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      Increased thalamic resting‐state connectivity as a core driver of LSD‐induced hallucinations

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          Abstract

          Objective

          It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system.

          Method

          100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI‐to‐ ROI and ROI‐to‐voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects.

          Results

          LSD caused significant alterations in all dimensions of the 5D‐ ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD‐induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects.

          Conclusion

          Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5‐ HT 2A‐receptor in altered states of consciousness.

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          Most cited references38

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          Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action.

          Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antagonist and typical antipsychotic haloperidol. These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation, independently of dopamine stimulation. Thus, serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics.
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            Consciousness and complexity.

            Conventional approaches to understanding consciousness are generally concerned with the contribution of specific brain areas or groups of neurons. By contrast, it is considered here what kinds of neural processes can account for key properties of conscious experience. Applying measures of neural integration and complexity, together with an analysis of extensive neurological data, leads to a testable proposal-the dynamic core hypothesis-about the properties of the neural substrate of consciousness.
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              Decoding wakefulness levels from typical fMRI resting-state data reveals reliable drifts between wakefulness and sleep.

              The mining of huge databases of resting-state brain activity recordings represents state of the art in the assessment of endogenous neuronal activity-and may be a promising tool in the search for functional biomarkers. However, the resting state is an uncontrolled condition and its heterogeneity is neither sufficiently understood nor accounted for. We test the hypothesis that subjects exhibit unstable wakefulness, i.e., drift into sleep during typical resting-state experiments. Analyzing 1,147 resting-state functional magnetic resonance data sets, we revealed a reliable loss of wakefulness in a third of subjects within 3 min and demonstrated the dynamic nature of the resting state, with fundamental changes in the associated functional neuroanatomy. Implications include the necessity of wakefulness monitoring and modeling, taking measures to maintain a state of wakefulness, acknowledging the possibility of sleep and exploring its consequences, and especially the critical assessment of possible false-positive or false-negative results. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                stefan.borgwardt@upkbs.ch
                Journal
                Acta Psychiatr Scand
                Acta Psychiatr Scand
                10.1111/(ISSN)1600-0447
                ACPS
                Acta Psychiatrica Scandinavica
                John Wiley and Sons Inc. (Hoboken )
                0001-690X
                1600-0447
                21 September 2017
                December 2017
                : 136
                : 6 ( doiID: 10.1111/acps.2017.136.issue-6 )
                : 648-657
                Affiliations
                [ 1 ] Department of Psychiatry (UPK) University of Basel Basel Switzerland
                [ 2 ] Division of Clinical Pharmacology and Toxicology Department of Biomedicine and Department of Clinical Research University Hospital Basel University of Basel Basel Switzerland
                Author notes
                [*] [* ] Stefan Borgwardt, Department of Psychiatry (UPK), University of Basel, Wilhelm Klein‐Strasse 27, Basel, Switzerland.

                E‐mail: stefan.borgwardt@ 123456upkbs.ch

                Author information
                http://orcid.org/0000-0002-5792-3987
                Article
                ACPS12818
                10.1111/acps.12818
                5698745
                28940312
                7508b16d-67a9-4954-9ba8-c920f453029d
                © 2017 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 05 September 2017
                Page count
                Figures: 4, Tables: 0, Pages: 10, Words: 6381
                Funding
                Funded by: Swiss National Science Foundation
                Award ID: 320030_170249
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                acps12818
                December 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.6 mode:remove_FC converted:22.11.2017

                Clinical Psychology & Psychiatry
                hallucinogens,psychedelics,fmri,functional connectivity,thalamus
                Clinical Psychology & Psychiatry
                hallucinogens, psychedelics, fmri, functional connectivity, thalamus

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