This study aims to investigate whether a specific brain region mediates the cognitive deficit in long COVID brain fog, and whether targeted modulation of this region can improve cognition.

In observational study, the objective was to identify potential intervention targets for patients with long COVID brain fog. A total of 120 patients with long COVID were enrolled. Brain fog (BF) severity was quantified using the Brain Fog Assessment (BFA). Participants completed a continuous random-dot motion (cRDM) task during 128-channel electroencephalography (EEG) and underwent structural MRI and standardized neuropsychological testing.

In interventional study, 40 participants with persistent BF symptoms were enrolled for transcranial ultrasound stimulation (TUS). On Day 1, participants completed the BFA and provided demographic data, then performed the baseline cRDM task; 20 minutes later, structural MRI and baseline resting-state MRI were acquired. On Day 2, participants received 60 seconds of TUS (active or sham) according to randomized allocation. Twenty minutes post-stimulation, an 8-minute resting-state MRI scan was obtained, followed immediately by the follow-up cRDM task.

Inclusion Criteria:

• Patients should have a history of COVID-19 infection (positive test results for either polymerase chain reaction or rapid antigen test) and report persistent brain fog (BF) symptoms at least 4 weeks after recovering from acute COVID-19.

Exclusion Criteria:

• 1. Presence of any symptoms of cognitive impairment or other neurological symptoms prior to COVID-19 infection;
• 2. Structural MRI revealing significant intracranial lesions or structural abnormalities;
• 3. Development of severe neurological complications after COVID-19 infection, including delirium, cerebrovascular diseases, encephalitis, and epilepsy;
• 4. Other disorders that may cause cognitive impairment, including Dementia, Schizophrenia spectrum disorders, stroke, Alzheimer's disease, and Parkinson's disease.