RECOVERS - Realigning Emotion and COgnition Via PrEcision Regulation NetworkS

In this research study, the investigators are examining how brain activity (electrical and blood flow) changes during tests of emotional processing, attention and memory in the magnetic resonance imaging (MRI) scanner and outside the MRI using functional near-infrared spectroscopy (fNIRS). Investigators are also using non-invasive brain stimulation to probe different parts of the brain and measuring brain activity (electrical and blood flow).

Study 1

This study includes healthy participants and researchers hope this will help us develop improved brain-based treatments for emotional difficulties like depression.

Study 2

This study includes participants with depression and researchers hope this will help us develop improved brain-based treatments for emotional difficulties like depression.

Investigators hypothesize that targeted neuroplastic changes induced by individually-tailored rTMS will substantially reduce clinical symptoms underlying depression, anxiety and suicidality, and in general, revolutionize non-invasive treatments of mental health disorders. Investigators hypothesize that functional coupling in cognitive flexibility (CF) and emotion regulation (ER) networks is indexed by the phase of the brain's alpha oscillations. Using a novel integrated instrument that enables simultaneous functional magnetic resonance imaging (fMRI), electroencephalography (EEG) and transcranial magnetic stimulation (TMS), investigators propose to identify individualized stimulation parameters that reflect the strongest coupling of the CF/ER networks. Investigators will also use an instrument that enables simultaneous functional near-infrared spectroscopy (fNIRS), EEG, and TMS in attempt to identify the same parameters outside the scanner. The neuromechanistic model further posits that by applying repetitive TMS (rTMS) with these individualized parameters, one can induce entrainment in brain networks that drive neuroplastic changes in CF and ER.

Study 1

This study is a proof-of-principle study in healthy control participants.

Study 2

This study is a proof-of-principle study in participants with depression.

Eligibility Criteria:
Study 1

Inclusion Criteria

* Male or female
* Age 18-65
* Endorse good health with no history of mental or physical illness or implanted metal
* English as a primary language
* Capacity to consent
* Negative urine pregnancy test if female of childbearing potential
* Willingness to adhere to the study schedule and assessments

Exclusion Criteria

* Any current psychiatric diagnosis or current Clinical Global Impression ratings of psychiatric illness \> 1
* Neurodevelopmental disorders, history of CNS disease, concussion, overnight hospitalization, or other neurologic sequela, tumors, seizures, meningitis, encephalitis, or abnormal CT or MRI of the brain
* Any head trauma resulting in loss of consciousness
* Visual impairment (except the use of glasses)
* Inability to complete cognitive testing
* Active participation or plan for enrollment in clinical trial affecting the psychosocial function
* Repeated abuse or dependence upon drugs (excluding nicotine and caffeine) or taking medications including stimulants, modafinil, thyroid medication, or steroids
* Implanted devices/ferrous metal of any kind
* History of seizure or epilepsy, currently taking medications that lower seizure thresholds
* Claustrophobia or other conditions that would prevent the MRI assessment.
* Pregnancy (or suspected/possible pregnancy or plan to become pregnant in the short term).

  o Urine Pregnancy Test: If the subject is a woman of childbearing potential and /or a man capable of fathering a child before, during, and/or after participation precautions should be taken. Examples of acceptable methods of birth control for participants involved in the study include birth control pills, patches, IUDs, condoms, sponges, diaphragm with spermicide, or avoiding sexual activity that could cause the subject to become pregnant.
* Inability to adhere to the treatment schedule

Study 2

Inclusion Criteria

* Male or female
* Age 18-65
* Endorse current depression, identified via the Hamilton Depression Rating Scale (HAM-D scores ≥ 17), but no history of psychosis or mania, determined via the Quick Structured Clinical Interview for DSM-5 Disorders (SCID).
* English as a primary language
* Capacity to consent
* Negative urine pregnancy test if female of childbearing potential
* Willingness to adhere to the study schedule and assessments

Exclusion Criteria

* Neurodevelopmental disorders, history of CNS disease, concussion, overnight hospitalization, or other neurologic sequela, tumors, seizures, meningitis, encephalitis, or abnormal CT or MRI of the brain
* Any head trauma resulting in loss of consciousness
* Visual impairment (except the use of glasses)
* Inability to complete cognitive testing
* Active participation or plan for enrollment in clinical trial affecting the psychosocial function
* Repeated abuse or dependence upon drugs (excluding nicotine and caffeine) or taking medications including stimulants, modafinil, thyroid medication, or steroids
* Implanted devices/ferrous metal of any kind
* History of seizure or epilepsy, currently taking medications that lower seizure thresholds