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.
Pranayama
refers to a set of yoga breathing exercises. Recent evidence suggests that the practice of
pranayama
has positive effects on measures of clinical stress and anxiety. This study explored the ...impact of a
Bhastrika pranayama
training program on emotion processing, anxiety, and affect. We used a randomized controlled trial design with thirty healthy young adults assessed at baseline and after 4 weeks of
pranayama
practices. Two functional magnetic resonance imaging (MRI) protocols were used both at baseline and post-intervention: an emotion task as well as a resting-state acquisition. Our results suggest that
pranayama
significantly decreased states of anxiety and negative affect. The practice of
pranayama
also modulated the activity of brain regions involved in emotional processing, particularly the amygdala, anterior cingulate, anterior insula, and prefrontal cortex. Resting-state functional MRI (fMRI) showed significantly reduced functional connectivity involving the anterior insula and lateral portions of the prefrontal cortex. Correlation analysis revealed that changes in connectivity between the ventrolateral prefrontal cortex and the right anterior insula were associated with changes in anxiety. Although it should be noted that these analyses were preliminary and exploratory, it provides the first evidence that 4 weeks of
B. pranayama
significantly reduce the levels of anxiety and negative affect, and that these changes are associated with the modulation of activity and connectivity in brain areas involved in emotion processing, attention, and awareness. The study was registered at
https://www.ensaiosclinicos.gov.br/rg/RBR-2gv5c2/(RBR-2gv5c2)
.
With the aim of further advancing the understanding of the human brain's functional connectivity, we propose a network metric which we term the
. This metric quantifies the Shannon entropy of the ...distance distribution to a specific node from all other nodes. It allows to characterize the influence exerted on a specific node considering statistics of the overall network structure. The measurement and characterization of this structural information has the potential to greatly improve our understanding of sustained activity and other emergent behaviors in networks. We apply this method to study how the psychedelic infusion Ayahuasca affects the functional connectivity of the human brain in resting state. We show that the geodesic entropy is able to differentiate functional networks of the human brain associated with two different states of consciousness in the awaking resting state: (i) the ordinary state and (ii) a state altered by ingestion of the Ayahuasca. The functional brain networks from subjects in the altered state have, on average, a larger geodesic entropy compared to the ordinary state. Finally, we discuss why the geodesic entropy may bring even further valuable insights into the study of the human brain and other empirical networks.
Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent ...evidence from a randomized controlled trial (RCT) supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients (MD) and in healthy volunteers (C). Subjects received a single dose of ayahuasca or placebo (dosing session), and both plasma and awakening salivary cortisol response were measured at baseline (before dosing session) and 48 h after the dosing session. Baseline assessment (D0) showed blunted awakening salivary cortisol response and hypocortisolemia in patients, with respect to healthy controls. Salivary cortisol was also measured during dosing session, and we observed higher increases for both C and MD that ingested ayahuasca than placebo. After 48 h from the dosing session with ayahuasca, patients' awakening salivary cortisol response is similar to the ones detected in controls. No significant changes in plasma cortisol levels were observed 48 h after the sessions. Therefore, these findings point to new evidence on the modulation of salivary cortisol levels as a result of an ayahuasca session, both in healthy and depressive volunteers. Considering that cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes, it is assumed to be critically involved to the etiology of depression and its regulation seems to be important for the treatment and remission of major depression, ayahuasca use as antidepressant should be further investigated. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders.
Abstract
The physical basis of consciousness is one of the most intriguing open questions that contemporary science aims to solve. By approaching the brain as an interactive information system, ...complex network theory has greatly contributed to understand brain process in different states of mind. We study a non-ordinary state of mind by comparing resting-state functional brain networks of individuals in two different conditions: before and after the ingestion of the psychedelic brew Ayahuasca. In order to quantify the functional, statistical symmetries between brain region connectivity, we calculate the pairwise information parity of the functional brain networks. Unlike the usual approach to quantitative network analysis that considers only local or global scales, information parity instead quantifies pairwise statistical similarities over the entire network structure. We find an increase in the average information parity on brain networks of individuals under psychedelic influences. Notably, the information parity between regions from the limbic system and frontal cortex is consistently higher for all the individuals while under the psychedelic influence. These findings suggest that the resemblance of statistical influences between pair of brain regions activities tends to increase under Ayahuasca effects. This could be interpreted as a mechanism to maintain the network functional resilience.
O objetivo principal da mecânica estatística é relacionar a física microscópica regida pelas leis de Newton, ou então pela mecânica quântica, com a física macroscópica regida pelas leis da ...termodinâmica. Conceitos macroscópicos, tais como a temperatura, que não fazem sentido do ponto de vista microscópico, surgem na mecânica estatística como propriedades emergentes quando o número de partículas torna-se suficientemente grande. O sucesso da mecânica estatística em explicar e prever uma variedade de fenômenos macroscópicos motivou a aplicação de conceitos e métodos da física estatística ao estudo de sistemas complexos e redes complexas, inclusive em neurociência. Nosso objetivo neste trabalho é aplicar essa abordagem a um problema chave na neurociência: como entender quantitativamente os correlatos neurais de estados mentais alterados de consciência induzidos por substâncias psicodélicas? Vamos primeiro introduzir alguns conceitos básicos sobre a conectividade funcional das regiões do cérebro. Discutimos então a fenomenologia e a neurociência relacionadas aos psicodélicos. Finalmente, resumimos alguns estudos que aplicaram a física estatística e a teoria de redes complexas para tentar melhor entender o comportamento do cérebro sob influência dos psicodélicos.
The primary aim of statistical mechanics is to relate the micropscopic physics governed by Newton’s laws, or else by quantum mechanics, to the macroscopic physics governed by the laws of thermodynamics. Macroscopic properties, such as temperature, may have no meaning at the microscopic level, but they arise as emergent properties in statistical mechanics when the number of particles becomes sufficiently large. The success of statistical mechanics in explaining and predicting a variety of macroscopic phenomena has motivated the application of concepts and methods of statistical physics to study complex systems and complex networks, including in neuroscience. Our aim here is to apply this approach to a key problem in neuroscience: how can we quantitatively understand the neural correlates of altered mental states induced by psychedelic substances? We first give an overview of basic concepts concerning functional connectivity of brain regions. We then discuss the phenomenology and the neuroscience related to psychedelics. Finally, we review some studies that have applied statistical physics and the theory of complex networks to try to gain a better understanding of the brain under the influence of psychedelics.
Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.
To test the antidepressant effects of ayahuasca, we ...conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).
To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).
Abstract Functional magnetic resonance imaging (fMRI) has just completed 20 years of existence. It currently serves as a research tool in a broad range of human brain studies in normal and ...pathological conditions, as is the case of epilepsy. To date, most fMRI studies aimed at characterizing brain activity in response to various active paradigms. More recently, a number of strategies have been used to characterize the low-frequency oscillations of the ongoing fMRI signals when individuals are at rest. These datasets have been largely analyzed in the context of functional connectivity, which inspects the covariance of fMRI signals from different areas of the brain. In addition, resting state fMRI is progressively being used to evaluate complex network features of the brain. These strategies have been applied to a number of different problems in neuroscience, which include diseases such as Alzheimer's, schizophrenia, and epilepsy. Hence, we herein aimed at introducing the subject of complex network and how to use it for the analysis of fMRI data. This appears to be a promising strategy to be used in clinical epilepsy. Therefore, we also review the recent literature that has applied these ideas to the analysis of fMRI data in patients with epilepsy. This article is part of a Special Issue entitled “NEWroscience 2013”.
The simultaneous acquisition of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data potentially allows measurement of brain signals with both high spatial and temporal ...resolution. Partial directed coherence (PDC) is a Granger causality measure in the frequency domain, which is often used to infer the intensity of information flow over the brain from EEG data. In the current study, we propose a new approach to investigate functional connectivity in resting-state (RS) EEG-fMRI data by combining time-varying PDC with the analysis of blood oxygenation level-dependent (BOLD) signal fluctuations. Basically, we aim to identify brain circuits that are more active when the information flow is increased between distinct remote neuronal modules. The usefulness of the proposed method is illustrated by application to simultaneously recorded EEG-fMRI data from healthy subjects at rest. Using this approach, we decomposed the nodes of RS networks in fMRI data according to the frequency band and directed flow of information provided from EEG. This approach therefore has the potential to inform our understanding of the regional characteristics of oscillatory processes in the human brain.
The physical basis of consciousness is one of the most intriguing open questions that contemporary science aims to solve. By approaching the brain as an interactive information system, complex ...network theory has greatly contributed to understand brain process in different states of mind. We study an non-ordinary state of mind by comparing resting-state functional brain networks of individuals in two different conditions: before and after the ingestion of the psychedelic brew Ayahuasca. In order to quantify the functional, statistical symmetries between brain region connectivity, we calculate the pairwise information parity of the functional brain networks. Unlike most of usual network quantification, which is done on a local or global scale, information parity quantifies the pairwise statistical similarities considering the entire network structure. We detect an increase in the average information parity on brain networks of individuals under psychedelic influences. Notably, the information parity between regions from the limbic system and frontal cortex is consistently higher for all the individuals while under the psychedelic influence.
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