scholarly journals A mechanistic model of the neural entropy increase elicited by psychedelic drugs

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rubén Herzog ◽  
Pedro A. M. Mediano ◽  
Fernando E. Rosas ◽  
Robin Carhart-Harris ◽  
Yonatan Sanz Perl ◽  
...  
Keyword(s):  
Subjective Experience ◽  
Brain Activity ◽  
Mechanistic Model ◽  
Mechanistic Explanation ◽  
Long Term Effects ◽  
Whole Brain ◽  
Entropy Increase ◽  
Psychedelic Drugs ◽  
Brain Entropy

Abstract Psychedelic drugs, including lysergic acid diethylamide and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain’s anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.

scholarly journals A mechanistic model of the neural entropy increase elicited by psychedelic drugs

2020 ◽  
Author(s):  
Rubén Herzog ◽  
Pedro A.M. Mediano ◽  
Fernando E. Rosas ◽  
Robin Carhart-Harris ◽  
Yonatan Sanz Perl ◽  
...  
Keyword(s):  
Subjective Experience ◽  
Brain Activity ◽  
Mechanistic Model ◽  
Mechanistic Explanation ◽  
Long Term Effects ◽  
Whole Brain ◽  
Entropy Increase ◽  
Psychedelic Drugs ◽  
Brain Entropy

ABSTRACTPsychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, encoding both acute alterations in consciousness and mediating long-term effects. However, no clear mechanistic explanation for this ‘entropic’ phenomenon has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain’s anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.

scholarly journals Mitochondrial calcium homeostasis: Implications for neurovascular and neurometabolic coupling

2016 ◽  
Vol 37 (2) ◽  
pp. 381-395 ◽  
Author(s):  
Sridhar S Kannurpatti
Keyword(s):  
Energy Metabolism ◽  
Neuronal Activity ◽  
Brain Activity ◽  
Mechanistic Model ◽  
System Level ◽  
Neuronal Signaling ◽  
Neurometabolic Coupling ◽  
Wide Range

Mitochondrial function is critical to maintain high rates of oxidative metabolism supporting energy demands of both spontaneous and evoked neuronal activity in the brain. Mitochondria not only regulate energy metabolism, but also influence neuronal signaling. Regulation of “energy metabolism” and “neuronal signaling” (i.e. neurometabolic coupling), which are coupled rather than independent can be understood through mitochondria’s integrative functions of calcium ion (Ca2+) uptake and cycling. While mitochondrial Ca2+ do not affect hemodynamics directly, neuronal activity changes are mechanistically linked to functional hyperemic responses (i.e. neurovascular coupling). Early in vitro studies lay the foundation of mitochondrial Ca2+ homeostasis and its functional roles within cells. However, recent in vivo approaches indicate mitochondrial Ca2+ homeostasis as maintained by the role of mitochondrial Ca2+ uniporter (mCU) influences system-level brain activity as measured by a variety of techniques. Based on earlier evidence of subcellular cytoplasmic Ca2+ microdomains and cellular bioenergetic states, a mechanistic model of Ca2+ mobilization is presented to understand systems-level neurovascular and neurometabolic coupling. This integrated view from molecular and cellular to the systems level, where mCU plays a major role in mitochondrial and cellular Ca2+ homeostasis, may explain the wide range of activation-induced coupling across neuronal activity, hemodynamic, and metabolic responses.

Automated System for Epileptic Seizures Prediction based on Multi-Channel Recordings of Electrical Brain Activity

2018 ◽  
pp. 115-122 ◽  
Author(s):  
V. A. Maksimenko ◽  
A. A. Harchenko ◽  
A. Lüttjohann
Keyword(s):  
Epileptic Seizure ◽  
Brain Activity ◽  
Epileptic Seizures ◽  
Automated System ◽  
Brain Computer Interfaces ◽  
Electrical Brain Activity ◽  
Computer Interfaces ◽  
Prediction And Prevention ◽  
The Brain

Introduction: Now the great interest in studying the brain activity based on detection of oscillatory patterns on the recorded data of electrical neuronal activity (electroencephalograms) is associated with the possibility of developing brain-computer interfaces. Braincomputer interfaces are based on the real-time detection of characteristic patterns on electroencephalograms and their transformation  into commands for controlling external devices. One of the important areas of the brain-computer interfaces application is the control of the pathological activity of the brain. This is in demand for epilepsy patients, who do not respond to drug treatment.Purpose: A technique for detecting the characteristic patterns of neural activity preceding the occurrence of epileptic seizures.Results:Using multi-channel electroencephalograms, we consider the dynamics of thalamo-cortical brain network, preceded the occurrence of an epileptic seizure. We have developed technique which allows to predict the occurrence of an epileptic seizure. The technique has been implemented in a brain-computer interface, which has been tested in-vivo on the animal model of absence epilepsy.Practical relevance:The results of our study demonstrate the possibility of epileptic seizures prediction based on multichannel electroencephalograms. The obtained results can be used in the development of neurointerfaces for the prediction and prevention of seizures of various types of epilepsy in humans. 

scholarly journals TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
You Shuai ◽  
Zhonghua Ma ◽  
Weitao Liu ◽  
Tao Yu ◽  
Changsheng Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Mechanistic Model ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Reporter Assays

Abstract Background Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms. Methods LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays. Results It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions. Conclusions Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.

scholarly journals Whole-brain 3D MR fingerprinting brain imaging: clinical validation and feasibility to patients with meningioma

2021 ◽  
Author(s):  
Thomaz R. Mostardeiro ◽  
Ananya Panda ◽  
Robert J. Witte ◽  
Norbert G. Campeau ◽  
Kiaran P. McGee ◽  
...  
Keyword(s):  
White Matter ◽  
Statistical Significance ◽  
Relaxation Times ◽  
Brain Structures ◽  
Centrum Semiovale ◽  
In Vivo Evaluation ◽  
Whole Brain ◽  
Mean Values ◽  
Caudate Head

Abstract Purpose MR fingerprinting (MRF) is a MR technique that allows assessment of tissue relaxation times. The purpose of this study is to evaluate the clinical application of this technique in patients with meningioma. Materials and methods A whole-brain 3D isotropic 1mm3 acquisition under a 3.0T field strength was used to obtain MRF T1 and T2-based relaxometry values in 4:38 s. The accuracy of values was quantified by scanning a quantitative MR relaxometry phantom. In vivo evaluation was performed by applying the sequence to 20 subjects with 25 meningiomas. Regions of interest included the meningioma, caudate head, centrum semiovale, contralateral white matter and thalamus. For both phantom and subjects, mean values of both T1 and T2 estimates were obtained. Statistical significance of differences in mean values between the meningioma and other brain structures was tested using a Friedman’s ANOVA test. Results MR fingerprinting phantom data demonstrated a linear relationship between measured and reference relaxometry estimates for both T1 (r2 = 0.99) and T2 (r2 = 0.97). MRF T1 relaxation times were longer in meningioma (mean ± SD 1429 ± 202 ms) compared to thalamus (mean ± SD 1054 ± 58 ms; p = 0.004), centrum semiovale (mean ± SD 825 ± 42 ms; p < 0.001) and contralateral white matter (mean ± SD 799 ± 40 ms; p < 0.001). MRF T2 relaxation times were longer for meningioma (mean ± SD 69 ± 27 ms) as compared to thalamus (mean ± SD 27 ± 3 ms; p < 0.001), caudate head (mean ± SD 39 ± 5 ms; p < 0.001) and contralateral white matter (mean ± SD 35 ± 4 ms; p < 0.001) Conclusions Phantom measurements indicate that the proposed 3D-MRF sequence relaxometry estimations are valid and reproducible. For in vivo, entire brain coverage was obtained in clinically feasible time and allows quantitative assessment of meningioma in clinical practice.

scholarly journals The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wuyang Huang ◽  
Ky Young Cho ◽  
Di Meng ◽  
W. Allan Walker
Keyword(s):  
Lactic Acid ◽  
Mechanistic Model ◽  
Transcriptomic Analysis ◽  
Dependent Manner ◽  
Protective Effects ◽  
Very Preterm Infants ◽  
Anti Inflammatory ◽  
The Impact

AbstractAn excessive intestinal inflammatory response may have a role in the pathogenesis of necrotizing enterocolitis (NEC) in very preterm infants. Indole-3-lactic acid (ILA) of breastmilk tryptophan was identified as the anti-inflammatory metabolite involved in probiotic conditioned media from Bifidobacteria longum subsp infantis. This study aimed to explore the molecular endocytic pathways involved in the protective ILA effect against inflammation. H4 cells, Caco-2 cells, C57BL/6 pup and adult mice were used to compare the anti-inflammatory mechanisms between immature and mature enterocytes in vitro and in vivo. The results show that ILA has pleiotropic protective effects on immature enterocytes including anti-inflammatory, anti-viral, and developmental regulatory potentials in a region-dependent and an age-dependent manner. Quantitative transcriptomic analysis revealed a new mechanistic model in which STAT1 pathways play an important role in IL-1β-induced inflammation and ILA has a regulatory effect on STAT1 pathways. These studies were validated by real-time RT-qPCR and STAT1 inhibitor experiments. Different protective reactions of ILA between immature and mature enterocytes indicated that ILA’s effects are developmentally regulated. These findings may be helpful in preventing NEC for premature infants.

scholarly journals Using Regional Homogeneity to Reveal Altered Spontaneous Activity in Patients with Mild Cognitive Impairment

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yumei Wang ◽  
Xiaochuan Zhao ◽  
Shunjiang Xu ◽  
Lulu Yu ◽  
Lan Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Spontaneous Activity ◽  
Healthy Aging ◽  
Early Stage ◽  
Brain Activity ◽  
Regional Homogeneity ◽  
Whole Brain ◽  
Spontaneous Brain Activity ◽  
Regional Brain Activity

Most patients with mild cognitive impairment (MCI) are thought to be in an early stage of Alzheimer’s disease (AD). Resting-state functional magnetic resonance imaging reflects spontaneous brain activity and/or the endogenous/background neurophysiological process of the human brain. Regional homogeneity (ReHo) rapidly maps regional brain activity across the whole brain. In the present study, we used the ReHo index to explore whole brain spontaneous activity pattern in MCI. Our results showed that MCI subjects displayed an increased ReHo index in the paracentral lobe, precuneus, and postcentral and a decreased ReHo index in the medial temporal gyrus and hippocampus. Impairments in the medial temporal gyrus and hippocampus may serve as important markers distinguishing MCI from healthy aging. Moreover, the increased ReHo index observed in the postcentral and paracentral lobes might indicate compensation for the cognitive function losses in individuals with MCI.

scholarly journals Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons

2014 ◽  
Vol 306 (2) ◽  
pp. L170-L182 ◽  
Author(s):  
Anna A. Shvedova ◽  
Naveena Yanamala ◽  
Elena R. Kisin ◽  
Alexey V. Tkach ◽  
Ashley R. Murray ◽  
...  
Keyword(s):  
Lung Tumor ◽  
Inhalation Exposure ◽  
Geometric Feature ◽  
Width Ratio ◽  
Long Term Effects ◽  
Genotoxic Effects ◽  
Pulmonary Exposure ◽  
Pharyngeal Aspiration

The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF), high length to width ratio, makes them similar to a hazardous agent, asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here, we compared inflammatory, fibrogenic, and genotoxic effects of CNF, SWCNT, or asbestos in mice 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that these particles can be visualized in the lung at 1 yr postexposure, whereas some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic, and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K-ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 yr postexposure to SWCNT, CNF, and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF, and asbestos is defined, not only by their chemical composition, but also by the specific surface area and type of exposure.

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