Background: Lacunar cerebral infarction(LI)is one of risk factors of vascular dementia and correlates significantly with longitudinal cognitive decline in subcortical function,such as executive functions.Spatial navigationskill is specific to subcortical function,however,little is known on spatial navigation deficits and its underlyingmicrostructural basis of white matter in lacunar infarctionpatients with or without MCI.Therefore,our aim was to investigate whether the spatial navigation impairment would be correlated the structural integrity changes of white matter in lacunar infarction patients with MCI.Methods:Thirty patients with lacunar infarctionwere included in the study and subdivided into LI-MCI group(n=17)and non MCI(LI-No)group(n=13)according neuropsychological tests.Fourteen healthy cognitive normal controls(CN)were matchedwith similar age,gender and education.The changes of structural integrity of white matter were assessed byfractional anisotropy(FA)and mean diffusivity(MD)from diffusion tensor imaging(DTI).The spatial navigation ability,including egocentric and allocentric,was assessed by a computerized human analogue of the Morris Water Maze at follow-up ranged from 6 months to 14 months after MRI examination.Results: LI-MCI patients had significantly lower scores on the Symbol digit modalities test(F=4.76,P=0.01),Reversed digit span total numbers recalled(F=3.67,P=0.03),Verbal fluency test(F=6.61,P<0.01),RAVLT delayed recall(F=3.54,P=0.04)and recognition test(F=9.23,P<0.01).The LI-MCI group performed worse than the CN group and LI-No group on ego(F=3.46,P=0.04),and delayed(F=5.62,P=0.01)spatial navigation subtests.Lower FA values in the left inferior fronto-occipital fasciculus,left hippocampus,left uncinate fasciculus and higher MD scores in the both side anterior thalamic radiation were predictive of worse egocentric navigation skillat following-up.Similarly,lower FA scores in the right posterior limb of internal capsule,right retrolenticular of internal capsule,both side corticospinal tracts,both side hippocampus and higher MD scores in the both side anterior thalamic radiation were predictive of worseallocentric navigation skillat following-up.Conclusions: These results offered strong evidence that there were spatial navigation deficits in lacunar infarction patients with MCI.The results also emphasized that microstructural abnormality in diffusebrain regions,including hippocampus,uncinate fasciculus,which may contribute to the spatial navigation impairment at following-up.