Better brain zaps: new study tests precision targeting for depression treatment

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: Cohort 1: Capacity and willingness to participant in TMS, and fMRI as well as satisfying criteria for diagnosis. * Between 18 and 89 years of age. * Ability to obtain a Motor Threshold (MT) with single pulse TMS * Ability to safely and comfortably undergo an MRI and TMS * Able to read, verbalize, understand and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments * Depression (PHQ-9 \>= 10 and functional impairment present indicated with "difficulty" question OR sufficiently depressed to be enrolled in rTMS therapy) * Confirmed diagnosis of Major Depressive Disorder (MDD) * Can maintain all existing treatments (e.g. psychopharmacology, psychotherapy, etc.,) throughout course of the three sessions (psychological / functional assessments, MRI, and TMS), with modifications only as needed for clinical management * Is a Veteran Cohort 2: * Between 18 and 89 years of age * Ability to safely and comfortably undergo an MRI and tES * Ability to read, verbalize, understand, and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments * Depression (PHQ-9 \>= 10) and endorse that the COVID-19 pandemic has worsened their depression OR have a score on the COVID Stress Scale (CSS) on any item of 3 or greater indicating stressor is "very" or "often" a problem will allow the Veteran to enter the study Exclusion Criteria: * Participants who can not safely and comfortably undergo MRI OR TMS (or TES for Cohort 2) * If their language is not primarily English they may be excluded depending on how dependent the imaging and cognitive tasks are on language * Additionally, participants may be excluded if they do not fully understand the consenting process and cannot communicate sufficiently in English to participate in the therapy (d/t language barrier, etc.) * An example of safety screen details for an MRI is detailed in the Stanford University MRI screening form * MRI exclusions include having any non-removable device or implant that makes scanning unsafe, claustrophobia, and size (e.g. weight, girth) beyond the constraints of the MRI and scanner bed * For TMS the investigators will follow safety guidelines set by Rossi et. al.,2009 * Specifically, the investigators will not include subjects whose Motor Threshold (MT) is greater than 84% of maximum device output because mathematically they would not be able to be safely stimulated using the standard 120% of MT (i.e. the device cannot stimulate more than 100% of its potential output) * The investigators will report these high MT data in our secondary analyses. Additional TMS exclusions include any history or condition that puts patients at risk for a seizure * Pregnant or planning to become pregnant within the next 3 months * Lifetime history of moderate or severe traumatic brain injury, current unstable medical conditions, current (or past if appropriate) significant neurological disorder, or lifetime history of: * seizure disorder * primary or secondary CNS tumors * stroke * cerebral aneurysm * Significant cognitive impairment (Montreal Cognitive Assessment \[MoCA\] \< 16) * Comorbidities (e.g. PTSD) determined not to be the primary diagnosis * Have a lifetime diagnosis of schizophrenia, schizoaffective disorder, schizophreniform, delusional disorder, or current psychotic symptoms * Have a diagnosis of obsessive-compulsive disorder assessed by a study investigator to be causing greater impairment than MDD * Have active suicidal intent or plan in which case Dr. Rosen will determine whether the patient needs to be referred for hospitalization * Presence of any other condition or circumstance that, in opinion of the investigator team, has the potential to prevent study completion and/or to have a confounding effect on outcome assessments Exclusion Criteria for Cohort 2: * Participants who cannot safely and comfortably undergo MRI or TES * Pregnant or lactating female or planning to become pregnant within the next 3 months * Lifetime history of moderate or severe traumatic brain injury or tumor * Significant cognitive impairment (Montreal Cognitive Assessment \[MoCA\] \< 16 OR equivalent score on \[MoCA-BLIND\] and judgement of a clinician that the test is validly reflecting a significant disabling cognitive impairment * Have a lifetime diagnosis of: * schizophrenia * schizoaffective disorder * schizophreniform * delusional disorder * or current psychotic symptoms * Have a diagnosis of obsessive-compulsive disorder or unstable substance use disorder * Presence of actively infections/contagious disease such as the flu or SARS-CoV-2