The Effects of SAINT® Neuromodulation System on Explicit and Implicit Suicidal Cognition

Inclusion Criteria:

1. Adults of all genders between the ages of 18 and 75 years at the time of screening.

2. Able to read, understand, and provide written, dated informed consent prior toscreening.

3. Proficiency in English sufficient to complete questionnaires / follow instructionsduring fMRI assessments and aiTBS treatments. Stated willingness to comply with allstudy procedures, including availability for the duration of the study, and tocommunicate with study personnel about adverse events and other clinically importantinformation.

4. Currently diagnosed with either Major Depressive Disorder (MDD) and meets criteriafor a current Major Depressive Episode (MDE) according to the criteria defined inthe Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, TextRevision (DSM-5).

5. Medical records confirming a history of moderate to severe treatment-resistance asdefined by a score of 7-14 on the Maudsley Staging Method (MSM).

6. Endorses clinically significant explicit suicidal cognitions (score ≥ 9 on the M-SSIand score ≥ 6 on the BSS self-report) at screening.

7. MADRS score of >/=20 at screening (visit 1).

8. rTMS/iTBS naive.

9. Access to ongoing psychiatric care before and after completion of the study.

10. Access to clinical rTMS after hospital discharge.

11. In good general health, as evidenced by medical history.

12. For females of reproductive potential: use of highly effective contraception for atleast 1 month prior to screening and agreement to use such a method during studyparticipation.

13. Agreement to adhere to Lifestyle considerations:

• Abstain from becoming pregnant from the screening visit (Visit 1) until afterthe final study visit (Visit 9).

• Abstain from caffeine- or xanthine-containing products (e.g., coffee, tea, coladrinks, and chocolate) for 3 hours before the start of each dosing sessionuntil after the final TMS session.

• Abstain from alcohol for 24 hours before the start of each dosing session untilafter collection of the final MRI.

• Participants who use tobacco products will be instructed that use of cigaretteswill not be allowed during the trial.

Exclusion Criteria:

1. Females who are pregnant or planning to become pregnant during the course of thestudy or any female that is breastfeeding

2. The presence or diagnosis of prominent anxiety disorder, personality disorder, ordysthymia in which in the Investigator's opinion is predominant to MDD

3. Depressed mood/dysphoria as a result of an illness other than MDD (e.g. genderdysphoria)

4. Current severe insomnia (must sleep a minimum of 5 hours each night beforestimulation)

5. Current mania or psychosis

6. Bipolar Affective Disorder I and primary psychotic disorders.

7. Autism Spectrum disorder or Intellectual Disability

8. A diagnosis of obsessive-compulsive disorder (OCD)

9. Current moderate or severe substance use disorder or demonstrating signs of acutesubstance withdrawal.

10. Urine screening test positive for illicit substances.

11. Any history of ECT (greater than 8 sessions) without meeting responder criteria

12. No recent (during the current depressive episode) or concurrent use of a rapidacting antidepressant agent (i.e., ketamine or a course of ECT).

13. History of significant neurologic disease, including dementia, Parkinson's orHuntington's disease, brain tumor, unexpected seizure/epilepsy disorder, subduralhematoma, multiple sclerosis, or history of significant head trauma.

14. Untreated or insufficiently treated endocrine disorder.

15. Contraindications to receiving rTMS (e.g., metal in head, history of seizure, knownbrain lesion)

16. Contraindications to MRI (ferromagnetic metal in their body).

17. Any current or past history of any physical condition which in the investigator'sopinion might put the subject at risk or interfere with study resultsinterpretation.

18. Treatment with another investigational drug or other intervention within the studyperiod.

19. Depth-adjusted SAINT® treatment dose > 65% maximum stimulator output (MSO)

20. Any other condition deemed by the PI to interfere with the study or increase risk tothe participant.