Detecting moving objects is crucial in the animal kingdom and is fundamental to vision. In the vertebrate retina, starburst amacrine cells (SACs) 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 (ER) extending through the dendritic branches of SAC and the submicron diameter of the ER in SAC dendrites suggests that the ER is not luminally connected between the soma and the distal tips. We construct a computational model of a SAC dendrite with an ER to simulate the Ca2+-induced Ca2+ release (CICR)-based calcium waves in the presence of an unsaturated buffer to test the hypothesis a CICR mechanism can sustain constant calcium wave propagation in the centrifugal direction. Here, we focus on a working hypothesis, in which a CICR mechanism in the presence of local ER underlies the preference for directionality in the centrifugal direction and rather than the centripetal direction. Modeling the heterogeneity of calcium ER in simulated SACs sheds light on a possible explanation for the cause of speed tuning of direction-selective Ca2+ responses in dendrites of SACs. A simulation of the calcium-induced-calcium release-based Ca2+ waves in the presence of an unsaturated buffer is presented using an analytically derived solution of the two-pool model for cytosolic calcium. We find the conditions that support the calcium-induced calcium-release-based propagating Ca2+ wavefront in the centrifugal direction and its relation to where measurements are made. This suggests CICR from the ER can provide an initial seed underlying directionality in SAC.

​Epileptic seizures are often described as transitions into hypersynchrony, disorder or increased entropy. Prior neurotopological work argued that epileptic pathology may also be interpreted as breakdown of network geometry rather than entropy increase alone (Salazar Chon & Kadhim, 2025). Here, I report an expanded exploratory reconstruction of transition structure in a public HUP intracranial EEG cohort. The analysis used 85 derived ictal runs from 22 subjects and expanded the interictal control layer to 42 interictal pseudo-onset runs from 21 subjects. Markers were organized into algorithm-defined transition families, temporal first-crossing sequences, circular time-shift null controls and expanded ictal-versus-interictal screening. Across the expanded control, ictal runs showed stronger transition-risk escalation than interictal pseudo-onset segments at run level, subject level and matched-subject level. Early risk gain was higher in ictal runs at run level (median 0.4573 versus -0.0932, p

Catherine Reason’s no-supervenience theorem argues that a physicalist theory cannot consistently account for a self-aware system that establishes with certainty its own conscious condition. This Perspective reconstructs the argument as a conditional no-go result and examines its implications for theories of consciousness and multiscale neuroscience. The central distinction is between an intrinsic conscious function and a system’s metacognitive certification that this function is present and reliably known. Physical supervenience constrains the relationship between physical states and the properties they determine; it does not, by itself, guarantee infallible internal access to those states or their conscious significance. A simple countermodel therefore demonstrates that physical supervenience can be maintained while self-certification remains fallible. Reason’s diagonal argument nevertheless identifies an important limitation: its secure conclusion applies to a class of theoretical models that adopt substantive premises concerning objectivity, modal reasoning, and self-certainty. It does not, independently of those premises, establish the existence of nonstandard physical consciousness or refute physical structure–function dependence as such. As a constructive alternative, this Perspective proposes a relational, heterarchical structure–function formulation for multiscale neuroscience. Neural organization, intrinsic function, metacognitive judgement, and conscious report are treated as distinguishable but empirically related objects of investigation across explicitly defined observational resolutions. The formulation neither claims to resolve the explanatory gap nor assumes that conscious reports constitute consciousness itself. Instead, it establishes a falsifiable framework for investigating resting-state activity, stimulus-evoked responses, and perturbational neurophysiology, with event definitions, cross-resolution mappings, dependencies, uncertainties, and potential adverse findings specified in advance. Reason’s theorem is thus retained as a constraint on claims of infallible self-verification, rather than elevated into an unconditional refutation of physical structure–function dependence.