Increased functional connectivity after stroke correlates with behavioral scores in non-human primate model

Carlos R Hernandez-Castillo,Juan Fernandez-Ruiz,Jason Gallivan,Joseph Y Nashed,Douglas J Cook,Justin Wang

doi:10.1038/s41598-017-07175-y

Abstract

Here we characterized the functional connectivity (FC) changes occurring after a controlled MCA stroke in a primate model. We hypothesize that if FC can inform about the neural changes after a stroke in the non-human primate (NHP) stroke model, then significant FC changes after the stroke would have to correlate with the remaining behavioral capacities. Eleven cynomolgus monkeys underwent an experimental middle cerebral artery occlusion while five monkeys remained as the control group. One month later the neurological function was assessed with a set of fine motor tasks and the Nonhuman Primate Stroke Scale (NHPSS). Structural and functional connectivity analyses were done to compare both groups. Three FC changes showed significant behavioral correlations: right sensorimotor-right lateral intraparietal FC with the six-well task; left posterior intraparietal-left dorsal premotor FC with the hill task; and right visual-left primary motor FC with the NHPSS. In the three instances, stronger FC correlated with better behavioral outcome. The results show that the functional changes correlating with behavioral outcomes involved sensorimotor cortices that were not restricted to the affected hemisphere. These results show that the FC analysis in NHP stroke model is a relevant methodology suitable to inform the neural changes occurring after a stroke.

Highlights

Animal models in biomedical research have had a paramount impact in treating a number of conditions
A critical goal of this research was to test if functional connectivity (FC) changes correlated with the behavioral outcome in a chronic stage in the stroke non-human primate (NHP) model previously designed by our group[2]
The second functional connection was between the left posterior intraparietal area (PIP) and the left dorsal premotor area 6 (DPA6), which showed a significant increase in relation to the control group

Summary

Introduction

Animal models in biomedical research have had a paramount impact in treating a number of conditions. Non-human primate (NHP) models provide the capacity to test variables closely related to the human central nervous system function[1] In this regard, a recent study successfully developed a gyrencephalic NHP stroke model using a middle cerebral artery (MCA) occlusion method, becoming the model that most closely resembles the most common stroke type in humans[2, 3]. The aim of the current study was to characterize the functional connectivity changes occurring after a controlled MCA stroke in the NHP model

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