Neurovascular Coupling is Preserved in Chronic Stroke Recovery After Targeted Photothrombosis

Abstract

Stroke is one of the leading causes of long-term disability worldwide. While most stroke survivors experience some degree of spontaneous recovery over time, recovery is highly variable among individuals and rehabilitation is the primary treatment to improve recovery. Functional neuroimaging, which measures hemodynamic responses to brain activity, has great potential for monitoring recovery in stroke patients and guiding rehabilitation. However, hemodynamic responses after stroke are almost always altered relative to responses in healthy subjects and it is still unclear if these alterations reflect the underlying brain physiology or if the alterations are purely due to vascular injury. In other words, we do not know the effect of stroke on neurovascular coupling and are therefore limited in our ability to use functional neuroimaging to accurately interpret stroke pathophysiology. To address this challenge, we simultaneously captured neural activity, through fluorescence calcium imaging, and hemodynamics, through intrinsic optical signal imaging, during longitudinal stroke recovery. Our data suggest that neurovascular coupling was preserved in the chronic phase of recovery (2 weeks and 4 weeks post-stoke) and resembled pre-stroke neurovascular coupling. This indicates that functional neuroimaging faithfully represents the underlying neural activity.  Stroke also resulted in increases in global brain oscillations, which showed distinct patterns between calcium and hemodynamics. Increased calcium excitability in the contralesional hemisphere was associated with increased intrahemispheric connectivity. Additionally, sub-acute increases in hemodynamic oscillations were associated with improved sensorimotor outcomes. Collectively, these results support the use of hemodynamic measures of brain activity post-stroke for predicting functional and behavioral outcomes.

Keywords: Neurovascular coupling, photothrombosis, stroke recovery, intrinsic optical signal imaging