Theta Burst Transcranial Magnetic Stimulation of Fronto-parietal Networks: Modulation by Mental State
Condition: Healthy
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): TMS; n-back working memory task
Intervention type(s): Device; Behavioral
Intervention description(s): Intermittent theta burst stimulation TMS applied to the cortex to excite cerebral cortex; Subjects perform an executive function task, in which they view the serial presentation of letters and decide whether or not a letter matches a letter presented 'n' letters back (2 letters or 1 letter)
Other intervention name(s): intermittent theta burst stimulation (iTBS)
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Intervention model description: All participants will have 3 MRI sessions subsequent to the baseline visit and these will occur in a counterbalanced order.
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: functional magnetic resonance imaging; Transcranial Magnetic Stimulation; dorsolateral prefrontal cortex