Project Summary For task-based functional magnetic resonance imaging (fMRI), the positive blood-oxygen-level-dependent (BOLD) response has been widely used and often assumed that it linearly reflects local neural activity. However, a significant portion of brain regions responds with signal decreases upon activation, known as the negative BOLD response (NBR). Although the negative BOLD response (NBR) and its origin have been explored extensively, temporal characteristics and spatial structure of the NBR, and corresponding underlying physiological dynamics are still poorly understood. We propose to investigate dynamics of the NBR evoked by a brief stimulus –the negative hemodynamic response function (nHRF) and its underlying neurovascular and neurometabolic responses using our novel experimental paradigms with high spatiotemporal resolution BOLD and arterial spin labelling (ASL) fMRI modalities. High spatial and temporal resolution BOLD measurements will resolve temporal dynamics of the nHRF as a functional of cortical depth and distance from adjacent positive BOLD responses along the cortical surface. We also evaluated shift-invariant temporal linearity by measuring dynamics of the NBR for varying stimulus durations. Fine spatiotemporal sampling ASL measurements in conjunction with a novel stimulus- onset-time dithering scheme will provide accurate quantification of the cerebral blood flow associated with the NBR within gray matter. We advance our novel computational model based on prompt arterial dynamics observed in recent experimental studies, enabling estimation of realistic neurometabolic response associated with the nHRF. The model will offer a better detailed interpretation of the underlying physiological components associated with the nHRF. Our proposed research will provide a detailed understanding of neurovascular and neurometabolic (de-)coupling associated with nHRF, expanding our knowledge of normal brain functions. Such details with precision to understand the NBR and its physiology was not available in previous studies. Ultimately, success of our proposed research will motivate use of the proposed fMRI approaches and modeling schemes for brain pathologies that involve neurovascular and neurometabolic coupling.