A time-delay model of dopamine-modulated prefrontal–limbic interactions in schizophrenia

We revisit a nonlinear mathematical model of prefrontal–limbic interactions, aimed to capture both healthy and pathological activation patterns in emotion regulatory circuits. The model’s parameter space encapsulates the strengths of the projection pathways and of other interactions between the system’s neural and dopamine units. These nonlinear parameters can be assigned physiological interpretation (representing, e.g., the control level of arousal, or the vulnerability of the system to elevated stress cortisol). In the current work, we explore the possibility, based on recent literature on the role of midbrain dopamine systems, that dopamine-mediated pathways act not simply as nonlinearities in the system, but also along a different timeline than other interactions, which may explain their specific signature on neural dynamics. We found that dopamine fluctuations can be as impactful on controlling dynamics as changes in strength of synaptic pathways. We also documented that higher dopamine levels allow for complexities of temporal patterns which are not accessible at lower levels. Our conclusions underline the importance of considering the timeline of dopamine contributions to limbic–prefrontal regulation of emotion. More generally, our study supports the value of considering time delays when modeling brain circuits in which timing of interactions is of essence. • We expand on an existing model of the prefrontal–limbic emotion regulatory system. • Our model introduces time-delays to capture the efficiency of the dopamine response. • We analyze the effects of key vulnerability factors on the circuit’s functional dynamics. • We observe how these effects are modulated by fluctuations in the dopamine response. • Delays in dopamine revealed complex patterns, associated with abnormal dynamics.