Biology subjects

Chesebro, A. G.

Publications and source records attributed to Chesebro, A. G..

3 recordsLinked to original sources

bioRxiv2023

Leveraging Julia's automated differentiation and symbolic computation to increase spectral DCM flexibility and speed

Using neuroimaging and electrophysiological data to infer neural parameter estimations from theoretical circuits requires solving the inverse problem. Here, we provide a new Julia language package designed to i) compose complex dynamical models in a simple and modular way with ModelingToolkit.jl, ii) implement parameter fitting based on spectral dynamic causal modeling (sDCM) using the Laplace approximation, analogous to MATLAB implementation in SPM12, and iii) leverage Julias unique strengths to increase accuracy and speed by employing Automatic Differentiation during the fitting procedure. To illustrate the utility of our flexible modular approach, we provide a method to improve correction for fMRI scanner field strengths (1.5T, 3T, 7T) when fitting models to real data.

neuroscience↗

bioRxiv2023

Ketosis regulates K+ ion channels, strengthening brain-wide signaling disrupted by age.

Aging is associated with impaired signaling between brain regions when measured using resting-state fMRI. This age-related destabilization and desynchronization of brain networks reverses itself when the brain switches from metabolizing glucose to ketones. Here, we probe the mechanistic basis for these effects. First, we established their neuronal basis using two datasets acquired from resting-state EEG (Lifespan: standard diet, 20-80 years, N = 201; Metabolic: individually weight-dosed and calorically-matched glucose and ketone ester challenge, age = 26.9 {+/-} 11.2 years, N = 36). Then, using the multi-scale Larter-Breakspear neural mass model, we identified the unique set of mechanistic parameters consistent with our clinical data. Together, our results implicate potassium (K+) gradient dysregulation as a mechanism for age-related neural desynchronization and its reversal with ketosis, the latter finding of which is consistent with direct measurement of ion channels.

neuroscience↗

bioRxiv2022

Ion Gradient-driven Bifurcations of a Multi-Scale Neuronal Model

Metabolic limitations within the brain frequently arise in the context of aging and disease. As the largest consumers of energy within the brain, ion pumps that maintain the neuronal membrane potential are the most affected when energy supply becomes limited. To characterize the effects of such limitations, we analyze the ion gradients present in the Larter-Breakspear neural mass model. We show the existence and locations of Neimark-Sacker and period-doubling bifurcations in the sodium, calcium, and potassium reversal potentials, and demonstrate that these bifurcations form physiologically relevant bounds of ion gradient variability. Within these bounds, we show how depolarization of the gradients will cause decreased neural activity. We also show that the depolarization of ion gradients decreases inter-regional coherence, causing a shift in the critical point at which the coupling occurs and thereby inducing loss of synchrony between regions. In this way, we show that the Larter-Breakspear model captures ion gradient variability present at the microscale level and propagates these changes to the macroscale effects congruent with those observed in human neuroimaging studies.

neuroscience↗