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Online ISSN 2653-4983
Online first articles
Articles not assigned to any issue
REVIEW
A Multiscale Psychopathological–Psychophysiological Nexus in Anxiety-Related Pathways
Lleuvelyn A. Cacha and Roman R. Poznanski​
​This review examines the psychopathological–psychophysiological nexus underlying anxiety-related behavior from a multiscale neuroscience perspective. Anxiety is conceptualized as emerging from dynamic interactions among neural circuits, metabolic processes, and neuroendocrine systems that regulate stress and threat responses in adaptive or maladaptive ways, thereby shaping vulnerability to psychopathology. Central to this framework is the bidirectional coupling of hypothalamic–pituitary–adrenal (HPA) axis activity with amygdala–hippocampal circuitry within forebrain threat-processing pathways, together with modulation by the behavioral inhibition system. Dysregulation across these interacting systems provides a mechanistic basis for the cognitive and behavioral manifestations of anxiety-related disorders.
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Magnetic Resonance Spectroscopy (MRS) provides a non-invasive means of interrogating in vivo biochemical processes, extending magnetic resonance methodologies beyond structural and hemodynamic imaging into the domain of cellular metabolism. Unlike conventional Magnetic Resonance Imaging (MRI), which primarily captures anatomical organization and indirect functional signals, MRS resolves metabolite-specific spectral features, enabling the quantification of neurochemical states within intact tissue. Advances over recent decades (including ultra-high-field systems, improvements in radiofrequency coil design, optimized pulse sequences, and increasingly sophisticated spectral modelling) have significantly enhanced signal fidelity and metabolite resolution. These developments have expanded the applicability of MRS across neurology, psychiatry, oncology, and metabolic research. However, such progress has also exposed fundamental interpretative challenges, particularly regarding spectral overlap, macromolecular contributions, and the limited specificity with which individual metabolites can be mapped onto discrete biological processes. Accordingly, the utility of MRS cannot be understood solely in terms of improved detection sensitivity or expanded clinical deployment. Rather, its interpretative power depends on how spectroscopic signals are situated within a broader multiscale framework linking molecular metabolism, cellular function, and systems-level dynamics. This mini-review therefore moves beyond purely technical accounts by critically examining the assumptions underlying metabolite attribution and emphasizing the necessity of multimodal integration. By synthesizing physical principles, methodological constraints, and neurobiological interpretation, this work advances a more constrained and context-sensitive framework for MRS analysis. Emerging developments (including multimodal imaging integration and machine learning assisted spectral decomposition ) are evaluated in this light, with particular attention to their implications for translational neuroscience and precision medicine.
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REVIEW
Effects of Blue Light Blocking Glasses on Visual Performance, Sleep, Neuroendocrine Regulation: A narrative review​
Mariel Coronel, Vania De la Luz, Sidra Hassaan, Joseph Varon, Matthew Halma
The widespread adoption of LED screens has substantially increased human exposure to short-wavelength blue light (400–490 nm), particularly during evening hours. This spectral range preferentially activates melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), which regulate circadian timing and melatonin secretion via the suprachiasmatic nucleus. Nighttime activation of these non-visual pathways has been linked to melatonin suppression, delayed sleep onset, and altered sleep architecture. Prolonged screen use is also associated with digital eye strain, including visual fatigue, dry eyes, and headaches. Blue light blocking glasses have been proposed as a simple, non-pharmacological strategy to mitigate these effects. This narrative review examines the evidence for blue light blocking glasses across three domains: sleep and circadian regulation, visual performance and digital eye strain, and neuroendocrine and neurophysiological outcomes. While some randomized controlled trials report improvements in sleep onset, melatonin profiles, and subjective visual comfort, other well-designed studies show minimal or inconsistent effects. Emerging evidence on hyperpolarized lenses and electroencephalographic markers of neural arousal suggests additional mechanisms worth investigating. Overall, results vary considerably depending on population, timing of use, and lens properties, and robust evidence supporting routine use remains limited.
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REVIEW
Angelos Kalafatas
ORIGINAL RESEARCH
Quasipolaritonic process geometry as the generative constraint underlying quantum-scale consciousness
Roman R. Poznanski
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Quasipolaritonic Process Geometry (QPG) identifies the functional-relational organization of quasipolaritonic process as the generative constraint underlying quantum-scale consciousness. Within QPG, consciousness is a non-emergent, physically grounded process ontology constituted by reflexively stabilized quasipolaritonic dynamics, exhibiting poststructural dynamics rather than existing as a higher-level property of cognitive or computational systems. The framework addresses the explanatory gap between quantum-scale quasipolaritonic dynamics and unified conscious dispositions by proposing that relational stabilization itself constitutes phenomenality rather than producing it as an emergent output. Under Embedded Quantum Physicalism (EQP), labile quasipolaritonic interactions within cortical microcavities at the submolecular scale become functionally organized through reflexive stabilization formalized by the Self-Intending Projection Framework (SIPF), giving rise to conscious dispositions and the functional organization of phenomenality. Intrinsic quasipolaritonic interactions exhibit functional selectivity governed by the effective quantum potential (Q*), which operates as a dynamic operator of functionally selective constraint modulating which relational configurations can emerge, cohere, and persist. Negentropic functional organization arises from functional uncertainty within Q*-modulated dynamics, biasing stabilization toward coherent dispositional modes through the constrained, intermittent realization of quasipolaritonic spikes. Phenomenal consciousness is identified with reflexively stabilized relational configuration that attains translocal intentional coherence formed through phase-consistent quasipolaritonic transitions across relational domains (ontophysical dynamical organization) within EQP, under microcavity-constrained boundary conditions (physical confinement loci). QPG therefore advances a non-reductive account unifying labile quantum-scale quasipolaritonic dynamics, negentropic functional organization, and intrinsic process curvature within a single ontophysical framework. A sufficient condition for quantum-scale consciousness is the reflexively stabilized, self-intending projective closure of negentropic functional organization within quasipolaritonic process geometry. QPG/SIPF replaces representational and inferential theories of consciousness with an ontophysical materialist account in which reflexively stabilized quasipolaritonic process is consciousness.
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ORIGINAL RESEARCH
Focusing on a novel upstream target for Alzheimer’s Disease therapy: Identification of potential BACE1 inhibitors Using In Silico Methods
Matteo Bulgini and Jack A. Tuszynski​
Alzheimer’s Disease (AD) is the most common form of dementia and one of the most prevalent neurodegenerative diseases in the world. Currently, there’s no definitive cure for this disease. The most widely accepted hypothesis involves the accumulation of β-amyloid into plaques and of the MAP τ protein into neurofibrillary tangles located between and inside the neurons, respectively. These processes cause neuronal degeneration and a disruption of the functionality of the brain. The β-amyloid plaques are due to the action of the β -secretase protein, which cleaves the APP protein in the Aβ region, resulting in β -amyloid fragments that aggregate, as opposed to the production of α-amyloid, which can stimulate neuroplasticity and neuroregenerative capabilities. Previous research showed that mutations in the sequence of the APP protein can inhibit the formation of these fragments, but this route is not conducive to therapeutic approaches. Several trials have been conducted into developing pharmaceutical compounds that can inhibit the cleavage site and in particular the catalytic dyad (Asp32−Asp228). Using the data from these trials, the aim of the research reported in this paper was to widen the possibilities of drug discovery by parsing a wide database of bioactive molecules, simulating their interactions with the BACE1 protein. By forming bonds with the pocket responsible for the cleavage of the APP protein, these ligands may be putative inhibitors. Here, we report the identification of several bioactive compounds predicted to be active inhibitors of the β-secretase 1, which is the main enzyme responsible for the formation of the β amyloid plaques in the pathogenesis of AD. To this end we performed database parsing, selecting clinical-stage drugs and similar compounds, which then were computationally docked to a mature chain of BACE1 protein using Boltz2 AI-based software. From the resulting compounds the top 27, ranked for confidence, affinity and accounting for the wider base possible, were then investigate for binding affinity to the target using the GROMACS suite to predict their docking poses to the protein. This was done by calculating free energy applying the MM-GBSA algorithm for the resulting structures. The highest ranked compounds can be validated by in vitro and in vivo studies and potentially represent drug candidates for AD therapies.
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ORIGINAL RESEARCH
Intracellular Calcium Dynamics in Starburst Amacrine Cell Dendrites:
The Onset of Cardinal Direction Selectivity and Speed Tuning*
N.L. Iannella
​Detecting moving objects is crucial in the animal kingdom and is fundamental to vision. In the vertebrate retina, starburst amacrine cells are directionally selective in terms of their calcium responses to stimuli that move centrifugally from the soma. The mechanism by which starburst amacrine cells show calcium bias for centrifugal motion is still to be determined. Recent morphological studies using fluorescent microscopy and immunostaining have shown that the endoplasmic reticulum is omnipresent in the soma, extending to the distal processes of starburst amacrine cells. Electron microscopy for ChAT SAC in adult rat retina unequivocally proves the presence of local endoplasmic reticulum. The submicron in diameter dendrites implies that the endoplasmic reticulum is not luminally connected between the soma and the distal tips. We construct a computational model of SAC dendrites with ER to simulate the Ca2+-induced Ca2+ release (CICR)-based calcium waves in the presence of unsaturated buffer to test the hypothesis that CICR mechanism can sustain constant calcium wave propagation in the centrifugal direction. The veto mechanism with a 100msec delay for the operation of retinal direction selectivity. is a working hypothesis, in which a CICR mechanism in the presence of local endoplasmic reticulum underlies speed tuning for directionality and propagation failure in the centripetal direction due to a build-up of calcium hyperexcitability in the distal regions of starburst amacrine cells. Modeling the heterogeneity of calcium endoplasmic reticulum in simulated starburst amacrine cells sheds light on a possible explanation for the cause ...
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