Cerebrovascular Reactivity Has Negligible Contribution to Hemodynamic Lag After Stroke: Implications for Functional Magnetic Resonance Imaging Studies

Background:Functional magnetic resonance imaging (fMRI) is ubiquitously used to study poststroke recovery. However, the fMRI-derived hemodynamic responses are vulnerable to vascular insult which can result in reduced magnitude and temporal delays (lag) in the hemodynamic response function (HRF). The cause of HRF lag remains controversial, and a better understanding of it is required to ensure accurate interpretation of poststroke fMRI studies. In this longitudinal study, we investigate the relationship between hemodynamic lag and cerebrovascular reactivity (CVR) following stroke. Methods:Voxel-wise lag maps were calculated relative to a mean gray matter reference signal for 27 healthy controls and 59 patients with stroke across 2 time points (approximate to 2 weeks and approximate to 4 months poststroke) and 2 conditions: resting-state and breath-holding. The breath-holding condition was additionally used to calculate CVR in response to hypercapnia. HRF lag was computed for both conditions across tissue compartments: lesion, perilesional tissue, unaffected tissue of the lesioned hemisphere, and their homolog regions in the unaffected hemisphere. CVR and lag maps were correlated. Group, condition, and time effects were assessed using ANOVA analyses. Results:Compared with the average gray matter signal, a relative hemodynamic lead was observed in the primary sensorimotor cortices in resting-state and bilateral inferior parietal cortices in the breath-holding condition. Whole-brain hemodynamic lag was significantly correlated across conditions irrespective of group, with regional differences across conditions suggestive of a neural network pattern. Patients showed relative lag in the lesioned hemisphere which significantly reduced over time. Breath-hold derived lag and CVR had no significant voxel-wise correlation in controls, or patients within the lesioned hemisphere or the homologous regions of the lesion and perilesional tissue in the right hemisphere (mean r<0.1). Conclusions:The contribution of altered CVR to HRF lag was negligible. We suggest that HRF lag is largely independent of CVR, and could partly reflect intrinsic neural network dynamics among other factors.