Atrial fibrillation (AF) predisposes patients to develop cognitive decline and dementia. Clinical and epidemiological data propose that catheter ablation may provide further benefit to improve neurocognitive function in patients with AF, but the underlying mechanism is poorly available. Here, we conducted a pilot prospective study to investigate whether AF ablation can alter regional cerebral blood flow (rCBF) and brain microstructures, using multimodal magnetic resonance imaging (MRI) technique. Eight patients (63 ± 7 years) with persistent AF underwent arterial-spin labeling (ASL) perfusion, 3D T1-structural images and cognitive test batteries before and 6 months after intervention. ASL and structural MR images were spatially normalized, and the rCBF and cortical thickness of different brain areas were compared between pre- and 6-month post-treatment. Cognitive–psychological function was improved, and rCBF was significantly increased in the left posterior cingulate cortex (PCC) (p = 0.013), whereas decreased cortical thickness was found in the left posterior insular cortex (p = 0.023). Given that the PCC is a strategic site in the limbic system, while the insular cortex is known to play an important part in the central autonomic nervous system, our findings extend the hypothesis that autonomic system alterations are an important mechanism explaining the positive effect of AF ablation on cognitive function.