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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Hum. Neurosci.</journal-id>
<journal-title>Frontiers in Human Neuroscience</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Hum. Neurosci.</abbrev-journal-title>
<issn pub-type="epub">1662-5161</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnhum.2016.00423</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Neuroscience</subject>
<subj-group>
<subject>General Commentary</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Commentary: The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Papo</surname> <given-names>David</given-names></name>
<xref ref-type="author-notes" rid="fn001"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/73751/overview"/>
</contrib>
</contrib-group>
<aff><institution>GISC and Laboratory of Biological Networks, Center for Biomedical Technology, Universidad Polit&#x000E9;cnica de Madrid</institution> <country>Madrid, Spain</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Michael A. Silver, University of California, Berkeley, USA</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Olivia Carter, University of Melbourne, Australia</p></fn>
<fn fn-type="corresp" id="fn001"><p>&#x0002A;Correspondence: David Papo <email>papodav&#x00040;gmail.com</email></p></fn>
</author-notes>
<pub-date pub-type="epub">
<day>30</day>
<month>08</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection">
<year>2016</year>
</pub-date>
<volume>10</volume>
<elocation-id>423</elocation-id>
<history>
<date date-type="received">
<day>27</day>
<month>04</month>
<year>2016</year>
</date>
<date date-type="accepted">
<day>09</day>
<month>08</month>
<year>2016</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2016 Papo.</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>Papo</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<related-article id="RA1" related-article-type="commentary-article" journal-id="Front Hum Neurosci" journal-id-type="nlm-ta" vol="8" page="20" xlink:href="24550805" ext-link-type="pubmed">A commentary on<article-title>The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs</article-title> by Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., et al. (2014). Front. Hum. Neurosci. 8:20. doi: <object-id>10.3389/fnhum.2014.00020</object-id></related-article>
<kwd-group>
<kwd>metastability</kwd>
<kwd>scaling</kwd>
<kwd>criticality</kwd>
<kwd>entropy</kwd>
<kwd>brain activity</kwd>
<kwd>temporal complexity</kwd>
</kwd-group>
<counts>
<fig-count count="0"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="32"/>
<page-count count="3"/>
<word-count count="2272"/>
</counts>
</article-meta>
</front>
<body>
<p>The &#x0201C;entropic brain hypothesis&#x0201D; holds that the quality of conscious states depends on the system&#x00027;s entropy (Carhart-Harris et al., <xref ref-type="bibr" rid="B9">2014</xref>). Brain activity is said to become &#x0201C;more random and so harder to predict in primary states &#x02013; of which the psychedelic state is an exemplar.&#x0201D; Psychedelic-induced brain activity would be associated with elevated entropy in some of its aspects with respect to normal wakeful consciousness. This would indicate that psychedelic-induced brain activity would exhibit criticality, while normal wakeful consciousness would be subcritical.</p>
<p>But can <italic>entropy</italic> be a unique indicator of the &#x0201C;quality of consciousness?&#x0201D; Are there reasons to believe that psychedelic-induced activity is <italic>not</italic> critical?</p>
<sec id="s1">
<title>Entropy</title>
<p>Complex systems such as the brain are neither completely regular nor completely random. Entropy a measure of randomness, may then seem ill-qualified, <italic>per se</italic>, to account for brain activity. Indeed to account for the complex blend of regularity and randomness, a wealth of so-called complexity measures have been proposed (Crutchfield, <xref ref-type="bibr" rid="B10">2012</xref>), some specifically for brain activity (Tononi et al., <xref ref-type="bibr" rid="B28">1994</xref>; Tognoli and Kelso, <xref ref-type="bibr" rid="B27">2014</xref>). A single-scale indicator of randomness to describe the consciousness spectrum simply boils down to a complexity measure depurated of its integration or disequilibrium term.</p>
<p>Efforts to characterize brain states, and consciousness in particular, in terms of entropy of the associated dynamics have a 20-year long history. For instance, a significant reduction in EEG entropy (Pezard et al., <xref ref-type="bibr" rid="B19">1996</xref>), and co-variation between entropy and mood improvement were found in depressive patients (Thomasson et al., <xref ref-type="bibr" rid="B26">2000</xref>). Furthermore, entropy monitoring is now a standard method to evaluate the depth of anesthesia (Bein, <xref ref-type="bibr" rid="B3">2006</xref>; Jordan et al., <xref ref-type="bibr" rid="B13">2008</xref>; Olofsen et al., <xref ref-type="bibr" rid="B17">2008</xref>).</p>
</sec>
<sec id="s2">
<title>Metastable states and metastability</title>
<p>A system is metastable when it spends an extended time in a configuration other than the system&#x00027;s least energy state (Kitzbichler et al., <xref ref-type="bibr" rid="B14">2009</xref>; Allegrini et al., <xref ref-type="bibr" rid="B1">2010</xref>; Tognoli and Kelso, <xref ref-type="bibr" rid="B27">2014</xref>). Activity shows a <italic>dwell</italic> and <italic>escape</italic> dynamics: <italic>Within</italic> a metastable state, physical quantities, e.g., energy, fluctuate reversibly around a constant value, while the escape part of the dynamics is associated with shifts from one metastable state to another. Metastability is characterized in terms of dynamical variables, e.g., avalanche size and duration, or inter-burst intervals.</p>
<p>Carhart-Harris and colleagues define metastability as a &#x0201C;measure of the variance in the network&#x00027;s intrinsic synchrony&#x0201D; (p. 10). However such a measure quantifies (the number of) <italic>metastable states</italic> (Haldeman and Beggs, <xref ref-type="bibr" rid="B11">2005</xref>; Shanahan, <xref ref-type="bibr" rid="B22">2010</xref>), rather than <italic>metastability</italic>, so that entropy, metastability, and variance turn out to provide essentially the same information. Carhart-Harris&#x00027; entropy is a <italic>configurational entropy</italic>, which essentially counts the metastable states of the energy landscape. A genuine configurational entropy establishes a connection between the topography of the energy landscape and the system&#x00027;s dynamics. However, the coarse-graining level must be drastic for one to claim that a few hundred time-points (Carhart-Harris et al., <xref ref-type="bibr" rid="B8">2012</xref>) sufficiently explore the brain&#x00027;s phase space, (how the number of metastable states scales with coarse-graining level is also unknown). Thus, the associated entropy cannot be considered a genuine configurational entropy.</p>
</sec>
<sec id="s3">
<title>Psychedelic state and criticality</title>
<p>Criticality of the psychedelic state is inferred through the following reasoning: Criticality maximizes the amount of metastable states (Haldeman and Beggs, <xref ref-type="bibr" rid="B11">2005</xref>), and therefore entropy; psychedelic states are associated with more metastable states than normal wakefulness; therefore, the corresponding state is critical, while normal wakefulness is subcritical (Priesemann et al., <xref ref-type="bibr" rid="B21">2014</xref>).</p>
<p>Even from a complexity view-point, some value of the configuration entropy may well correspond to brain activity patterns for which the system is critical. However, there are reasons to doubt that psychedelic-associated activity is critical. (1) Criticality implies (a set of) scaling variables, e.g., avalanche size and duration. Nothing guarantees that the dynamics producing these metastable states in Carhart-Harris et al. (<xref ref-type="bibr" rid="B9">2014</xref>) would also generate a dynamics showing scaling as in Haldeman and Beggs (<xref ref-type="bibr" rid="B11">2005</xref>). Furthermore, the few hundred timepoints in Carhart-Harris&#x00027; data (Carhart-Harris et al., <xref ref-type="bibr" rid="B8">2012</xref>) are insufficient to show temporal scaling behavior. (2) While Carhart-Harris&#x00027; data show that the psychedelic state is associated with more variance than normal wakefulness, other states could in principle be associated with yet more variance than the one associated with the psychedelic state. Furthermore, increasing variance from a subcritical state doesn&#x00027;t guarantee that the system will become critical or that it will have a better power-law fit. (3) Recent evidence shows that, unless parameters are fine-tuned, cortical neural networks dynamics lies in a relatively broad pseudo-critical region, where it is either subcritical or supercritical, a state termed <italic>self-organized quasi-criticality</italic> (Bonachela and Mu&#x000F1;oz, <xref ref-type="bibr" rid="B6">2010</xref>), or <italic>extended criticality</italic> (Longo et al., <xref ref-type="bibr" rid="B15">2012</xref>), corresponding to Griffiths phases (Moretti and Mu&#x000F1;oz, <xref ref-type="bibr" rid="B16">2013</xref>). Accordingly, the &#x0201C;natural world&#x0201D; is presumably not &#x0201C;more critical&#x0201D; than the brain, a notion that would be inconsistent with a recently proposed mechanism of information transfer in complex systems (West et al., <xref ref-type="bibr" rid="B29">2008</xref>; Aquino et al., <xref ref-type="bibr" rid="B2">2011</xref>).</p>
<p>Furthermore, there is an essential contradiction in the suggestion that primary consciousness would be a &#x0201C;psychological atavism&#x0201D; and a &#x0201C;suboptimal mode&#x0201D; and, at the same time, &#x0201C;more critical&#x0201D; than normal states (p. 12). On the one hand, intuitively, the psychedelic state wouldn&#x00027;t appear to be functionally optimal. The hyper-connectivity which characterizes it (Tagliazucchi et al., <xref ref-type="bibr" rid="B25">2016</xref>) is in general associated brain pathology (Whitfield-Gabrieli et al., <xref ref-type="bibr" rid="B30">2009</xref>; Supekar et al., <xref ref-type="bibr" rid="B24">2013</xref>; Hillary et al., <xref ref-type="bibr" rid="B12">2015</xref>). During the psychedelic state the number of forbidden connectivity patterns may decrease, but some of these patterns may be associated with suboptimal (possibly even functionally detrimental) states. On the other hand, however, criticality has been shown to be optimal in terms of transmission and storage of information, computational capabilities, large network stability and sensitivity to sensory stimuli (Shew et al., <xref ref-type="bibr" rid="B23">2009</xref>; Bonachela and Mu&#x000F1;oz, <xref ref-type="bibr" rid="B6">2010</xref>). In what sense can the brain be at the same time critical and suboptimal? And if primary consciousness is critical, and therefore in so many ways optimal, what&#x00027;s the evolutionary meaning of secondary states? A possible understanding of criticality and optimality of the psychedelic state is suggested by the results of Zare and Grigolini (<xref ref-type="bibr" rid="B31">2013</xref>) suggest. In this study, genuine temporal complexity was found to occur earlier than avalanche-size complexity, in a narrow range where information transfer becomes maximal. Interpreting this information transport enhancement as a signature of criticality, power law avalanches become a manifestation of supercriticality. Accordingly, normal waking and the psychedelic state may respectively lie in the critical and supercritical regimes.</p>
</sec>
<sec sec-type="conclusions" id="s4">
<title>Conclusions</title>
<p>A true configurational entropy requires extensive phase space exploration, otherwise it merely reflects the random side of complexity. Under these conditions, quantifying the number of metastable states is not enough, <italic>per se</italic>, to assess criticality. Rather than just moving brain activity toward or away from criticality, context-specific demands can modulate the scaling properties of brain fluctuations (Popivanov et al., <xref ref-type="bibr" rid="B20">2006</xref>; Bianco et al., <xref ref-type="bibr" rid="B5">2007</xref>; Buiatti et al., <xref ref-type="bibr" rid="B7">2007</xref>; Bhattacharya, <xref ref-type="bibr" rid="B4">2009</xref>; Zilber et al., <xref ref-type="bibr" rid="B32">2012</xref>), by modifying the scale at which they show scaling or by inducing transitions between different scaling regimes or cross-overs between universality classes (Papo, <xref ref-type="bibr" rid="B18">2014</xref>).</p>
</sec>
<sec id="s5">
<title>Author contributions</title>
<p>The author confirms being the sole contributor of this work and approved it for publication.</p>
<sec>
<title>Conflict of interest statement</title>
<p>The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
</sec>
</body>
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