Low-Intensity Focused Ultrasound Targeting the Dorsolateral Prefrontal Cortex for Preventive Treatment of Chronic Migraine

Prior treatment

• Use of opioid-containing analgesics for more than 4 days within 1 month before baseline or during baseline period.
• Use of any migraine preventive medication within 1 month prior to screening.
• Use of devices or surgical interventions for migraine treatment within 1 month before baseline, including transcranial magnetic stimulation, greater occipital nerve block, or invasive/non-invasive neuromodulation procedures.
• History of myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months before screening.

Other illness

• History of epilepsy, brain tumor, or traumatic brain injury.
• History of transcranial magnetic stimulation, transcranial direct current stimulation, or electroconvulsive therapy within the past 3 months.
• Presence of MRI-incompatible metallic implants, including but not limited to vascular stents, cardiac pacemakers, or ventriculoperitoneal shunts.
• Clinically significant comorbid chronic pain conditions, such as fibromyalgia, chronic low back pain, or complex regional pain syndrome.
• Diagnosis of acute or active temporomandibular disorder.
• History or diagnosis of other primary headache disorders, including chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or atypical migraine subtypes.
• History of malignant tumors within the past 5 years, except adequately treated localized basal cell carcinoma or carcinoma in situ of the cervix.
• History of severe psychiatric disorders, including schizophrenia, other psychotic disorders, bipolar disorder, obsessive-compulsive disorder, or post-traumatic stress disorder.

Other

• Severe anxiety, depression, or manic symptoms according to predefined scale thresholds (SAS, SDS, and BRMS).
• Significant risk of self-harm or harm to others based on the Columbia Suicide Severity Rating Scale (C-SSRS) assessment or investigator judgment.
• Pregnancy or breastfeeding.
• Claustrophobia or inability to undergo MRI examination.

• Participants diagnosed with chronic migraine according to the International Classification of Headache Disorders, 3rd edition (ICHD-3), with a history of migraine for at least 12 months before screening.
• Migraine onset at or before 50 years of age.
• During the 3 months before screening, participants have headache occurring on at least 15 days per month, with migraine features or migraine-specific treatment on at least 8 days per month.
• During the baseline prospective electronic headache diary period, participants record at least 8 migraine days and 15 to 27 headache days.
• Participants are able to comply with electronic headache diary recording requirements, with data recorded for at least 24 of the 28 days during the screening period.
• Age between 18 and 65 years at screening visit.
• Participants are willing and able to provide written informed consent and comply with study procedures.