Background and Objectives: Vascular cognitive impairment no dementia represents cognitive deficits due to vascular causes but falls short of a dementia diagnosis. Cognitive training has emerged as a safe and effective intervention for vascular cognitive impairment no dementia, though its underlying mechanisms remain obscure. This study investigates how subcortical vascular cognitive impairment no dementia and computerized cognitive training affect a brain fundamental organization feature named functional lateralization. Methods: In a randomized, active-controlled trial, patients with subcortical vascular cognitive impairment no dementia were divided into training and control groups, and underwent neuropsychological assessments and resting-state functional magnetic resonance imaging at baseline, end of 7-week intervention, and 6-month follow-up. Additionally, a healthy older group provided baseline data. Two types of functional lateralization indices (LIs) were defined based on resting-state functional connectivity: LI of intrahemispheric functional connectivity (LI_intra) which represents the left-right difference of functional connectivity strength within the same hemisphere, and LI of interhemispheric heterotopic functional connectivity (LI_he) which represents the left-right difference of functional connectivity strength across bilateral hemispheres. Results: Initially, patients (28 in training group and 28 in control group) showed a fronto-parietal network lateralization pattern akin to healthy older adults (N = 26). However, enhanced right-lateralized LI_he was associated with better memory solely in healthy adults. After the intervention, only the training group exhibited a reduction in LI_he in the fronto-parietal network, indicating a lateralization shift towards bilateral network connectivity. This shift, especially towards leftward lateralization, was linked with improved executive and memory functions in the training group. Notably, these changes disappeared at the 6-month follow-up. Discussion: These findings suggest that subcortical vascular cognitive impairment no dementia modifies the relationship between fronto-parietal network lateralization and cognitive function, rather than altering the lateralization pattern itself. Through hemispherical reorganizing and balancing of the fronto-parietal network, short-term computerized cognitive training facilitates executive and memory functions by leveraging functional compensation by reorganization. This study illuminates the neural plasticity induced by cognitive training in vascular cognitive impairment no dementia, highlighting its potential to transform cognitive outcomes by tapping into the brain's capacity for reorganization and adaptation. Trial registration: The trial was registered under ClinicalTrials.gov (NCT02640716) and conducted under both CONSORT statement and CONSORT statement for nonpharmacological interventions.

The authors have declared no competing interest.

NCT02640716

This study was funded by the National Key R&D Program of China (2022YFC3602600), National Natural Science Foundation of China (81970996, 82220108009), and Scientific Foundation of Institute of Psychology, Chinese Academy of Sciences (E1CX172005).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of Ethics Committee of Xuanwu Hospital, Capital Medical University gave ethical approval for this work

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All data produced in the present study are available upon reasonable request to the authors