Validation of cerebral blood flow connectivity as imaging prognostic biomarker on subcortical stroke

Stroke is a major cause of vascular cognitive dysfunction, such as memory impairment. We aimed to explore the neural substrates underlying verbal memory impairment in subcortical stroke patients by the methods of voxel-wise cerebral blood flow (CBF) and the functional covariance network (FCN). Sixty patients with chronic subcortical stroke and 60 normal controls (NCs) were recruited into this study. We used a three-dimensional pseudo-continuous arterial spin-labeling imaging to measure alterations in CBF and FCNs. We mapped the overall CBF alterations in a voxel-wise manner and compared CBF measurements using a two-sample t test. Correlations between CBF and verbal memory were also investigated. Subsequently, we constructed FCNs by calculating the correlation between specific regions and all other voxels of a whole brain, separately within the two groups. Thereafter, by comparing differences of the FCN patterns between the patient and NC groups, we investigated the connection alterations within the FCN maps. The stroke patients showed verbal short-term memory (VSTM) deficits compared to NCs. The patients exhibited decreased CBF in the ipsilesional insula and ventral sensorimotor network, and increased CBF in contralesional frontal cortical and subcortical regions (putamen and thalamus). Meanwhile, the CBF in the ipsilesional insula was positively correlated, and the contralesional frontal cortical was negativity correlated, with VSTM scores. Moreover we found that stroke patients exhibited disordered connection within FCNs compared to NCs. The study suggests that the underlying imaging biomarker of VSTM impairment in patients with subcortical stroke was associated with disconnection of the frontal lobe network.