Cycloserine rTMS Plasticity Augmentation
Condition: Motor Activity
Study type: Interventional
Phase: Phase 1

Summary: 
      Transcranial magnetic stimulation (rTMS) is an investigational and therapeutic modality that
      impacts the connection strength between neurons by delivering patterned energy. In response
      to this patterned energy neurons fire and adapt by changing their connection strengths. This
      change in connection strengths is believed to be the underlying mechanism whereby this
      intervention has therapeutic benefit for this intervention in conditions such as depression.
      The purpose of this study is to test a means of enhancing the effect of rTMS using a
      medication (cycloserine) that has been shown to augment and stabilize activity dependent
      neuronal changes. The investigators wish to use the motor system, where the associated muscle
      response to brain stimulation can be measured, to probe activity dependent changes in
      connection strength between neurons.
    

Detailed description: 
      This randomized, placebo-controlled, crossover trial will enroll 12 healthy participants. In
      one arm of the study, participants will randomly receive either 100mg of d-cycloserine (DCS,
      an antibiotic) or a placebo capsule, and participants will receive the other intervention one
      week later.

        1. The investigators will recruit 12 healthy participants through community advertisement,
           carefully screened for exclusion factors related to rTMS and DCS.

        2. Participants will be randomly assigned by random number sequence with allocation
           concealment to one of two first arms of the crossover study: a) placebo-DCS 100mg and b)
           DCS 100mg-placebo.

        3. Participants will complete the QIDS-SR (Quick Inventory of Depressive Symptoms-Self
           Report), the MDQ (Mood Disorders Questionnaire), the BAI (Beck Anxiety Inventory), and
           the STAI (State Trait Anxiety Inventory).

        4. Participants will take their blinded capsule at least 30 minutes hours prior to TBS. (we
           anticipate that it will take approximately 30 minutes to do steps 5-7).

        5. Electromyographic (EMG) electrodes will be positioned over the first dorsal interosseous
           (FDI) bilaterally to record motor evoked potentials (MEPs). These are non-invasive
           electrodes that use an adhesive to stick to the skin.

        6. Using neuronavigation in conjunction with an atlas brain, the M1 hand strip will be
           localized using single pulse TMS (MagPro X100).

        7. Motor evoked potentials are measurements of muscle activation, in this case in response
           to TMS stimulation of the brain. The investigators will use single pulse TMS to record
           the magnitude of responses. As a baseline, the investigators will collect twenty
           single-pulse (120% resting motor threshold (RMT), 0.25Hz) MEPs every 5 minutes for the
           15 minutes preceding TBS rTMS.

        8. TBS rTMS will be applied to the FDI 'hotspot'. TBS consists of 2s trains every 10s.
           Trains are composed of 3 pulses at 50Hz, 200ms intervals, 80% RMT. Total time 190s and
           600 pulses.

        9. After TBS, twenty MEPs will be acquired (single pulse, 120% RMT, 0.25Hz) every 5 minutes
           for the first 30 minutes, at 60 minutes, at 90 minutes, and at 16Hrs (the following
           morning).

       10. At the 16 Hrs time point, the investigators will characterize stimulus response curves
           (MEPs at stimulus intensities ranging from 100-150% resting motor threshold presented in
           random order).

      As this is a cross-over study, participants will return 1 week later to repeat the second arm
      of the protocol and will repeat steps 2-10).
    

Intervention name(s): Transcranial Magnetic Stimulation; Cycloserine; Placebo Oral Tablet
Intervention type(s): Device; Drug; Drug
Intervention description(s): Single-pulse transcranial magnetic stimulation and theta-burst stimulation; Cycloserine 100mg; Placebo capsule matched to cycloserine capsule
Intervention MeSH terms: Cycloserine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science