Human depression: a new approach in quantitative psychiatry

The biomolecular approach to major depression disorder is explained by the different steps that involve cell membrane viscosity, Gsα protein and tubulin. For the first time it is hypothesised that a biomolecular pathway exists, moving from cell membrane viscosity through Gsα protein and Tubulin, which can condition the conscious state and is measurable by electroencephalogram study of the brain's γ wave synchrony

On the role of the plasmodial cytoskeleton in facilitating intelligent behavior in slime mold physarum polycephalum

© Richard Mayne, Andrew Adamatzky, and Jeff Jones. The plasmodium of slime mold Physarum polycephalum behaves as an amorphous reaction-diffusion computing substrate and is capable of apparently ‘intelligent’ behavior. But how does intelligence emerge in an acellular organism? Through a range of laboratory experiments, we visualize the plasmodial cytoskeleton—a ubiquitous cellular protein scaffold whose functions are manifold and essential to life—and discuss its putative role as a network for transducing, transmitting and structuring data streams within the plasmodium. Through a range of computer modeling techniques, we demonstrate how emergent behavior, and hence computational intelligence, may occur in cytoskeletal communications networks. Specifically, we model the topology of both the actin and tubulin cytoskeletal networks and discuss how computation may occur therein. Furthermore, we present bespoke cellular automata and particle swarm models for the computational process within the cytoskeleton and observe the incidence of emergent patterns in both. Our work grants unique insight into the origins of natural intelligence; the results presented here are therefore readily transferable to the fields of natural computation, cell biology and biomedical science. We conclude by discussing how our results may alter our biological, computational and philosophical understanding of intelligence and consciousness

Can A Quantum Field Theory Ontology Help Resolve the Problem of Consciousness?

The hard problem of consciousness arises in most incarnations of present day physicalism. Why should certain physical processes necessarily be accompanied by experience? One possible response is that physicalism itself should be modified in order to accommodate experience: But, modified how? In the present work, we investigate whether an ontology derived from quantum field theory can help resolve the hard problem. We begin with the assumption that experience cannot exist without being accompanied by a subject of experience (SoE). While people well versed in Indian philosophy will not find that statement problematic, it is still controversial in the analytic tradition. Luckily for us, Strawson has elaborately defended the notion of a thin subject—an SoE which exhibits a phenomenal unity with different types of content (sensations, thoughts etc.) occurring during its temporal existence. Next, following Stoljar, we invoke our ignorance of the true physical as the reason for the explanatory gap between present day physical processes (events, properties) and experience. We are therefore permitted to conceive of thin subjects as related to the physical via a new, yet to be elaborated relation. While this is difficult to conceive under most varieties of classical physics, we argue that this may not be the case under certain quantum field theory ontologies. We suggest that the relation binding an SoE to the physical is akin to the relation between a particle and (quantum) field. In quantum field theory, a particle is conceived as a coherent excitation of a field. Under the right set of circumstances, a particle coalesces out of a field and dissipates. We suggest that an SoE can be conceived as akin to a particle—a SelfOn—which coalesces out of physical fields, persists for a brief period of time and then dissipates in a manner similar to the phenomenology of a thin subject. Experiences are physical properties of selfons with the constraint (specified by a similarity metric) that selfons belonging to the same natural kind will have similar experiences. While it is odd at first glance to conceive of subjects of experience as akin to particles, the spatial and temporal unity exhibited by particles as opposed to fields and the expectation that selfons are new kinds of particles, paves the way for cementing this notion. Next, we detail the various no-go theorems in most versions of quantum field theory and discuss their impact on the existence of selfons. Finally, we argue that the time is ripe for a rejuvenated Indian philosophy to begin tackling the three-way relationship between SoEs (which may become equivalent to jivas in certain Indian frameworks), phenomenal content and the physical world. With analytic philosophy still struggling to come to terms with the complex worlds of quantum field theory and with the relative inexperience of the western world in arguing the jiva-world relation, there is a clear and present opportunity for Indian philosophy to make a worldcentric contribution to the hard problem of experience

Cytoskeletal Signaling: Is Memory Encoded in Microtubule Lattices by CaMKII Phosphorylation?

Memory is attributed to strengthened synaptic connections among particular brain neurons, yet synaptic membrane components are transient, whereas memories can endure. This suggests synaptic information is encoded and ‘hard-wired’ elsewhere, e.g. at molecular levels within the post-synaptic neuron. In long-term potentiation (LTP), a cellular and molecular model for memory, post-synaptic calcium ion (Ca2+) flux activates the hexagonal Ca2+-calmodulin dependent kinase II (CaMKII), a dodacameric holoenzyme containing 2 hexagonal sets of 6 kinase domains. Each kinase domain can either phosphorylate substrate proteins, or not (i.e. encoding one bit). Thus each set of extended CaMKII kinases can potentially encode synaptic Ca2+ information via phosphorylation as ordered arrays of binary ‘bits’. Candidate sites for CaMKII phosphorylation-encoded molecular memory include microtubules (MTs), cylindrical organelles whose surfaces represent a regular lattice with a pattern of hexagonal polymers of the protein tubulin. Using molecular mechanics modeling and electrostatic profiling, we find that spatial dimensions and geometry of the extended CaMKII kinase domains precisely match those of MT hexagonal lattices. This suggests sets of six CaMKII kinase domains phosphorylate hexagonal MT lattice neighborhoods collectively, e.g. conveying synaptic information as ordered arrays of six “bits”, and thus “bytes”, with 64 to 5,281 possible bit states per CaMKII-MT byte. Signaling and encoding in MTs and other cytoskeletal structures offer rapid, robust solid-state information processing which may reflect a general code for MT-based memory and information processing within neurons and other eukaryotic cells

The “conscious pilot”—dendritic synchrony moves through the brain to mediate consciousness

Cognitive brain functions including sensory processing and control of behavior are understood as “neurocomputation” in axonal–dendritic synaptic networks of “integrate-and-fire” neurons. Cognitive neurocomputation with consciousness is accompanied by 30- to 90-Hz gamma synchrony electroencephalography (EEG), and non-conscious neurocomputation is not. Gamma synchrony EEG derives largely from neuronal groups linked by dendritic–dendritic gap junctions, forming transient syncytia (“dendritic webs”) in input/integration layers oriented sideways to axonal–dendritic neurocomputational flow. As gap junctions open and close, a gamma-synchronized dendritic web can rapidly change topology and move through the brain as a spatiotemporal envelope performing collective integration and volitional choices correlating with consciousness. The “conscious pilot” is a metaphorical description for a mobile gamma-synchronized dendritic web as vehicle for a conscious agent/pilot which experiences and assumes control of otherwise non-conscious auto-pilot neurocomputation

The Zinc Dyshomeostasis Hypothesis of Alzheimer's Disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized microtubules, their binding to MAP-tau, and molecular dynamics involved in cognition. Further, our theory supports novel AD therapeutic strategies targeting intra-neuronal zinc homeostasis and microtubule dynamics to prevent neurodegeneration and cognitive decline

Do preferences and beliefs in dilemma games exhibit complementarity?

Blanco et. al. (2014) show in a novel experiment the presence of intrinsic interactions between the preferences and the beliefs of participants in social dilemma games. They discuss the identification of three effects, and we claim that two of them are inherently of non-classical nature. Here, we discuss qualitatively how a model based on complementarity between preferences and beliefs in a Hilbert space can give an structural explanation to two of the three effects the authors observe, and the third one can be incorporated into the model as a classical correlation between the observations in two subspaces. Quantitative formalization of the model and proper fit to the experimental observation will be done in the near future, as we have been given recent access to the original dataset

Anaesthesia and PET of the Brain

Although drugs have been used to administer general anaesthesia for more than a century and a half, relatively little was known until recently about the molecular and cellular effects of the anaesthetic agents and the neurobiology of anaesthesia. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have played a valuable role in improving this knowledge. PET studies using 11C-flumazenil binding have been used to demonstrate that the molecular action of some, but not all, of the current anaesthetic agents is mediated via the GABAA receptor. Using different tracers labelled with 18F, 11C and 15O, PET studies have shown the patterns of changes in cerebral metabolism and blood flow associated with different intravenous and volatile anaesthetic agents. Within classes of volatile agents, there are minor variations in patterns. More profound differences are found between classes of agents. Interestingly, all agents cause alterations in the blood flow and metabolism of the thalamus, providing strong support for the hypothesis that the anaesthetic agents interfere with consciousness by interfering with thalamocortical communication.</p