Coupling of neural activation to blood flow in the somatosensory cortex ofrats is time-intensity separable, but not linear

Changes in cerebral blood flow (CBF) because of functional activation are u sed as a surrogate for neural activity in many functional neuroimaging stud ies. In these studies, it is often assumed that the CBF response is a linea r-time invariant (LTI) transform of the underlying neural activity. By usin g a previously developed animal model system of electrical forepaw stimulat ion in rats (n = 11), laser Doppler measurements of CBF, and somatosensory evoked potentials, measurements of neural activity were obtained when the s timulus duration and intensity were separately varied. These two sets of ti me series data were used to assess the LTI assumption. The CBF data were mo deled as a transform of neural activity (N-1-P-2 amplitude of the somatosen sory evoked potential) by using first-order (linear) and second-order (nonl inear) components. Although a pure LTI model explained a large amount of th e variance in the data for changes in stimulus duration, our results demons trated that the second-order kernel (i.e., a nonlinear component) contribut ed an explanatory component that is both statistically significant and appr eciable in magnitude. For variations in stimulus intensity, a pure LTI mode l explained almost all of the variance in the CBF data. In particular, the shape of the CBF response did not depend on intensity of neural activity wh en duration was held constant (time-intensity separability). These results have important implications for the analysis and interpretation of neuroima ging data.