Modeling Nonlinear Evoked Hemodynamic Responses in Functional Ultrasound

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Functional ultrasound (fUS) is a high-sensitivity neuroimaging technique that images cerebral blood volume changes, which reflect neuronal activity in the corresponding brain area. fUS measures hemodynamic changes which are typically modeled as the output of a linear time-invariant system, characterized by an impulse response known as the hemodynamic response function (HRF), and a binary representation of the stimulus signal as input. In this work, we quantify the difference between a linear and a nonlinear time-invariant HRF model in terms of data fitting and prediction performance. Our results on fUS data obtained from two mice reveal that: (a) including nonlinearities in the HRF achieves a significantly more precise modeling of the fUS signal compared to the linear assumption under certain stimulus conditions and (b) a second-order Volterra series approximation can be used to characterize the nonlinear model and predict responses to stimuli.