The neurovascular impulse response function differentially reflects intrinsic neuromodulation across cortical regions

Neuromodulatory transmitters have vasoactive properties. Therefore, the impulse response function (IRF) linking spontaneous neuronal activity with hemodynamics may depend on neuromodulation. To test this hypothesis, we used optical imaging to measure norepinephrine (NE) or acetylcholine (ACh), calcium (Ca²⁺) activity of cortical neurons and hemodynamics in cerebral cortex in awake mice. We show that modeling of hemodynamics as a weighted sum of Ca²⁺-specific and NE-specific IRFs (IRF_Ca2+ and IRF_NE) convolved with the respective time courses dramatically improved the model performance compared to using IRF_Ca2+ alone. In contrast to NE, ACh was largely redundant with Ca²⁺ and, therefore, did not improve the hemodynamic estimation. Because NE covaried with arousal, we observed instances of the diminished hemodynamic coherence between cortical regions during high arousal despite coherent behavior of the underlying neuronal Ca²⁺ activity. We conclude that, without accounting for noradrenergic neuromodulation, diminished hemodynamic coherence can be falsely interpreted as neuronal desynchronizations in neuroimaging studies.