A Conductance Based Amygdala Model of Threat Processing in Anxiety and Depression

Abstract

Anxiety and depressive disorders are increasingly viewed as dysregulations along continuous stress-regulatory dimensions. However, existing computational approaches seldom connect interpretable circuit level mechanisms to autonomic physiology. Methods: This study develops a mechanistic framework that links amygdala dysregulation to cardiovascular stress responses for digital phenotyping and clinical interpretation. We formulated a compact, nine equation, conductance based model of the amygdala hypothalamus cardiovascular pathway. The framework extends Hodgkin Huxley formalism with three clinically grounded modulators: coping capacity, perceived stress load, and prefrontal regulatory strength. A slow, history-dependent internal state, adaptive thresholding, graded threat acknowledgement, and baroreflex coupled hypothalamic integration were used to generate heart rate and blood pressure trajectories. Results: Distinct strong, moderate, and weak regulatory regimes emerged as stable operating states of a single closed-loop system. Robust analyses showed that stochastic variability and parameter perturbation preserved regime separation, while ablation studies identified the adaptive threshold as the principal mechanism driving quantitative regime separation. Simulated cardiovascular responses remained within reported stress physiology ranges. Furthermore, external evaluation across three independent datasets supported robust agreement with real world, stress related autonomic patterns. Conclusion: A compact, mechanistic model can jointly link psychometric modulators, amygdala excitability, and downstream cardiovascular output within a single, interpretable framework. Significance: This work provides a computationally tractable basis for mechanism informed digital phenotyping, patient specific stress monitoring, and future digital twin approaches for mental health decision support.