TBS,TMS, Suicidal Ideation, Magnetic Resonance Imaging, Dorsolateral Prefrontal Cortex, Ventrolateral Prefrontal Cortex

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique, its approved therapeutic indication is high-frequency stimulation to the left dorsolateral prefrontal cortex (DLPFC) for treatment resistant.

investigators design a prospective three-year study to exam the effect of TBS on reducing suicidality targeted at left DLPFC vs VLPFC, and guided by task fMRI neuronavigation and sham. Investigators will adopt personalized left DLPFC and VLPFC localization from baseline task fMRI data. Due to the global brain atrophic changes in the older adults, this issue has been even more important. Investigators will enroll 163 late life depression cases, they will be randomly allocated to either DLPFC group (65 cases), or VLPFC group (65 cases) and sham group (33 cases). To sum up, investigators seek to evaluate the impact of an acute course of TBS guided by tsked fMRI neuronavigation on suicidal ideation, and through follow-up for 6 months, investigators expect to examine (1) suicidal ideation, structural and functional brain differences, inflammatory markers pre/post TBS treatment, explore the link between the mechanism underlying of TBS on brain connectivity and therapeutic effects (2) Association of suicide ideation and neurocognitive function, inflammatory factors and brain imaging data. Exploratory analysis will assess suicide ideation as mediator in the association of neurocognitive deficit and functional connectivity or neurocognitive deficit as mediator in the association of suicide ideation and brain imaging data (3) The trajectories of suicidal ideation in late life depression, to analysis whether the association of cognitive dysfunction and suicidal ideation occurs across time and the prediction of neurocognitive function.(4) Explore the association of suicidal ideation the depression severity, to test if suicidal ideation could be an independent treatment target (5) Investigate the plausible predictors of neuropsychological profiles or neuroimaging findings associated to the effect of TBS in reducing suicidal ideation, which could provide a more efficient strategy for suicide prevention in the elder.

Eligibility Criteria:
Inclusion Criteria:

1. Age \> 50 years.
2. Major depressive disorder (MDD).
3. Right handiness
4. with a score ≥ 12 on the Beck Scale of Suicidal Ideation (BSSI) and a score of at least 3 on Question #3 (Suicide: 3 ideas and gestures of suicide) of the HAMD

Exclusion Criteria:

1. Inability to provide informed consent.
2. Dementia, as defined by MoCA 23/24. Other major mental or current psychotic symptoms
3. Active current suicidal intent as evidenced or the endorsement of an actual attempt, interrupted attempt,
4. Have known preexisting noise-induced hearing loss, concurrent treatment with ototoxic medications, or with cochlear implants are on medications known to lower seizure threshold.
5. Alcohol or other substances abuse of or dependence on within the past 3 months Organic brain, head trauma,
6. Elevated risk of seizure due to TBI
7. Participation in concurrent clinical trial
8. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
9. Unstable medical illness, including delirium, malignancy, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. Unstable cardiac disease or recent (\<3m) myocardial infarction
10. Mental implement in the brain, claustrophobia
11. Ever received ECT, TMS Consent procedures.