Complexity of multi-dimensional spontaneous EEG decreases during propofol induced general anaesthesia

Emerging neural theories of consciousness suggest a correlation between a specific type of neural dynamical complexity and the level of consciousness: When awake and aware, causal interactions between brain regions are both integrated (all regions are to a certain extent connected) and differentiated (there is inhomogeneity and variety in the interactions). In support of this, recent work by Casali et al (2013) has shown that Lempel-Ziv complexity correlates strongly with conscious level, when computed on the EEG response to transcranial magnetic stimulation. Here we investigated complexity of spontaneous high-density EEG data during propofol-induced general anaesthesia. We consider three distinct measures: (i) Lempel-Ziv complexity, which is derived from how compressible the data are; (ii) amplitude coalition entropy, which measures the variability in the constitution of the set of active channels; and (iii) the novel synchrony coalition entropy (SCE), which measures the variability in the constitution of the set of synchronous channels. After some simulations on Kuramoto oscillator models which demonstrate that these measures capture distinct ‘flavours’ of complexity, we show that there is a robustly measurable decrease in the complexity of spontaneous EEG during general anaesthesia

Shannon entropy of brain functional complex networks under the influence of the psychedelic Ayahuasca

The entropic brain hypothesis holds that the key facts concerning psychedelics are partially explained in terms of increased entropy of the brain's functional connectivity. Ayahuasca is a psychedelic beverage of Amazonian indigenous origin with legal status in Brazil in religious and scientific settings. In this context, we use tools and concepts from the theory of complex networks to analyze resting state fMRI data of the brains of human subjects under two distinct conditions: (i) under ordinary waking state and (ii) in an altered state of consciousness induced by ingestion of Ayahuasca. We report an increase in the Shannon entropy of the degree distribution of the networks subsequent to Ayahuasca ingestion. We also find increased local and decreased global network integration. Our results are broadly consistent with the entropic brain hypothesis. Finally, we discuss our findings in the context of descriptions of "mind-expansion" frequently seen in self-reports of users of psychedelic drugs.Comment: 27 pages, 6 figure

Large-scale signatures of unconsciousness are consistent with a departure from critical dynamics

Loss of cortical integration and changes in the dynamics of electrophysiological brain signals characterize the transition from wakefulness towards unconsciousness. The common mechanism underlying these observations remains unknown. In this study we arrive at a basic model, which explains these empirical observations based on the theory of phase transitions in complex systems. We studied the link between spatial and temporal correlations of large-scale brain activity recorded with functional magnetic resonance imaging during wakefulness, propofol-induced sedation and loss of consciousness, as well as during the subsequent recovery. We observed that during unconsciousness activity in frontal and thalamic regions exhibited a reduction of long-range temporal correlations and a departure of functional connectivity from the underlying anatomical constraints. These changes in dynamics and anatomy-function coupling were correlated across participants, suggesting that temporal complexity and an efficient exploration of anatomical connectivity are inter-related phenomena. A model of a system exhibiting a phase transition reproduced our findings, as well as the diminished sensitivity of the cortex to external perturbations during unconsciousness. This theoretical framework unifies different empirical observations about brain activity during unconsciousness and predicts that the principles we identified are universal and independent of the causes behind loss of awareness.Comment: to appear in Journal of the Royal Society Interfac

Factoring the brain signatures of anesthesia concentration and level of arousal across individuals.

Combining resting-state functional magnetic resonance imaging (fMRI) connectivity and behavioral analysis during sedation, we factored out general effects of the anesthetic drug propofol and a specific index of conscious report, participants' level of responsiveness. The factorial analysis shows that increasing concentration of propofol in blood specifically decreases the connectivity strength of fronto-parietal cortical loops. In contrast, loss of responsiveness is indexed by a functional disconnection between the thalamus and the frontal cortex, balanced by an increase in connectivity strength of the thalamus to the occipital and temporal regions of the cortex

Altered dynamical integration/segregation balance during anesthesia-induced loss of consciousness

In recent years, brain imaging studies have begun to shed light on the neural correlates of physiologically-reversible altered states of consciousness such as deep sleep, anesthesia, and psychedelic experiences. The emerging consensus is that normal waking consciousness requires the exploration of a dynamical repertoire enabling both global integration i.e., long-distance interactions between brain regions, and segregation, i.e., local processing in functionally specialized clusters. Altered states of consciousness have notably been characterized by a tipping of the integration/segregation balance away from this equilibrium. Historically, functional MRI (fMRI) has been the modality of choice for such investigations. However, fMRI does not enable characterization of the integration/segregation balance at sub-second temporal resolution. Here, we investigated global brain spatiotemporal patterns in electrocorticography (ECoG) data of a monkey (Macaca fuscata) under either ketamine or propofol general anesthesia. We first studied the effects of these anesthetics from the perspective of band-specific synchronization across the entire ECoG array, treating individual channels as oscillators. We further aimed to determine whether synchrony within spatially localized clusters of oscillators was differently affected by the drugs in comparison to synchronization over spatially distributed subsets of ECoG channels, thereby quantifying changes in integration/segregation balance on physiologically-relevant time scales. The findings reflect global brain dynamics characterized by a loss of long-range integration in multiple frequency bands under both ketamine and propofol anesthesia, most pronounced in the beta (13–30 Hz) and low-gamma bands (30–80 Hz), and with strongly preserved local synchrony in all bands

A synergistic workspace for human consciousness revealed by Integrated Information Decomposition.

How is the information-processing architecture of the human brain organised, and how does its organisation support consciousness? Here, we combine network science and a rigorous information-theoretic notion of synergy to delineate a synergistic global workspace, comprising gateway regions that gather synergistic information from specialised modules across the human brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the human brains default mode network, whereas broadcasters coincide with the executive control network. We find that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information

Changes in resting neural connectivity during propofol sedation.

BACKGROUND: The default mode network consists of a set of functionally connected brain regions (posterior cingulate, medial prefrontal cortex and bilateral parietal cortex) maximally active in functional imaging studies under "no task" conditions. It has been argued that the posterior cingulate is important in consciousness/awareness, but previous investigations of resting interactions between the posterior cingulate cortex and other brain regions during sedation and anesthesia have produced inconsistent results. METHODOLOGY/PRINCIPAL FINDINGS: We examined the connectivity of the posterior cingulate at different levels of consciousness. "No task" fMRI (BOLD) data were collected from healthy volunteers while awake and at low and moderate levels of sedation, induced by the anesthetic agent propofol. Our data show that connectivity of the posterior cingulate changes during sedation to include areas that are not traditionally considered to be part of the default mode network, such as the motor/somatosensory cortices, the anterior thalamic nuclei, and the reticular activating system. CONCLUSIONS/SIGNIFICANCE: This neuroanatomical signature resembles that of non-REM sleep, and may be evidence for a system that reduces its discriminable states and switches into more stereotypic patterns of firing under sedation

Consciousness, Anesthesia and Brain Resting State Networks

Consciousness is a great mystery to science. Despite several attempts, none of the current theories have managed to explain how and why it exists. Theories struggle with fundamental philosophical questions, such as the hard problem, that contests how something mental, like consciousness, can be explained by physical phenomena such as neural activity. Modern neuroscientific study of consciousness puts aside this and a few other yet unreachable questions. It focuses on finding the neural correlates of consciousness (NCC) comprising the physical phenomena, which correlate with certain aspects of consciousness. In the NCC studies, consciousness is usually taken to have two aspects: the states of consciousness, encompassing awake, dreaming, and unconscious states, and contents of consciousness, such as an experienced perceptual stimulus. Experimental anesthesia and functional brain imaging are essential tools for the search of the NCC. Anesthesia offers a reliable and reversible method to alter the subject's state of consciousness. The brain function during these altered states of consciousness can be measured with functional imaging methods, such as functional magnetic resonance imaging (fMRI). It measures neuronal activity via a blood oxygen level dependent (BOLD) signal. Functional connectivity analysis of the BOLD-signal can be used to explore the organization of spatially distinct brain areas into functional networks, which are associated with specific cognitive functions such as attention control and emotional regulation. Recently, several studies have shown that changes in functional connectivity between and within these networks are also associated with altered states of consciousness induced by anesthetic drugs. This review will cover the essential questions and methodology of current exploration of neural correlates of states of consciousness, focusing on the resting state networks and the use of fMRI and experimental anesthesia as research tools. Effects of different anesthetics on these networks are also compared. Different anesthetics used in experimental anesthesia have quite distinct pharmacological mechanisms of action, even though the induced brain functional connectivity patterns resemble each other. Propofol-induced unconsciousness is mediated either from corticocortical or thalamocortical disconnection. The nonspecific thalamic nodes, related to arousal and distribution of information, may have an important role in propofol-induced unconsciousness. Dexmedetomidine has similar patterns in connectivity changes as propofol, but the connectivity between deeper brain regions and thalamus remains less affected, possibly explaining the easier arousal from dexmedetomidine-induced unconsciousness. Ketamine increases the overall functional connectivity but disrupts the connectivity in the higher-order networks of the brain inducing “dissociative anesthesia”. The role of thalamic functional connectivity during ketamine anesthesia has not been studied and would be an interesting subject for future studies.Tietoisuuden syntymekanismi on yksi suurimmista ratkaisemattomista mysteereistä. Filosofiset kysymykset, kuten tietoisuuden niin kutsuttu vaikea ongelma ja selityksellinen kuilu, ovat edelleen ajankohtaisia ja ne kyseenalaistavat esimerkiksi pystytäänkö tietoisuuden syntymekanismeja koskaan selittämään tieteellisin keinoin. Nykyinen neurotieteellinen tutkimus pyrkii selvittämään tietoisuuden hermostollisia vastineita, eli kuvaamaan tiettyyn tietoisuuden tilaan tai sisältöön liittyviä aivotoiminnan mekanismeja. Näitä vastineita tutkittaessa käytetään jakoa tietoisuuden tiloihin, joita ovat hereillä olo, unennäkö ja tajuttomuus tai tietoisuuden komponentteihin joita ovat esimerkiksi koettu auditorinen tai visuaalinen ärsyke. Tässä katsausartikkelissa käydään läpi nykyisen tietoisuuden tutkimuksen ja sen tilojen neurologisten vastineiden etsimisen perusteet, keskittyen funktionaaliseen magneettikuvaukseen, lepotilaverkostoihin ja anestesiaan. Artikkelissa myös vertaillaan aikaisempien sellaisten tutkimusten tuloksia, jotka käsittelevät eri anesteettien vaikutuksista lepotilaverkostoihin. Kokeellista anestesiaa ja toiminnallista aivokuvantamista käytetään työkaluina tietoisuuden tiloihin liittyvien aivotoiminnan mekanismien tutkimisessa. Anestesian avulla voidaan luotettavasti ja palautuvasti aiheuttaa muutoksia koehenkilöiden tajunnan tilaan. Samalla tutkimuskysymyksiin etsitään vastauksia kuvantamalla tiettyihin tajunnan tiloihin tai niiden muutoksiin liittyviä aivotoiminnan mekanismeja. Kuvantamismenetelmistä toiminnallisella magneettikuvauksella pysytään mittaamaa hermokudoksen aktiivisuutta veren happipitoisuudesta riippuvalla signaalilla. Vertaamalla aktivoitumista tietyltä alueelta verraten sitä koko aivojen samanaikaiseen aktivoitumiseen, saadaan näkyviin toiminnallisia verkostoja, joilla on omia tehtäviä esimerkiksi kognitiivisessa prosessoinnissa ja tarkkaavaisuuden keskittämisessä. Myös tietoisuuden tasot korreloivat näiden verkostojen sisäisten ja keskinäisten yhteyksien sekä oikea-aikaisen aktivoitumisen kanssa. Kokeellista anestesiaa käytettäessä on huomioitava eri anesteettien erilaiset vaikutusmekanismit, vaikkakin aivokuvantamisella aktivoitumismuutokset muistuttavat toisiaan. Vertailtavissa anesteeteissa esiintyy yhtäläisyyksiä kortikaalisten verkostojen yhteyksien heikkenemiseen ja tietoisuuden häviämiseen liittyen. Propofolin keskeisenä mekanismina on joko yhteyksien katkaiseminen aivokuoren verkostoissa tai talamuksen ja aivokuoren välillä. Deksmedetomidiinin fMRI:llä mitatut vaikutukset muistuttavat paljon propofolia, mutta yhteys talamuksen ja syvempien aivoalueiden välillä säilyy, joka todennäköisesti mahdollistaa nopeamman heräämisen. Ketamiini lisää toiminnallista konnektiivisuutta verkostoissa, kuitenkin samalla hajottaen järjestäytymistä korkeamman asteen verkostoissa. Propofolista poiketen ketamiinin vaikutus toimintaverkostoon on vähäinen. Talamuksen merkitys yhteyksien muutoksissa yleisesti jää vielä epävarmaksi: ovatko muutokset syytä vai seurausta aivokuoren yhteyksien hajoamisesta

Anesthetic-induced unresponsiveness: Electroencephalographic correlates and subjective experiences

Anesthetic drugs can induce reversible alterations in responsiveness, connectedness and consciousness. The measures based on electroencephalogram (EEG) have marked potential for monitoring the anesthetized state because of their relatively easy use in the operating room. In this study, 79 healthy young men participated in an awake experiment, and 47 participants continued to an anesthesia experiment where they received either dexmedetomidine or propofol as target-controlled infusion with stepwise increments until the loss of responsiveness. The participants were roused during the constant drug infusion and interviewed. The drug dose was increased to 1.5-fold to achieve a deeper unresponsive state. After regaining responsiveness, the participants were interviewed. EEG was measured throughout the experiment and the N400 event-related potential component and functional and directed connectivity were studied. Prefrontal-frontal connectivity in the alpha frequency band discriminated the states that differed with respect to responsiveness or drug concentration. The net direction of connectivity was frontal-to-prefrontal during unresponsiveness and reversed back to prefrontal-to-frontal upon return of responsiveness. The understanding of the meaning of spoken language, as measured with the N400 effect, was lost along with responsiveness but, in the dexmedetomidine group, the N400 component was preserved suggesting partial preservation of the processing of words during anesthetic-induced unresponsiveness. However, the N400 effect could not be detected in all the awake participants and the choice of analysis method had marked impact on its detection rate at the individual-level. Subjective experiences were common during unresponsiveness induced by dexmedetomidine and propofol but the experiences most often suggested disconnectedness from the environment. In conclusion, the doses of dexmedetomidine or propofol minimally sufficient to induce unresponsiveness do not render the participants unconscious and dexmedetomidine does not completely abolish the processing of semantic stimuli. The local anterior EEG connectivity in the alpha frequency band may have potential in monitoring the depth of dexmedetomidine- and propofol-induced anesthesia.Anesteettien aiheuttama vastauskyvyttömyys: aivosähkökäyräpohjaiset korrelaatit ja subjektiiviset kokemukset Anestesialääkkeillä voidaan saada aikaan palautuvia muutoksia vastauskykyisyydessä, kytkeytyneisyydessä ja tajunnassa. Aivosähkökäyrään (EEG) pohjautuvat menetelmät tarjoavat lupaavia mahdollisuuksia mitata anestesian vaikutusta aivoissa, sillä niitä on suhteellisen helppo käyttää leikkaussalissa. Tässä tutkimuksessa 79 tervettä nuorta miestä osallistui valvekokeeseen ja 47 heistä jatkoi anestesiakokeeseen. Anestesiakokeessa koehenkilöille annettiin joko deksmedetomidiinia tai propofolia tavoiteohjattuna infuusiona nousevia annosportaita käyttäen, kunnes he menettivät vastauskykynsä. Koehenkilöt herätettiin tasaisen lääkeinfuusion aikana ja haastateltiin. Koko kokeen ajan mitattiin EEG:tä, josta tutkittiin N400-herätevastetta sekä toiminnallista ja suunnattua konnektiivisuutta. Prefrontaali-frontaalivälillä mitattu konnektiivisuus alfa-taajuuskaistassa erotteli toisistaan tilat, jotka erosivat vastauskykyisyyden tai lääkepitoisuuden suhteen. Konnektiivisuuden vallitseva suunta oli frontaalialueilta prefrontaalialueille vastauskyvyttömyyden aikana, mutta se kääntyi takaisin prefrontaalisesta frontaaliseen kulkevaksi koehenkilöiden vastauskyvyn palatessa. N400-efektillä mitattu puhutun kielen ymmärtäminen katosi vastauskyvyn menettämisen myötä. Deksmedetomidiiniryhmässä N400-komponentti säilyi, mikä viittaa siihen, että anesteettien aiheuttaman vastauskyvyttömyyden aikana sanojen prosessointi voi säilyä osittain. Yksilötasolla N400-efektiä ei kuitenkaan havaittu edes kaikilla hereillä olevilla henkilöillä, ja analyysimenetelmän valinnalla oli suuri vaikutus herätevasteen havaitsemiseen. Subjektiiviset kokemukset olivat yleisiä deksmedetomidiinin ja propofolin aiheuttaman vastauskyvyttömyyden aikana, mutta kokemukset olivat usein ympäristöstä irtikytkeytyneitä. Yhteenvetona voidaan todeta, että deksmedetomidiini- ja propofoliannokset, jotka juuri ja juuri riittävät aikaansaamaan vastauskyvyttömyyden, eivät aiheuta tajuttomuutta. Deksmedetomidiini ei myöskään täysin estä merkityssisällöllisten ärsykkeiden käsittelyä. Frontaalialueen sisällä EEG:llä mitattu konnektiivisuus alfataajuuskaistassa saattaa olla tulevaisuudessa hyödyllinen menetelmä deksmedetomidiini- ja propofolianestesian syvyyden mittaamiseksi

Critical Changes in Cortical Neuronal Interactions in Anesthetized and Awake Rats

Background: Neuronal interactions are fundamental for information processing, cognition and consciousness. Anesthetics reduce spontaneous cortical activity; however, neuronal reactivity to sensory stimuli is often preserved or augmented. How sensory stimulus-related neuronal interactions change under anesthesia has not been elucidated. Here we investigated visual stimulus-related cortical neuronal interactions during stepwise emergence from desflurane anesthesia. Methods: Parallel spike trains were recorded with 64-contact extracellular microelectrode arrays from the primary visual cortex of chronically instrumented, unrestrained rats (N=6) at 8%, 6%, 4%, 2% desflurane anesthesia and wakefulness. Light flashes were delivered to the retina by transcranial illumination at 5-15s randomized intervals. Information theoretical indices, integration and interaction complexity, were calculated from the probability distribution of coincident spike patterns and used to quantify neuronal interactions before and after flash stimulation. Results: Integration and complexity showed significant negative associations with desflurane concentration (N=60). Flash stimulation increased integration and complexity at all anesthetic levels (N=60); the effect on complexity was reduced in wakefulness. During stepwise withdrawal of desflurane, the largest increase in integration (74%) and post-stimulus complexity (35%) occurred prior to reaching 4% desflurane concentration – a level associated with the recovery of consciousness according to the rats\u27 righting reflex. Conclusions: Neuronal interactions in the cerebral cortex are augmented during emergence from anesthesia. Visual flash stimuli enhance neuronal interactions in both wakefulness and anesthesia; the increase in interaction complexity is attenuated as post-stimulus complexity reaches plateau. The critical changes in cortical neuronal interactions occur during transition to consciousness