Decoding and Modulating Affective Brain States

Generating personalized brain signatures of negative emotion along with personalized brain stimulation protocols to disrupt these patterns. We plan to use fMRI and muscle activity data to determine negative affect maps for each participant. We will then try a variety of patterned repetitive transcranial magnetic stimulation sequences while recording fMRI which will be the basis of two sessions of 3-day individualized brain stimulation designed to reduce negative affect.

The study involves 9 visits and 4 optional visits. Visit 1 will consist of a consenting and extended screening visit. Visit 2 will involve a 1hour MRI scan and an assessment session. The MRI scan will include both structural and functional scans, facial electromyography (EMG) recordings, cognitive tasks, and multiple questionnaires.Visit 3 will be a 2-hour TMS/fMRI session, where the participant will engage in behavioral tasks while interleaved rTMS rounds are delivered at different excitatory frequencies. This scan will be used to determine the optimal stimulation frequency for the participant. During the Visits 4-6, participants will receive rTMS using either the optimal or least optimal rTMS stimulation frequency. They will also complete a worry induction or relaxation task before and after rTMS, with assessments in between. We will counterbalance whether do worry or relax first. After these visits there will be two optional MRI scans, one similar to Visit 2, and another similar to TMS/fMRI visit. After two weeks, the study Visits 7-9 will mirror the Visits 4-6 study visits, however the rTMS stimulation frequency used would be counterbalanced. The order of optimized and least-optimized frequencies will be counterbalanced across participants between Visit 4-6 and Visit 7-9 (i.e. half of the participants will receive stimulations of the two frequencies in one order, and the other half will receive stimulations of the two frequencies in the reverse order). After this second round of neuromodulation, the same optional visits will be repeated. These optional visits will examine brain and behavioral changes after each round of neuromodulation. After completing all procedures, participants will receive the study compensation. Payment procedures completed may be given earlier if participants withdraw from the study.

All subjects will receive TMS using the optimized and least optimized frequencies, but the order is randomized and counterbalanced.

Through manipulation of brain state with a negative-affect task and using fMRI as the feedback signal, we aim to fine-tune repetitive Transcranial Magnetic Stimulation (rTMS) delivery to maximally impact the desired brain states in awake behaving study participants in a highly individualized manner (Visit 3: TMS/fMRI). The optimal rTMS stimulation frequency will be tested in a 3-day rTMS neuromodulation intervention.

We will compare the results of the optimal rTMS frequency neuromodulation with a separate 3-day neuromodulation session using the least optimal rTMS frequency, as determined by Visit 3: TMS/fMRI.

Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. The MagPro X100* magnetic stimulator and Cool-B65 Butterfly Coil are FDA-approved for rTMS treatments of depression.

Change in ruminative response scale (RRS) score after using the optimal rTMS stimulation frequency vs the least optimal rTMS stimulation frequency

By comparing the RRS score change pre/post rTMS of both neuromodulation sessions (Visits 4-6/7-9) we will see if our optimal rTMS stimulation frequency is more effective at improving clinical outcomes.

Inclusion criteria: 18-65 years old Right-handed Patient Health Questionnaire (PHQ-9 score) = or > than 10 Comprehension of instructions in the English language. Capacity to provide informed consent and follow study procedures. Availability for the duration of the study. Exclusion Criteria: Diagnosis of bipolar disorder (as PI discretion), schizophrenia or other psychotic disorder Recent use of psychoactive medications or substances as determined by investigators History of neurological disorder or traumatic brain injury (other than mild) Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data Unable to receive or tolerate TMS Implanted devices, such as an aneurysm clip or cardiac pacemaker History of stroke, epilepsy, or brain scarring Pregnant, nursing, or trying to become pregnant (self-attestation alone) Otherwise determined by investigator to be unfit for study