This study investigates whether unilateral and bilateral non-invasive brain stimulation, given for 20 minutes/once per day for twenty days (M-F) can reduce migraine pain. Fourty patients will receive treatment (20 unilateral treatment, and 20 bilateral treatment), while twenty will receive a "sham" procedure. Another 20 Episodic Migraine patients will be recruited for the observational aim of the study which does not include brain stimulation.

Clinical Trial:

This is a phase 2, single center, three-arm, double-masked, randomized investigation and modulation of the µ-opioid and D2/D3 mechanisms in chronic migraine (in vivo). We will enroll 60 patients with Chronic Migraine divided into 3 Lab/Home-Based groups: 20 for the active unilateral M11-2 HD-tDCS group, 20 for the active bilateral M11-2 HD-tDCS group, and 20 for the sham M11-2 HD-tDCS group. Patients will complete a screening visit, baseline visit with MRI and PET session, 20 days of HD-tDCS brain stimulation treatments, as well as follow-up visits with an MRI and PET session.

Observational Study Arm:

20 additional patients with low frequency EM (<8 attacks/month) patients (that did not undergo neuromodulation) will be recruited for the study. Historical data may be used in place of recruiting new participants. Data from these 20 EM volunteers will be compared to that of CM patients at baseline; however, they will not be part of the clinical trial.

Inclusion Criteria:

• Male or female, aged 18 to 65 (inclusive)

• Patients must have Episodic migraines that started before the age of 50, and currently experience:

  • Chronic migraine (ICHD-3-beta), headache occurring on 15 days/month for more than six months, which, on at least eight days/month, has the features of a migraine headache.
  • Episodic migraine (low frequency), specifically those with headache occurring less than 8 days/month.

• Willing to limit the introduction of new treatments and medications during the study period.

Exclusion Criteria:

• Significantly greater pain in body sites other than the head

• Active, untreated major concurrent systemic illness other than migraine

  • Medical conditions that can impair health status independent of migraine (including cardiopulmonary disorders, malignancy, uncontrolled endocrine or allergies)
  • Systemic rheumatic disorders (i.e., rheumatoid arthritis, systemic lupus erythematosus, gout, and fibromyalgia);

• History or current evidence of a psychotic disorder (e.g., bipolar disorder, schizophrenia) or severe major depression, as evidenced by Beck Depression score of >30*

• History of neurological disorder (e.g., epilepsy, stroke, neuropathy, neuropathic pain)

• Medication overuse headache (ICHD-3), regular intake for ≥10 days per month of ergotamine, triptans, combination analgesics, or any combination thereof OR ≥15 days per month of simple analgesics (acetaminophen, aspirin, NSAID), for more than 3 months

• Current use of opioid or dopaminergic drugs (or use within the last 3 months) or substance abuse (self-reported)

• Drug test positive for opioid or recreational drug (e.g., cannabis) at the time of the PET scan visits

• Allergic response to study radiotracers or chemically related drugs

• Excluded by MRI Center or PET Center safety screening checklist (as administered by study staff)

• Pregnant or lactating (negative urine pregnancy test must be available before any PET procedures are initiated)

• Prior use of tDCS

Patients will not know if they are receiving active or sham treatment