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Sam McKenzie

Publications and source records attributed to Sam McKenzie.

2 recordsLinked to original sources

Identifying Neural State Changes due to Gain versus Off-Manifold Displacement

Memory segmentation is thought to arise from rapid decorrelation in neural activity, often quantified by Euclidean distance or cosine angle. Although these metrics detect a transition, they do not reveal how the new state relates to the repertoire represented by the neural manifold. This matters because neuromodulators that drive state transitions also alter excitability, and learning may repurpose existing representations or create new ones. Here, I introduce a geometric decomposition that separates changes attributable to gain modulation of a nearby manifold state from movement within the manifold and genuine off-manifold displacement. The approach uses the radial axis of neural population activity to partition the normal space of a local manifold region. A central challenge is identifiability: given only a static reference manifold and a single test state, neither the state from which a perturbation began nor its gain magnitude and mechanistic decomposition can generally be recovered uniquely. I therefore formulate identifiability as a cascade of geometric gates specifying when each component can be interpreted. The gates distinguish structural failures, including the absence of a local chart or incorrect intrinsic dimensionality, from estimation error and systematic bias caused by reference sampling, tangent-frame error, gain-axis misalignment, anchor displacement, and poor ratio conditioning. Simulations show that neighborhood size, curvature, sampling density, ambient dimension, and noise act through a small set of geometric quantities. The framework specifies when assignments to gain or novelty are identifiable, how they become biased, and which diagnostics reveal the relevant failure regime. By quantifying the nature rather than only the magnitude of neural state change, it provides a clear, readily interpretable framework for evaluating mechanisms of neural state transitions.

q-bio.NC

Monosynaptic inference via finely-timed spikes

Observations of finely-timed spike relationships in population recordings have been used to support partial reconstruction of neural microcircuit diagrams. In this approach, fine-timescale components of paired spike train interactions are isolated and subsequently attributed to synaptic parameters. Recent perturbation studies strengthen the case for such an inference, yet the complete set of measurements needed to calibrate statistical models are unavailable. To address this gap, we study features of pairwise spiking in a large-scale in vivo dataset where presynaptic neurons were explicitly decoupled from network activity by juxtacellular stimulation. We then construct biophysical models of paired spike trains to reproduce the observed phenomenology of in vivo monosynaptic interactions, including both fine-timescale spike-spike correlations and firing irregularity. A key characteristic of these models is that the paired neurons are coupled by rapidly-fluctuating background inputs. We quantify a monosynapse's causal effect by comparing the postsynaptic train with its counterfactual, when the monosynapse is removed. Subsequently, we develop statistical techniques for estimating this causal effect from the pre- and post-synaptic spike trains. A particular focus is the justification and application of a nonparametric separation of timescale principle to implement synaptic inference. Using simulated data generated from the biophysical models, we characterize the regimes in which the estimators accurately identify the monosynaptic effect. A secondary goal is to initiate a critical exploration of neurostatistical assumptions in terms of biophysical mechanisms, particularly with regards to the challenging but arguably fundamental issue of fast, unobservable nonstationarities in background dynamics.

q-bio.NC