Abstract
Blood oxygenation level-dependent (BOLD) functional MRI (fMRI) has been extensively used as a marker of brain dysfunction and subsequent recovery following stroke. However, growing evidence suggests that straightforward interpretation of BOLD fMRI changes with aging and disease is challenging. In this study, we investigated the effect of calibrating task fMRI data by applying a hemodynamic calibration method using the resting-state fluctuation amplitude (RSFA). Task fMRI responses were obtained during a covert verbal fluency task in a group of early stage stroke patients and matched healthy normal controls. Fifteen acute left hemisphere stroke patients (less than 7 days from stroke; aged 44-84 years, average ~64 years) and 21 healthy controls (aged 55-77 years, average ~61 years) were prospectively studied. All subjects completed a 3-min covert verbal fluency task, and a 10-min eyes-closed resting-state fMRI scan, from which the calibration factor (RSFA) was computed. A behavioral measure on the verbal fluency task was also collected outside the scanner. Whole brain activation volumes and region-of-interest (ROI)-wise percent signal change and activation volumes before and after calibration were computed. Between-group differences in whole brain activation volumes, although statistically significant before calibration failed to be significant after calibration. There were significant within-group differences before and after calibration with RSFA. Statistically significant between-group differences on ROI-wise measures before calibration also significantly reduced after calibration. Exploratory brain-behavior correlations revealed a similar pattern: significant correlations before calibration failed to survive after calibration. BOLD fMRI changes with aging and disease is confounded by changes in neurofunctional coupling leading to challenges in the straightforward interpretation of task fMRI results. Application of the hemodynamic calibration using the RSFA technique in the current study appeared to mitigate any differences between stroke and age-matched healthy controls. Our study indicates that estimating neural activity after applying hemodynamic scaling is important for studies of aging and for studies tracking post-stroke changes. We recommend that further investigation of hemodynamic calibration with RSFA in healthy subjects and in stroke in larger samples is necessary.
Highlights
The blood oxygenation level-dependent (BOLD) contrast in functional MRI studies has been extensively used to study group differences and to relate brain response to overt behavior
Along with investigating within- and between-group differences in task-associated BOLD signal amplitude and activation volumes, we investigated the efficacy of this approach in select regions-of-interest (ROIs) typically activated during performance of this task
Pre-Calibration Activation Maps, BOLD Amplitude, and Activation Volumes Prior to calibration with resting-state fluctuation amplitude (RSFA), whole brain group activation volumes were significantly smaller in the patient group, compared to the controls during the verbal fluency task (p < 0.05)
Summary
The blood oxygenation level-dependent (BOLD) contrast in functional MRI (fMRI) studies has been extensively used to study group differences and to relate brain response to overt behavior. A key challenge, in investigating BOLD fMRI task-associated responses in aging and disease is that there may be considerable variability in the responses across subjects depending on the intrinsic vascular reactivity to neural activity [1,2,3]. There is growing evidence that neurovascular coupling is affected in healthy aging and in neurological disorders such as stroke, complicating straightforward interpretation of the BOLD signal. Blood oxygenation level-dependent (BOLD) functional MRI (fMRI) has been extensively used as a marker of brain dysfunction and subsequent recovery following stroke. Growing evidence suggests that straightforward interpretation of BOLD fMRI changes with aging and disease is challenging. Task fMRI responses were obtained during a covert verbal fluency task in a group of early stage stroke patients and matched healthy normal controls
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