149 research outputs found
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
Coherence of BOLD signal and electrical activity in the human brain during deep sevoflurane anesthesia
IntroductionChanges in neural activity induce changes in functional magnetic resonance (fMRI) blood oxygenation level dependent (BOLD) signal. Commonly, increases in BOLD signal are ascribed to cellular excitation.ObjectiveThe relationship between electrical activity and BOLD signal in the human brain was probed on the basis of burst suppression EEG. This condition includes two distinct states of high and low electrical activity.MethodsResting‐state simultaneous EEG and BOLD measurements were acquired during deep sevoflurane anesthesia with burst suppression EEG in nineteen healthy volunteers. Afterwards, fMRI volumes were assigned to one of the two states (burst or suppression) as defined by the EEG.ResultsIn the frontal, parietal and temporal lobes as well as in the basal ganglia, BOLD signal increased after burst onset in the EEG and decreased after onset of EEG suppression. In contrast, BOLD signal in the occipital lobe was anticorrelated to electrical activity. This finding was obtained consistently in a general linear model and in raw data.ConclusionsIn human brains exhibiting burst suppression EEG induced by sevoflurane, the positive correlation between BOLD signal and electrical brain activity could be confirmed in most gray matter. The exceptional behavior of the occipital lobe with an anticorrelation of BOLD signal and electrical activity might be due to specific neurovascular coupling mechanisms that are pronounced in the deeply anesthetized brain.In human brains exhibiting burst suppression EEG induced by sevoflurane, the positive correlation between BOLD signal and electrical brain activity could be confirmed in most gray matter. The exceptional behavior of the occipital lobe with an anticorrelation of BOLD signal and electrical activity might be due to specific neurovascular coupling mechanisms that are pronounced in the deeply anesthetized brain.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137770/1/brb3679.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137770/2/brb3679_am.pd
The effects of mindfulness meditation on rumination in depressed people
Mindfulness meditation is a practice of focus, awareness, and non-judgmental acceptance of one\u27s thoughts (Deyo et al., 2009; Kenny et al., 2007). Rumination is a maladaptive pattern of thought that is common in people with depression and other mood disorders. It can lead to further episodes of depression, and can be very destructive in that way (Nolen-Hoeksema, 2008). This paper reviews several studies on mindfulness meditation, depression, and rumination, with a focus on certain areas and phenomena such as alpha asymmetry (Keune et al 2013) and gamma band activity (Berkovich-Ohana et al., 2012). Modalities such as fMRI and EEG are both used in these studies. Finally, directions for further research are considered, while accepting the challenges unique to this and inherent in any neuroscientific research
Occipital alpha activity during stimulus processing gates the information flow to object-selective cortex.
Given the limited processing capabilities of the sensory system, it is essential that attended information is gated to downstream areas, whereas unattended information is blocked. While it has been proposed that alpha band (8–13 Hz) activity serves to route information to downstream regions by inhibiting neuronal processing in task-irrelevant regions, this hypothesis remains untested. Here we investigate how neuronal oscillations detected by electroencephalography in visual areas during working memory encoding serve to gate information reflected in the simultaneously recorded blood-oxygenation-level-dependent (BOLD) signals recorded by functional magnetic resonance imaging in downstream ventral regions. We used a paradigm in which 16 participants were presented with faces and landscapes in the right and left hemifields; one hemifield was attended and the other unattended. We observed that decreased alpha power contralateral to the attended object predicted the BOLD signal representing the attended object in ventral object-selective regions. Furthermore, increased alpha power ipsilateral to the attended object predicted a decrease in the BOLD signal representing the unattended object. We also found that the BOLD signal in the dorsal attention network inversely correlated with visual alpha power. This is the first demonstration, to our knowledge, that oscillations in the alpha band are implicated in the gating of information from the visual cortex to the ventral stream, as reflected in the representationally specific BOLD signal. This link of sensory alpha to downstream activity provides a neurophysiological substrate for the mechanism of selective attention during stimulus processing, which not only boosts the attended information but also suppresses distraction. Although previous studies have shown a relation between the BOLD signal from the dorsal attention network and the alpha band at rest, we demonstrate such a relation during a visuospatial task, indicating that the dorsal attention network exercises top-down control of visual alpha activity
Exploring the Electrophysiological Correlates of the Default-Mode Network with Intracerebral EEG
While functional imaging studies allow for a precise spatial characterization of resting state networks, their neural correlates and thereby their fine-scale temporal dynamics remain elusive. A full understanding of the mechanisms at play requires input from electrophysiological studies. Here, we discuss human and non-human primate electrophysiological data that explore the neural correlates of the default-mode network. Beyond the promising findings obtained with non-invasive approaches, emerging evidence suggests that invasive recordings in humans will be crucial in order to elucidate the neural correlates of the brain's default-mode function. In particular, we contend that stereotactic-electroencephalography, which consists of implanting multiple depth electrodes for pre-surgical evaluation in drug-resistant epilepsy, is particularly suited for this endeavor. We support this view by providing rare data from depth recordings in human posterior cingulate cortex and medial prefrontal cortex that show transient neural deactivation during task-engagement
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Cognitive Reserve Moderates the Association between Functional Network Anti-Correlations and Memory in MCI
Cognitive reserve (CR) shows protective effects on cognitive function in older adults. Here, we focused on the effects of CR at the functional network level. We assessed in patients with amnestic mild cognitive impairment (aMCI) whether higher CR moderates the association between low internetwork cross-talk on memory performance. In 2 independent aMCI samples (n = 76 and 93) and healthy controls (HC, n = 36), CR was assessed via years of education and intelligence (IQ). We focused on the anti-correlation between the dorsal attention network (DAN) and an anterior and posterior default mode network (DMN), assessed via sliding time window analysis of resting-state functional magnetic resonance imaging (fMRI). The DMN-DAN anti-correlation was numerically but not significantly lower in aMCI compared to HC. However, in aMCI, lower anterior DMN-DAN anti-correlation was associated with lower memory performance. This association was moderated by CR proxies, where the association between the internetwork anti-correlation and memory performance was alleviated at higher levels of education or IQ. In conclusion, lower DAN-DMN cross-talk is associated with lower memory in aMCI, where such effects are buffered by higher CR
Exploring memory impairment and post-traumatic amnesia following traumatic brain injury
Memory disturbances are among the most common and significant consequences of traumatic brain injury (TBI). The severity of these deficits can vary widely across the trajectory of recovery from TBI and can be highly heterogenous across individuals. In the acute stages memory disturbance can occur in the form of post-traumatic amnesia (PTA), but deficits are also present into the chronic stages of recovery. I present four studies that aim to understand the characteristics and underlying mechanisms of memory impairment following TBI.
I investigated the cognitive profile of acute TBI patients with and without PTA. I found PTA patients show a transient deficit in working memory binding. I then assessed electrophysiological abnormalities to test the hypothesis that the binding deficit is underpinned by pathological low frequency slow-wave activity. PTA patients showed a significantly higher delta to alpha power ratio that correlated with binding impairment. To understand how this disruption to cortical communication impacts upon large-scale networks I performed a dynamic functional connectivity analysis on the resting state fMRI of acute TBI patients. I found four independent brain states that showed striking anti-correlation between core cognitive control networks. Patients in a more profound period of PTA spent more time in fewer states than those with less cognitive impairment. These findings suggest that PTA is likely underpinned by disruption to communication required for integration of features in working memory.
Finally, I examined enduring memory failures in chronic TBI patients and found that patients with episodic memory impairment showed differential activation of key networks required for memory and attention. Memory impairment related to the white matter integrity directly underpinning the task-derived encoding networks. These findings suggest that in chronic TBI memory impairment may be associated with failed control of attentional resources.Open Acces
Understanding Neural Networks in Awake Rat by Resting-State Functional MRI: A Dissertation
Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive neuroimaging technique that utilizes spontaneous low-frequency fluctuations of blood-oxygenation-level dependent (BOLD) signals to examine resting-state functional connectivity in the brain. In the past two decades, this technique has been increasingly utilized to investigate properties of large-scale functional neural networks as well as their alterations in various cognitive and disease states. However, much less is known about large-scale functional neural networks of the rodent brain, particularly in the awake state. Therefore, we attempted to unveil local and global functional connectivity in awake rat through a combination of seed-based analysis, independent component analysis and graph-theory analysis. In the current studies, we revealed elementary local networks and their global organization in the awake rat brain. We further systematically compared the functional neural networks in awake and anesthetized states, revealing that the rat brain was locally reorganized while maintaining global topological properties from awake to anesthetized states. Furthermore, specific neural circuitries of the rat brain were examined using resting-state fMRI. First anticorrelated functional connectivity between infralimbic cortex and amygdala were found to be evident with different preprocessing methods (global signal regression, regression of ventricular and white matter signal and no signal regression). Secondly the thalamocortical connectivity was mapped for individual thalamic groups, revealing group-specific functional cortical connections that were generally consistent with known anatomical connections in rat. In conclusion, large-scale neural networks can be robustly and reliably studied using rs-fMRI in awake rat, and with this technique we established a baseline of local and global neural networks in the awake rat brain as well as their alterations in the anesthetized condition
Assessing neural network dynamics under normal and altered states of consciousness with MEG : methodological challenges and proposed solutions for atypical power spectra
Cette dernière décennie a vu un certain nombre d'avancées significatives en mathématiques, en apprentissage computationnel et en traitement de signal, qui n'ont pas encore été pleinement exploitées en neurosciences. En particulier, l'évaluation de la connectivité dans les réseaux neuronaux peut grandement bénéficier de ces travaux. Nous proposons ici d'exploiter ces outils pour combler partiellement le fossé considérable qui existe encore entre la recherche connectomique à grande échelle (largement centrée sur des mesures indirectes de l'activité cérébrale comme l'Imagerie par résonance magnétique fonctionnelle (IRMf)) et les mesures physiologiques plus directes de l'activité cérébrale. Il est particulièrement important de combler ce fossé pour l'étude des propriétés physiologiques associées à divers états de conscience normaux et anormaux, notamment les troubles psychiatriques, le sommeil, l'anesthésie ou les états induits par les drogues. Les travaux récents sur l'induction d'états de conscience altérés par des agonistes non sélectifs de la sérotonine, tels que la psilocybine et le Diéthyllysergamide (LSD), en sont de bons exemples.
Au cours des cinq dernières années, une résurgence rapide de la recherche sur la neurobiologie des tryptamines psychédéliques s'est produite, après une interruption d'un demi-siècle. Bien que ces substances présentent un grand potentiel pour éclairer des aspects jusqu'ici non interrogés du fonctionnement normal et anormal du cerveau, l'ampleur et le caractère inhabituel des changements qu'elles provoquent posent de sérieux défis aux chercheurs. La découverte de méthodes convaincantes et évolutives pour étudier ces données est d'une grande importance si nous voulons tirer parti de la fenêtre unique que ces substances atypiques offrent sur les aspects centraux de la conscience et des fonctions cérébrales anormales. Dans la présente thèse, nous résumons l'état actuel de la neuro-imagerie électrophysiologique en ce qui concerne l'étude des tryptamines psychédéliques, et nous démontrons un certain nombre de lacunes évidentes dans la recherche électrophysiologique actuelle sur les psychédéliques. Nous offrons également quelques modestes contributions méthodologiques au domaine. L'utilité de ces contributions est soutenue par quelques résultats empiriques intrigants, bien que préliminaires. Dans le premier chapitre, nous présentons l'histoire de la recherche neuroscientifique sur le LSD. Il a été rapporté que le LSD induit des déplacements de pics dans les spectres de puissance, en même temps que des diminutions de l'amplitude des pics. Le fait que ces effets soient liés entre eux et que la plupart des recherches menées jusqu'à présent n'aient pas cherché à les distinguer est uniformément négligé dans la littérature, ce qui, selon nous, peut conduire à de fausses interprétations.
Le chapitre 2 examine certains des avantages plausibles ainsi que les obstacles sérieux à la recherche sur la connectivité du cerveau entier par magnétoencéphalographie (MEG), et propose plusieurs stratégies pour surmonter ces limites méthodologiques. Celles-ci comprennent des stratégies d'imagerie de source convaincantes, des développements nouveaux et récents dans la décomposition spectrale, des mesures de connectivité insensibles à la conduction volumique, et des implémentations évolutives de métriques de couplage interfréquence bien établies. Nous montrons que ces techniques peuvent être étendues à une grille corticale et sous-corticale de plus haute résolution que celle qui existe actuellement. Nous discutons également d'une mise en œuvre allégée de statistiques non paramétriques adaptées à ces données. Le troisième chapitre a pour but de démontrer l'efficacité de ces procédures, en montrant les résultats empiriques d'une étude de la connectivité du cerveau entier sous LSD par MEG. Le quatrième et dernier chapitre discute de ces résultats, ainsi que des précautions nécessaires et des orientations futures prometteuses pour ce type de recherche. Il propose des approches computationnelles supplémentaires qui pourraient étendre la portée de ces recherches et, plus généralement, de l'électrophysiologie du cerveau entier. Dans l'ensemble, le cadre méthodologique proposé dans ce travail surmonte les limitations endémiques précédentes, non seulement dans la recherche sur les psychédéliques, mais aussi dans la recherche électrophysiologique en général, et jette une lumière nouvelle sur sur les mécanismes centraux qui sous-tendent ces états de conscience anormaux, ainsi que sur les importantes précautions à prendre dans la recherche électrophysiologique.The past decade has seen a number of significant advances in mathematics, computational learning, and signal processing, which have yet to be deployed in neuroscience. In particular the assessment of connectivity in neural networks has much to gain from this work. Here we propose these tools be leveraged to partially bridge the considerable gap that still exists between large-scale connectomics research (largely centered around indirect measures of brain activity such as fMRI), and more direct, physiological measures of brain activity. Bridging this gap is especially important to the study of physiological properties associated with various normal and abnormal states of consciousness including Psychiatric conditions, sleep, anaesthesia or drug-induced states. Exemplary of such research, is recent work surrounding the induction of altered states of consciousness by non-selective serotonin agonists such as Psilocybin and LSD.
During the past five years, a rapid resurgence of research into the neurobiology of Psychedelic tryptamines has transpired, following a half-century hiatus. While these substances hold great potential to illuminate hitherto uninterrogated aspects of normal and abnormal brain function, the scope and unusual character of the changes they illicit pose serious challenges to researchers. Uncovering cogent and scalable methods for investigating such data is a matter of great importance if we are to leverage the unique window such atypical substances provide into central aspects of consciousness and abnormal brain function. In the present thesis, we summarize the current state of electrophysiological neuroimaging as it pertains to the study of Psychedelic tryptamines, and demonstrate a number of clear shortcomings in current electrophysiological research on Psychedelics. We also offer some modest methodological contributions to the field. The utility of these contributions is supported by some intriguing, albeit preliminary, empirical findings. In the first chapter, we present the history of neuroscientific research on LSD. LSD has been reported to induce peak shifts in power spectra, alongside decreases in peak amplitude. The fact that these effects are inter-related and most research so far has not sought to disambiguate them is uniformly overlooked in the literature, which we believe may lead to false interpretations.
Chapter Two discusses some of the plausible advantages as well as serious barriers to whole-brain connectivity research in MEG, proposing several strategies to overcome these methodological limitations. These include cogent source imaging strategies, novel and recent developments in spectral decomposition, connectivity measures insensitive to volume conduction, and scalable implementations of well-established cross-frequency coupling metrics. We show that these techniques can be extended to a higher resolution cortical and subcortical grid than previously shown. We also discuss a lightweight implementation of non-parametric statistics suitable to such data. Chapter Three serves to demonstrate the efficacy of these procedures, showing empirical results from a whole-brain study of connectivity under LSD in MEG. The fourth and final chapter discusses these results, as well as necessary precautions and promising future directions for this kind of research. It proposes additional computational approaches that might extend the scope of such research and whole-brain electrophysiology more generally. Taken together, the methodological framework proposed in this work overcomes previous limitations endemic not only in Psychedelics research, but electrophysiological research broadly, and sheds new light on central mechanisms underlying these abnormal states of consciousness, as well as important precautions in electrophysiological research
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