Temporo-spatial Theory of Consciousness (TTC) – Bridging the gap of neuronal activity and phenomenal states

Behavioural Brain Research, Год журнала: 2022, Номер 424, С. 113788 - 113788

Опубликована: Фев. 8, 2022

Язык: Английский

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Is Target-Based Drug Discovery Efficient? Discovery and “Off-Target” Mechanisms of All Drugs

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 66(18), С. 12651 - 12677

Опубликована: Сен. 6, 2023

Target-based drug discovery is the dominant paradigm of discovery; however, a comprehensive evaluation its real-world efficiency lacking. Here, manual systematic review about 32000 articles and patents dating back to 150 years ago demonstrates apparent inefficiency. Analyzing origins all approved drugs reveals that, despite several decades dominance, only 9.4% small-molecule have been discovered through "target-based" assays. Moreover, therapeutic effects even this minimal share cannot be solely attributed reduced their purported targets, as they depend on numerous off-target mechanisms unconsciously incorporated by phenotypic observations. The data suggest that reductionist target-based may cause productivity crisis in discovery. An evidence-based approach enhance seems prioritizing, selecting optimizing molecules, higher-level observations are closer sought-after using tools like artificial intelligence machine learning.

Язык: Английский

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The strength of weak integrated information theory

Trends in Cognitive Sciences, Год журнала: 2022, Номер 26(8), С. 646 - 655

Опубликована: Июнь 1, 2022

The integrated information theory of consciousness (IIT) is unprecedentedly ambitious in that it proposes a universal mathematical formula, derived from fundamental properties conscious experience, to describe the quality and quantity for any physical system possesses it.IIT proponents believe may solve 'hard problem' why how processes can be accompanied by subjective experience.However, current formulation, IIT formulae are not always well-defined empirical evidence does support level specificity present theory.At same time, available weaker, less prescriptive version theory.We argue distinguishing 'weak' 'strong' flavour provide useful theoretical umbrella ongoing work, widening overall appeal applicability theory. divisive: while some provides an powerful approach address problem', others dismiss on grounds untestable. We greatly widened if we distinguish two flavours theory: strong IIT, which identifies with specific associated maxima information; weak tests pragmatic hypotheses relating aspects broader measures dynamics. review challenges explain existing findings well explained without needing commit entirety discuss outlook both IIT. Divide conquerIIT (see Glossary) has gained considerable prominence among theories consciousness, large part because its claim specify necessary sufficient basis substrate [1.Tononi G. et al.Integrated substrate.Nat. Rev. Neurosci. 2016; 17: 450Crossref PubMed Scopus (568) Google Scholar]. distilling fundamentals phenomenology into small set axioms, posited Scholar,2.Oizumi M. al.From mechanisms consciousness: Integrated Information Theory 3.0.PLoS Computat. Biol. 2014; 10e1003588Crossref (499) Furthermore, practically applicable IIT-inspired 'complexity' neural dynamics [3.Massimini al.Breakdown cortical effective connectivity during sleep.Science. 2005; 309: 2228-2232Crossref (1012) Scholar, 4.Casali A.G. al.A theoretically based index independent sensory processing behavior.Sci. Transl. Med. 2013; 5198ra105Crossref (566) 5.Sarasso S. al.Consciousness complexity: consilience evidence.Neurosci. Conscious. 2021; (Published online August 30, 2021)https://doi.org/10.1093/nc/niab023Crossref Scholar] behave concordance predictions have found important clinical application assessment brain injury patients suffering disorders [6.Re V.L. al.Role transcranial magnetic stimulation (TMS) combined electroencephalography (EEG) (DOC).J. Neurol. Sci. 429118507Abstract Full Text PDF Scholar,7.Casarotto al.Stratification unresponsive independently validated complexity.Ann. 80: 718-729Crossref (175) However, formula intractable, except certain 'toy' systems, ill-defined cases (including key case human brain) [8.Barrett A.B. Mediano P.A. Phi measure general systems.J. Stud. 2019; 26: 11-20Google Scholar,9.Moon K. Exclusion underdetermined qualia.Entropy. 21: 405Crossref (6) Thus, do (e.g., other possible similar theories); instead, they demonstrate correlations between macroscopic activity also been recognised as potentially relevant frameworks [10.Dehaene al.Toward computational processing.Curr. Opin. Neurobiol. 25: 76-84Crossref (207) Scholar,11.Luppi A.I. synergistic workspace revealed decomposition.bioRxiv. 2020; November 26, 2020)https://doi.org/10.1101/2020.11.25.398081Google combination IIT's claims these difficulties testing most specific, distinctive generated confusion polarisation [12.Michel al.An informal internet survey state science.Front. Psychol. 2018; 9: 2134Crossref (16) Scholar,13.Francken J. academic foundations, common assumptions field science.PsyArXiv. June 14, 2021)https://doi.org/10.31234/osf.io/8mbskGoogle Scholar], criticism [14.Merker B. al.The mistaken identity.Behav. Brain 45e41PubMed 15.Michel Lau H. On dangers conflating versions consciousness.PhiMiSci. December 2021)https://doi.org/10.33735/phimisci.2020.II.54Crossref 16.Doerig A. unfolding argument: causal structure cannot consciousness.Conscious. Cogn. 72: 49-59Crossref (44) With international projects now underway attempting pit against competing [17.Melloni L. al.Making hard problem easier.Science. 372: 911-912Crossref (42) crucial clarify landscape surrounding so research better matched claims.Here, propose Strong/weak distinctions long history science, prominent examples being artificial intelligence [18.Searle J.R. Minds, brains, programs.Behav. 1980; 3: 417-424Crossref (2722) emergence [19.Bedau Downward causation autonomy emergence.Principia. 2002; 6: 5-50Google 20.Chalmers D.J. Strong emergence.in: Davies P. Clayton Re-Emergence Emergence: Emergentist Hypothesis From Science Religion. Oxford University Press, 2006: 244-256Google 21.Seth A.K. Measuring via Granger causality.Artif. Life. 2010; 16: 179-196Crossref (52) Broadly, perspective tends ontological flavour, prescribing things are; whereas aims phenomenon, explaining simulating properties. These only conceptually but scientifically productive, enable scientists range philosophies, objectives, approaches engage question.In context play out follows Table 1 itemised view). In states identified system. By contrast, will test explanatory correlates [22.Seth Explanatory challenges.Cogn. Comput. 2009; 1: 50-63Crossref (86) integration consciousness. considers property, such charge or mass [23.Balduzzi D. Tononi discrete dynamical systems: motivation framework.PLoS 2008; 4e1000091Crossref (249) assumes universally describing obtained, physics drivers construction. Weak agnostic whether this hence accommodate philosophical perspectives. Moreover, circumvent tractability issues directly formulated empirically observable neurophysiological variables. practice, emphasises developments inform new measures, focuses applications guide Together, foster complementary mutually enriching programmes.Table 1Key differences IITStrong IITWeak IITAddresses [67.Chalmers Facing up consciousness.J. 1995; 2: 200-219Google Scholar]Addresses 'real [68.Seth Real Problem. Aeon, 2016Google Scholar]Claims identity maximally cause–effect structuresUses consciousnessApplies all systemsApplies (so far) systems onlyFocuses fundamental, rather than practical, measuresFocuses practical real data Open table tab After brief overview challenges, article outlines principles behind sets advantages offers over especially terms interpretation data. conclude paths ahead best contribute development science.Brief [2.Oizumi attempts derive five phenomenology, referred axioms Scholar,24.Barbosa L.S. al.Mechanism information.Entropy. 23: 362Crossref (11) (See Box IIT.) first property intrinsicality, says experience subjective, intrinsic subject experience. second composition, structured, composed several phenomenal exist within it; example, single one piano, blue colour, book, countless spatial locations, sounds, various emotions, on. Third, information, reflects experiences informative, sense each rules potential were priori possible. Integration unified, subdivided parts experienced separately. Finally, exclusion definite, there simultaneous overlapping systems. addition existence, 'zeroth axiom' substrates must terms. An innovative aspect addresses 'backwards', proceeding phenomenological mechanisms, opposed trying go consciousness.Box 1History IITIIT grew intuition complexity, understood coexistence differentiation (the having elements functionally dynamically distinct) behaving coherently whole), ought feature since (arguably) [70.Tononi Edelman G.M. Consciousness complexity.Science. 1998; 282: 1846-1851Crossref (1045) Scholar,71.Tononi al.Complexity coherency: integrating brain.Trends 474-484Abstract (491) This idea was operationalised mutual information-based complexity [72.Tononi functional segregation nervous system.Proc. Natl. Acad.Sci. U. 1994; 91: 5033-5037Crossref (1042) then Φ 1.0, number statistical interdependencies components [73.Tononi Sporns O. integration.BMC 2003; 4: 31Crossref (181) Scholar,74.Tononi consciousness.BMC 2004; 5: 42Crossref (962) Scholar].The (IIT 2.0) introduced transitions next – time identifying transitions. At emphasised role interelement connections determinants Conscious contents, arise collectively informational relationships subsets [75.Balduzzi Qualia: geometry information.PLoS 1-24Crossref (146) principle describable exploring subsets.The recent 3.0) three additional (existence, exclusion), adding them (which reframed information) integration, extend formalism formulate measure, ΦMax While still emphasis 3.0 more establishing mapping it. Specifically, 'conceptual structure' relations identical conceptual structures. writing, 4 work-in-progress [24.Barbosa contains intrinsicality 'axiom' main text).As stated articles Scholar,25.Tononi Koch C. Consciousness: here, everywhere?.Philos. Trans. R. Soc. B 2015; 37020140167Crossref (335) posits postulates about nature (PSC). constructed probability occurrence past future given state, assuming equally likely (i.e., technical language, 'maximum entropy' prior). Applying depend provided subset subsets. And, applying depends extent whole carry nonoverlapping collections their parts. comes maximisations information: (i) grainings system, space, components; (ii) process culminates level, 'amount' consciousness).In specifying studies contents gives rise maximum (Box 1). relatively comprehensive accounting presence, degree, character experiences. Importantly, though, rest ways specified postulates.The full computing involves amount detail yet, currently stands, major problems: logical inconsistency [26.Mørch H.H. Is intrinsic?: A theory.J. 133-162Google Two reasons (amongst others) are: so-called entropy prior relies 'memory' non-Markovian [27.Fuliński al.Non-Markovian ionic fluctuations membrane channels.Phys. E. 58: 919Crossref (115) transition system); involved result ties, leaves remainder calculation leads 'underdetermined qualia (while situation unlikely aiming at level) [9.Moon Scholar,28.Krohn Ostwald Computing information.Neurosci. 2017; 2017nix017Crossref requires extrinsic, maximisation comparisons due optimisations coarse-grainings subsets, complicated procedure calculate becomes intractable reasonable degree mechanistic [28.Krohn Scholar].Despite issues, core rests simple elegant idea: It remains formulation aforementioned problems, those out, could plausible [29.Kleiner Tull theory.Front. Appl. Math. Stat. 74Crossref (4) Scholar,30.Barrett physics.Front. 63Crossref (31) Work characterising distribution spaces way Scholar,31.Barbosa information.Sci. Rep. 10: 1-9Crossref (9) Meanwhile, debate continues veracity, consistency, universality Scholar,32.Bayne T. axiomatic foundations consciousness.Neurosci. 2018niy007Crossref Scholar].Empirical remain challenging, precisely high ambition identify PSC universally. tested considering difference inactive versus inactivated neurons discern if, suggests [33.Haun Why space feel does? Towards principled account experience.Entropy. 1160Crossref (49) brain's structure, beyond mere activity, responsible consciousness), no experimental finding favours it, indeed weaker assumptions. alternatively distinct framework, committing dramatic namely turn.Weak IITThe goal outlined search measurable shares many motivations focus particular, preserves idea, central inception, reflect observations: moment highly informative (it vast repertoire experiences); coherent whole) 2). crucially, longer relationship; correlate strictly condition Accordingly, make generalisation brain.Box 2Integrated dynamicsThe argument should sense.The that, phenomenologically, (or unified), form cohesive changing would change altogether [76.Bayne Unity Consciousness. 2010Crossref (116) multiple (from shapes colours sounds evoked memories) encoded different regions brain. Therefore, give through interactions spanning [77.Rosas F.E. al.Quantifying high-order multivariate extensions information.Phys. 100032305Crossref Scholar].Similarly, rich life generated, part, available. words, particular virtue ruling alternative Dynamically, translates statement access spontaneously visit diverse onto (as accessible principle, necessarily visited practice). related pre-IIT concept (cf. 1): fully correlated, therefore, needed informative.Taken together, (brief) arguments suggest link dynamics: specifically, joint yet statistically interdependent.Separating helps interpret work previously lumped together under banner. differentiation, and/or test) fact, much already carried what considered datasets [4.Casali Scholar,34.Lord L.D. al.Understanding using whole-brain connectomics: implications neuropsychiatric disorders.Philos. Phys. Eng. 37520160283PubMed 35.Luppi al.Consciousness-specific dynamic diversity.Nat. Commun. 1-12Crossref (68) 36.Canales-Johnson al.Dissociable perceptual bistable perception.Cereb. Cortex. 30: 4563-4580Crossref (13) Previously, described providing IIT; however, parsimonious interpretation, results. concerns raised Scholar,26.Mørch problematic consider Φ-like designed actually approximation IIT.Weak allows researchers developing experimentally intuitions contentious (especially claim) open problems ΦMax.

Язык: Английский

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Electromagnetism’s Bridge Across the Explanatory Gap: How a Neuroscience/Physics Collaboration Delivers Explanation Into All Theories of Consciousness

Frontiers in Human Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Июнь 16, 2022

A productive, informative three decades of correlates phenomenal consciousness (P-Consciousness) have delivered valuable knowledge while simultaneously locating us in a unique and unprecedented explanatory cul-de-sac. Observational are demonstrated to be intrinsically very unlikely explain or lead fundamental principle underlying the strongly emergent 1st-person-perspective (1PP) invisibly stowed away inside them. That lack is now solidly evidenced practice. To escape our impasse, this article focuses on physics (the standard model particle physics), which brings light foundational argument for how brain an essentially electromagnetic (EM) field object from atomic level up. is, multitude P-Consciousness actually descriptions specific EM behaviors that posed (hypothesized) as "the right" correlate by particular theory consciousness. Because this, 30 years empirical progress can reinterpreted as, effect, delivery large body evidence model's quadrant deliver 1PP. all theories are, end, merely recipes select subset totality expression tissue. With universal convergence EM, science becomes collaborative effort between neuroscience physics. The collaboration acts pursuit unified explanation applicable remaining mindful process still contains no real why fields apparent continued however, different: time, way forward opened through its direct connection This first result (Part I). Part II posits, general terms, structural (epistemic) add-on/upgrade has potential missing route subjectivity fields. revised model, under neuroscience/physics collaboration, intimately integrates with existing "correlates of-" paradigm, source evidence. No lost invalidated.

Язык: Английский

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The Integrated Information Theory of Consciousness as Pseudoscience

Опубликована: Сен. 16, 2023

The media, including news articles in both Nature and Science, have recently celebrated the Integrated Information Theory (IIT) as a ‘leading’ empirically tested theory of consciousness. We are writing researchers with some relevant expertise to express our concerns.

Язык: Английский

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Prefrontal functional connectivities in autism spectrum disorders: A connectopathic disorder affecting movement, interoception, and cognition

Brain Research Bulletin, Год журнала: 2023, Номер 198, С. 65 - 76

Опубликована: Апрель 21, 2023

The prefrontal cortex is included in a neuronal system that includes the basal ganglia, thalamus, and cerebellum. Most of higher more complex motor, cognitive, emotional behavioral functions are thought to be found primarily frontal lobes. Insufficient connectivity between medial (mPFC) other regions brain distant from each involved top-down information processing rely on global integration data multiple input sources enhance low level perception processes (bottom-up processing). reduced deactivation mPFC rest Default Network during task consistent with integrative modulatory role served by mPFC. We stress importance understanding degree which sensory movement anomalies individuals autism spectrum disorder (ASD) can contribute social impairment. Further investigation neurobiological basis symptoms its relationship clinical features ASD required Treatment perhaps should not first behaviorally based but rather facilitating motor development.

Язык: Английский

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What makes a theory of consciousness unscientific?

Nature Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Язык: Английский

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From Shorter to Longer Timescales: Converging Integrated Information Theory (IIT) with the Temporo-Spatial Theory of Consciousness (TTC)

Entropy, Год журнала: 2022, Номер 24(2), С. 270 - 270

Опубликована: Фев. 13, 2022

Time is a key element of consciousness as it includes multiple timescales from shorter to longer ones. This reflected in our experience various short-term phenomenal contents at discrete points time part an ongoing, more continuous, and long-term 'stream consciousness'. Can Integrated Information Theory (IIT) account for this multitude consciousness? According the theory, relevant spatiotemporal scale one which system reaches maximum cause-effect power; IIT currently predicts that occurs on order short timescales, namely, between 100 300 ms (theta alpha frequency range). can well integration single inputs into particular content. However, such leave open temporal relation specific others during course ongoing time, is, stream consciousness. For purpose, we converge with Temporo-spatial Consciousness (TTC), which, assuming different take view other over time. On neuronal side, detailed by considering those mechanisms driving non-additive interaction pre-stimulus activity input resulting stimulus-related activity. Due their interaction, not only integrated 100-300 (alpha theta frequencies) (as predicted IIT) but, same also virtually expanded its (and spatial) features; related (delta slower are carried Such pre-stimulus-input amounts temporo-spatial expansion mechanism TTC constitution including embedding or nesting within dynamic, i.e., In conclusion, propose converging postulated (100-300 range) (in delta TTC.

Язык: Английский

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Assessing the commensurability of theories of consciousness: On the usefulness of common denominators in differentiating, integrating and testing hypotheses

Consciousness and Cognition, Год журнала: 2024, Номер 119, С. 103668 - 103668

Опубликована: Фев. 27, 2024

How deep is the current diversity in panoply of theories to define consciousness, and what extent do these share common denominators? Here we first examine different are commensurable (or comparable) along particular dimensions. We posit logical (and, when applicable, empirical) commensurability as a necessary condition for identifying denominators among theories. By consequence, dimensions inclusion set logically empirically consciousness can be proposed. Next, compare limited subset neuroscience-based terms commensurability. This analysis does not yield denominator that might serve minimally unifying model consciousness. Theories seem akin by one remote another. suggest methodology comparing via multiple probing questions, allowing discern overall (dis)similarities between Despite very background definitions conclude that, if attention paid search methological approach brain-consciousness relationships, it should possible principle overcome Babylonian confusion tongues eventually integrate merge

Язык: Английский

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Apical amplification—a cellular mechanism of conscious perception?

Neuroscience of Consciousness, Год журнала: 2021, Номер 2021(2)

Опубликована: Окт. 1, 2021

Abstract We present a theoretical view of the cellular foundations for network-level processes involved in producing our conscious experience. Inputs to apical synapses layer 1 large subset neocortical cells are summed at an integration zone near top their trunk. These inputs come from diverse sources and provide context within which transmission information abstracted sensory input basal perisomatic can be amplified when relevant. argue that amplification enables perceptual experience makes it more flexible, thus adaptive, by being sensitive context. Apical provides possible mechanism recurrent processing theory avoids strong loops. It broadcasting hypothesized global neuronal workspace theories feasible while preserving distinct contributions individual receiving broadcast. also mechanisms contribute holistic aspects integrated theory. As is highly dependent on cholinergic, aminergic, other neuromodulators, relates specific contents mental states fluctuations arousal awake. conclude dendrites context-sensitive selective cardinal prerequisite perception.

Язык: Английский

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