A Safety, Tolerability, and Preliminary Efficacy of Low-intensity Focused Ultrasound Neuromodulation in Patients With Drug-resistant Epilepsy

Inclusion Criteria:

1. Male or female patients ≥ 18 years of age at the time of enrollment.

2. Patients with drug-resistant temporal lobe epilepsy (DR-TLE), defined as failure ofadequate trials of two tolerated, appropriately chosen and used anti-epileptic drugschedules (whether as monotherapies or in combination).

3. Focal-onset seizures with or without secondary generalization and no more than twoknown seizure onset zones (seizure foci), at least one which is in the mesialtemporal lobe.

4. At least 4 focal-onset seizures with objectively visible or significantly disablingmanifestations in the 8-week baseline and at least one seizure per month in thebaseline.

5. MRI and EEG within the past 3 years. At least one prior EEG should demonstrateinterictal or ictal focal epileptiform findings.

6. Patients with the central of FUS exposure region are located at least 30 mm distancebeneath the skull bone.

7. Patients must be on a stable regimen of anti-epileptic drugs (AEDs) for at least 30days at the time of enrollment, except for rescue benzodiazepines or occasionalextra doses of ongoing medicines, as required.

8. Females of childbearing potential must have a negative pregnancy test prior to thefirst treatment. Females of childbearing potential and male patients with a partnerof childbearing potential must agree to follow acceptable method of contraception (as outlined below) from prior to the first study treatment to 3 months after thelast study treatment. Standard acceptable methods include use of highly effectivemethod of contraception, including: hormonal contraception, diaphragm, cervical cap,vaginal sponge, condom, spermicide, vasectomy, intrauterine device, and abstinencefrom sex.

9. Patients are able and willing to have their hair shaved in the region where thecoupling membrane will touch (or if they prefer, whole head).

10. Patients are able to complete all clinical trial-related questionnaires in English,including with the use of a suitable interpreter.

11. Patients or their legal representatives are able to provide written informed consentfor participation in the trial and comply with study requirements in the opinion ofthe Investigator during the study period.

Exclusion Criteria:

1. Patients who have primary generalized epilepsy, mixed focal and generalizedepilepsy, or any history of non-epileptic seizures.

2. Patients who have experienced tonic-clonic status epilepticus in the 12 monthsbefore the time of enrollment in the study. Subjects with focal status epilepticusmay be considered at the discretion of the Investigator.

3. The only feasible sonication pathway to the seizure onset zones involves either:

4. Skull area is covered by previous surgical site(s), scars, scalp disorders (e.g., eczema, psoriasis), or scalp atrophy.

5. Clips or other metallic implanted objects in the skull or brain, except shunts.

6. A prior craniotomy site.

7. Patients with a potentially acute or progressive neurologic disorder (e.g., braintumor, multiple sclerosis, dementia, or intracranial vascular lesion).

8. Implanted electronic device, for example, implanted cardioverter-defibrillator (ICD), cardiac pacemaker, permanent medication pumps, cochlear implants, responsiveneurostimulator, deep brain stimulation (DBS), or other electronic devices implantedin the brain. If a patient has a working Vagus Nerve Stimulator (VNS) in place, thesettings should remain stable throughout the trial and the device will be turned offprior to each sonication treatment and then turned back on afterward.

9. Patients with severe depression, active suicidal ideation or behavior (as per theC-SSRS), active psychosis (excluding time-limited postictal psychosis), orpsychiatric hospitalization in the year before time of enrollment.

10. Patient has an IQ < 70, based on the Wechsler Abbreviated Scale of Intelligence (WASI-II or other Wechsler IQ measure).

11. Coexisting medical problems of sufficient severity to limit compliance with orinterpretation of the study.

12. Patients have received an investigational drug or an investigational device within 4weeks prior to the first treatment.

13. Radiofrequency thermocoagulation (RFTC) within 2 months before time of enrollment.

14. Known history of substance or alcohol abuse within the past year, not countingmarijuana.

15. Pregnant or breast-feeding women.

16. Any other condition that, in the Investigator's judgment, might affect studyendpoints or might increase the risk to the patients or decrease the chance ofobtaining satisfactory data needed to achieve the objectives of the study.