An integrative view of the role of prefrontal cortex in consciousness

Neuron, Год журнала: 2024, Номер 112(10), С. 1626 - 1641

Опубликована: Май 1, 2024

Язык: Английский

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Measuring the dynamic balance of integration and segregation underlying consciousness, anesthesia, and sleep in humans

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 24, 2024

Consciousness requires a dynamic balance of integration and segregation in brain networks. We report an fMRI-based metric, the integration-segregation difference (ISD), which captures two key network properties: efficiency (integration) clustering (segregation). With this we quantify state transitions from conscious wakefulness to unresponsiveness induced by anesthetic propofol. The observed changes ISD suggest profound shift towards networks during anesthesia. A common unimodal-transmodal sequence disintegration reintegration occurs during, respectively, loss return responsiveness. Machine learning models using data accurately identify awake vs. unresponsive states their transitions. Metastability (dynamic recurrence non-equilibrium transient states) is more effectively explained integration, while complexity (diversity neural activity) closely linked with segregation. parallel analysis sleep produces similar findings. Our results demonstrate that reliably indexes consciousness.

Язык: Английский

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Unravelling consciousness and brain function through the lens of time, space, and information

Trends in Neurosciences, Год журнала: 2024, Номер 47(7), С. 551 - 568

Опубликована: Май 31, 2024

Disentangling how cognitive functions emerge from the interplay of brain dynamics and network architecture is among major challenges that neuroscientists face. Pharmacological pathological perturbations consciousness provide a lens to investigate these complex challenges. Here, we review recent advances about brain's functional organisation have been driven by common denominator: decomposing function into fundamental constituents time, space, information. Whereas unconsciousness increases structure-function coupling across scales, psychedelics may decouple structure. Convergent effects also emerge: anaesthetics, psychedelics, disorders can exhibit similar reconfigurations unimodal-transmodal axis. Decomposition approaches reveal potential translate discoveries species, with computational modelling providing path towards mechanistic integration.

Язык: Английский

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Deciphering Consciousness: The Role of Corticothalamocortical Interactions in General Anesthesia

Pharmacological Research, Год журнала: 2025, Номер 212, С. 107593 - 107593

Опубликована: Янв. 8, 2025

General anesthesia is administered to millions of individuals each year, however, the precise mechanism by which it induces unconsciousness remains unclear. While some theories suggest that shares similarities with natural sleep, targeting sleep-promoting areas and inhibiting arousal nuclei, recent research indicates a more complex process. Emerging evidence highlights critical role corticothalamocortical circuits, are involved in higher cognitive functions, controlling states modulating transitions between different conscious during anesthesia. The administration general anesthetics disrupts connectivity within these resulting reversible state unconsciousness. This review elucidates how impair interactions, thereby affecting flow information across various cortical layers disrupting higher-order functions while preserving basic sensory processing. Additionally, prefrontal cortex regulating through both top-down bottom-up pathways was examined. These findings highlight intricate interplay subcortical networks maintaining restoring consciousness under anesthesia, offering potential therapeutic targets for enhancing management.

Язык: Английский

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Dopaminergic modulation of propofol-induced activation in VLPO neurons: the role of D1 receptors in sleep-promoting neural circuits

Frontiers in Neuroscience, Год журнала: 2025, Номер 18

Опубликована: Янв. 8, 2025

The ventrolateral preoptic nucleus (VLPO) is a crucial regulator of sleep, and its neurons are implicated in both sleep-wake regulation anesthesia-induced loss consciousness. Propofol (PRO), widely used intravenous anesthetic, modulates the activity VLPO neurons, but underlying mechanisms, particularly role dopaminergic receptors, remain unclear. This study aimed to investigate effects PRO on NA (-) determine involvement D1 D2 receptors mediating these effects. Using vitro patch-clamp techniques, we identified characterized (+) based their morphological, pharmacological, electrophysiological properties. We assessed spontaneous excitatory postsynaptic currents (sEPSCs) inhibitory (sIPSCs) presence absence receptor modulators. significantly increased firing frequency while decreasing neurons. activation was mediated through GABA_A as evidenced by sEPSCs altered sIPSCs dynamics. Dopamine (DA) attenuated PRO-induced increase suppression via not receptors. Blocking with SCH23390 reversed DA changes, antagonist sulpiride had minimal impact. Our findings demonstrate that excites sleep-promoting VLPO, primarily modulation occurring These results provide new insights into neural mechanisms general anesthesia highlight potential signaling modulating anesthetic sleep-related circuits.

Язык: Английский

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Spatiospectral Dynamics of Electroencephalography Patterns during Propofol-Induced Alterations of Consciousness States

NeuroImage, Год журнала: 2025, Номер 309, С. 121084 - 121084

Опубликована: Фев. 12, 2025

Язык: Английский

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Harnessing the Second Power of Anesthesia for Disorders of Consciousness: 2025 T. H. Seldon Memorial Lecture

Anesthesia & Analgesia, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Anesthesia's ability to ablate consciousness and eliminate the perception of pain revolutionized surgical practice; its discovery was named one most important medical developments in a thousand years by editors New England Journal Medicine.1 The state reversible, controlled unconsciousness caused anesthetics facilitates hundreds millions surgeries across world each year.2 Although this common, international use suggests that powers are widely understood accepted, anesthesia harbors another power has been largely untapped date. In 1947, Harvard anesthesiologist Henry Knowles Beecher published prescient article Science entitled "Anesthesia's Second Power: Probing Mind."3 it, he wrote: "…we seem have tool for producing holding at will, little risk, different levels consciousness—a promises be great help studies mental phenomena." This "second power" can probe neural substrates undergird mind, which particular promise individuals disorders (DOC). These involve prolonged reduced wakefulness awareness self environment after brain injury or progressive damage. acute DOC, families clinical care providers faced with 2 sets urgent questions. first involves patient's current level consciousness. is commonly assessed bedside using behavioral measures such as Glasgow Coma Scale (GCS), misdiagnosis rate patients liminal (ie, minimally conscious [MCS]) unconscious unresponsive syndrome [UWS]) extraordinarily high.4 International guidelines begun support functional magnetic resonance imaging (fMRI) electroencephalography (EEG) detect through activation response cognitive tasks.5,6 resultant state, motor dissociation (CMD), detected approximately 25% without an observable commands.7 second set questions DOC capacity consciousness: whether they will regain consciousness, timeline recovery, what treatments resources required get there. answers these critical determinants goals care, knowledge post-acute recovery trajectories remained remarkably limited, predictions often imprecise. converging evidence late independence possible many severe injuries, 70% deaths during traumatic associated withdrawal life-sustaining treatments.8 How address diagnostic prognostic DOC? field science, it common practice define absence: "what vanishes every night when we fall into dreamless sleep."9 Let us consider variation definition: anesthetized." Through lens, appearance disappearance markers induced withdrawn from patient whose underlying unknown may indeed fulfill Beecher's prediction anesthesia's mind. WHAT VANISHES WHEN WE ARE ANESTHETIZED idea perturbation assess deep roots. Today's validated index perturbational complexity (PCI), captures brain's direct noninvasive cortical transcranial stimulation (TMS) EEG. spatiotemporal TMS successfully differentiates various anesthetic agents, categories DOC.10 exquisite accuracy TMS-EEG assessment reflected European American Academy Neurology's inclusion PCI diagnosis coma patients. Despite this, faces large translational barriers broad implementation, including low availability equipment techniques, challenges integrating environment, length testing time. Our team built on type perturbation: anesthesia. We provided brief reversible propofol challenge reliably disrupted activity allowed reconfiguration. By measuring EEG changes exposure repurposed stress test hypothesis straightforward: high would significantly change exposure, while remain same before approach highly compatible where admitted. For one, administered limited distress contraindications. were all exposed intubated ICU negative effects, suggesting likelihood safe administration study; participants hemodynamically stable throughout experimental protocol. Additionally, responses did not require perform any sensory, motor, tasks, thus independent their willingness react external stimuli commands. anesthetized hypothesized network-level process, gross suppression processing primary sensory cortex.11 Accordingly, examined alterations network known healthy brain. Functional connectivity networks undergo large-scale reconfiguration upon reversal posterior anterior areas rich (eg, hubs), corresponding dominant direction connectivity.12,13 calculated metrics, combined them called Adaptive Reconfiguration Index (ARI). pilot case series 12 adults acquired injury, ARI predicted 100% responsiveness 3-month follow-up.14 All who recovered had adaptive (Figure 1); static.Figure 1.: Reproduced permission Blain-Moraes et al.15 A example features diagnosed within 3 mo recording. recorded participant (A) baseline, propofol-exposure, postexposure periods; (B) spectrogram; (C) alpha topographic map; (D) phase-amplitude coupling; (E) phase lag index; (F) directed (G) hub location. indicates electroencephalogram.In contrast remarkable ARI, exceed chance levels. other words, but Investigating explanations result, turned our attention spectral density (PSD) study participants. PSD represents distribution signal frequencies: oscillatory peaks co-occur broadband nonoscillatory aperiodic) activity. Traditionally, analysis focused patterns specific frequency bands. followed conventional calculating focusing constructed band 8–14 Hz). However, exhibits total absence theta peaks. Indeed, dataset 43 patients, peak could only identified 13 participants.16 As alter aperiodic component general anesthesia,17,18 concerned might underpinned entirely signal. slope expanded group (n = 16) baseline propofol. expected, steepened 30 45 Hz range, 1 range 1A, 1C). Importantly, absolute participant's measured Recovery Scale-Revised (CRS-R) score 1B, 1D). Patients higher CRS-R demonstrated larger steepening anesthesia-induced non-oscillatory corresponded CRITICAL MECHANISM What anesthetic-induced revealing about dynamics awareness? compelling explanation found concept criticality, comes complex systems science. Briefly, criticality describes behavior system precisely poised between dynamical regimes, chaos stability. At fine balance point, displays optimal computation capacity, information richness, maximal sensitivity perturbation.19 system's reaction depend preperturbed distance just stone thrown water generate depending icy pond, calm lake stormy sea. Criticality increasingly explored requirement function emergence Many approaches taken brain, edge chaos—which meeting point regimes stability—and avalanche criticality—which amplification dissipation. characteristics general, Lempel-Ziv (LZC)—a measure number unique embedded To investigate potential mechanism underpinning observations, relationship metrics pre-perturbation discovered slope, information-richness, relied pre-anesthetic characteristics. results suggested brains operate far resulting weaker susceptibility global perturbations anesthesia, predict magnitude 2).Figure 2.: Alterations Power Baseline (red) Anesthesia (blue) log-log scale, averaged (MCS; top), (UWS; middle), (bottom). Illustration hypothesis: posited critical. Propofol shifts subcritical state. MCS (purple), UWS (green), (orange) distant degrees propofol.While compelling, based correlational analysis. strengthen evidence, then conducted secondary collected types (propofol, xenon, ketamine) doses roughly comparable vis-à-vis loss humans. Crucially, also contained PCI.20 states xenon diverge ketamine (where experienced vivid dreams) maintain close-to-critical dynamics. further resting-state (i.e., PCImax). confirmed predictions: ketamine, shift away increased chaoticity.21 Most importantly, PCImax, 3). provide neuronal necessary condition Beyond explanatory mechanism, major practical implications individual subjects' PCImax short 60-channel recording obtained intervention mean average error below 7%, raising intriguing possibility accurately requiring anesthesia.Figure 3.: Prediction Individual points represent subjects predrug (light green: eyes closed [EC]; dark open [EO]), (blue), (black), conditions. Conscious (yellow) separated individual-subject (based figure Maschke al21). index.PROBING THE MIND Do last suggest chasing red herring, does reveal anything beyond consciousness? short—no. First, rather than remains promising prognostication Second, due contain meaningful insights above final cannot alone. exhibited heterogenous reactions anesthesia: majority some displayed opposite pattern—a flatter accompanied more criticality.16 heterogeneity observed Toker al's included proximity edge-of-chaos 4 patients22: unintuitively chaoticity regaining heterogeneous phenotypically indistinguishable similar lack responsiveness), theoretically deviate towards too stable), supercritical chaotic). Endotyping scientific gaps Curing Campaign,23 presents identifying treatment. paradoxical increase consciousness-related complexity) propofol.24 recapitulate arousing effect zolpidem (a GABAergic drug) 10% patients.25 drugs closer supporting return Other possibilities probing mind scattered like breadcrumbs literature. example, LZC impairment times tasks responsiveness,26 entropy brain-injured children PICU variously propofol, midazolam, dexmedetomidine degree recovery.27 Such examples illustrate emerging embrace innate reactivity resilience powerful hidden capacities, mechanisms re-establish persistent unconsciousness. ACKNOWLEDGMENTS 2025 T. H. Seldon Memorial Lecture delivered Research Society. DISCLOSURES Conflicts Interest: None. Funding: S. funded Canada Chair (Tier II) Consciousness Personhood Technologies; Canadian Institutes Health Project Grant (480995) Natural Sciences Engineering Council Discovery (RGPIN-2023-03619). manuscript handled by: Peter A. Goldstein, MD.

Язык: Английский

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Characterization of neuronal spiking patterns in the medial prefrontal cortex under varied general anesthetics in mice

Anesthesiology and Perioperative Science, Год журнала: 2025, Номер 3(1)

Опубликована: Фев. 25, 2025

Abstract Purpose The mechanisms underlying reversible unconsciousness induced by general anesthetics remain unclear. This study aimed to investigate the effects of four commonly used on neuronal spiking patterns in layer 5 medial prefrontal cortex (mPFC). Methods In vivo multi-channel recordings were performed mPFC a mouse model. Neuronal regular-spiking and fast-spiking neurons measured compared across wakefulness loss righting reflex (LORR), recovery (RORR). Four anesthetic/sedative drugs (sevoflurane, propofol, ketamine, dexmedetomidine) tested. Results During LORR, most cortical inhibited, while small subset was excited. Fast-spiking exhibited significant suppression all anesthetics. Among these, firing rate inhibited closely associated with transitions between LORR RORR. Sevoflurane, dexmedetomidine similar modulatory neurons, whereas ketamine stronger excitatory both regular- neurons. Conclusions exert comparable mPFC, induces distinct effects. Inhibited are

Язык: Английский

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От мозга к сознанию: преодоление объяснительного разрыва

Труды кафедры богословия Санкт-Петербургской Духовной Академии, Год журнала: 2025, Номер 1(25), С. 59 - 82

Опубликована: Март 4, 2025

Психическое и физическое принадлежат разным «полюсам» бытия. Физическое в пределе обращается ничто, а психическое есть благодать. Возникает вопрос об образе соединения онтологически разнородных начал природе человека. Предполагается, что формируется из нетварных энергий посредством формирующегося тварного, вещественного тела. Формирующаяся душа также тварна, поскольку ограничена моментом своего возникновения. Формирование души подобно отраженному свету, где исходный свет — нетварные энергии, зеркало тело. Эта модель позволяет преодолеть объяснительный разрыв осмыслении связи процессов мозге с сознанием. «Трудная проблема сознания» может быть разрешена дополнением антропологической модели тварной природы человека нетварными Божественными энергиями, сообщающими творению существуемость всего и, главное, Творца. The mental and physical belong to different “poles” of being. ultimately turns into nothing, the is grace. question arises about image unification ontologically heterogeneous principles in human nature. It assumed that formed from uncreated energies by means a forming created, material body. soul also since it limited moment its emergence. formation like reflected light, where original light energies, mirror This model allows us overcome explanatory gap understanding connection between processes brain consciousness. “difficult problem consciousness” can be resolved supplementing anthropological created nature man with Divine which impart creation existence everything and, most importantly, Creator.

Язык: Русский

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Using the Envelope of the Electroencephalogram as a Model for Gaussianity during Sleep and Anesthesia

IFAC-PapersOnLine, Год журнала: 2025, Номер 59(1), С. 295 - 300

Опубликована: Янв. 1, 2025

Язык: Английский

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