Quantifying control circuit regulation in the human brain

Abstract

As a field, control systems engineering has developed quantitative methods to characterize the regulation of systems or processes, whose functioning is ubiquitous within synthetic systems. In this context, a control circuit is objectively ″well regulated″ when discrepancy between desired and achieved output trajectories is minimized, and ″robust″ to the degree that it is able to regulate well in response to a wide range of stimuli. Most psychiatric disorders are assumed to reflect dysregulation of brain circuits. Yet, probing circuit regulation requires fundamentally different analytic strategies than the correlations relied upon for analyses of connectivity and their resultant networks. Here, we demonstrate how well-established methods for system identification in control systems engineering may be applied to functional magnetic resonance imaging (fMRI) data to extract generative computational models of human brain circuits. These provide two quantitative measures of direct relevance for psychiatric disorders: a circuit′s sensitivity to external perturbation and its dysregulation.

Development of an MRI-Compatible Nasal Drug Delivery Method for Probing Nicotine Addiction Dynamics

“…While both pharmacological intervention via drugs like bupropion or varenicline [55], and brain stimulation techniques like transcranial magnetic stimulation (rTMS) [56][57][58], have shown promise as therapeutics in nicotine addiction, it is extremely difficult to probe neural pathways and neuromodulatory targets non-invasively for personalized treatment. Our device, along with recent analytical methods developed for single-subject-level analysis [59], can be used for probing oscillating antagonistic sub-circuits associated with addiction. These sub-circuits modulate repeated-cycle transitions between periods of craving (affecting the nucleus accumbens and prefrontal-limbic circuit associated with aversive stimuli/emotional stress [7,60,61]), reward following partial drug administration (affecting the nucleus accumbens and activating the substantia nigra subcomponents of the basal ganglia circuit [62]), and transient satiety (affecting the prefrontal-limbic circuit and the caudate and pallidum subcomponents of the basal ganglia circuit).…”