Temporal Interference Brain Stimulation

This is an investigational early phase testing of temporal interference (TI) stimulation in
humans. The overall aim of the study is to assess the safety, feasibility, focality, and
steerability of TI stimulation by selectively modulating activity in subregions of a cortical
area (calcarine cortex - the primary visual cortex)

Healthy subjects who meet inclusion and exclusion criteria will be entered into the study.
The study will recruit up to 20 subjects with the aim to complete 12 subjects.

Study Visits:

The study will consist of up to 6 study visits. The screening and baseline visit, the MRI
visit, and up to 4 TI study. The screening and baseline visit and TI visits will occur at
Beth Israel Deaconess Medical Center in the Berenson-Allen Center. The MRI visit will take
place at the Boston University Cognitive Neuroimaging Center. After Informed Consent is
obtained, the following screening and baseline procedures will be completed:

- Inclusion and exclusion criteria review

- Subject demographics

- Handedness assessment

- Medical history and medication review

- Physical and Neurological exam conducted by a Neurologist or Neurologic Nurse
Practitioner

- Baseline perimetry assessment

- Baseline EEG

- The Mini International Neuropsychiatric Interview (MINI) assessment

- All female subjects will undergo a pregnancy test and pregnant women will be excluded

- Screening for retinotopic mapping - assessing the participant's ability to hold fixation
with their eyes for experimental trials

- MRI safety review

The MRI session will take place at the Boston University Cognitive Neuroimaging Center under
a Boston University submitted and approved protocol that is specific to this study. An MRI
scan of the brain will be conducted while the participant views visual stimuli to obtain each
individual's retinotopic map. This data will be provided to the study team at Beth Israel
Deaconess Medical Center (BIDMC) to conduct the study visit and for analysis.

Each subject will then undergo up to 4 TI stimulation sessions (2 minimum) separated by at
least 2 days to minimize the risk of carry over effects of the stimulation. In each visit,
the participant will receive TI stimulation to one of four regions of retinotopic
representation in the calcarine fissure:

1. peripheral visual field in the deep region of the fissure

2. foveal visual field in the polar region of the fissure

3. superior quadrant of the visual field in the lower bank of the fissure

4. inferior quadrant of the visual field in the upper bank of the fissure The cortical
targets will be defined by electrical field modelling that will be used to optimize the
electrode placement. Regions #1 and #2 will be stimulated in the first two visits with
the order of stimulation regions to be counterbalanced between participants. If an
effect is noted, participants will be asked to complete the additional 2 visits in which
regions #3 and #4 will be stimulated.

Each visit will consist of up to 4 blocks of stimulation paired with a visual discrimination
task and assessment of visual disturbance with an Amsler grid. The stimulation blocks will
each be completed at a different frequency - a control stimulation where TI visual effect is
not anticipated (e.g 2 or 20 hertz (Hz)), a no offset stimulation (e.g. matched carrier
stimulation frequencies such as no envelope modulation is anticipated) and up to 2
frequencies ranging from 8 to 12. The most common signal from visual cortex during wakeful
relaxation is in the frequency range (8-12 Hz). It is hypothesized that TI with a residual
effective stimulation frequency of 1-20 Hz will be ideally suited for activation of the
targeted visual cortex.

Participants will be monitored throughout he visit for any adverse effects and a tES
side-effect questionnaire will be administered at the beginning and end of each stimulation
visit to additionally track any adverse effects. Although any visual disruption induced by
the stimulation is expected and anticipated to be transient in nature, a visual perimetry
assessment will be completed to compare to baseline.

Inclusion Criteria:

- Normal healthy volunteer

- 18-35 years of age

- Normal vision

- Right handed

Exclusion Criteria:

- Corrected-to-Normal vision, or visual impairment.

- Any current or past history of a psychiatric disorder

- Any current or past history of neurological disorders or acquired neurological disease
(e.g. stroke, traumatic brain injury), including intracranial lesions

- History of head trauma resulting in prolonged loss of consciousness; or a history of
>3 grade I concussions

- Current history of poorly controlled headaches including intractable or poorly
controlled migraines

- Any systemic illness or unstable medical condition that may cause a medical emergency
in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma,
etc.)

- History of fainting spells of unknown or undetermined etiology that might constitute
seizures

- History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG, or
family history of treatment resistant epilepsy with the exception of a single seizure
of benign etiology (e.g. febrile seizures) in the judgment of a board-certified
neurologist

- Possible pregnancy. All female participants of child bearing age are required to have
a pregnancy test

- Any metal in the brain, skull or elsewhere unless approved by the responsible MD

- Any medical devices (i.e. cardiac pacemaker, deep brain stimulator, medication
infusion pump, cochlear implant, vagal nerve stimulator) unless otherwise approved by
the responsible MD

- Substance abuse or dependence within the past six months

- Pregnancy; all female participants of child bearing age will be required to have a
pregnancy test; any participant who is pregnant will not be enrolled in the study.

- Not on any medications with the exception of birth control unless approved by the
responsible MD.