A Multiscale “Working Brain” Model

By modeling salient features of the corticothalamic system over multiple spatial and temporal scales, physiologically based neural field theory has yielded numerous successful predictions that interrelate stimuli, neural activity, and measurements. Likewise, physiologically based neural mass theories of the brainstem-hypothalamus sleep-wake switch and associated systems have recently been developed and shown to quantitatively reproduce a wide variety of arousal-state phenomena. In both cases, model parameters have been independently constrained, and each model has integrated multiple phenomena and measurements into a single unified framework, thereby validating the modeling approach and enabling these features to be interrelated and interpreted in terms of underlying physiology and anatomy. Here, a first integration of the corticothalamic and arousal-state models is carried out by incorporating a simple model of their couplings: upward via the neuromodulatory effects of the ascending arousal system, and downward via the gating of light inputs by higher-level behavior. The resulting “working brain” system has a neural-mass-like limit, governed by delay differential equations that enable it to respond correctly to light-dark cycles, sleep deprivation, jetlag, and pharmacological inputs, while driving the corticothalamic system into parameter regions where it reproduces associated electroencephalograms, evoked response potentials, and other phenomena, whose properties are further elucidated by retaining the appropriate neural field equations. Overall, the combined model provides a simple, highly flexible framework for quantitatively modeling a variety of mesoscale to macroscale brain phenomena, ranging from normal behaviors to highly nonlinear dynamics such as found in seizures, and for examining interactions between such phenomena. these findings are illustrated with representative examples. Fitting of the model to data can be used to infer brain states and underlying parameters.