Theta Burst Transcranial Magnetic Stimulation of Fronto-parietal Networks: Modulation by Mental State

The purpose of this study is to improve understanding of the way transcranial magnetic stimulation (TMS), a form of non-invasive brain stimulation, affects the brain. The study hypothesis that when theta burst stimulation (TBS) is applied during a controlled mental state, network changes will be facilitated, compared to stimulation when mental state is uncontrolled. This study will focus on the dorsolateral prefrontal cortex (dlPFC) and the associated frontoparietal network (FPN), which subserves cognitive control - the ability to flexibly adapt and regulate behavior, an ability known to be impaired in neuropsychiatric conditions such as depression and dementia.

Healthy volunteers that qualify for this study will have psychological assessments and cognitive measures (due to Covid, some of these were done via teleconference), as well as functional Magnetic Resonance Imaging (fMRI) scans, completed after administration of TMS. Participants will be asked to come in for a total of five visits that include; a screening and assessment visit; a baseline functional magnetic resonance imaging (fMRI) scan, followed by TMS session; Visits 3, 4, and 5 will be the experimental TMS session, followed by fMRI scan.

We will test the broad hypothesis that when TBS is applied during a controlled mental state, network changes will be facilitated, compared to stimulation when mental state is uncontrolled. We will focus on the dorsolateral prefrontal cortex (dlPFC) and the associated fronto-parietal network (FPN), which subserves cognitive control -- the ability to flexibly adapt and regulate behavior, an ability known to be impaired in neuropsychiatric conditions such as depression and dementia. We will use an 'n-back' task tapping cognitive control and the FPN. We will employ a within-subjects design with 40 healthy subjects in 4 MRI sessions. Each MRI session will consist of blood oxygenation level-dependent (BOLD) fMRI during an n-back task, resting state BOLD fMRI to measure connectivity and resting state arterial spin labeling (ASL) MRI to measure cerebral blood flow (rCBF) and examine effects on resting activity level. BOLD activation during the n-back will identify the FPN and the target site for dlPFC TBS. After a baseline fMRI session, subsequent sessions over different days will entail TBS, immediately followed by an MRI session to assess the effects of stimulation. TBS will involve: 1) dlPFC stimulation by active iTBS (600 pulses) alone or 2) while simultaneously performing an n-back cognitive task or 3) vertex (control) iTBS stimulation, alone.

Eligibility Criteria:
Inclusion Criteria:

* Women of child bearing age can not be pregnant or trying to become pregnant
* Ability to tolerate small, enclosed spaces without anxiety
* Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 lbs, men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly
* Ability and willingness to give informed consent to participate
* Alcohol or drug dependence (if in remission for greater than 5 years)

Exclusion Criteria

* History of past or current mental illness (except simple phobias)
* History of closed head injury, for example, loss of consciousness \> approximately 5 minutes, hospitalization, neurological sequela;
* Metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition (for example; aneurysm clips, retained particles or metal workers with exposures, neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, cerebral spinal fluid (CSF) shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, and automatic implantable defibrillators).
* Prescription or non-prescription, with psychotropic effects (birth control medications allowed)
* First-degree family members with a history of epilepsy
* History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure