Research
Neurovascular coupling and decoupling in human brain
We investigate neurovascular coupling in human brain from the blood oxygen level dependent (BOLD) response evoked by a brief stimulus, called the hemodynamic response function (HRF) with high-resolution fMRI. The ability to non-invasively characterize neural activity using fMRI will be of huge utility in research for normal human brain functions. This BOLD HRF is extensively exploited in popular functional imaging methods such as fMRI and reflectance-based optical imaging. Proper interpretation and utilization of these imaging techniques requires a detailed understanding the HRF. Moreover, because the brain is continually active, transient responses are likely to be important in normal operation of the healthy brain.
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 HRF. The model will offer a more detailed interpretation of the underlying physiological components associated with the HRF. Our proposed research will provide a detailed understanding of neurovascular coupling and decoupling associated with the HRF, expanding our knowledge of normal brain functions. Such details with precision to understand the BOLD HRF 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 coupling.
Characterization of negative BOLD response in human brain
For task-based fMRI, the positive BOLD response has been widely used and is often assumed to linearly reflect local neural activity. However, many brain regions exhibit signal decreases upon activation, known as the negative BOLD response (NBR). Although the NBR and its origins have been studied extensively, the temporal characteristics, spatial structure, and corresponding underlying physiological dynamics of the NBR are still not well understood. We specifically investigate the dynamics of the NBR evoked by a brief stimulus—known as 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 labeling (ASL) fMRI modalities.
High spatial and temporal resolution BOLD measurements will resolve the temporal dynamics of the nHRF as a function of cortical depth and distance from adjacent positive BOLD responses along the cortical surface. We also evaluated the shift-invariant temporal linearity by measuring the dynamics of the NBR for varying stimulus durations. Fine spatiotemporal sampling with ASL measurements, coupled with a novel stimulus-onset-time dithering scheme, will provide accurate quantification of cerebral blood flow associated with the NBR within gray matter.
Quantitative human subcortical HRF with high spatiotemporal resolution fMRI
Subcortical human brain regions play critical roles in functions ranging from homeostasis to cognition, yet there has been limited research on fully assessing human subcortical health. Quantitative characterization of subcortical responses has great potential to reveal the mechanisms of various neurodegenerative disorders, including Alzheimer’s, Huntington’s, and Parkinson’s disease, as well as cerebrovascular pathologies such as traumatic brain injury (TBI). The HRF can serve as a useful indicator of vascular and brain tissue health, given that neurovascular coupling is crucial for brain function. Cerebral hemodynamic abnormalities are clear pathophysiological features. For instance, a substantially delayed BOLD response with a lower hyperoxic peak has been observed in patients with stroke, mild cognitive impairment, and Alzheimer’s disease. However, the relationship between the HRF and vascular pathology has not yet been quantitatively characterized. It is evident that a better understanding of the physiological processes underlying the HRF in human subcortical regions is needed.
We develop new metrics to assess subcortical vascular health. By measuring HRF in healthy subjects and incorporating various structural MR metrics, we aim to establish a normative database that will be vital for future clinical research.
Morphology-based cortical thickness and depth calculation in human brain
Conventional human BOLD fMRI studies with relatively large voxel sampling sizes (~3 – 6 mm) can blur data across white matter (WM), gray matter (GM), and pial vasculature. This is particularly concerning in the convoluted human cerebral cortex, which has a thickness ranging from 1.5 – 4.5 mm, with the thinnest GM typically located in the depths of the sulci. Additionally, the pial vessels that supply and drain cortical blood are expected to have their own dynamics of coupling with the HRF in the parenchyma. Furthermore, partial sampling between adjacent sides of a sulcus can further complicate matters by mixing contributions from different parts of the cortical surface. A conventional fMRI voxel may therefore contain significant portions of undesirable signals, which can substantially alter the HRF compared to what is found in localized regions of GM where neuronal activity occurs.
To better understand these contributions, full characterization of the depth dependence of the HRF in gray matter, as well as its adjacent white matter and pial vasculature, is needed. We introduce new methods to calculate 3D depth by combining a signed-distance function with an algebraic morphing definition of distance. This new scheme is simpler than methods relying on deformable surface propagation.
We also extend this approach to characterize depth and thickness relationships within the dorsal midbrain in humans by using two depth metrics from the superficial surface of the midbrain and the cerebral aqueduct as references.