Brain network integration dynamics are associated with loss and recovery of consciousness induced by sevoflurane

Funder: Canadian Institute for Advanced Research; Id: http://dx.doi.org/10.13039/100007631Funder: Gates Cambridge Trust; Id: http://dx.doi.org/10.13039/501100005370Funder: Queens College CambridgeFunder: Stephen Erskine FellowshipFunder: Royal College Of Anaesthetists; Id: http://dx.doi.org/10.13039/501100001297Funder: British Oxygen ProfessorshipFunder: Technische Universität München; Id: http://dx.doi.org/10.13039/501100005713Abstract: The dynamic interplay of integration and segregation in the brain is at the core of leading theoretical accounts of consciousness. The human brain dynamically alternates between a sub‐state where integration predominates, and a predominantly segregated sub‐state, with different roles in supporting cognition and behaviour. Here, we combine graph theory and dynamic functional connectivity to compare resting‐state functional MRI data from healthy volunteers before, during, and after loss of responsiveness induced with different concentrations of the inhalational anaesthetic, sevoflurane. We show that dynamic states characterised by high brain integration are especially vulnerable to general anaesthesia, exhibiting attenuated complexity and diminished small‐world character. Crucially, these effects are reversed upon recovery, demonstrating their association with consciousness. Higher doses of sevoflurane (3% vol and burst‐suppression) also compromise the temporal balance of integration and segregation in the human brain. Additionally, we demonstrate that reduced anticorrelations between the brain's default mode and executive control networks dynamically reconfigure depending on the brain's state of integration or segregation. Taken together, our results demonstrate that the integrated sub‐state of brain connectivity is especially vulnerable to anaesthesia, in terms of both its complexity and information capacity, whose breakdown represents a generalisable biomarker of loss of consciousness and its recovery

COVID-19-associated Large Vessel Stroke in a 28-year-old Patient

Während der COVID-19-Pandemie zeigte sich eine Zunahme an psychischen Belastungen bei Kindern und Jugendlichen. Inwieweit Kinder und Jugendliche notwendige stationäre Behandlung erhielten und ob sich die in Studien gefundene Zunahme an affektiven und Essstörungen auch in der Krankenhausbehandlung wiederfindet, ist bisher unklar. Deshalb wurde anhand von Krankenhaus-Routinedatenfiles nach § 21 KHG (Krankenhausfinanzierungsgesetz) des Instituts für das Entgeltsystem im Krankenhaus (InEK) ein präpandemischer und ein pandemischer Halbjahreszeitraum (1. HJ 2019 vs. 1. HJ 2021) hinsichtlich der Fallzahlen, Diagnosen und Verweildauern in der Kinder- und Jugendpsychiatrie und -psychotherapie (KJPP) und der Pädiatrie deskriptiv analysiert. Zusätzlich wurde die Zahl der Notfallaufnahmen in der KJPP ausgewertet. Es zeigte sich eine Zunahme internalisierender Störungen (Depression, Anorexia nervosa, Belastungsstörungen) und eine Abnahme von Störungen des Sozialverhaltens mit emotionaler Störung in der KJPP. Daneben bildete sich eine deutliche Zunahme von Anorexien in der Pädiatrie ab, während die Behandlungen wegen Alkoholintoxikation sich dort halbierten. Das Notfallaufkommen in der KJPP veränderte sich im Bundesdurchschnitt nicht. In Regionen mit niedriger Bettenmessziffer (BMZ) wurde die Notfallversorgung in der KJPP priorisiert und die Verweildauer nahm ab, in Regionen mit guter BMZ und in der Pädiatrie nahm die Verweildauer tendenziell zu. Ein kontinuierliches Monitoring der Krankenhausversorgung unter Pandemiebedingungen unter Berücksichtigung sozial benachteiligter Kinder und Jugendlicher ist zu empfehlen

Changes in Whole Brain Dynamics and Connectivity Patterns during Sevoflurane- and Propofol-induced Unconsciousness Identified by Functional Magnetic Resonance Imaging

Background: A key feature of the human brain is its capability to adapt flexibly to changing external stimuli. This capability can be eliminated by general anesthesia, a state characterized by unresponsiveness, amnesia, and (most likely) unconsciousness. Previous studies demonstrated decreased connectivity within the thalamus, frontoparietal, and default mode networks during general anesthesia. We hypothesized that these alterations within specific brain networks lead to a change of communication between networks and their temporal dynamics. Methods: We conducted a pooled spatial independent component analysis of resting-state functional magnetic resonance imaging data obtained from 16 volunteers during propofol and 14 volunteers during sevoflurane general anesthesia that have been previously published. Similar to previous studies, mean z-scores of the resulting spatial maps served as a measure of the activity within a network. Additionally, correlations of associated time courses served as a measure of the connectivity between networks. To analyze the temporal dynamics of between-network connectivity, we computed the correlation matrices during sliding windows of 1 min and applied k-means clustering to the matrices during both general anesthesia and wakefulness. Results: Within-network activity was decreased in the default mode, attentional, and salience networks during general anesthesia (P < 0.001, range of median changes: –0.34, –0.13). Average between-network connectivity was reduced during general anesthesia (P < 0.001, median change: –0.031). Distinct between-network connectivity patterns for both wakefulness and general anesthesia were observed irrespective of the anesthetic agent (P < 0.001), and there were fewer transitions in between-network connectivity patterns during general anesthesia (P < 0.001, median number of transitions during wakefulness: 4 and during general anesthesia: 0). Conclusions: These results suggest that (1) higher-order brain regions play a crucial role in the generation of specific between-network connectivity patterns and their dynamics, and (2) the capability to interact with external stimuli is represented by complex between-network connectivity patterns

In vivo mapping of pharmacologically induced functional reorganization onto the human brain’s neurotransmitter landscape

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain's rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganization of the brain's functional architecture

In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape.

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain's rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganization of the brain's functional architecture.Gates Cambridge Trust (OPP 1144) [to AIL]; Wellcome Trust Research Training Fellowship (grant no. 083660/Z/07/Z), Raymond and Beverly Sackler Studentship, and the Cambridge Commonwealth Trust [to RA]; Canadian Institute for Advanced Research (CIFAR; grant RCZB/072 RG93193) [to DKM and EAS]; Cambridge Biomedical Research Centre and NIHR Senior Investigator Awards and the British Oxygen Professorship of the Royal College of Anaesthetists [to DKM]; Stephen Erskine Fellowship at Queens’ College, Cambridge [to EAS]; Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant RGPIN #017-04265) and Canada Research Chairs Program [to BM]; Helmholtz International BigBrain Analytics & Learning Laboratory, the Natural Sciences 1435 and Engineering Research Council of Canada, and Fonds de reserches de Québec [to JYH]; Canada Excellence Research Chairs program (215063) [to AMO]; L’Oreal-Unesco for Women in Science Excellence Research Fellowship to LN]; Imperial College President’s Scholarship [to LR]; Belgian National Funds for Scientific Research (F.R.S-FNRS) [to PC and NLNA]; GIGA-Doctoral School for Health Sciences (University of Liège) [to PC]; Human Brain Project [to NLNA]; Italian Department of Education [Fondo per gli Investimenti della Ricerca di Base (FIRB) 2003; Programmi di Ricerca di Rilevante Interesse nazionale (PRIN) 2008 [to SLS]; Alex Mosley Charitable Trust and supporters of the Centre for Psychedelic Research, Ralph Metzner Distinguished Professorship at UCSF [to RLC-H]

In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape.

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain's rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganization of the brain's functional architecture

Mapping pharmacologically-induced functional reorganisation onto the brain’s neurotransmitter landscape

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.

Report of the Topical Group on Physics Beyond the Standard Model at Energy Frontier for Snowmass 2021

International audienceThis is the Snowmass2021 Energy Frontier (EF) Beyond the Standard Model (BSM) report. It combines the EF topical group reports of EF08 (Model-specific explorations), EF09 (More general explorations), and EF10 (Dark Matter at Colliders). The report includes a general introduction to BSM motivations and the comparative prospects for proposed future experiments for a broad range of potential BSM models and signatures, including compositeness, SUSY, leptoquarks, more general new bosons and fermions, long-lived particles, dark matter, charged-lepton flavor violation, and anomaly detection

Report of the Topical Group on Physics Beyond the Standard Model at Energy Frontier for Snowmass 2021

This is the Snowmass2021 Energy Frontier (EF) Beyond the Standard Model (BSM) report. It combines the EF topical group reports of EF08 (Model-specific explorations), EF09 (More general explorations), and EF10 (Dark Matter at Colliders). The report includes a general introduction to BSM motivations and the comparative prospects for proposed future experiments for a broad range of potential BSM models and signatures, including compositeness, SUSY, leptoquarks, more general new bosons and fermions, long-lived particles, dark matter, charged-lepton flavor violation, and anomaly detection