Twenty-nine participants (15 women) underwent an auditory "local-global" oddball paradigm during wakefulness and an 8 h sleep opportunity monitored via polysomnography. We focused on "local" mismatch responses to a deviating fifth tone after four standards. ERP analyses showed that prediction error processing continued throughout all sleep stages (N1-N3, REM). Mutual information analyses revealed a substantial reduction in encoded prediction error information particularly during N3 and REM, although ERP amplitudes increased with deeper NREM sleep. We also observed delayed information encoding during sleep, and co-information analyses showed neural dynamics became increasingly redundant with increasing sleep depth. TGA revealed a largely shared neural code between N2 and N3, though it differed between wakefulness and sleep. We demonstrate how the neural code of the "sentinel processing mode" changes from wake to light to deep sleep and REM, characterized by delayed processing, more redundant and less rich neural information in the human cortex as consciousness wanes. This altered stimulus processing reveals how neural information evolves with variations in consciousness across the night.
Microglia, the brain's resident immune cells, constantly monitor their environment for signs of tissue damage or pathogens. Upon activation by stimuli like lipopolysaccharide (LPS), microglia undergo metabolic changes and release pro-inflammatory mediators. However, variations between human and rodent microglia, as well as differences between in vitro and in vivo conditions, likely influence microglial cellular functions and their responses to stimulation. In the present study, we compared several rodent and human model systems, including cell lines, primary cultures, induced pluripotent stem cell (iPSC)-derived cultures, and acutely isolated microglia, and revealed striking differences in LPS-induced metabolic changes and nitric oxide (NO) production. Using the murine microglial cell line BV-2, we demonstrated that NO was critical for restricting metabolism to glycolysis by blocking oxidative phosphorylation. In contrast, human iPSC-derived microglia and acutely isolated microglia from intraperitoneally injected rats maintained mitochondrial respiration upon LPS activation and did not show significant NO production and inducible nitric oxide synthase (iNOS) expression, respectively. Furthermore, we found that NO was not required for the increase in glycolysis rate or the release of pro-inflammatory cytokines upon LPS stimulation. Our results suggest that glycolysis is essential for microglial activation and cytokine production irrespective of NO production. However, the specific metabolic pathways involved may differ between species and experimental conditions. Understanding these differences is crucial for developing effective therapeutic strategies targeting microglial dysfunction in neurological diseases.
Memory is a fundamental brain function relying on complex neurological mechanisms that involve the processes of experiencing, encoding, consolidating and retrieving. A disorder primarily characterized by the loss of (autobiographical) memory owing to stressful or traumatic events is dissociative amnesia, the underlying mechanisms of which are poorly understood and further research is warranted. In this review, we first outline the memory systems and associated brain areas, then introduce the neural suppression pathways of memory retrieval and discuss the neural correlates and influential theoretical models of dissociative amnesia. After reviewing notable consciousness theories, we finally examine dissociative amnesia through the lens of higher-order theories of consciousness. We propose a theoretical model, the metarepresentational system of memory suppression which learns, through self-organizing processes, to downregulate or block access to a negatively colored autobiographical content. More specifically, we hypothesize that dissociative amnesia, primarily addressing some of its selective forms, may emerge from a functional disconnect between first-order representations, located in the neocortex and hippocampus and higher-order representations, the metarepresentations, located in the dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (DLPFC) which evaluate and regulate conscious access. Additionally, we discuss that the inhibitory mechanisms in the metarepresentational system are flexible and dynamic and can reverse the suppression given the appropriate conditions, as seen in actual dissociative amnesia cases. Although empirical evidence is needed to support our theory, we suggest that disruptions in conscious access, such as those seen in dissociative amnesia, offer a powerful window into the broader mechanisms of consciousness.
The aim of this paper is to make and defend three simple propositions about what can and cannot be conscious in the human brain and to elucidate their implications for research and theory on consciousness. The first proposition is that the fact that some information is conscious should be, but often is not, distinguished from the information itself. The second proposition is that, treating the brain as an information processing system, information can be conscious (or not) but processes that operate on information cannot be conscious. This is illustrated with analysis of voluntary action generation, such as making a verbal report. The third proposition is that access consciousness is just access. Adding the word "consciousness" to it makes no difference to how it operates. An information processing system exactly like the human brain but in which no information was conscious would function in exactly the same way as human brains in which some information is conscious. Conscious experience must be explained by means of a generative mechanism; no such mechanism has yet been proposed.
Interpersonal, caress-like touch evokes pleasant sensations and can reduce stress, anxiety and pain. These effects likely stem from stimulation of C-Tactile (CT) fibers, activating brain regions involved in affective processing. Imagined touch, tactile imagery, elicits similar brain activation and pleasant sensations. However, a direct comparison of CT-optimal touch perception during imagery and stimulation is lacking. Moreover, it is unclear whether individuals can imagine touch at CT-optimal velocities. Here we compared perceived pleasantness of CT-optimal and CT-non-optimal touch during imagery and stimulation in 48 healthy adults. We additionally recorded imagery durations, to investigate whether individuals can differentially imagine slower, CT-optimal (3 cm/s), and faster, CT-non-optimal (18 cm/s) stroking. Participants first performed tactile imagery of slow or fast stroking with a brush or stick, followed by equivalent stimulation by an assessor. Overall, pleasantness scores were slightly, albeit significantly, lower for imagery than stimulation. Importantly, in both imagery and stimulation, slow stroking and brush stroking (CT-optimal) were perceived as significantly more pleasant. Moreover, relative pleasantness scores for imagery and stimulation showed significant positive correlations. Importantly, participants took significantly longer to imagine slow stroking, suggesting that individuals can accurately imagine CT-optimal touch velocities. Our findings illustrate parallels between imagery and stimulation in terms of temporal congruency and affective appreciation of touch. This suggests that similar top-down processes are likely involved, and confirms tactile imagery's potential for future clinical applications.
Chronic exposure to pesticide residues from large-scale agro-livestock operations remains insufficiently characterized, particularly among rural populations living near industrial pig farming facilities. This study examined the association between co-exposure to organophosphate and pyrethroid pesticide residues in soil and well water and mental health outcomes among adults residing near an industrial pig farming facility in rural Chile. A cross-sectional study was conducted with 82 adults. Peridomestic soil and well water samples were analyzed using gas chromatography–tandem mass spectrometry to detect five pesticides: chlorpyrifos, diazinon, pirimiphos-methyl, cypermethrin, and lambda-cyhalothrin. Mental health outcomes included depressive symptoms, anxiety, emotional affect, and health-related quality of life, assessed with validated instruments. Robust linear regression models were used, adjusting for age, sex, education level, and body mass index. Higher chlorpyrifos concentrations in water were associated with increased depressive symptom scores (β = 0.180; 95% CI: 0.016, 0.345) and lower mental health-related quality of life (β = −0.713; 95% CI: −1.288, − 0.137). Cypermethrin concentrations in water were associated with higher psychological distress (β = 0.324; 95% CI: 0.124, 0.525). In soil, pirimiphos-methyl was positively associated with depressive symptoms (β = 21.29; 95% CI: 1.78, 40.79), whereas cypermethrin showed an inverse association (β = −3.66; 95% CI: −6.99, − 0.33). Lambda-cyhalothrin concentrations in soil were inversely associated with overall quality of life (β = −15.13; 95% CI: −27.42, − 2.84). Male sex was positively associated with overall quality of life (β = 14.96; 95% CI: 3.14, 26.79). These findings indicate associations between environmental pesticide residues in soil and water and multiple dimensions of mental health among rural populations living near industrial pig farming operations. Longitudinal studies are needed to clarify temporal relationships and potential cumulative effects. The online version contains supplementary material available at 10.1038/s41598-026-40098-1.
One of the central debates in experimental psychology concerns the extent to which information outside conscious awareness can influence behavior. This study aims to assess whether two novel approaches to unconscious perception, a regression-based Bayesian generative model and Sensitivity vs. Awareness curves derived from General Recognition Theory (GRT), produce convergent results when examining the visual processing of briefly presented masked stimuli. While both investigate "unconscious processing," they differ not only in how they define "unconscious" (chance-level discrimination vs. absence of subjective awareness) and "processing" (priming vs. detection), but also in their underlying mathematical frameworks. To investigate this, we examined the grouping of local elements into global shapes using two prime-mask stimulus onset asynchronies (SOA): a shorter baseline SOA of 40 ms (Experiment 1) and a longer SOA of 67 ms (Experiment 2). Both methods provided evidence for the unconscious processing of the primes' global shape in Experiment 2. However, while GRT analyses also supported unconscious processing at the shorter 40 ms SOA, the Bayesian generative models produced strong evidence against it. We show that discrepancies between both approaches may arise not only from their operational definitions, but also their underlying mathematical frameworks and validity. While the plausibility of the Goldstein model's assumptions remains debated, preliminary SvA simulations suggest limited robustness of the GRT-based model, warranting caution pending further validation. Although both approaches provide refined tools for studying unconscious perception, persistent methodological challenges remain, highlighting the need for clearer definitions of unconscious processing and more thorough validation of the methods employed.
Adolescence is a period of profound behavioral changes associated with high brain vulnerability to negative stimuli including psychotropic drugs misuse which may contribute to the development of psychiatric disorders. Ketamine, an NMDA receptor antagonist, is an anesthetic agent used in a recreational manner in night clubs and raves, especially by intranasal route. The psychedelic effects of ketamine include euphoria, reward and mood swings, leading to an altered state of consciousness. Ketamine use has increased among adolescents and young adults, becoming a relevant global public health concern. At these events, drug consumption is often episodic but intense, which may disrupt diverse neuromodulation processes leading to behavioral impairments. Here, we investigated the mnemonic consequences of ketamine withdrawal following recreational exposure in adolescent female rats. To mimic weekend recreational use, adolescent female Wistar rats (n = 8 animals per group) received intranasal ketamine or saline (10 mg/kg/day) for three consecutive days. Twenty-four hours after the last ketamine administration, animals were submitted to a battery of behavioral tasks including novel object recognition, social recognition and Y-maze paradigms to assess episodic, social and working memories. Hippocampal and prefrontal cortex samples were collected for neurochemical analysis. Early ketamine withdrawal following acute exposure impaired all memory types evaluated in the current study. Additionally, a significant reduction in serotonin and norepinephrine levels were observed in the hippocampus and prefrontal cortex of ketamine exposure rats. These findings indicated cognitive and monoaminergic impairments in adolescent female rats at early ketamine withdrawal periods following acute exposure.
Reports of Extrasensory Perception (ESP)-like experiences have been associated with altered temporal sensitivity, sense of agency, and alpha-band neural activity. However, evidence for these associations has been drawn largely from clinical or clinically enriched samples, limiting understanding of whether similar processes characterize individuals recruited outside explicitly clinical contexts who report persistent ESP-like experiences. The present study compared an ESP-like experience group, comprising individuals reporting persistent ESP-like experiences and no self-reported psychiatric diagnosis, with a non-ESP comparison group, comprising participants who did not report such experiences. Participants completed behavioural measures of temporal sensitivity (double-flash illusion) and sense of agency (judgement of agency), together with resting-state Electroencephalography (EEG) measures of posterior alpha power and Individual Alpha Frequency (IAF). A subset of participants in the ESP-like experience group also completed EEG during a self-reported active ESP-like state. Relative to the non-ESP comparison group, the ESP-like experience group showed reduced temporal sensitivity and a broader SoA window, consistent with broader temporal integration across perceptual and agentive domains. Resting-state EEG further revealed higher posterior alpha power and higher IAF in the ESP-like experience group. Multivariate analyses indicated that temporal sensitivity uniquely predicted group membership, whereas alpha measures explained shared, but not independent, variance. Exploratory within-participant analyses additionally suggested state-dependent modulation of alpha dynamics, with higher IAF during the active ESP-like state than during rest. These findings indicate that persistent ESP-like experiences in a sample recruited outside explicitly clinical contexts are associated with altered temporal integration and alpha-band dynamics.
Time perception is fundamental to human behavior and decision-making, yet its underlying processes remain debated. Interoception and exteroception, as channels of internal bodily and external environmental information, are both implicated in shaping duration perception, but their respective contributions have rarely been directly compared. Here, we employed a dual-task paradigm combining a heartbeat discrimination task with interval production to systematically contrast the effects of interoceptive and exteroceptive processing on timing accuracy and precision. Results revealed distinct patterns between the two channels: although interoceptive and exteroceptive timing showed comparable accuracy, the factors supporting this accuracy differed, with interoceptive perceptual accuracy linked to both perceptual and metacognitive indicators, whereas exteroceptive perceptual accuracy was not predicted by either. By contrast, the two channels diverged in temporal precision, with interoceptive timing becoming more precise at longer intervals and shaped by both metacognitive and perceptual indicators, while exteroceptive precision depended primarily on perceptual performance. These findings suggest that the brain achieves similar behavioral outcomes while relying on different patterns of perceptual and metacognitive involvement optimized for channels with different signal-to-noise profiles, consistent with predictive coding accounts. Future research should investigate the neural and computational bases of these partially separable mechanisms.