The human brain is sensitive to stimuli from the outside world. Those stimuli could induce physiological and neuronal reactions in the brain (e.g. neuron firing and blood flow changes). Those reactions can be measured by several neuroimaging modalities and recorded as physiological and neuronal signals. Interestingly, current studies tend to remove the physiological signal from the brain (e.g., respiration) to focus on the neuronal signal. However, physiological signals in the brain contain some useful information. For example, previous research showed that the averaged signal in the brain, which was commonly removed as physiological noise, can track cerebral blood flow (CBF). Also, by giving physiological stimuli, we can expose hidden deficits in the brain in some cases. Therefore, understanding both physiological signals in the brain and physiological effects on the brain is important. The goal of my study is to investigate physiological signal characterizes various physiological stimuli in the brain using multimodal imaging. Functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) were applied in the following studies. In the first study, the physiological parameters were exploited from fMRI scans, which were recorded after a person drinking coffee. The results derived from fMRI scans illustrated that caffeine decreases the blood vessels' size and increased the blood flow speed in blood vessels in the brain. In the second study, vasoactive stress tests (i.e., hypercapnia, the elevated partial pressure of arterial CO2 (PaCO2)) were introduced as a dominant physiological stimulus (caused an increase of CBF) and measured by fMRI and NIRS concurrently. The results indicated that the cerebral and extracerebral reactivity to elevated PaCO2 depended on the rate of the CO2 increase. Later, my third study comparing hyperoxia (elevated partial pressure of arterial O2 (PaO2)) and hypercapnia effects on the brain measured by fMRI and NIRS. Since NIRS measured both oxy- and deoxy- hemoglobin concentrations, NIRS signals have advantages to differentiate hypercapnia and hyperoxia effects on the brain compared to fMRI. To further understand physiological signals in the brain, coupling between hemodynamic and the inflow effect of CSF dynamic was investigated using fMRI in my fourth study.