Further nonlinearities in neurovascular coupling in rodent barrel cortex

An essential prerequisite for the accurate interpretation of noninvasive functional brain imaging techniques, such as blood oxygen level dependent (BOLD) fMRI, is a thorough understanding of the coupling relationship between neural activity and the haemodynamic response. The current study investigates this relationship using rat barrel cortex as a model. Neural input was measured by applying current source density (CSD) analysis to multi-laminar field potentials to remove ambiguities regarding the origin of the signal inherent in single electrode recordings. Changes in cerebral blood flow (CBF) were recorded with a laser Doppler flowmetry probe. The magnitude of neural and CBF responses were modulated over a large range by altering both the intensity and frequency of electrical whisker pad stimulation. Consistent with previous findings [Devor, A., et al., 2003. Neuron 39, 353-359; Sheth, S.A., et al., 2004. Neuron 42, 347-355] a power law function well described the relationship between neural activity and haemodynamics. Despite the nonlinearity of the coupling over the whole data set, the relationship was very well approximated by a linear function over mid-range stimuli. Altering the frequency of stimulation at 1.2 mA shifted the neural activity and corresponding haemodynamic response along this linear region, reconciling recent reports of a nonlinear relationship [Devor, A., et al., 2003. Neuron 39, 353-359; Jones, M., et al., 2004. NeuroImage 22, 956-965; Sheth, S.A., et al., 2004. Neuron 42, 347-355] with previous work that found a linear coupling relationship when altering stimulation frequency [Martindale, J., et al., 2003. J. Cereb. Blood Flow Metab. 23, 546-555; Ngai, A.C., et al., 1999. Brain Res. 837, 221-228; Sheth, S., et al., 2003. NeuroImage 19, 884-894]. Using stimuli within this linear range in imaging studies would simplify the interpretation of findings.