There is considerable uncertainty regarding the impact of microembolic signals (MESs) on neuropsychological abilities in patients receiving pulmonary vein isolation and beyond using the cryoballoon technique. We conducted the largest prospective observational study on this topic, providing insights into the gradual unmasking of procedure-related MESs and their impacts on neuropsychological outcomes. MESs were continuously detected periprocedurally using transcranial Doppler ultrasonography. Neuropsychological status was evaluated comprehensively using the CERAD Plus test battery, which consists of 11 neuropsychological subtests. Patients with atrial fibrillation were included in the study with an equal distribution (50:50) of paroxysmal or persistent presentations. Of 167 consecutive eligible patients, 100 were included within the study enrollment period from February 2021 to August 2022. The study, including the documentation of all follow-up visits, ended in November 2022. This paper focuses on describing the study protocol and methodology and presenting the baseline data.